The Laboratory Assistant Guide From BUCHI PDF

The Laboratory
Assistant
The Laboratory
Assistant
Impressum
Project/ Technical editing

First edition Caroline Portmann, Samuel Flückiger,
Thomas Ziolko, Andreas Tauer,
Alex Wiprächtiger, Jörg Müller
Third edition Sabine Kleinhans, Cordin Arpagaus,
Gerhard Schönenberger
Büchi Labortechnik AG, CH-9230 Flawil
Design by Cavelti AG, Druck und Media, CH-9201 Gossau
CTP and Printing by Cavelti AG, Druck und Media, CH-9201 Gossau
Bound by Brülisauer Buchbinderei AG, CH-9201 Gossau
Copyright © 2007 by Büchi Labortechnik AG,

CH-9230 Flawil
Further publications: Laboratory Chromatography Guide,

ISBN 3-033-00339-7
Third edition All rights reserved. No part of this book may be reprinted, or reproduced, or
Printed in Switzerland utilized in any form or by any electronic or mechanical means, now known or
hereafter invented, including photocopying and recording, or in any information
ISBN 978-3-033-01315-5 storage and retrieval system, without permission in writing from the publisher.
«The Laboratory Assistant» – an indispensable aide for your daily
laboratory work!
The stimulus for innovation is the conversion of visions into the reality. Since de-
cades, Buchi has supported this philosophy very successfully with new product
innovations for evaporation and separation. With the continual development of
methods and technologies for the laboratory, we have the pleasure of presenting
the revised edition of the «Laboratory Assistant».
This guide will help you acquire a broader and deeper understanding of several
of the most widely used laboratory instruments, as rotary evaporators, vacuum
pumps, and instruments for melting point determination. The equipment shown
in the illustrations are all products of Büchi Labortechnik.
The chapters of the book, have been created in as general terms as possible
so that they will also apply to equipment supplied by other m anufacturers.
I wish all readers of this «Laboratory Assistant» an interesting time in reading
the book, and a challenging and successful work in the laboratory!
Dr. Reinhardt Büchi

Contents
Part A eparation of mixtures using a rotary evaporator,

S
the glass oven and a spray dryer

1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.2 Areas where rotary evaporators, drying ovens and spray dryers
are utilized. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
1.3 Historical development of the rotary evaporator. . . . . . . . . . . . . . . . . . . 14

2 Theoretical basis for distillation
2.1. Thermodynamic basis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.1 Conditions of state, phase transitions . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.2 Boiling point, vapor pressure, and evaporation heat. . . . . . . . . . . . . . . . 19
2.1.3 Vapor pressure curves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.1.4 Evaporation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2.1.4.1 Retarded boiling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1.5 Condensation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1.6 Sublimation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1.7 Transport of gas through the equipment . . . . . . . . . . . . . . . . . . . . . . . . 24
2.2 Separation of mixtures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.2.1 Separation by distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
2.2.1.1 Separation effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.2.1.2 Ideal mixtures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
2.2.1.3 Non-ideal and azeotropic mixtures . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2.1.4 Improvement of the separation effect. . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2.2.2 Drying. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

3 Design of the rotary evaporator
3.1 Schematic design of a rotary evaporator. . . . . . . . . . . . . . . . . . . . . . . . 32
3.2 Heat supply. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.2.1 The heat source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.2.2 Heat transfer media. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.3 The drive and the support frame. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.3.1 The motor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.3.2 The jack . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.3.3 Controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.3.4 The sealing system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.4 The glassware. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.4.1 The evaporation flask . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.4.2 The glass assembly. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.4.3 The receiving flask. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.5 The vacuum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.6 Description of important accessory equipment . . . . . . . . . . . . . . . . . . . 39
3.6.1 The temperature probes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.6.2 The Combi-Clip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3.6.3 Other accessory equipment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
4 Rotary evaporator applications
4.1 Possible distillations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
4.2 Determining the optimum conditions for temperature and pressure. . . . 41
4.3 The distillation process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.3.1 Preparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
4.3.2 Starting distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.3.3 Distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.3.4 Ending distillation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.4 Drying. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.5 Environmental distillation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.6 Distillation of mixed solvents using the automatic function. . . . . . . . . . . 48
4.7 Safety precautions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
5 Design of the glass oven

5.1 Schematic design of the glass oven . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
5.2 The control section. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
5.3 The heater section. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.4 Accessories. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.4.1 The drying accessory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.4.2 The distillation accessory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
5.4.3 The sublimation accessory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
5.5 The bulb-tube drive. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
5.6 The freeze drying accessory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
6 Glass oven applications

6.1 Possible applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.2 Determing the optimum conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.3 Distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.3.1 Single distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
6.3.2 Fractional distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
6.4 Drying. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
6.5 Sublimation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
6.6 Safety precautions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
6.7 Ecological and economic considerations. . . . . . . . . . . . . . . . . . . . . . . . 63
6.8 Table of solvents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
6.9 Working pressures for different vapor temperatures
of various solvents [mbar] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
6.10 Vapor pressure curves for various solvents . . . . . . . . . . . . . . . . . . . . . . 66

Contents
Part B Spray Drying
1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
1.1 What is Spray Drying?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
1.2 Particle shapes and structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
1.3 History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
2 Theoretical basis of the spray drying process. . . . . . . . . . . . . 70

2.1 Feed preparation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2.2 Atomization and hot gas contact. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
2.3 Evaporation, particle shape formation and drying . . . . . . . . . . . . . . . . . 72
2.4 Separation of the dried product from the gas and discharge. . . . . . . . . 73

3 Design of the Mini Spray Dryer B-290. . . . . . . . . . . . . . . . . . . . 74
3.1 Spray drying principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
3.2 Open and closed mode configurations . . . . . . . . . . . . . . . . . . . . . . . . . 75
3.3 Spray chilling accessory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

4 Optimizing the spray drying process parameters. . . . . . . . . . 78
4.1 Inlet temperature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.2 Aspirator rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.3 Feed pump rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.4 Feed concentration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.5 Gas spray flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
4.6 Procedure to run a spray drying experiment . . . . . . . . . . . . . . . . . . . . . 81

5 Spray drying applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

6 Safety precautions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

6 Literature. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

Part C Generation of a vacuum
1 Introduction
1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
1.2 History of the development of vacuum generation. . . . . . . . . . . . . . . . . 90
1.3 Applications for vacuums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
2 Theoretical basis for the generation of vacuum

2.1 Definition of a vacuum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
2.2 Basic gas theory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
2.2.1 The laws of gases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
2.2.2 Transport processes within the gas. . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
2.3 Measurement of vacuum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
3 Vacuum regulation
3.1 Changes in pressure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
3.1.1 Leakage air. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
3.1.2 Leak detection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
3.2 Maintaining a constant pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
4 Survey of types of pumps

4.1 Oil-sealed rotary pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.2 Oil-free displacement pumps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
4.3 Vapor pumps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
5 Vacuum pump technology

5.1 The diaphragm pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
5.1.1 Design and operation of the diaphragm pump. . . . . . . . . . . . . . . . . . . . 107
5.1.2 Economic and ecological considerations. . . . . . . . . . . . . . . . . . . . . . . . 109
5.2 The water jet pump. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
5.2.1 Design and operation of the water jet pump . . . . . . . . . . . . . . . . . . . . . 110
5.2.2 Economic and ecological considerations. . . . . . . . . . . . . . . . . . . . . . . . 110
6 Application of vacuum systems in the laboratory

6.1 Selection of vacuum systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
6.1.1 Suction output. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
6.1.2 Final vacuum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
6.1.3 User-friendliness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
6.1.4 Financial aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
6.1.5 Reduction of emissions into the exhaust air and waste water . . . . . . . . 113
6.2 Comparison of the PTFE-diaphragm pump and the water injector pump. . 114
6.3 Design of a complete vacuum system based on
a PTFE-diaphragm pump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
6.4 Instructions, parameters, and special features of
several laboratory applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
6.4.1 Vacuum for distillation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
6.4.2 Vacuum for filtration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
6.4.3 Vacuum for drying. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
6.5 Precautionary actions and dangers involved . . . . . . . . . . . . . . . . . . . . . 117
Contents
Part D Melting point

1 Introduction
1.1 What is a melting point? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
1.2 Why measure melting points?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
1.3 Who measures melting points?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
1.4 The boiling point. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
2 Theoretical basis for the measurement of boiling points

and melting points
2.1 Physical states . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
2.2 Phase transitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
2.2.1 Phase diagrams for 1-material systems (state diagrams). . . . . . . . . . . . 124
2.3 What happens during melting? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
2.4 The boiling point, or «What happens during evaporation»? . . . . . . . . . . 127
2.5 The range between the boiling point and the melting point . . . . . . . . . . 129
2.6 Melting point depression and the mixed melting point. . . . . . . . . . . . . . 129
2.6.1 Melting point depression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
2.6.2 Mixed melting point. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
2.6.3 The eutectic point. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
3 Principles and methods of melting point determination

3.1 Methods of melting point determination. . . . . . . . . . . . . . . . . . . . . . . . . 131
3.1.1 Determining the melting point in the capillary tube. . . . . . . . . . . . . . . . . 131
3.1.2 Immediate melting point . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
3.2 Principles of melting point determination. . . . . . . . . . . . . . . . . . . . . . . . 134
3.2.1 Melting point determination according to the pharmacopoeia . . . . . . . . 134
3.2.2 Thermodynamic determination of melting points. . . . . . . . . . . . . . . . . . 134
3.3 Melting point determination yesterday and today – an overview. . . . . . . 136
3.3.1 Instruments for melting point determination
over the course of the years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
3.3.2 From silicone oil to the metal block. . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
3.3.3 Data Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
4 Melting point determination using the Büchi B-545

4.1 Operating Principle of the Büchi B-545. . . . . . . . . . . . . . . . . . . . . . . . . 138
4.1.1 Automatic Determination of the melting points. . . . . . . . . . . . . . . . . . . . 138
4.1.2 Metal heating block. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
4.2 Structure of the Büchi Melting Point B-545. . . . . . . . . . . . . . . . . . . . . . 140
4.3 Melting point determination procedure with the Büchi B-545. . . . . . . . . 141
4.3.1 Preparation of the samples. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
4.3.2 Temperature settings and rate of heat rise. . . . . . . . . . . . . . . . . . . . . . . 141
4.3.3 Calibration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
4.4 Flow charts for a melting point determination with the Büchi B-545. . . . 143
4.4.1 Substances with a known melting point or range. . . . . . . . . . . . . . . . . . 144
4.4.2 Substances with an unknown melting point or range. . . . . . . . . . . . . . . 145
4.5 Boiling point determination with the Büchi Melting Point B-545. . . . . . . 146
4.6 Troubleshooting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
5 Data quality – accuracy control
5.1 Pharmacopoeia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
5.2 Avoiding errors in melting point determination. . . . . . . . . . . . . . . . . . . . 148
5.3 GLP (Good Laboratory Practice) regulations . . . . . . . . . . . . . . . . . . . . . 149
5.4 GMP (Good Manufacturing Practice) regulations. . . . . . . . . . . . . . . . . . 150
6 Technical terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
Appendix
Bibliography Part A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Bibliography Part B. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Bibliography Part C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Bibliography Part D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
A Separation of mixtures
using a rotary evaporator, a
glass oven and a spray dryer
B Spray Drying
C Generation of a vacuum
D Melting point
Separation of mixtures
using a rotary evaporator,
a glass oven and a spray dryer
A
14 Part A Separation of mixtures using a rotary evaporator, a glass oven and a spray dryer
1 Introduction
1.1 Overview
This chapter describes the equipment used for thermal separation of mixtures
of materials. The name given to the process differs according to the condition in
which the materials being separated are present. Whenever two liquids are being
separated, one speaks of distillation. Whenever a liquid is being separated from
a solid, one speaks of drying. Sublimation is a separation of solids by evaporat-
ing them, bypassing their liquid phase, and then re-solidifying them. Spray drying
involves the drying of a solution or a suspension of a compound by spraying it
into a hot air stream. Nevertheless, most of these procedures are based on the
same principle. This being that different materials have different vapor pressures.
The mixture is heated until it evaporates and then is re-condensed. The substance
with the lower vapor pressure accumulates in the vapor and in the condensate.
There are a great number of devices available to carry out distillation, drying, and
sublimation. This chapter restricts itself to the rotary evaporator, glass oven and
the spray dryer.
The first section presents the theoretical fundamentals for an understanding
of thermal separation processes. The sections that follow deal with the design
and applications of the rotary evaporator, the glass oven, the spray dryer and
important accessory equipment.
1.2 Areas where rotary evaporators, drying ovens and spray dryers
are utilized
Rotary evaporators carry out single distillations and drying quickly and sparingly.
The rotation increases the surface area of the mixture, thereby improving the
heat transfer. This makes vaporization easier and avoids local overheating and in-
crustation. It also reduces retarded boiling and foaming. The vacuum lowers the
boiling point, making low-temperature distillation possible. In addition, the use of
special glass attachments enables carrying out extractions, (re-)crystallizations,
and reflux reactions as well as distillation and drying.
Glass ovens are suitable for separating small amounts of mixed substances.
They can be used in all separation processes. The possibility of connecting dry-
ing ovens to a rotary motor and their vacuum strength make them similar to small
rotary evaporators. In addition, they can use bulb-tube distillation to separate
multi-component mixtures. Glass ovens are ideal for work being performed on
a micro-scale. During the spray drying process a solution or suspension is dis-
persed into millions of individual droplets with the help of a spray nozzle. The
surface area is strongly increased and the solvent, usually water, evaporates in a
stream of hot air. Within few seconds the product is present as either a powder,
granulate or agglomerate. Spray drying technology is commonly utilized for the
reduction of weight and volume in the chemical and foodstuffs industries, as well
for the preservation of food.
1.3 Historical development of the rotary evaporator

Distillation, or «drop-by-drop separation», is an art that has been in practice for
a long time. The Persians are thought to have invented it in about 3,500 B.C.
in order to produce rose water. From Persia, it spread very quickly across the
whole of Europe, North Africa, and Asia. In addition to being used for produc-
Part A Introduction 15
Figure 1:
Historical distillation equip-
ment (2nd century).
ing essences, distillation was also used by mariners for desalinating sea water.
Alchemists also practiced distillation. The teachings of alchemy, which arose in
Egypt during the 2nd centrury, represented a combination of religious aspects
and chemistry. This was the first «science» that concerned itself in a practical
way with material. Aristotelian natural philosophy had postulated the existence
of a fundamental material with no qualities, the «prima materia». The alchemists
Figure 2:
An air-cooled and a
water-cooled distillation
device for laboratory use
(16th century).
sought to transform natural materials chemically into this basic material, and
thento impart to it the new qualities desired, e.g., those of gold (transmutation). In
their search they discovered a large number of chemical compounds, improved
existing processes and equipment, and discovered new processes that have
later been adopted and used in modern chemistry. They also developed distilla-
tion apparatus that, from a design-related stand-point, is still being used today.
Four classical components of the design include: the heating bath, the bubble
flask, the head, and the condenser.
During the 17th and 18th centuries, the focus was on the improvement of ex
isting equipment. The equipment was insulated, the process of continuous distil-
lation was introduced, and water was used as a coolant. The vapor distillation
process was also discovered during this time. In selecting the materials for their
apparatus, scientists departed more and more from metal and concentrated on
glass.
At the end of the 17th century, the Irish physicist Robert Boyle (1627–1691)
who had involved himself intensively with vacuums, performed the first vacuum
distillations. Finally, during the 19th century, there came the first rectifying col-
umns that made multi-stage distillation possible. A innovative explosion occurred
in the mid-19th century with the arrival of organic chemistry. New equipment
16 Part A Introduction
Figure 3:
Büchi’s first rotary
evaporator.
was specially designed for the needs of the laboratory. Financial involvement
by the alcohol industry in France brought about a rapid development on a large
industrial scale as well.
The use of a vacuum in distillation processes has played a decisive role ever
since Boyle’s first experiments. Invention of the pressure regulator and improve-
ment of pumps also enabled a more directed use of the vacuum. In the begin-
ning, only bubble equipment was used for vacuum distillations. Articles by C.C.
Draig (1950) and M.E. Volk (1955) published the operating principle behind the
rotary evaporator. This process has a far better heat transfer rate than the flask
process, which spares the product and increases output. Only two years after
Volk’s article appeared in early 1957, Büchi Labortechnik in Flawil brought the
first rotary evaporator to the market.
For more detailed information on this topic:

– E. Krell: Handbuch der Laboratoriumsdestillation
This book provides an interesting history of distillation. Unfortunately, its
presentation concentrates mainly on the development of the equipment and
less on the individuals who took part in it.
Part A Theoretical basis for distillation 17
2 Theoretical basis for distillation
2.1 Thermodynamic basis
2.1.1 Conditions of state, phase transitions

Depending on pressure and temperature, any material may be present in three
different phases: solid, liquid, and gaseous. In the solid phase the smallest par-
ticles behave as a solid showing only small degrees of motion due to a high
binding energy. They swing in a fixed position in their molecular lattices and usu-
ally rotate around their axes. The higher the temperature, the more violently they
swing or rotate and the distance between the particles usually increases. When
heat is applied to a solid material, its kinetic energy increases steadily until, at
the melting point, the kinetic energy becomes strong enough to overcome the
forces of attraction. The material liquefies. The individual molecules are now able
to move about more or less freely within the substance, but the attracting energy
between them is still too strong for them to separate from the other molecules.
Additional heating of the material removes that energy barrier up to the boiling
point. The molecules then have sufficient kinetic energy to enable them to move
freely within space without being held back by the forces of attraction. The mate-
rial is now a gas.
Figure 4:
Particle model of the
3 phases: solid, liquid,
and gas.
These phase transitions are reversible. When a gas turns into a liquid, people
talk of condensation. When a liquid turns into a solid, it freezes or solidifies. If
the right conditions are selected, a solid can also be transformed directly into
its gaseous phase, bypassing the liquid state. This process, in either direction,
is called sublimation. The existing phase is influenced both by the temperature
and by the pressure. The lower the pressure, the weaker the forces of attraction
between the molecules. This means that both the melting point and the boiling
point are lower at low pressures.
A given material may have several solid phases that differ in their crystalline
lattice structure but, with the exception of helium, it can have only one liquid and
one gaseous phase.
Fig. 5 shows the relationships between temperature, pressure, and volume.
This diagram shows various possible paths for going from the solid into the gas-
eous phase.
– Path from A to F: A solid is being heated under constant atmospheric pressure.
When it reaches the melting point, there is a sudden increase in volume: the
material liquefies. With further heating, its volume increases steadily until the
18 Part A Theoretical basis for distillation
Figure 5:
p-V-T surface of a pure
material. V has been
graphed logarithmically.
liquid
k
v=v
T=c
onst
melting zone
T=const
t
ns
solid co
p=
pk
p=
t
o ns
p=c K
freezing line
melting line
F
M
T=
Tk
L D
p E
t
ns
co
p=
B
C
A
dew lin
e
gas phase
H T=c
ons
triple t
G line
T
e
lin
wet steam zone

ion
0.15 Vk
at
m
bli
de I
su
Vk su
bli
v lin mat
e io
10 Vk n
100 Vk
sublimation zone
temperature reaches the boiling point. The liquid starts to boil, changing into
a gas with an enormous increase in its volume. It continues to expand when
heated. This is the normal path for a transformation from a solid to a gas.
– Path from G to I: Here the work is being done under reduced pressure. Due
to the low pressure, the material begins not to melt but to sublimate. It passes
directly into the gas phase.
– Path from L to M: This is a special process. Here the heating is taking place
under a higher pressure so that the liquid is transformed into a gas without
boiling or evaporating.
Several selected points and zones on this diagram are worth mentioning:
– The triple point: This is the point where a certain pressure and a certain
temperature are present at which all three phases are in equilibrium. This
combination of values for p and T is referred to as the «triple point».
– The boiling curve / dew point curve: This is that group of combinations for p
and T at which the substance begins to boil and/or to condense.
– The melting curve / solidification curve: This is that group of combinations
for p and T at which the substance starts to melt or solidify.
– The sublimation line: This is that group of combinations for p and T at which
sublimation starts.
– The critical point (K): At pressures and temperatures above this point, no
boundaries exist between the gas and liquid phases.
2.1.2 Boiling point, vapor pressure, and evaporation heat

As already shown, a liquid transforms into the gaseous state at its boiling point.
This means that no liquid can assume a temperature higher than its boiling point.
Experience, of course, tells us that a liquid can also give off gas before it boils: it
evaporates at far lower temperatures. When a liquid is evaporating, a few of the
molecules on its surface can gather up enough energy to enable them to over-
come the forces of attraction and escape into the environment as a gas. This cools
the liquid, since an amount of energy is withdrawn from it. The higher the tempera-
ture, the more likely it is that a particle will be able to gather up enough energy to
escape into the gas phase. The escaping molecules exert a pressure counter to
the outside pressure. The more particles that can free themselves from the liquid,
the higher that pressure. This vapor pressure depends upon temperature and dif-
fers from one compound to the next. It is a measurement for the volatility of a com-
pound. Since the number of particles able to leave the liquid keeps increasing as
the temperature keeps rising, vapor pressure rises rapidly with temperature. Once
it becomes equal to the outside pressure, there is no longer any force present that
can hold the gaseous molecules back in the fluid. The fluid starts to boil.
The Clausius-Clapeyron equation shows how vapor pressure depends on

temperature:
dIn p Lv L
= In p = – v + c
(2.1) (2.2)
dT RT 2 RT
p is the vapor pressure, T the temperature, R the universal gas constant

(8.3145 J · (mol · K–1)), and Lv the molar heat of evaporation.
Figure 6:
Logarithmic graph of the
vapor pressure curve.
Lnp
Lv/T
Shown in the form of a graph, Equation 2.2 appears as the straight line shown
in Fig. 6. Its slope depends on the heat of evaporation. Because the heat of
evaporation is largely independent of temperature and pressure, it is a constant
specific to the given material. Thus, the slopes of the vapor pressure curves for
different materials also differ from one another.
The difference in the volatility (vapor pressures) of compounds is the criti-
cal factor that makes distillation possible. During the heating process, the more
volatile components of a mixture accumulate in the vapor, and thus in its con- p1 = Partial vapor pressure
densate as well. The French chemist François Raoult examined the dependence solvent 1
p1* = vapor pressure of pure
of vapour pressure on the composition of a component mixture. Through the
solvent 1
investigation of mixtures from similar component mixtures (e.g. from benzene x1 = mole fraction of
and toluene) he found that the quotient p1/p1* is proportional to the mole fraction solvent 1 in the liquid
(x) of solvent 1 in the liquid:
Raoult's law: p1 = p1* · x1

The heat of evaporation is a very important parameter in connection with boil-

ing. As already stated above, molecules need more than a high vapor pressure
to enable their escape from the liquid: They must also be supplied with the en-
ergy they need to overcome the forces of attraction binding them. The heat of
evaporation always remains the same, regardless of whether the liquid is boiling
or is evaporating. This is defined as that amount of heat which must be supplied
in order to evaporate 1 kg of the liquid. Whenever a liquid is heated to its boiling
point and the source of heat is then removed, the boiling stops immediately be-
cause the energy needed for evaporation has been withdrawn from the heating
source. The liquid now cools to below its boiling point. Thus, heat must be
supplied continually to keep a liquid boiling.
As can be seen, two amounts of heat are needed for vaporization:
1. The energy needed to raise the liquid to its boiling point (to raise its vapor
pressure to the ambient pressure level), and
2. The heat of evaporation needed to free the molecules from the liquid.
The evaporation heat does not depend in any way on the vapor pressure
or the boiling point. A high boiling point does not necessarily mean a high evapo-
ration heat. Water, with a boiling point of 100 °C, needs an evaporation heat
of 2,261 kJ/kg, while xylol, with a boiling temperature of 144 °C, only needs
345 kJ/kg.
2.1.3 Vapor pressure curves

The last chapter discussed vapor pressure, showing that it depends on tem-
perature. We have also seen that a liquid starts to boil when its vapor pressure
equals the outside pressure. Vapor pressures can be recorded as a functions of
temperature on vapor pressure diagrams. The locations and the slopes of the
curves produced differ along with the materials (Fig. 7).
The diagram shows the vapor pressures for water (W), chloroform (C), and
amyl alcohol (A). By definition, the pairings of vapor pressures and temperatures
are also the pairings for the system pressure and the boiling point. The boil-
Figure 7:
10 000
Vapor pressure curves for
water (W), chloroform (C),
and amyl alcohol (A). 1000
pressure: log (p) (hPa)
100
C W A
10
bp. diff. bp. diff.
1 10 100 1000
temperature: log (T) (°C)
ingpoints for amyl alcohol (A), chloroform (C) and water (W) under atmospheric
pressure are shown in Fig. 7. They are, respectively, 137 °C (amyl alcohol) and
61,3 °C (chloroform). There is thus a difference of 75 °C between the boiling
points. If the pressure is now reduced to 10 mbar, the boiling point for amyl alco-
hol is only 38 °C, and that for chloroform is about –35 °C (a difference of 73 °C
between the boiling points). This example shows how much the boiling point can
be lowered by reducing the pressure. The fact still remains that the greater the
difference in boiling points is, the more easily a mixture can be separated. How-
ever, such differences between boiling points can only be compared with one
another for different mixtures at one given pressure. To compare the separation
effect for one and the same mixture under differing conditions of distillation, the
relative volatilities must be compared (refer to Chap. 2.2). Generally, a vacuum
improves relative volatilities. Vacuum distillation thus not only allows more favor-
able conditions: it often makes a better separation possible.
To do vacuum distillation, it is necessary to know how to read these vapor
pressure curves. This is the simplest way to find out the pressure at which the
temperature of the bath must be set. Chapter 4.2 provides more information
about this problem. The Appendix also shows additional vapor pressure curves,
in a linear rather than in a logarithmic presentation.
2.1.4 Evaporation
Evaporation is the shift from the liquid phase to the gaseous phase. It starts as
soon as the conditions for pressure and temperature reach the boiling curve. At
that point, all the particles have sufficient kinetic energy to overcome the forces of
mutual attraction binding them. It is now no longer a question of just a few mol-
ecules on the surface breaking away from the liquid. The shift from liquid to gas is
now taking place all throughout the liquid. The boiling point is important for distilla-
Figure 8:
Vapor bubble Nucleate boiling.
tions because the liquid to be removed now vaporizes far more quickly than during
evaporation. Because the molar voume of a gas is several times greater than that of
a liquid, the material expands 1,000- to 2,000-fold during boiling. Care must there-
fore be taken to ensure that the system can handle this volume. Whether the gas is
to be drawn off or to be condensed depends on the application in question.
The first stage in boiling is nucleate boiling. The heat causes bubbles of gas
enclosed within the walls of the container to start expanding. The vaporized
particles leave the liquid and go into these bubbles, causing them to grow. Once
the bubbles reach a point where their buoyancy can overcome the forces of
adhesion, they break away incompletely from the wall of the vessel and rise to
the surface. The part of the bubble that remains serves as the germ for a next
bubble at the same point. A drift flow forms behind the bubble, improving mixing
within the liquid. As the liquid becomes warmer, more and more bubbles form
until, finally, there is an uninterrupted film of vapor covering the wall of the vessel.
This stage is referred to as film boiling.
Figure 9:
Free convection.
cold
warm
One important aspect of boiling is the transfer of heat from the heat source to
the liquid. Because the liquid generally comes into contact with the heat source
only at the wall of the container, its outer layers become warm first. The top layers
remain colder. The warm layers rise due to convection, and the colder layers take
their place. This brings about an equalization of temperatures, but progresses
very slowly.
As a matter of fact, the additional mixing at the start of nucleate boiling does
improve the heat transfer, but the situation is still unsatisfactory. The heat transfer
can be improved considerably by keeping the liquid in motion with a mixer or in
a rotating flask (a rotary evaporator). This continual mixing or forced convection
enables excellent heat transfer, better expulsion of the gas formed, and thus a
quicker distillation.
Figure 10:
a) Start of retarded boiling
(1. bumping), (2. Temp.
2
profile, 3. Convection)
b) Retarded boiling
(1. bumping) at the
surface.
1
a) b)
2.1.4.1 Retarded boiling (bumping)

Free convection also brings along with it the problem of retarded boiling (bump-
ing). Whenever the container includes no seeds for bubbles, or only a few of
them, the liquid cannot evaporate properly close to the heater. The gas particles
that form are present as individuals and thus lack the buoyancy they need to
escape quickly from the liquid. The liquid therefore superheats above its boiling
point, and is carried upward only slowly by convection. When it reaches the sur-
face, it vaporizes almost explosively. The air bubbles then tear large portions of
the liquid off with them, which can damage equipment and present a great risk
of personal injury. That risk can be reduced by the use of boiling chips or forced
convection.
2.1.5 Condensation
Condensation is the reversal of this boiling process in which a substance trans-
forms from its gaseous into its liquid state. Since the heat of evaporation trans-
ferred to the particles during the boiling now has to be removed from them,
condensation requires cooling.
The vapor leaving the point of vaporization reaches the condensation sec-
tion. Because the temperature of the condenser is lower than the condensation
temperature of the vapor, the vapor precipitates out and a film of liquid forms
immediately as its molecules strike the condenser. Since this film impedes the
heat transfer, provisions must be taken to ensure that it can flow off. Condensers
therefore always have a vertical or diagonal design. The condensate flowing off
collects in a collection flask. Because the volume of the gas being condensed is
considerably greater than that of the liquid produced, the heat cannot be carried
off easily. This is why coolers usually have very large surface areas.
To ensure good condensation throughout the entire distillation process, work
is done using a cooling medium that can be continually refreshed, e.g., flowing
tap water, or with a good heat sink, e.g., a cooling trap containing a mixture of
acetone and dry ice. Due to the low temperatures at which they operate, cooling
traps are used mainly for low-boiling solvents.
Boiling results in a great increase in pressure. In condensation, a very great
deal of pressure is dissipated. The condenser acts as a pump.
2.1.6 Sublimation
Sublimation is the vaporization of a substance out of its solid phase, followed
by a «condensation» back into its solid phase, bypassing the liquid phase. This
process is used for solids that have a sufficient vapor pressure even at a tem-
perature lower than their melting point. Such substances can usually be detect-
Figure 11:
Sublimation of a solid (1)
and re-sublimation on a
2 cooling bar (2).
1
ed by an odor. Because the melting and the boiling temperatures of solids are
extremely high, solids cannot be distilled easily. Their sublimation temperature is
clearly lower than their boiling temperature and is therefore important for a spar-
ing treatment of the product. Any substance can be sublimated provided that the
necessary conditions of temperature and pressure can be attained at tempera-
tures under their triple point. Materials that can sublimated under atmospheric
pressure are extremely rare, however, so a vacuum is usually necessary at this
point. The pressure must be reduced until it drops below the vapor pressure of
the substance at the given operating temperature. Re-sublimation takes place
on the cooling finger in the same way as condensation on a condenser. The sub-
stance re-sublimates on the cooling equipment in the form of needles or a crust,
like frost on windowpanes. If the crystals have a good heat transfer capacity, the
vapor produced condenses out mainly on the germs of crystals already present.
If they do not, the vapor condenses out everywhere and a crust is formed.
Sometimes the material is melted for sublimations. This speeds up the pro-
cess considerably, but requires higher sublimation temperatures. This process is
referred to as quasi-sublimation.
2.1.7 Transport of gas through the equipment

A distillation consists of a vaporization and a subsequent condensation. Be-
cause the points where the vaporization and the condensation occur are usually
well separated, the vapor must be transported. This is easily done. As indicated
Figure 12:
The thermal pump (P)
and local differences P
in temperature within
the rotary evaporator.
above, boiling produces up to a 20,000-fold increase in volume. A local overpres-

sure builds up. Because a gas distributes itself evenly within the space available,
it flows from the evaporator side to the condenser side, where it liquefies. This
produces an equivalent drop in volume. A local vacuum results. The condenser
side therefore always draws gas, while the evaporator side always supplies the
same amount of gas. The dynamic difference in pressure created moves the va-
por through the apparatus at high speeds. The force maintaining this flow is the
heat of evaporation supplied to the gas during vaporization. During condensation
this heat is withdrawn again from it. This phenomenon is therefore also referred
to as a thermal pump (P).
In order to maintain a balanced difference in dynamic pressure, it is important

that the speed of condensation and the speed of evaporation be attuned to one
another. Whenever more substance is being vaporized than is being condensed
in the cooler, the pressure within the apparatus will rise and the vacuum pump
will have to draw continually, pulling in the vaporized solvent and pumping it out
into the environment. It is best to work with a boiling temperature about 20 °C
higher than the temperature of the cooling water. This ensures that the heat bal-
ance will be kept in equilibrium.
2.2 Separation of mixtures

The methods of separation to be discussed here are those that can be carried
out with the use of a rotary evaporator or a glass oven: distillation (liquid – liquid),
sublimation (solid – solid), and drying (liquid – solid).
2.2.1 Separation by distillation

Distillation is the separation of two liquids. This process is based on the differ-
ence between the vapor pressures of the substances. The mixture is heated
until it is vaporized and is then re-condensed. In this process, the more volatile
component builds up in the vapor, and thus in the condensate as well, resulting
in separation. The enriched vapor, directed through the equipment, reaches the
condenser where it liquefies and is gathered in a collection vessel. At the same
time, the less volatile component accumulates in the boiling flask. Chapter 2.1
provides more detailed information on these processes.
But as the thermodynamic principles presented in previous chapters show,
what results here is not a complete separation. The greater the difference in rela-
tive volatility, the better the separation. If the boiling points of two materials differ
by more than 80 °C, a good separation can be attained with a single distillation.
Single distillation is used mainly to separate highly volatile solvents from high-
boiling materials. It makes no difference here whether it is the solvent (cleaning of
cooling area
Figure 13:
receiving
area Design of classical
distillation equipment.
separation 3
zone
2 1 evaporation zone
solvents) or the residue (cleaning of a product of reaction) that is to be regained.

Whenever the boiling points of the two components being separated are too
close together, the distillation process must be repeated several times. This pro-
cedure is called rectification.
Fig. 13 shows the classical apparatus used for distillation. A heat source (1)
supplies the heat needed for vaporization. The vaporization process takes place
within a boiling flask (2). The actual separation takes place in the separation zone
(3). The more volatile component accumulates in the vapors, while the less vola-
tile component is held back. The vapor is directed into the condenser (4), where
it condenses and is gathered in the collection vessel (5). Because the composi-
tion of the vapor changes along with the changing composition in the raw mate-
rial, the condensates are often collected in different vessels as fractions.
This classical equipment is no longer frequently used because developments
in the field of distillation technology have produced a great number of devices
and methods that have been specially optimized for certain applications. The
rotary evaporator is one such piece of equipment. It was designed to provide
gentle 1-stage distillation.
2.2.1.1 Separation effect

The purpose of distillation is to separate a mixture of substances. It is therefore
of interest to ensure that the separation be done as well as possible, and that the
distillation produces a good separation effect. The lesser the amount of the high-
boiling phase that enters into the vapor, the better the separation effect will be.
The critical factor here is the relative volatility. A component’s volatility (F), or
the readiness with which the liquid passes over into the vapor phase, is the vapor
pressure of the pure material (p*1) or the quotient obtained by dividing its partial
vapor pressure (p1) by its proportion in the mix (x1) (Raoult's law):
p1
F = p1* = (2.4)
x1
The relative volatility α, i.e. the evaporability of a material 1 in comparison to

the evaporability of the material 2 is the quotient obtained by dividing the vapor
pressures of the pure materials:
p1 *
α= (2.5)
p2 *
Usually, the higher vapor pressure is selected as p1*. This means that α≥1.
The larger the value for α, the greater the difference in volatility is, and the better
the separation effect from a single distillation will be.
Consideration of the relative volatility alone is not enough when considering
the separation effect. The special properties of the mixtures at hand must also be
dealt with since the proportional amounts of the components within the mix also
exert a great influence on its separability and the attainable separation effect.
The total vapor pressure p is derived from the partial pressures p1+p2:
p = p 1 +p 2
p 1 = y1 ⋅ p = x 1 ⋅ γ 1 ⋅ p 1* (2.6)
p 2 = y2 ⋅ p = x 2 ⋅ γ 2 ⋅ p 2*
The activities coefficient γ is a measure for the deviation of the real behavior
to the ideal behavior. In ideal liquids, γ is = 1.
2.2.1.2 Ideal mixtures

Ideal mixtures are soluble in one another in any proportions desired, and the
reciprocal effect between two molecules of the same type is the same as that
between two molecules of the different types. (The activity coefficient γ1 resp. γ2
in ideal mixtures are always 1.) Each molecule has the molar fraction x1 resp. x2 in
its liquid phase, the molar fraction y1 resp. y2 in the vapor, and the partial pressure
p1 resp. p2 in the vapor with the total pressure p. The index 1 is always assigned
to the lower-boiling component.
With it comes (for ideal mixtures)

p 1 = x 1 ⋅ p 1*
(2.7)
p 2 = x 2 ⋅ p 2*
Several informative diagrams with regard to the carrying out of a distillation and
the attainable separation effect can now be set up based on these conditions.
Figure 14:
p Vapor pressure diagram.
T = const.
p1*
120
TS,2 p = 1,013 bar
vapor pressure
+ p2 ~y (T)
= p1 T °C 1
p
100 dew point curve
p2* p1
boiling-curve ~
x1 (T)
80
p2 ~x ~y TS,1
1 1
~x , ~
0 100 1 y1
x1 [Mole %] Figure 15:

Figure 14 Figure 15 Temperature diagram.
The vapor pressure diagram (Fig. 14) shows the partial vapor pressures and
the total pressure as functions of the composition, showing how the composition
of the liquid phase and that of the vapor phase are related at a given constant
temperature.
The temperature diagram (Fig. 15) shows how the boiling and dew points
(condensation points) of x1 and y1 depend on one another at a constant pres-
sure. TS,1 and TS,2 are the boiling points of the pure materials. It can be seen that
there is no linear relationship even in linear mixtures.
Figure 16:
100
p = const. Composition diagram.
composition of the vapor phase
y1[Mole %]
0 xa xb 100
x1[Mole %]
composition of the liquid
There is a wet vapor range between the boiling curve and the dew point curve
in which the liquid and the gas coexist side-by-side.
Fig. 16 is a composition diagram showing how the composition of the vapor
phase depends on the composition of the liquid phase at a given temperature.
The temperature changes as one moves along the curve. The more strongly the
curve arches upward, the better the possibilities of separation. When the curve
lies on the straight line, the composition of the vapor is the same as that of the
liquid and no separation is possible.
2.2.1.3 Non-ideal and azeotropic mixtures

Most mixtures are not ideal. Their behavior when leaving the liquid phase and en-
tering the gas phase is influenced by interactions within the liquid mixture. For this
reason, Equation 2.6 must be expanded to include an activity coefficient γ ≠ 1:
p1 = γ1 ⋅ x1 ⋅ p1 * (2.8)
Figure 17:
Vapor pressure diagram 100
for a liquid mixture of an T = const. pa
p = const.
azeotrope.
p1*
pa
+ p2
p1
vapor pressure
p=
y1 [Mole %]
p2* p1
p2
0 xa 100
Figure 18:
0 xa = ya 100
Composition diagram x1 [Mole %]
for a liquid mixture of an x1 [Mole %]
azeotrope. Figure 17 Figure 18
The curves discussed in Sect. 2.2.1.2 therefore assume other shapes that
can vary quite widely. Let us look at the curves for mixture of an azeotrope here
as example.
At the highest point on the curve in Fig. 17, the mixture has its maximum
vapor pressure (its lowest boiling point). In this concentration, the curve in Fig. 18
intersects the straight line, which means that the compositions of the vapor and
the liquid are the same and that separation is no longer possible. This critical
molar fraction is referred to as the azeotropic point. An azeotrope is a mixture
with a boiling point usually lower than that of its individual constituents. Distillation
can be carried out only down to the azeotropic point (Fig. 18).
2.2.1.4 Improvement of the separation effect

There are several ways in which the separation effect can be improved. The
greatest improvement is attained by means of multi-stage distillation, multi-stage
build-up, and rectification.
Optimization of the pressure and temperature relationships also brings about
an improvement (refer to 4.2). This includes continual adaptation of the para
meters since, as mentioned above, these parameters change as the composi-
tion changes.
Figure 19:
100
Dependence of the
azeotropic point on system
pressure.
rr
To
rr
1
To
y1 [Mole %]
rr
To
10
0
76
0
0 100
x1 [Mole %]
A further improvement can be attained by working in a vacuum. The vapor

pressure curves differ in slope and are wider apart, i.e., the relative volatility is
higher in a zone where temperatures are low. Because lower temperatures are
possible when working under a vacuum, one can take advantage of this higher
relative volatility. The vacuum also has a positive effect on the separability of
azeotropic mixtures. As the pressure drops, the concentration of the lower-boil-
ing component increases at the azeotropic point. The azeotropic point drifts
higher and higher and often disappears completely.
Installing fillers e.g., activators, brings about a partial condensation in the evap-
oration range, producing a counter-flow enriched with the higher-boiling compo-
nent. The principle is also referred to as countercurrent distillation. Keeping the
mixture in motion by stirring it or rotating it also improves the separation effect be-
cause it prevents the depletion of the lighter-boiling substances at the surface.
2.2.2 Drying
Drying is the separation of a liquid from a solid. The vapor is carried away from
the material and allowed to escape from the drier. Whenever organic solvents are
used, it is recommended that they be condensed out. Whenever a product is moist
enough, the speed of drying at the start depends on the same factors as the speed
of distillation (vapor pressure, system pressure, heat supplied). Only after the liquid
has evaporated from the surface is a point reached where the thermal conductivity
of the solid and the wandering of the moisture from its inside to the surface (pore
structure, hygroscopic behavior) start to have a large influence on the evaporation
rate. Because the vapor pressure of a solid is very slight in comparison to that of the
liquid being removed, complete separations are theoretically possible.
However, several difficulties arise in the drying of solids that do not exist with a
mixture of liquids. The product being dried can be present in three forms: either
as a moist solid, as a pulp or paste, or in the form of a solution, suspension, etc.
The procedures required are different in each of these cases.
A solid can easily be dried by supplying heat to it in a drying oven. The use of
a vacuum reduces the drying time and makes a gentler treatment of the material
possible. Keeping the product in rotation whilst drying it prevents the formation
of solid coatings on the surface that would make it difficult for the liquid phase to
leave. Whenever a pulp-like product is being dried, a good deal more liquid must
be evaporated off. With this type of substance, no rotation should be used during
the drying process. Rotating such a mixture causes it to form small balls that dry
out very quickly on their outside and prevent the escape of the liquid contained
within them. This means a massive increase in the drying time required. In the
case of solutions, the solvent must be distilled off, e.g., in a rotary evaporator,
until the solid has crystallized out completely. The solvent that remains can then
be drained off and the crystals can be finish-dried in a drying chamber.
Moreover, the liquids being removed also vary in nature. Distinctions must
be made between adherent liquids, capillary liquids, swelling liquids, and water
of crystallization. An adherent liquid spreads as a film across the surface of the
substance. It can be evaporated off in the normal way.
Figure 20:
Capillary liquid.
Figure 21:
Water of crystallization.
The gray points represent
the water molecules within
the lattice.
Capillary liquids are enclosed in the pores within the substance. The removal of
this liquid is somewhat delayed. If the pores are small, capillary forces come into
play that reduce the pressure. This means that the temperature needed to vapor-
ize it will be higher than that necessary for boiling the liquid in the open. Moreover,
the microcapillaries also take moisture back up from the environment. The mate-
rial is hygroscopic and must be kept in closed containers. Suspensions contain a
solid that has not really dissolved but has been swollen by a solvent, the swelling
liquid. As a result, the solution does not merely wet the substance, but is partially
bound to it. Additional heat must be supplied to dissolve these bonds.
Water of crystallization is a fixed component in the crystalline structure of a
compound and affects its color and shape. In order to drive out this water, the
temperature reached must be high enough so that the crystal decomposes and
releases the water. The solid re-crystallizes in a new structure. High temperatures
are often required for such a process, even when working under a vacuum.
In addition, the term «drying» is occasionally used for the removal of water
from high-boiling liquids. Spray drying is a widespread industrial method for dry-
ing aqueous solutions, emulsions and dispersions. A solution is sprayed into a
hot drying medium and undergoes drying. However spray drying is only possible
if the final product behaves as solid and does not show liquid or sticky properties.
The dried product is present after a few seconds in the form of a homogeneous
powder. Thermally sensitive substances such as enzymes, antibiotics etc. can
remain active after spray drying.

– H.D. Baehr: Thermodynamik
Very useful for an understanding of the basics of thermodynamics. The de-
scriptions of phase transitions, vapor pressures, and the heat of vaporization
are especially good here.
– E. Bertele, F.A. Humbel: Neukonzeption eines Ofens zur Beheizung kleiner
Mengen – insbesondere für die K-R-Destillation
This book describes the principle of bulb-tube distillation.
– R. Billet: Grundlagen der thermischen Flüssigkeitszerlegung
This very short booklet provides a brief and almost too cursory overview of
distillation.
– Büchi Labortechnik, Training documents: Grundlagen der Destillation, Um-
weltschonendes Destillieren
These training documents provide a quick, easy insight into distillation theory.
Particularly valuable here is the treatment of the rotary evaporator.
– W. Frank, D. Kutsche: Buchreihe Verfahrenstechnik:
(2) Die schonende Destillation
This book provides an in-depth look at gentle distillation processes. It also
includes a detailed chapter on the rotary evaporator. Its presentation of im-
provement of the separation effect is also interesting.
– G. G. Haselden: Cryogenic Fundamentals
Very good chapter about heat transfer theory.
– E. Krell: Handbuch der Laboratoriumsdestillation
This book is generally very informative on the topic of distillation. Unfortu-
nately, it is quite old and scarcely treats vacuum distillation at all. On the other
hand, it presents a great deal of information with regard to distillation technol
ogy in general.
– R. H. Perry: Chemical engineers' handbook
Comprehensive description of basics for chemical engineering.
– Andreas Pfalz, Reinhard Keese: Grundoperationen der präparativen organi
schen Chemie
This book presents the relationship between practice and theory.
– K. Sattler: Thermische Trennverfahren
This book is oriented primarily toward the construction and planning of pro-
cess technology installations. On the other hand, a great deal of theoretical
detail can be found here, particularly on the topics of drying and sublimation,
that may be treated inadequately in other literature.
– E. U. Schlünder, F. Thurner: Destillation, Absorption, Extraktion
The theory of separation processes is discussed here in a brief and clearly
understandable form.
– K. Masters: Spray Drying in Practice, 2002
A good introduction in the process of spray drying with many applications
from the industry.
32 Part A Design of the rotary evaporator
3 Design of the rotary evaporator
3.1 Schematic design of a rotary evaporator

A rotary evaporator consists of three parts. The heating bath (A) that supplies the
energy, the support frame (B) that holds the parts together and accommodates
the jack (1), the rotary motor (2), and the control device (3), and the glass as-
sembly (C) in which the processes of distillation take place. The glass assembly
consists of the evaporation flask (4), the sealing system (5), the glass condenser
(6), and the receiving flask (7). Various applications are possible, depending on
which model of the glass assembly is provided. Fig. 22 shows the schematic
design of a rotary evaporator.
Figure 22:
Schematic design of a
rotary evaporator.
6
3
B
2+5
4
7
1 A
Part A Design of the rotary evaporator 33
3.2 Heat supply
3.2.1 The heat source

In the rotary evaporator, the heat needed for the distillation is transferred to the
mixture being separated via a liquid bath. This liquid is heated with a heater
located underneath the metal bath. A plastic housing on the outside protects
against physical contact. The geometry of the metal bath can accommodate
even fairly large flasks. The temperature of the water bath is set and regulated
by a thermostat and, depending on the type of bath, is also displayed digitally.
A water bath can be operated within the range of temperatures from 20 °C to
100 °C, an oil bath in the range from 20 °C to 180 °C. A safety switch for excess
temperature protects the heater from burning out.
To reduce heat losses to the environment and thus to reduce power consump-
tion, floating plastic balls can be introduced into the heating medium. These act
like a cover, but do not prevent flask rotation.
3.2.2 Heat transfer media

The heating medium in the water bath is water. Whenever de-ionized or distilled
water is used instead of tap water, 0.2% Borax (Na2B4O7 · 10H2O) must be added
to it. Water has many advantages as a heating medium. Its high thermal capacity
allows a good utilization of the heat. Water has good thermal conductivity, is in-
expensive and readily available, and does not make the pan dirty. Because water
can only be heated to 100 °C, the risk of personal injury is significantly less than
with an oil bath, where the temperature may reach 180 °C. For vacuum distilla-
tion, water should always be used as the heating medium wherever the boiling
point under normal pressure is less than 160 °C.
Whenever a higher-boiling solvent is to be distilled off, the rotary evaporator
must be heated with an oil bath. The advantage of oil is that its high boiling point
means it can be heated to higher temperatures. In addition, it has a good thermal
conductivity and a high thermal capacity. Several points must be noted however
when selecting the oil for the bath:
– Is the oil still sufficiently fluid at low temperatures so that it will not impede the
rotation of the flask?
– Does the oil polymerize at high temperatures?
– Does the oil give off poisonous fumes to the room?
– Does it leave an oily precipitate on the environment surrounding the heating
bath?
– Is it highly flammable? Does it burn well?
Typical oils include Polyethylene glycol (PEG, water-soluble), Silicone oil, Car-
bowax and other special bath oils.
3.3 The drive and the support frame

The support frame holds the rotary evaporator together. The drive unit holds
the glass assembly in position on the frame, which also accommodates the
control unit and the motor driving the flask. Its sturdy, solid construction lends the
complete unit great stability.
3.3.1 The motor

The motor is used to rotate the flask.
3.3.2 The jack

The jack enables quick introduction and removal of the flask from the heating
bath. The jack has a stop-nut built into it to prevent the system from
being pressed too far downward (which could break the glass).
3.3.3 Controls
Control units differ widely from one model to the next. In the least expensive
rotary evaporators, the unit consists of the main power switch and the knob
for adjusting rotating speed. In costlier models, it also includes a digital display
for the rotational speed and the vapor temperature. Top-of-the-line rotary
evaporators also include a Vacuum Controller that measures and controls the
vacuum, and can be used for carrying out automatic distillations. Well-thought
out vacuum controllers even have an automatic distillation function, a gradient
function for special distillation applications and a repeat function for the repro-
ducible repetition of a distillation under optimal process conditions.
3.3.4 The sealing system

The sealing system provides the link between the rotating flask and the static
condenser. This connection must be both leak-resistant and provide a smooth,
and easy slide.
3.4 The glassware

The glassware is the most important structural component in the rotary evapora-
tor. This is where the vaporization and condensation take place. The glassware
consists of the evaporation flask, the sealing system, the glass assembly, and the
receiving flask. There are various glass assemblies available, designed either for
general use or for special applications. Because rotary evaporators usually oper-
ate under a vacuum, the glassware must be vacuum-proof. To provide protection
from splintering glass and the spray of poisonous gasses, Büchi Labortechnik
also offers glass assemblies that have a chemically resistant plastic coating,
Plastic + Glas.
3.4.1 The evaporation flask

The mixture to be separated is put into the evaporation flask and heated in the
heating bath. The evaporating flasks for rotary evaporators are usually pear-
shaped to enable better immersion in the heating medium. In addition to normal
evaporation flasks, there are also special drying flasks available that, with the
baffles built into them, have been designed for drying powdered substances.
Rotation constantly mixes the powder at the baffle plates, thereby speeding the
drying process and preventing formation of a crust. Beaker flasks are available
for working with highly viscous or dry materials. Because they can be opened,
they can be emptied and cleaned effortlessly. The latest developments are aimed
at parallel evaporation. A parallel evaporator with several sample positions is
combined with a rotary evaporator. The vacuum pump and the condenser are
used together to enable a fast and efficient parallel evaporation.
3.4.2 The glass assembly

The glass assembly is used to condense the vapor. Büchi Labortechnik pro-
duces several types here, offering different possibilities. These various glass as-
semblies are presented here.
Glass assembly A, a diagonal cooler, is the simplest unit. Cooling uses a cool-
ing coil (1) filled with water or some other coolant. It can be evacuated and aer-
ated across the vacuum connection (2). To enable working without interruption,
the evaporation flask may be continually replenished through a hose fastened to
the stopcock (3). This glass assembly is very well-suited for single distillations
with a high through-flow, for boiling down, for drying, and for initiating crystalliza-
tion processes, however, it takes up a great deal of space.
Figure 23:
Glass assembly A.
3
1 2
Figure 24:
Glass assembly V.
Glass assembly V is a vertical condenser. Cooling here is also provided by a

cooling coil (1). A special temperature probe can be installed to enable automatic
distillations. The distillation flask can be replenished via a stopcock and feed tube
on the condenser to allow greater throughput. This unit is suitable for the same
applications as glass assembly A, but it requires 22 cm less space.
Figure 25:
Glass assembly C.
Glass assembly C has a different cooling system. The cold trap (1) allows the
use of very cold coolant mixtures such as dry-ice/acetone. The cooler can be
evacuated and aerated at the vacuum connection (2). A hose can be attached
for replenishment. Due to its low condensing temperatures, this cooler is also
suitable for distilling extremely volatile solvents and for sublimations.
Figure 26:
Glass assembly S.
2
3
6
4
Glass assembly S can accommodate the widest range of applications. The

condensation takes place in a cooling coil (1). The supply line to the collec-
tion flask can be closed with a shut-off valve (2), enabling a flow back into the
evaporation flask so that reflux reactions can be carried out. With the installation
of a Soxhlet unit between the condenser and the distributor (3), it becomes pos-
sible to do solid – liquid extractions. Moreover, replenishment of the evaporation
flask (4), measurement of the vapor temperature, and the installation of a Auto-
Dest probe are likewise possible. The vacuum adapter (6) allows an aeration of
the collection flask without having to aerate the entire apparatus. This is helpful
whenever the collection flask has to be emptied while the unit is in operation.
Figure 27:
2
Glass assembly E.
Glass assembly E works with a descending cooler. The vapor first enters an
expansion chamber (1). From there, it is then directed into the condenser with its
cooling coil (3) through a U-tube (2) from above. The system is evacuated and
aerated at the vacuum adapter (4). The vapor temperature can be measured,
and the evaporation flask continually replenished. The use of activators within
the expansion chamber makes it possible to improve the separation effect with
counterflow distillation. The use of an expansion chamber renders this glass as-
sembly particularly well suited for the distillation of high-foaming products or sol-
vents that have a low heating level of evaporation (retarded boiling). An improved
separation effect can be used to ensure good cleaning of high-purity chemicals.
Figure 28:
Glass structure CR.
The design of glass assembly CR is the same as that of glass assembly S,

the only difference being the use of a cold trap (1) for cooling (refer to glass as-
sembly C).
3.4.3 The receiving flask

The receiving flask is a round flask that catches the condensate coming from the
condenser. It is connected to the glass assembly across a ball joint and held in
place by a metal clamp.
Figure 29:
Receiving flask.
3.5 The vacuum

Vacuum plays an important role in connection with the rotary evaporator because
it lowers the boiling temperature needed for the distillation. The vacuum may be
controlled either manually or automatically if a Vacuum Controller has been in-
stalled. The vacuum is built up in a vacuum source outside the rotary evaporator.
This is either a pump in the laboratory, often a water jet pump or a diaphragm
pump, or an in-house vacuum line. The operation of a laboratory pump can be
regulated with a Vacuum Controller, which saves water and/or electricity.
The Rotavapor is evacuated and re-aerated across the vacuum connection

on the glass assembly. The location of this connection on the equipment is of
importance. It must be at the area where the local overpressure built up by the
vaporization is being dissipated again by the condensation. This is at the very top
of a rising cooler and at the very bottom of a descending cooler.
More information on the theory and practice of a vacuum system can be
found in the section «Vacuum Generation» in this laboratory manual.
3.6 Description of important accessory equipment
3.6.1 The temperature probes

In doing distillations, it is helpful if the temperatures of the vapor can be moni-
tored. There are several different temperature probes available.
The vapor temperature probe measures the vapors from distillation. A Auto-
Dest probe installed in the condenser detects the condensation limit and
regulates the pressure accordingly in conjunction with the vacuum controller. This
combination is particularly suitable for solvent mixtures and for gentle distilla-
tions to dryness. Chapter 4.6 describes in detail how the temperature probe
operates.
3.6.2 The Combi-Clip

The Combi-Clip is a user-friendly innovation that deserves a brief description. Nor-
mal ground-glass joints often seize when used with a vacuum. A considerable
amount of force must then be used to take these connections apart, all too often
causing broken glass and personal injuries. One turn of the Combi-Clip forces the
evaporation flask away from the vapor duct, thereby releasing it (a). Turning it in the
other direction, releases the vapor duct tube from the rotor (b), even if it was seized
in. The metal bracket holds the evaporation flask firmly in place (c).
Figure 30:
Principle of Combi-Clip
operation.
a
c
3.6.3 Other accessory equipment

The Soxhlet attachment is used for solid-liquid extractions, which is, for example,
the process used to remove the oil from peanuts. The mixture of solid and liquid
is inserted in a filter casing (1). The solvent is vaporized in the evaporation flask
and directed into the condenser, where it condenses and drips into the filter cas-
ing. It dissolves the oil out and flows through the pores in the filter and into the
evaporation flask. Once all the oil has been dissolved out completely, the extrac-
tion assembly is removed and the supply line to the receiving flask on the rotary
evaporator is reopened. The solvent can now be distilled off. The product that
1 was dissolved out earlier remains behind in the evaporation flask.
The Reitmeyer attachment works as bump trap, particularly for foam. This unit
catches the foam and particles carried along by the vapors before they can enter
into the receiving flask and contaminate the condensate. The Reitmeyer attach-
ment is installed between of the vapor duct and the evaporation flask.
Figure 31:
Soxhlet unit.
Figure 32:
Reitmeyer attachment.

Büchi Labortechnik: Training documents, Destillation mit dem Rotationsver-
dampfer and Umweltschonendes Destillieren
These describe the features of the rotary evaporators offered by Büchi Labortech-
nik and the accessory equipment available for them in depth.
Büchi Labortechnik: Various operating manuals.

Information on the installation and operation of the apparatus can be obtained
here.
E. Krell: Handbuch der Laboratoriumsdestillation

This book deals intensively with the various kinds of apparatus and glassware
available. However, it does not provide any special treatment of rotary evapora-
tors.
Part A Rotary evaporator applications 41
4 Rotary evaporator applications
4.1 Possible distillations

The rotary evaporator has been specifically designed for quick and gentle evap
oration and condensation of solvents. Since it is used only for 1-stage distilla-
tions, no strong separation effect should be expected, even despite the vacuum.
It is therefore normally used for separating highly volatile solvents from liquids or
solids with a high boiling point.
The rotary evaporator can be used to:

– Distill off solvents, i.e., to remove a solvent from the final stage of a reaction.
When it is the solvent that is to be distilled off, it is the product remaining be-
hind in the boiling flask that is of interest. To produce efficient separation, the
boiling points of the product and the solvent at atmospheric pressure should
differ from one another by approx. 80 °C.
– Distill off mixed solvents. The rotary evaporator is also suitable for separating
mixed solvents (without fractionation).
– Condense solutions and suspensions. Here the liquid component is distilled
off long enough to precipitate the dissolved or suspended material out of it, as
is the case, for example, whenever a solid material has been synthesized in a
liquid form and then must be obtained in pure form.
– Concentrate liquids. The concentration of the dissolved material can be raised
by removing the solid.
– Bring about re-crystallization. A contaminated solid material is dissolved.
When the solvent is distilled off, the solubility of the material is decreased and
it precipitates out, leaving the impurities behind in the solution.
– Dry powders and granulates. A powder or a granular solid material containing
inclusions of water or solvents can be dried in the rotary evaporator.
– Synthesize chemicals. The reactants are brought to a boil in reflux reactions,
providing the conditions under which they can react to form the products are
present. The evaporation of the reactants would, however, produce only a
very low yield. This is improved by mounting a condenser on top of the boiling
vessel on which the evaporated vapors can condense and flow back into the
reaction mixture. This process can also be carried out using a rotary evapora-
tor equipped with a glass assembly permitting reflux reactions.
– Soxhlet extractions. These are separations of solids from fluids that function
on the same principle as an automatic drip coffee maker.
– Recycle solvents. Distillation can be used to clean contaminated solvents.
In this process, the cleaned solvent condenses out into the collection flasks
while the less volatile contaminants remain behind in the boiling flask.
4.2 Determining the optimum conditions for temperature and pressure

A good distillation involves more than just a clean separation. Special attention
must also be given to sparing the products as must as possible, i.e., to seeing
that the boiling point is kept as low as possible. In addition, a full separation is
necessary in order to prevent the emission of poisonous solvents into the en-
vironment. These considerations lead to three standards that can be used to
calculate the optimum combination of temperature and pressure: the amount of
energy supplied, the amount of energy carried off, and the boiling point.
42 Part A Rotary evaporator applications
In addition, for mixed solvents, the parameters relevant for a distillation change
along with the concentrations in the mixture, and the conditions have to be re-
adjusted continually through the full rotation. The selecting of correct equipment
and the structural design of the apparatus are also important for obtaining opti-
mum results in a distillation.
Figure 33:
a) Optimum condenser
loading, and
b) a condenser that has
penetrated.
a b
– The removal of energy across the condenser. The condenser has to dissipate
the heat of evaporation that was transferred to the particles during vaporiza-
tion. This means that it must have a certain difference in temperature from the
vapor. It is easy to tell whether or not a condenser has reached its full capac-
ity. Whenever the condensate covers approximately two-thirds of the height
of the condenser, the setting for the distillation is at its optimum. The top
third must remain clear so that it can act as a safety barrier to protect against
fluctuations in pressure and the effects of any lowboiling solvents that might
be carried along. Whenever the pump has to draw continually, that is a clear
sign that the distillation is running too quickly. Whenever the condensate level
is too low, that is a sign that the distillation is running too slowly and that the
output could be increased. The output of the distillation depends mainly on
the amount of heat supplied by the heating bath. This output could also be
improved by using a larger flask or by increasing the rotational speed.
These three temperatures – the cooling water temperature, the boiling point, and
the temperature of the bath – must be attuned to one another. A simple rule of
thumb can be used to find the optimum parameters: the 20/40/60 °C Rule. This
states that with a cooling water temperature of 20 °C at the given pressure, the
boiling temperature should be set at 40 °C and the heating bath should have a
temperature of 60 °C. The advantage of this combination is that the distillation
is carried out at mild temperatures and that the temperature of the heating bath
is at a level where the flask can be changed, therefore eliminating any risk of
scalding.
Figure 34:
1300
Dependence of the speed
1100 pm of distillation on rotation
5r pm rpm
22 0r speed.
15 50
900
700
water [g/h]
500
300
100
0 10 20 30 40 50
Temperature difference bath temperature - boiling temperature [°C]
Example:
Distillation of water. The pressure to initiate boiling at 40 °C is 72 mbar (from the
Table in the Appendix). The optimum parameters are thus: cooling water tem-
perature = 20 °C, system pressure = 72 mbar, bath temperature = 60 °C.
To make the 20/40/60 °C Rule easier to apply, the table of solvents in the Ap-
pendix shows the system pressures needed for a boiling point of 40 °C. Gener-
ally the temperature of the cooling water is less than 20 °C, which means that
the condenser is not running exactly at its optimum. But this does not have any
negative effects on the distillation because a full condensation is ensured.
To enable the successful performance of a distillation, not only the setting of
optimum parameters is of importance, but also their constancy.
The rule of thumb may be expanded into a ∆T=20 °C Rule. This states that
there should be a 20 °C difference between the cooling and the boiling tempera-
tures, and between the boiling and the bath temperatures. This rule becomes
particularly important whenever the product in the solvent must not be heated
to 40 °C, or whenever the solvent boils at a temperature lower than 40 °C under
atmospheric pressure. If the temperature of the cooling water permits, distillation
is also possible with a boiling point lower than 40 °C.
Supplying less heat saves energy. A Table in the Appendix shows the system
pressures needed for various boiling points.
Example:
1.) The product must not be heated above 24 °C. The vapor pressure diagram
(in the Appendix) shows that the solvent being separated off must be evacuated
to 30 mbar for a boiling point of 24 °C. According to the ∆T = 20 °C Rule, this
distillation requires a cooling water temperature of 4 °C, → 4/24/44 °C.
2.) Under atmospheric conditions, diethyl ether has a boiling point of 35 °C. To
distill this substance, the cooling water temperature must be less than 15 °C, →
15/35/55 °C.
The parameters desired can also be calculated mathematically. Two equations are
used for calculating the boiling temperature and the system pressure (4.1), (4.2):
Ts
Tp = (4.1)
(3.006 – log p) · b + 1
Ts −T p
log p = 3.006 − (4.2)
b⋅ T p
wherein Ts [K] is the boiling temperature at atmospheric pressure and Tp [K] is

the boiling temperature at operating pressure p [mbar]. The constant b can be
obtained from the Table of Solvents in the Appendix.
Examples:
1.) One would like to vaporize xylol at a pressure of 15 mbar. How high is its boil-
ing point? p = 15 mbar, b = 0.199, Ts = 140 °C = 413.15 K (b and Ts from the
table of solvents).
413 .15 K
Tp = = 302.86 K = 29.7 °C
( 3.006 − log 15) ⋅ 0.199 + 1
The boiling point is at 29.7 °C. Parameters: 10/30/50 °C
2.) One would like to vaporize benzene at 15 °C. What vacuum pressure must be
attained in the system? Tp = 35 °C = 308.15 K, Ts = 80 °C = 353.15 K, b = 0.202.
35315
. K − 30815
. K
log p = 3.006 – = 2.283; p = 191.9 mbar
0.202⋅ 30815
. K
The system pressure required for applying the parameters 15/35/55°C is 192 mbar.
Setting the parameters becomes more complicated when working with a mix-
ture of several solvents. The optimum parameters here depend on the chemical
composition, with the properties of the lower-boiling component dominating at the
start. The distillation is started using the parameters for that component. This now
decreases sharply in amount within the mixture. The influence of the higher-boil-
ing component increases its boiling point. This means that the distillation output
decreases and can, under some circumstances, come to a standstill. The pres-
sure must be reduced one small step at a time until the volatile phase has been
separated off completely. Thereafter the pressure can be brought back down in a
single step to the optimum pressure for distillation of the higher-boiling phase.
Figure 35:
1
Manual distillation of a
mixture of solvents. 0.9
0.8
0.7
pressure in bar
0.6
0.5
0.4
0.3
0.2
0.1
time
4.3 The distillation process
4.3.1 Preparations
Before starting any work on the actual distillation, the equipment must be ad-
justed for the application intended. Normally an adjustment is needed only for
special applications, e.g., Soxhlet extraction, distillation using extremely low-boil-
ing solvent (cooling «fingers»), etc.
1) At first it is a matter of putting the equipment into operation. When doing so,
all seals, joints, etc. should be checked, greased if necessary, and locked
in position. PTFE gaskets must never be greased. Next, the hoses must be
connected. Water hoses should be secured with hose clamps. All vacuum
hoses should be of the same inside diameter and kept as short as possible.
For more information on the correct construction of a vacuum system, refer
to the section «Vacuum Generation» in this laboratory manual. Last of all, any
electrical parts present should be connected to the Vacuum Controller.
2) Next the optimum pressure and temperature values must be determined.
Usually the ∆T = 20 °C Rule described in Chapter 4.2 is used for this.
3) Once those values have been determined, the bath must be pre-heated to
its operating temperature.
4) To enable better distillation, the apparatus should be checked for leaks with-
out the solvent in it.
5) Once this test has been passed, the flow of cooling water is switched on.
The flow rate should be between 40 and 50 L/hr.
6) The flask can now be filled with the solvent and connected to the rotary
evaporator. If the environ-mental impact of the distillation is to be reduced,
the solvent may also be drawn in later through the replenishment hose, after
having first evacuated the flask.
7) The pressure setpoint and the hysteresis on the Vacuum Controller are set
and the system is evacuated. This adjustment is not made if the distillation is
to be run automatically (4.6).
8) Adjustment of the rotation speed completes the preparations for distillation.
Figure 36:
Hose connections on a
rotary evaporator:
Black = air
Gray = control cable
2 (1) = rotary evaporator
(2) = valve unit
5 (3) = pump
(4) = secondary condenser
3
(5) = cooling water valve
Vacuum
controller
4
4.3.2 Starting distillation

9) The distillation is started by lowering the evaporation flask into the preheated
heating bath. Whenever the mixture tends to foam, the evaporation flask
should be lowered one step at a time. The first condensate begins to appear
on the condenser even after a short while.
4.3.3 Distillation
10) The distillation must be monitored at regular intervals. This includes monitor-
ing the bath temperature, the vapor temperature, and the system pressure.
One must also check that the height of the condensate on the cooler is still
OK (< 2/3). Any foaming up that might occur can be suppressed by venting
briefly. Whenever distilling a mixture, the pressure requires constant readjust-
ment.
11) Once the lower-boiling component has evaporated away completely when
in the distillation of a mixture, the pressure must be reduced to the vapor
pressure of the higher-boiling component. To replace the receiving flask con-
taining the volatile component, the distillation process must first be inter-
rupted (4.3.4) and then restarted using the new values.
4.3.4 Ending distillation

12) When distillation has been completed, the first thing to be shut off is the
rotation.
13) Next, the evaporation flask is lifted out of the bath.
14) The system must then be aerated before making any changes on the rotary
evaporator.
15) Finally, the heating bath is switched off and the cooling water shut off. Distil-
lation has now been completed. The solvent is now in the receiving flask and
the residues are in the evaporation flask.
4.4 Drying
The process for drying is essentially the same as that for distillation. The differ-
ences lie mainly in the selection of the material. Whenever dealing with a powder
or a granulate, it is a good idea to use a drying flask with built-in baffle plates.
Whenever concentrating a solution down to a dry state, it is advisable, particu-
larly in the final phase, that the collection flask be emptied regularly. To attain
complete dryness, the work must be done at low pressures.
4.5 Environmental distillation

The rotary evaporator is used mainly to evaporate a solvent off. The user is most-
ly interested in the residue, and his calculations of yield do not take losses of
solvents into account. The user often forgets that these solvents escape into the
environment and can cause harm there. This gives reason to pause when one
realizes how large the amount of these solvent losses from all distillation equip-
ment is. Worldwide, there are about 400,000 rotary evaporators and other distil-
lation systems currently in use. Figuring a solvent throughput of 1 L/hr, 4 working
hours per day, and a solvent loss of 10%, then 160,000 Liters of solvents are
being discharged into the air or the water every day. The purpose of this chapter
is to point out the reasons for these losses and suggest possibilities for holding
them within bounds.
One important step here is optimization of distillation conditions as already

discussed in Chapter 4.2. A consistent application of the ∆T = 20 °C Rule results
in an efficient distillation. Part of this efficiency involves the solvents to a large
extent, being re-condensed at the cooler. This prevents the penetration of the
cooler, which is one of the major causes of solvent loss.
A great deal of solvent could also be saved by means of correct design and
correct selection of equipment. Adjusting the water bath temperature to the
cooling water with the ∆T = 20 °C Rule does not do any good if the surface area
of the condenser is too small to dissipate the heat. This is seldom a problem
since the coolers available on today’s market usually have a large enough cooling
surface. Another important cause of solvent loss is leakage from the system. Air
penetrating into the apparatus through points that are not tightly sealed must be
drawn off again by the pump. It becomes saturated with the solvent on its way
from the leak to the vacuum duct. The result is a flow of carrier air that is continu-
ously transporting solvents out of the system. A system that is well-sealed off
well (losses of <10 mbar / 5 min) and has a controlled vacuum keep such losses
within bounds. They do not become a problem unless the leaks are large, or un-
less secondary air (a needle valve) is being used to control them.
By recognizing some of the physical processes involved and taking them into
consideration during the proccess of distillation, the loss of solvents can be kept
low. The time when the solvent is introduced into the flask is also important. Nor-
mally the flask is filled with it, and then connected to the apparatus and evacu-
ated. But prior to that evacuation, the air within the rotary evaporator becomes
saturated with the solvent. That saturated air is then removed from the system
during the evacuation. This loss can be restricted by not filling the flask with
solvent until later, and drawing the solvent into the system through the replenish-
ment valve only after the evacuation process has been completed. Only then
should the flask be immersed in the heating bath.
Figures 37 and 38:

Figure 37 Phase 1 Phase 2 Phase 3 Comparative solvent
losses when filling the flask
start of distillation, before and after it has been
Rotary lowering the flask
evaporator evacuation into the water bath evacuated.
solvent
in the flask
solvent
Figure 38
not evacuated evacuated drawn in solvent,

to set-point pressure start of distillation
solvent drawn in
after evacuation
solvent
loss of solvent vapor
air molecules
Because an increased temperature in the water bath makes more energy

available for vaporization, the distillation output obtained is higher. In actual prac-
tice, the flask is often immersed into the water bath before the bath has reached
its full temperature. The user then waits in vain for condensation to take place,
and starts to reduce the system pressure until it does start. But the water bath
continues getting hotter, and the distillation output rises. By the time the water
bath has reached its prescribed temperature, the condenser is generally over-
loaded and can no longer dissipate the amount of heat being supplied to it.
Even if all these actions are taken to restrict the loss of solvents, there will still
be losses, particularly when working with low-boiling solvents. By installing a
secondary condenser on the pressure side of the pump, even these last vapors
can be separated off.
Care is required when distilling a mixture of solvents. If the parameters for
temperature and pressure are optimized for the higher-boiling component, the
lower-boiling component vaporizes off too quickly to re-condense and is dis-
charged into the environment.
There are also other ways available, in addition to the restraining of solvent
losses, in which an ecological distillation process can be ensured. A Vacuum
Controller offers even more possibilities here. This can regulate the flow of water
in a water jet pump, reducing water consumption to a fraction of what it had
been. It also can regulate the operation of a diaphragm pump, reducing its power
consumption and increasing its service life. It can also regulate the flow of cool-
ing water.
4.6 Distillation of mixed solvents using the automatic function

By their very nature, distillations using mixtures of solvents tend to produce espe-
cially high solvent emission levels. Particularly sensitive because, in actual prac-
tice, the mixtures usually involve solvents that differ widely in their boiling points,
and the desire, naturally, is to distill them off as quickly as possible.
The problem here lies in finding the «ideal» working pressure. Clearly, a modern
vacuum controller with an automatic function accomplishes this more easily and
without requiring special supervision by the operating staff. An automatic control-
ler of this type determines the ideal working pressure at the start of distillation
automatically and keeps optimizing it throughout the entire process with regard to
the speed of distillation and the minimum possible solvent emissions. Whenever
distillation down to dry is impossible for physical reasons, e.g., re-evaporation of
the low-boiling component, the distillation is stopped and the receiving flask must
be replaced. Environmentally conscious distillation can be that easy!
4.7 Safety precautions

There are three potential sources of danger in the rotary evaporator: the vacuum,
the heating bath, and the chemicals being distilled. For that reason, personal pro-
tective gear, a laboratory coat, protective eyewear, and gloves must always be
worn when working with the rotary evaporator. In addition, all individuals working
with the evaporator must be familiar with the unit and its operation, or must have
received instruction on it from an expert.
The vacuum represents a considerable potential risk. A vacuum system made
of glass implodes whenever any of its components does not withstand the
vacuum or becomes broken due to some external cause. During an implosion,
splinters of glass and the chemicals spraying out of the rotary evaporator are
hurled through the room at high speed and can cause severe injuries. In addition,
the poisonous gases present within the system escape all at once. To reduce
these risks, all safety rules must be followed when doing this work. Special at-
tention must be paid when setting up the apparatus to see that all glass parts
are fastened solidly, but without putting them under stress. In addition, the rotary
evaporator must be set up at a location where it is protected from unintentional
bumping and from objects falling from above. When selecting the glass parts,
ensure that they have been built for a vacuum (arched surfaces). Do not use
Erlenmeyer flasks, measurement flasks, glass beakers, etc. In addition, check to
see that none of the glassware being used has surface damage. The glassware
must not have any cracks, splinters, or the like. Protective shields and plastic-
coated glassware (e.g. Plastic + Glas) offer additional protection. For further in-
formation on the set-up, operation, and safety of a vacuum system, refer to the
section «Vacuum Generation» in this laboratory manual.
Depending on the temperature of distillation, the heating bath, the heat trans-
fer media, the evaporation flask, and the vapour duct can become heated to a
temperature that will cause burns if they are touched. Special care is necessary
when working with an oil bath, which can be as hot as 180 °C.
Heating baths must be set up so that they cannot tip over. In addition, for an
oil bath, it must not be possible for drops of water to drip into the hot bath (con-
densers located over the bath). That could cause a severe splattering of the very
hot oil. An overheated heat transfer medium can flash into flame or decompose,
releasing poisonous fumes.
The chemicals used present a particularly broad spectrum of dangers.
Serious risk exists when using materials that can explode due to impact, fric-
tion, heat, or sparking, e.g., explosives. But many solvents in common use also
produce fumes that are, in the correct proportions, highly explosive. A special
danger arises in connection with the peroxides that form from the reaction of
ethers together with the oxygen in the air under the influence of light. Since per-
oxides are less volatile than the ether, they accumulate in the distillation residues
and may explode. For that reason, ether must never be condensed down to dry.
In addition, it must always be stored in the dark and any bottles that have been
opened must be used quickly. The presence of peroxides in ether can be de-
tected as follows: Dissolve 200 mg of potassium iodide in inhibited hydrochloric
acid, top it with 3 ml of the ether, and shake well. The presence of peroxide is
indicated by a brownish color of the iodine released in the ether phase.
When distilling a mixture that contains several components, it must be ex-
pected that reactions will occur. The products of such reactions can be explo-
sive, poisonous, corrosive, etc. Whenever distilling a mixture, one should obtain
information as to its components or, if not possible, take special care while work-
ing. Reactions may also take place outside the rotary evaporator. The exhaust
from the pump is another area of uncertainty. There it is possible that the vapors
from the rotary evaporator might come into contact with and react with chemi-
cals from the outside. For example, smoking nitric acid reacts explosively with
acetone, ether, and alcohol. Such reactions outside the rotary evaporator can be
prevented by installing a secondary condenser on the pressure end. There can
also be unforeseen reactions that arise from working with a rotary evaporator
that has not been cleared adequately. Even when working with a non-danger-
ous mixture, there may be an additional agent present on the cooling coil, in the
collection flask, or in the Woulff bottle (an extractor between the rotary evapora-
tor and the vacuum pump). This may react with the distillate explosively or form
a poisonous material. For that reason, the rotary evaporator must always be
cleaned after every distillation. Especially important: many solvents are poison-
ous or carcinogenic. Poisoning usually takes place as the result of inhalation
or from skin contact. Therefore, familiarize yourself with the literature on how
poisonous the materials are, and take appropriate precautionary actions (gloves,
working in a protective cabinet, secondary condenser).

– Büchi Labortechnik: Training documents, Destillation mit dem Rotationsver-
dampfer und Umweltschonendes Destillieren
These brochures explain in a simple and understandable form how to work
with a rotary evaporator.
– Büchi Labortechnik: Various operating instructions
Always read the Operating Instructions before working with the rotary evap
orator.
– Büchi Labortechnik: Der automatische Vakuum Kontroller – ein Beitrag zum
aktiven Umweltschutz
A great deal of information on automatic distillation can be found here.
– W. Frank, D.Kutsche: Buchreihe Verfahrenstechnik: (2) Die schonende Destilla-
tion
This book deals not only with the theory but also with the practice of envi-
ronmental distillation. It elucidates these principles clearer with practical ex-
amples.
Part A Design of the glass oven 51
5 Design of the glass oven
5.1 Schematic design of the glass oven

The core of the glass oven is the two borosilicate glass tubes lying one within the
other. The outer tube (1) protects against damage to the heating tube, and at the
same time prevents contact with parts that are electrically live. A metal screen (2)
around the outer jacket provides additional protection. The inner tube (3) which
has been coated by vacuum evaporation with a fully transparent, electrically con-
ductive semi-conductor coating, does the actual heating. Temperatures up to
300 °C are attained, whereby the oven temperature is monitored via an inte-
grated temperature sensor (4). A thumb nut (5) can be used to tilt the oven and
to lock it in that position.
Figure 39:
Schematic design of the
glass oven.
1 2 3 4
5.2 The control section

A multifunction button is used for setting the desired oven temperature and the
rotation speed. The digital display (2) shows the current oven termperature and
the rotation speed. The connection for the power system is located on the back
of the control section and the power supply to the bulb-tube drive is located at
the side of the unit.
Figure 40:
2 Operating elements of the
glass oven.
1
52 Part A Design of the glass oven
5.3 The heater section

The necessity of sparing the mixture when doing distillations calls for gentle heat-
ing. The gentlest way of doing this is with indirect exogenous heating. At first,
the heat source warms an intermediate medium to a temperature that lies only
slightly above the setpoint. Generally, that medium is a liquid (water or oil). In
bulb-tube distillations, a semi-conductor coating is used to provide direct heat-
ing. The product may be heated directly because the heat source provides a
moderate heat radiation distributed evenly across the entire surface of the heater.
Because the thermal capacity and the thermal conductivity of the vapor-coated
glass are significantly better than those of the gas outside, most of the heat given
off is taken up by the glass and radiated inward. There are further advantages
in addition to the gentle heating. Because 75% of the heat is supplied to the
product through radiation and only 25% with heated gas, the oven heats up
very quickly. It cools down relatively quickly when it is switched off. In addition,
because the semi-conductor is fully transparent, the sample can be observed
during the drying process, so that any decomposition that starts can be identi-
fied and the countermeasures needed can be taken in time.
5.4 Accessories
5.4.1 The drying accessory

The drying accessory consists of three parts. While the drying is in progress, the
drying tube (1) into which the product is put either directly or inside a container,
is in the oven. The end cap (2) that catches the moisture evaporated off can be
filled with desiccants to improve the drying effect. A stop-cock is used to evacu-
ate or aerate the sample chamber. The aluminum flange ring (3) joins the two
glass sections in a screwed bottle joint, sealing them vacuum-tight. The flange
ring is also used to hold the drying accessory in position within the glass oven.
This drying accessory does not rotate.
Figure 41:
The drying accessory.
1 2
3
Figure 42:
The rotating flask.
2 1 3
For most solids, a quicker and/or a more thorough drying can be attained if
the material is kept in motion. A rotating drying flask driven by the bulb-tube drive
(5.5) is used to accomplish this. This flask (1) has notches (2) that act as baffles
to mix the product while rotating, thereby preventing the formation of a crust. The
vapor is directed off through the vapor duct. This vapor may either be released
into the environment or recaptured in a cooled flask. A P2 frit embedded into the
vapor duct tube (3) holds the product back in the flask and protects the vacuum
pump.
5.4.2 The distillation accessory

The glass oven can be used for two types of distillation: single distillation and
fractional distillation. The fractional distillation is a bulb to bulb distillation that
uses three or four bulbs and bulb cooling. The single distillation may be done ei-
ther as a bulb to bulb distillation using two bulbs and bulb cooling, or as a normal
distillation using one bulb as an evaporation flask, together with a condenser with
a cooling coil and a collection flask. In this latter application, the glass oven may
be viewed as a small rotary evaporator. Common to all three types of distillation
is the fact that they all work using the bulb-tube drive.
Figure 43:
Bulb-tube with four bulbs.
2 1
Bulb to bulb distillation uses a tube that consists of as many bulbs as there are
components in the mixture. Fig. 43 shows the bulb-tube for distilling a mixture
of four components. The vapor duct tube (1) is mounted upon the last of these
bulbs (2).
Figure 44:
Glass oven for bulb-tube
distillation.
3 1 2
The vapor duct tube is inserted through the bulb-tube drive (1) until it extends
past the vacuum seal on the right side of the housing and is then fastened by
the union nut (2). The last bulb is located outside the oven and serves as the
condenser and the collection vessel. A cooling shell (3) may be used for cool-
ing the bulb. The coolant may be water, ice, dry ice, or a mixture of dry ice and
solvent. Because the cooling shell is made of polyethylene, it is not resistant to
chlorinated solvents. The bulb-tube can be evacuated and aerated across the
vacuum duct (4), therefore making vacuum distillation also possible.
5.4.3 The sublimation accessory

The sublimation accessory is inserted into the drying tube (2) instead of the end
cover with the bottle connection (1). The solid re-sublimates out on the cooling
finger (3), which is cooled with water supplied at the inlet at the side, (4) and
removed again at the inlet at the top (5). A cock (6) has been installed to permit
evacuation and aeration. Because sublimations are generally carried out under
a vacuum, care must be taken to see that the O-ring flange gasket (7) has been
inserted properly into the holder. Like the drying accessory, the complete subli-
mation accessory is inserted into the oven.
Figure 45:
5
The sublimation accessory.
3 2 1
7 4
5.5 The bulb-tube drive

The bulb-tube drive is used whenever the product being distilled has to be
rotated.
It consists of the drive itself (1), its fastening (2), its suspension (3), the iris
diaphragm (4), and the control cable. Its speed of rotation can be adjusted con-
Figure 46:
The bulb-tube drive.
2 3
1 6
4 7
tinuously for speeds up to 50 rpm using the multifunction button (5). Because
the opening of the oven is not sealed off with a flange ring, an iris diaphragm
has been installed to close off the oven chamber. Because this can be adjusted
continuously, it can wrap tightly around both the thin vapor duct tube and the
thicker ground joints connecting the bulbs.
By pushing the drive back toward the oven and tilting it upwards, it can eas-
ily be pulled out of the oven and taken out or replaced in it. The housing also
contains a vacuum seal (6) that connects the rotating vapor duct tube to the
stationary vacuum connection (7).
5.6 The freeze drying accessory

The freeze drying insert enables the freeze drying of smaller sample quantities.
Additionally a condenser and a recirculation thermostat or a cold trap for dry ice
applications is also needed. The vacuum source must reach a final vacuum of
less than 2 mbar.
Figure 47:
The freeze drying accessory.

– E. Bertele, F.A. Humbel: Neukonzeption eines Ofens zur Beheizung kleiner
A great deal of information can be obtained here on bulb-tube distillation and
on the operation of the oven, particularly its heating system.
– Büchi Labortechnik: Training documents, Drying, Distillation and Sublimation
with the glass oven B-585
This brochure explains possible applications for the glass oven.
– Büchi Labortechnik: Operating Instructions for Glass Oven B-585
These Operating Instructions explain not only the individual steps in the
application, but also provide useful suggestions for actual practice.
Part A Glass oven applications 57
6 Glass oven applications
6.1 Possible applications

The glass oven is a working device that can fulfill many functions. It is mainly
used in the laboratory wherever the rotary evaporator comes up against its own
limitations. Its uses may be classed into three work areas: distillation, drying,
and sublimation. It is ideally suited for the processing of small amounts of sub-
stances. Its transparent heating tube enables observation of the sample, which
means that any initiation of decomposition can be identified in time to take ap-
propriate action.
The glass oven can be used for drying all solid substances. This drying may
be done either while stationary or using rotation. The use of a vacuum improves
and/or speeds up the drying process. With its high operating temperatures of up
to 300 °C, the oven can vaporize off high-boiling solvents that a rotary evapora-
tor no longer can handle. At the same time, the user can carry out all distillations
on a small scale. One special feature is the oven’s ability to fractionate mixtures
using bulb to bulb distillation. This method of distillation can separate all com-
ponents with a boiling point more than 20 °C below that of the next higher-boil-
ing component. The distillations can be carried out while rotating and under a
vacuum.
All solids for which pressure and temperature values below the triple point are
realizable can be sublimated. These are frequently substances that have
a distinct smell.
6.2 Determining the optimum conditions

How to determine the optimum conditions for pressure and temperature has
been discussed in detail in Chapter 4.2. The same considerations also apply for
applications using the glass oven – with, of course, the cooling relationships dif-
fering from those for the rotary evaporator. Because the cooling surface area is
very small when the cooling shell is used, ice or dry ice is normally used for cool-
ing. For that reason, the 20/40/60 °C Rule does not apply here without some
modification. The rule for distillations done in the glass oven is that the oven
temperature should lie 10 to 40 °C higher than the boiling temperature of the
liquid that is being separated off.
Parameters are seldom optimized for drying. Here, high temperatures and
a high vacuum are used to achieve the fastest and most complete drying as
possible.
The operating point selected for sublimation must be lower than the triple
point.
6.3 Distillation
6.3.1 Single distillation

Single distillation may be done either as a bulb to bulb distillation or as a normal
distillation with a water cooler.
For the bulb to bulb distillation, two bulbs and a vapor tube are connected
together. The ground joints are secured with clamps. If the work is being done
under a vacuum, they must be greased beforehand. The bulb-tube is set up in a
58 Part A Glass oven applications
Figure 48:
Positions of the cock plug.
vertical position and the liquid to be distilled is introduced into the bulb at the bot-
tom with a pipette. The bulb-tube is fastened in position in the drive unit and in-
serted into the oven down to the first bulb. The iris diaphragm is now closed, but
not so strongly as to cause any damage on the bulbs due to friction while they
are rotating. The cooling shell is filled with the coolant and raised until the second
bulb comes into contact with the coolant. The drive can now be switched on and
the system evacuated as required.
The distillation is started either by setting the temperature directly at 10 to
40 °C above the boiling point, or by slowly raising it until distillation starts. When-
ever the product of interest is the phase being distilled off and not the residues,
the vacuum used must not be too low. If the pressure is too low, it may turn out
that no full condensation will be possible because of the small condensation
area available. The vapor will be guided directly into the pump. While working
under a vacuum, it is particularly important to rotate the flask so as to prevent
retarded boiling. The vacuum is connected up at the connection cock to the right
of the drive. This connection cock can be brought into three positions. Position
A opens the duct at the top, B closes off the inner chamber, and C opens the
duct at the bottom. The vacuum source is generally connected to the duct at the
top. When the distillation has been completed, the bulb-tube is first aerated and
then withdrawn from the oven, and the bulbs are taken apart carefully. The first
bulb contains the residue, the second the distillate. The bulbs may still be hot
after the distillation.
For distillation with a water cooler, only one bulb is connected to the vapor
duct tube. Instead of the vacuum pipe, a water cooler with a collection flask is
installed on the drive. This set-up enables more complete condensation than is
possible in bulb to bulb distillation. Otherwise, the working method is similar. The
bulb is filled with the mixture, connected to the vapor duct tube, and fastened to
the drive. The tube is then inserted into the oven and the diaphragm closed. To
distill more than 30 ml ( the «max» mark on the largest flask), the oven tube may
be tilted slightly.
6.3.2 Fractional distillation

Fractional distillation is used for separating multi-component mixtures. If the dif-
ferences between boiling points are greater than 20 °C, it can succeed in doing
this. In principle, for fractional distillation, as many bulbs must be connected
together as there are components present in the mixture.
Figure 48:
Principle of bulb to bulb
distillation.
The procedure for bulb to bulb distillation of multi-component mixtures is the

same as that for distilling 2-component mixtures (6.3.1).
Figure 49:
Schematic of bulb to bulb
Heater
distillation.
Substance
Destillate
Cooling bath
The first bulb is filled with the mixture up to the «max» mark. The glass joints
are greased and fastened together with joint clamps. Finally, the vapor duct tube
is connected to the drive. The bulb-tube is then inserted into the oven, except for
its last bulb. The diaphragm is closed, and the rotation is switched on. The bulb
extending out of the oven is cooled in the cooling shell with coolants. The oven
temperature is raised slowly until condensation of the component with the lowest
boiling point starts in the cooled bulb. Distillation is carried out at that tempera-
ture. When the amount of distillate in the bulb stops increasing, the next bulb is
pulled from the oven and into the cooling bath. The temperature is then raised
again until the next component reaches its boiling point. It continues in this way
until the last component has been separated off. Here too, the use of a vacuum
is recommended so as to spare thermally labile substances.
6.4 Drying
The glass oven can also be used to dry solid substances. Unlike permanently
installed drying chambers, the drying oven only has to heat up a small volume. It
requires less energy, reaches the desired temperature more quickly, and thereby
reduces the time for drying. Moreover, operating in a vacuum, it has a signifi-
cantly tighter seal than a drying chamber.
There are three methods used for drying: direct drying, indirect drying, and
rotary drying. The drying accessory is used for direct and indirect drying, the
rotary flask for rotary drying.
Figure 50:
Filling the drying glass for
direct drying.
In direct drying, a fairly large amount of the product is introduced into the dry-
ing tube. If the size of the tube permits, pre-prepared glass boats or metal shells
may also be put into it. The drying accessory is then sealed and put into the
oven. If the work is to be done under a vacuum, the drying accessory is evacu-
ated at the duct at the top. Further optimization and speeding up of the drying
process can be achieved by filling the end cover with a desiccant. Care must be
taken when filling with loose desiccant. The neck between the end to the flange
and the vacuum duct should remain clean. Any desiccant left there will be car-
ried along by the incoming flow during aeration and can contaminate the prod-
uct being dried. Desiccants commonly used include silica gel, CaCl2 and P2O5.
Once all preparations have been completed, the oven is heated to the desired
temperature and the drying process starts. The drying temperature depends on
the substance at hand:
Figure 51:
The end cover on the
drying accessory,
filled with desiccants.
It should be as high as possible to ensure that a good degree of dryness can

be attained. On the other hand, the substance must not suffer any damage. After
drying has been completed, the heater is switched off and the system is aerated
via the duct at the bottom. When necessary, the drying tube may also be aerated
with an inert gas instead of with air.
The drying accessory is pulled from the oven, cooled, and opened. Then the
dried powder is put into another container. Direct drying should not be used for
hygroscopic substances. These take up a great deal of moisture from the envi-
ronment while being transferred. Here indirect drying should be selected.
Indirect drying differs from direct drying in that the product is filled into the
container in which it is later to be stored before it is dried, and is introduced into
the drying tube in this way. In this procedure, the oven is operated in a vertical
position. The advantage of indirect drying is that the container with the product
can be sealed air-tight immediately after drying, thereby avoiding any unneces-
sary exposure of hygroscopic substances to the moisture in the air.
The third type of drying is rotary drying. This requires a bulb-tube drive. The
drying is done in a rotary drying flask which has notches in it that act as baffle
plates and constantly mix the product being dried while it is rotating. This thor-
ough mixing prevents the formation of any solid coating on the surface of the
product that might impede the escape of moisture and considerably prolong the
time needed for drying. The flask is filled with the material and connected to the
vapor duct tube. The joint is greased and secured with a joint clamp. Then the
vapor duct tube is fastened in place in the drive, the flask inserted into the oven,
and the iris diaphragm closed. If necessary, a vacuum is built up.
The actual drying process can now be initiated by starting the drive and the
heater. It is ended by switching off the heater and the motor, and aerating the
drying flask. This type of drying has several advantages over stationary drying.
Drying done in this way is both quicker and more thorough.
Finally, two further examples for comparing stationary drying and rotary drying:
1) Drying of silica gel with indicator. Weigh-in 30 g, oven temperature 180 °C,
vacuum 20 mbar.
drying time without rotation 15 min
drying time with rotation 9 min
2) Dehydration of copper sulphate pentahydrate. Weigh-in 30 g, oven tempera-
ture 300 °C, vacuum 20 mbar.
water content, after drying, without rotation 3%
water content after drying, with rotation < 0.1%
Figure 52:
Filling the drying flask for
indirect drying.
Figure 53:
The rotary drying flask.
6.5 Sublimation
In sublimation, the mixture that is to be cleaned is put into the drying flask and
spread out evenly. The cooling finger is then introduced into the drying flask and
sealed off well with the flange bolting. When working under a vacuum, it is ne
cessary to check that the gasket ring is properly seated in its groove. Next, the
sublimation accessory is inserted into the drying oven. The cooling water is con-
nected up and the accessory is evacuated. The inlet at the side should be select-
ed as the cooling water inlet. Sublimation is then started by switching the heater
on. The temperature is steadily raised until the substance re-sublimates on the
cooling finger. Once sublimation has been completed, the heater is switched off
and the flask is aerated. The sublimation accessory is pulled from the oven and
cooled. The sublimate can now be removed from the cooling finger.
Typical application:
A mixture of 1 g (L) tartaric acid and 1 g Naphthalene are to be separated. The
mixture is put in and the oven is evacuated to 25 mbar. The temperature is raised
steadily until the first tartaric acid re-sublimates on the finger at 80 °C. This tem-
perature is held and the sublimation is watched. 60 minutes later the process has
been completed. The weight of sublimate obtained is 0.95 g, and the melting
point measured for purposes of checking is 168.1 °C (pure tartaric acid: 168 °C).
It can be seen that sublimation can provide both a very effective separation of the
components and a very good yield.
6.6 Safety precautions

Essentially the sources of danger with a glass oven are the same as with the ro-
tary evaporator. For that reason, all personal protective gear (protective eyewear,
gloves, laboratory coat) should be used when doing this work. Information can
be obtained on the risks and precautionary measures necessary when working
with a vacuum, chemicals, and broken glass from Chapter 4.7.
Because a glass oven operates at far higher temperatures, burns that result
from coming into contact with the oven’s hot parts can be serious even when
they do not cover large areas of the body. To a great extent, the protective guard
on the unit provides protection against burns due to carelessness.
The higher temperature means that work is being done closer to the flash
point of certain substances and mixtures than would be the case with the rotary
evaporator. Make certain that there are no flammable vapors or fumes anywhere
close to this equipment.
When working with dry ice and/or a mixture of dry ice and alcohol, the tem-
peratures present are so low (down to –80 °C) that there is a risk of personal
injury if the user comes in contact with them.
It is also important to remember that the semi-conductor coating operates at
power system voltage. The outer protective tube must not be removed. The oven
must not be operated if one of the shielding tubes are damaged.
The oven must be at least 30 cm away from the wall or any other equipment
for operation. There must not be any containers, chemicals, or other equipment
standing behind the glass oven. When selecting where the oven is to be placed,
also make sure that no objects can fall onto it from above and damage it.
6.7 Ecological and economic considerations

With only slightly more effort and expense, the use of this drying oven can be
made even more economical and more ecologically sound. We recommend
working with a vacuum so as to save heat energy. The oven can then be oper-
ated at lower temperatures thanks to the lower boiling points this brings. The
vacuum should be operated under automatic control, which enables the use
of defined conditions for drying and distillation and saves water (with a water
injector pump) or electricity (with a diaphragm pump), thereby reducing costs
as well.
A secondary condenser should be installed on the pressure end to prevent
the loss of solvents in vacuum distillations.
Whenever a distillation is using a mixture of dry ice and a solvent for cooling,
pay attention to the fact that there is always dry ice contained in the solvent. This
means that the solvent cannot simply diffuse out into the environment.

– E. Bertele, F. A. Humbel: Neukonzeption eines Ofens zur Beheizung kleiner
The detailed treatment of ball-tube distillation is of interest here.
– Büchi Labortechnik: Training documents, Drying, Distillation and Sublimation
with the glass oven B-585
This brochure explains quite a bit about possible applications of the glass
oven and provides several examples of such applications.
– Büchi Labortechnik: Operating instructions for glass oven B-585
These Operating Instructions explain the individual steps involved with the use
of a glass oven, and provide additional information to enable working more
efficiently.
6.8 Table of solvents
Solvent Formula MW Heat of bp °C Density Constant Working

vaporization [g/cm3] b pressure [mbar]
[J/mol] [cal/g] for boiling point
at 40 °C
Acetic acid C2H4O2 60.0 41689 166 118 1.049 0.183 44
Acetone C3H6O 58.1 31972 132 56 0.790 0.196 556
N-Amylalcohol,
n-Pentanol C5H12O 88.1 52281 142 137 0.814 0.158 11
Benzene C6H6 78.1 42904 131 80 0.877 0.202 236
n-Butanol C4H10O 74.1 45901 148 118 0.810 0.155 25
tert. Butanol
2-Methyl-2-Propanol C4H10O 74.1 43569 141 82 0.789 0.154 130
Carbontetrachloride,
tetra Chloromethane CCl4 153.8 34608 54 77 1.594 0.206 271
Chlorobenzene C6H5Cl 112.6 42250 90 132 1.106 0.202 36
Chloroform CHCl3 119.4 31382 63 62 1.483 0.203 474
Cyclohexane C6H12 84.0 32764 93 81 0.779 0.206 235
Diethylether C4H10O 74.0 29063 94 35 0.714 0.200 atmospheric
1,2,-Dichloroethane C2H4Cl2 99.0 33266 80 84 1.235 0.201 210
1,2,-Dichloroethylene
(cis) C2H2Cl2 97.0 31048 77 60 1.284 0.196 479
1,2,-Dichloroethylene
(trans) C2H2Cl7 97.0 30305 75 48 1.257 0.196 751
Di isopropyl ether C6H14O 102.0 32540 76 68 0.724 0.207 375
Dioxane C4H8O2 88.1 35757 97 101 1.034 0.200 107
DMF C3H7NO 73.1 153 0.949 0.180 11
Ethanol C2H6O 46.0 40476 210 79 0.789 0.159 175
Ethyl acetate C4H8O2 88.0 34732 94 77 0.900 0.189 240
Heptane C7H16 100.2 37358 89 98 0.684 0.200 120
Hexane C6H14 86.2 31912 88 69 0.660 0.206 335
Isopropyl alcohol C3H8O 60.1 42106 167 82 0.786 0.154 137
Isoamyl alcohol,
3-Methyl-1-Butanol C5H12O 88.1 52281 142 129 0.809 0.158 14
Methyl ethyl ketone C4H8O 72.1 34098 113 80 0.805 0.206 243
Methanol CH4O 32.0 39234 293 65 0.791 0.167 337
Methylenechloride,
Dichloromethane CH2Cl2 84.9 31683 89 40 1.327 0.194 atmospheric
Pentane C5H12 72.1 27594 91 36 0.626 0.214 atmospheric
n-Propyl alcohol C3H8O 60.1 47274 188 97 0.804 0.154 67
Pentachlorethane C2HCl5 202.3 41004 48 162 1.680 0.207 13
1,1,2,2,-Tetrachlor-
oethane C2H2Cl4 167.9 41493 59 146 1.595 0.198 35
1,1,1,-Trichloroethane C2H3Cl3 133.4 33525 60 74 1.339 0.206 300
Tetrachloroethylene C2Cl4 165.8 38662 56 121 1.623 0.202 53
THF C4H8O 72.1 67 0.889 0.192 357
Toluene C7H8 92.2 39198 102 111 0.867 0.202 77
Trichloroethylene C2HCl3 131.3 34789 63 87 1.464 0.202 183
Water H2O 18.0 40706 540 100 1.000 0.167 72
Xylene
(Isomers mixture) C8H10 106.2 41440 93 0.199 25
(o) 144 0.880
(m) 139 0.864
(p) 138 0.861
6.8 Working pressures for different vapor temperatures of various solvents [mbar]
Solvent bp. 20 °C bp. 30 °C bp. 40 °C bp. 50 °C bp. 60 °C
Acetone 239 370 556 815 atmospheric
n-Amylalcohol 3 6 11 20 35
Benzene 98 155 236 352 511
n-Butanol 7 14 25 44 76
tert. Butanol 41 74 130 220 361
Chlorobenzene 13 22 36 56 86
Chloroform 207 318 474 689 atmospheric
Cyclohexane 99 154 234 347 501
Diethylether 562 838 atmospheric atmospheric atmospheric
1,2-Dichloroethane 86 137 210 315 460
1,2-Dichloroethylene (cis) 204 317 479 705 atmospheric
1,2-Dichloroethylene (trans) 330 505 751 atmospheric atmospheric
Dichloromethane 451 685 atmospheric atmospheric atmospheric
Diisopropylether 164 251 375 545 776
Dioxan 42 68 108 165 246
Dimethylformamid (DMF) 5 8 14 23 37
Acetic acid 15 26 44 72 113
Ethanol 58 102 167 289 463
Ethylacetat 95 153 240 366 544
Heptane 47 77 120 183 273
Hexane 145 223 360 490 701
Isoamylalcohol 4 8 14 25 43
Isopropanol 43 78 136 231 378
Methanol 122 206 385 534 824
Methylethylketone (MEK) 103 160 243 359 518
Pentachlorethane 5 8 13 21 34
Pentane 563 819 atmospheric atmospheric atmospheric
n-Propanol 20 37 67 115 193
1,1,2,2-Tetrachloroethane 12 21 34 55 85
Tetrachloroethylene 20 33 53 83 126
Tetrachloromethane 115 179 270 398 573
Tetrahydrofurane (THF) 154 244 374 560 817
1,1,1-Trichlorethane 128 198 299 440 632
Trichlorethylene 75 119 183 275 402
Toluene 29 48 76 118 177
Water 23 42 72 120 194
Xylene 9 15 25 40 63
6.10 Vapor pressure curves for various solvents

If the solvent being sought is not included in this list, select the example with the boiling point closest to that
of the solvent and draw a curve with a similar path. In this way you can obtain approximately the boiling point
being sought.
7 14 6 2 13 12 10 9 3 5 18 21119 8 17 1 16
1000
900
800
700 4
600
pressure (mbar)
500
400
300
200
100
0
0 10 20 30 40 50 60 70 80 90 100 110 120
Boiling temperature (°C)
1 Acetic acid 118 °C 8 Dioxan 101° C 15 n-Propylalcohol 97 °C

2 Acetone 56 °C 9 Ethanol 79 °C 16 Tetrachlorethylene 121 °C
3 Benzene 80 °C 10 Ethylacetate 77 °C 17 Toluene 111 °C
4 Chlorobenzene 132 °C 11 Heptane 98 °C 18 Trichloroethylene 87 °C
5 1,2-Dichloroethane 84 °C 12 Hexane 69 °C 19 Water 100 °C
6 Dichloromethane 40 °C 13 Methanol 65 °C
7 Diethylether 35 °C 14 Pentane 36 °C
Spray Drying
B
68 Part B Spray Drying
1 Introduction
1.1 What is Spray Drying?

Spray drying is a widely applied method to convert aqueous or organic solutions,
emulsions, dispersions and suspensions into a dry powder. Applications are found
in all major industries ranging from industrial chemistry, pharmaceutical, biotech-
nology to food industry. Dry milk powder, instant soups, instant coffee, detergents
and dyes are just a few spray dried products currently available in every day life.
Figure 1:
Spray dried milk and instant
coffee products used in
everyday life.
A Spray Dryer atomizes a liquid feed into fine droplets and evaporates the
solvent or water by means of a hot drying gas. Typically, a nozzle is used to form
the droplets in a range of 20 to 180 micron size.
Spray drying is a very quick drying process compared to other drying tech-
niques and provides the advantage of weight and volume reduction. The trans-
formation of a liquid product into a dry powder is done in a single step, which
makes the method advantageous in terms of costs, scale-up and process sim-
plification. Moreover, temperature sensitive substances like enzymes, proteins,
antibiotics etc. can be spray dryied without major loss of activity.
1.2 Particle shapes and structure
Figure 2:
Particle shapes and struc-
Phase 1
tures formed during the
Spray Drying Process: Heat
1: solid, spherical Phase 2 Moisture release
2: shrivelled, mis-shapen (evaporation)
3: hollow, spherical
4: cenospherical Phase 3
5: disintegrated
The particle shape and structure depends strongly on the substance prop-
erties and the drying conditions (Fig. 2). This can range from solid particles to
hollow particles and even cenospheres (also called «donut shape»). Current re-
search trends in pharmaceutical technology lead to the development of inhal-
Part B Introduction 69
able particles for drug delivery. For example, Fig. 3 shows scanning electron
micrographs of spray dried biodegradable polymers in the size of 1 to 5 microns.
These particles are small enough to be inhalable into the lungs as drug carriers
for controlled drug release applications.
Intensive research and development during the last three decades has improved
spray drying to become a highly competitive drying technique for a wide variety of
products. The range of product applications is continuously expanding, so that to-
day spray drying has connections with many things we use daily. The application list
in Section 5 gives a short summary of currently available spray dryable products.
Figure 3:
SEM photographs of
spray dried biodegradable
polymers (Poly(D,L-lactide-
co-glycolide, Resomer
RG 502H 50:50) showing
particle sizes in the range
of 1 to 5 microns enabling
20µm 2µm 1µm
inhalation applications
Mag = 1,00 K x Signal A = SE2 Mag = 10,00 K x Signal A = SE2 Mag = 25,00 K x Signal A = SE2
EHT = 2,00 kW Photo No. = 2116 EHT = 2,00 kW Photo No. = 2117 EHT = 2,00 kW Photo No. = 2115
WD = 4 mm Date 30 May 2007 WD = 4 mm Date 30 May 2007 WD = 4 mm Date 30 May 2007
Time: 18:17:29 Time: 18:19:20 Time: 18:16:00
1.3 History
Historically, spray drying was first applied in the milk and detergents industries
in the 1920s [2]. Later, in 1975, it became really popular in the manufacture of
instant coffee. Nowadays, very big spray towers are used in industrial scale with
heights of over 25 m and air as the drying gas at up to 250°C temperature to
evaporate the water (Fig. 4).
Figure 4:
Industrial scale spray dryer
with cyclone scrubber (from
Niro [3])
In the dry coffee powder production plants, the powder is collected at the
bottom of the tower before being discharged for further processing. The result-
ing powder is free flowing, non-dusty and has a moisture content of several per-
cents. The fine particles are recirculated into the chamber to achieve agglomera-
tion. In the agglomeration process the surfaces of the coffee powder particles are
rewetted, so that other particles adhere to each other and form larger particles.
This granular powder allows easier handling and a faster dissolution rate.
70 Part B Theoretical basis of the spray drying process
2 Theoretical basis of the spray drying process
A complete spray drying process consists of a sequence of four steps:

1. Feed preparation
2. Atomization and hot gas contact
3. Evaporation, particle shape formation and drying
4. Separation of the dried product from the gas and discharge
2.1 Feed preparation

The first requirement is that the feed must be pumpable, homogenised and free
from impurities. A typical feed solution can be an emulsion, suspension or solu-
tion made up from a solvent and the interesting substance to spray dry. The feed
preparation has a big influence on the particle shape and particle coating. Typi-
cally some small percent of additives, like lubricants, defloccants or other special
agents are mixed into the feed to provide particle shape control and higher solids
concentrations in the feed. Organic binders, for example PVA, maltodextrin, or
gelatine are used to hold the material together after pressing. Glycerine or ethyl-
ene glycol are used to soften the particles. Increasing feed solids concentration
not only improves the thermal efficiency and plant capacity of the spray drying
operation but also has a strong influence in the bulk density of the final powder.
2.2 Atomization and hot gas contact

Different kinds of energy are used to disperse the liquid feed into fine droplets.
Typically used nozzle designs are based on two fluid nozzles, pressure nozzles,
rotary disk atomisers or ultrasonic nozzles (Fig. 5 and Table 1).The selection upon
the atomizer type depends upon the nature and amount of feed and the desired
characteristics of the dried product. The higher the energy for the dispersion, the
smaller the generated droplets. If, for example, 100 ml of a solution is sprayed
into 25 micron size droplets, a total number of about 800 million droplets results,
representing approximately 12 m2 of surface area. This clearly demonstrates the
extremely quick vaporization in spray drying.
Figure 5:
Atomizing principles:
A Two fluid nozzle
B Rotary atomizer
C Pressure nozzle
D Ultrasonic nozzle
Two fluid nozzle: In the case of a two fluid nozzle, the energy for atomization
is provided by rapid expansion of a spray gas, which is mixed with the liquid feed
within the nozzle body (internal mixing) or at its tip (external mixing). The droplet
size is controlled by the mass ratio of spray gas to liquid feed Mgas / Mliq and the
relative velocity between gas and liquid at the nozzle head vrel. The mean droplet
size produced follows the relation [2]:
) )
Mgas -ß
A
dDroplet = +B⋅ Equation 1
(vrel ⋅ gas )
2 α Mliq
Part B Theoretical basis of the spray drying process 71
where ρgas is the gas density and the exponents a and β are functions of the
nozzle design. A and B are constants involving both nozzle design and liquid
properties.
Atomization with two fluid nozzles is considered suitable for smaller scale
plants, due to its relatively low pressure consumption, low particle velocity and
thus shorter required drying length in the spray chamber. Dryers utilising two fluid
nozzles generally achieve smaller sized droplet diameters in compared to other
atomizing techniques but have an increased cylindrical height.
Rotary disks: The rotary disk nozzles are the most frequently used atomizing
devices in industrial scale spray dryers and provide high feed throughputs. They
are typically used for the production of fine particles in the size range 80-120
microns or where the evaporative capacity exceeds 2 tons per hour. Chambers
are generally of larger diameter than for two fluid or pressure nozzles.
In disk atomizers, the material to be sprayed flows onto a rapidly rotating at-
omizing disk and is converted into a fine mist. The drying gas flows in the same
co-current direction and the product is dried carefully.
Atomization occurs at the wheel periphery and the droplet size is determined
by the peripheral speed, which can go up to 180 m/s or higher. A fully abra-
sion-resistant wheel made from ceramic carbide is required to assure higher
lifetimes.
Rotary atomizer Pressure nozzle Two fluid nozzle Ultrasonic nozzle

Wheel Droplet Pressure Droplet Air-liquid Droplet Frequency Droplet
peripheral mean size (bar) mean size ratio mean size (kHz) mean size
velocity (m/s) (micron) (micron) (kg/kg) (micron) (micron)
>180 20-40 >100 20-40 >3:1 5-20 25 70
150-180 40-80 50-100 40-75 1.5-3:1 20-30 48 38
125-150 80-120 25-50 75-150 1.0-1.5:1 30-50 60 31
75-125 120-225 15-25 150-350 0.5-1.0:1 50-125 120 18
Pressure nozzle: This nozzle type is the preferred choice when big drop- Table 1:
lets in the range 150-350 microns are required. The basic function of pressure Comparison droplet mean
size of different atomizers
nozzles is to convert the pressure energy supplied by the high pressure pump (adapted from [1])
into kinetic energy in form of a thin film. The droplet size produced varies with
feed rate and feed viscosity. Most commercially available pressure nozzles are
designed with a swirl chamber giving the liquid a rotation and a hollow spray
cone. For high capacities multi-nozzle systems are applied.
Ultrasonic atomizers: The droplet size in an ultrasonically produced spray is
governed by the frequency at which the nozzle vibrates, and by the surface ten-
sion and density of the liquid being atomized. However, the frequency is the pre-
dominant factor. Median droplet size is inversely proportional to the frequency to
the 2/3 power. Thus, the higher the frequency the smaller the median drop size.
Ultrasonic atomizers are available with different frequencies and are precise at
converting various liquids into fine droplets. Without the use of air pressure, the
liquid is pumped to the vibrating surface used in making fine particles. The vi-
brating surface can come in many shapes and styles for different coating and
process applications. Ultrasonic atomizers have the advantage of a more uniform
particle size distribution than two fluid nozzles.
72 Part B Theoretical basis of the spray drying process
2.3 Evaporation, particle shape formation and drying

As soon as the droplets come into contact with the hot drying gas, evaporation
takes place at the saturated vapour film, which is quickly established on the
droplet surface. Due to the high specific surface area and the existing tempera-
ture and moisture gradients an intense heat and mass transfer results in an ef-
ficient drying. The evaporation leads to a cooling of the gas temperature and thus
to a small thermal load on the product.
Fig. 6 illustrates the temperature profiles of the gas and the droplet (product)
in the spray chamber. The gas temperature decreases with time. The droplet
temperature increases at the beginning to the cooling limit temperature and re-
mains constant during evaporation. The droplets can shrink, agglomerate or lose
sphericity as moisture is evaporated. At the end, the dried particle surface tem-
perature (product curve) approximates the temperature of the surrounding gas,
which determines the final outlet temperature. The outlet temperature is a result
of the applied aspirator rate, inlet temperature and the liquid feed rate. A higher
inlet temperature moves the outlet temperature to higher values. A lower liquid
feed rate increases the outlet temperature due to the fact that less liquid has to
be evaporated in the same time. A lower aspirator rate decreases the slope of
the gas temperature profile and leads to a lower outlet temperature.
Figure 6:
Temperature profiles of the
product and gas during T [°C]
spray drying in co-current Inlet
mode temperature
Aspirator Gas
rate
Tout
Product
Feed rate
Time or Distance
The manner in which the sprayed liquid droplets contact the drying gas is an
important factor in spray drying design. It has great influence on the droplet’s
behaviour and the dried product properties. The commonly used flow configura-
tions in spray dryers are illustrated in Fig. 7.
Co-current flow: The material is sprayed in the same downwards direction
as the flow of the hot gas. The droplets come into contact with the hot gas at the
top and exit the spray chamber at the bottom, where the gas temperature is the
lowest. Therefore, the product is treated with care and is good for the treatment
of heat sensitive products.
Counter-current flow: The material is sprayed in the opposite direction to
the hot gas. The hot gas enters at the bottom and flows upwards, while the
product falls through increasingly hot gas into the spray chamber. The residual
moisture is evaporated and the product becomes hotter at the end in compari-
son with the co-current mode. This method is suitable only for thermally stabile
products.
Part B Theoretical basis of the spray drying process 73
Figure 7:
Co-current Counter-current Mixed-flow Flow configurations of Spray
Air in
Dryers (adapted from
Atomizer K. Masters)
Air in
Air in Atomizer
Air in
Atomizer
Air in
Air in
= Air = Product = Fluid feed
Combined mode (also called mixed mode or fountain mode): The advantages
of both spraying methods are applied. The product is sprayed upwards and only
remains in the hot zone for a short time to evaporate the solvent. However, this
method increases the residence time of the droplets in the gas and allows drying
of bigger droplets compared to the co-current or counter-current mode. Gravity
pulls the product back into the cooler zone again. Due to the fact that the product
is only in the hot zone for a short time, the product is treated with care.
2.4 Separation of the dried product from the gas and discharge
The primary separation of the dried particulates from the drying gas takes place
at the base of the spray drying chamber. The finer particles can be recovered
from the drying gas by a separation device, such as a cyclone (Fig. 8).
Figure 8:
Cyclone separation principle
gas
particles
+
gas
particles
Based on inertial forces, the particles flow to the cyclone wall and separate from
the gas as a downwards strain. Other systems for particle separation are electric
precipitators, bag (textile) filters or wet collectors like scrubbers. The two powder
streams are subsequently mixed or segregated. Often the grain fraction is recov-
ered as product, whilst the fine material is recycled into the process due to its
superior press characteristics.
74 Part B Design of the Mini Spray Dryer B-290
3 Design of the Mini Spray Dryer B-290
The Mini Spray Dryer B-290 [5] is a laboratory scale system to perform spray
drying processes down to 50 ml batch volume or up to one litre throughput
per hour. Due to its glassware, the complete drying process from the two fluid
nozzle down to the collection vessel is visible. For small batch sizes e.g. in phar-
maceutical applications, a small spray dryer is particularly interesting to obtain
small product volumes within a short time. Thermo sensitive components such
as enzymes or antibiotics remain fully active.
3.1 Spray drying principle

The Mini Spray Dryer B-290 (Fig. 9) works according to the same principle as
the co-current flow atomizer i.e. the sprayed product and the drying air flow in
the same direction. The peristaltic pump feeds the liquid sample from the feed
solution container to the nozzle. The integrated two fluid nozzle disperses the
fluid feed and compressed air/nitrogen spray gas into a spray cone. The inlet gas
is heated up by an electrical heater, blown through the system by an aspirator,
and is used as the drying gas. The spray gas is used to disperse the liquid feed
into fine droplets, which are subsequently dried in the spray cylinder. The cyclone
separates the particles from the gas stream and the dried particles fall into a
product collection vessel. The outlet filter captures very fine particles, preventing
them from leaving the system. This prevents environmental pollution and pos-
sible corrosion and abrasion of the aspirator by these fine particles.
Figure 9:
Mini Spray Dryer B-290
1 Air inlet (optional with 2

attached inlet filter) 3
8
1
2 Electric heater
3 Concentric inlet of the hot
4
air around the spray nozzle
4 Spray cylinder
5 Cyclone to separate par- 7
5
ticles from gas stream
6 Product collection vessel
7 Outlet filter 6
8 Aspirator to pump air
through system
1 Solution, emulsion or
dispersion of the product
4
2 Peristaltic feed pump 6
5 2
3 Two fluid nozzle
4 Cooling water connection
5 Compressed air or inert
gas supply connection 3
6 Nozzle cleaning device,
consisting of needle pneu-
matically pushed through 1
the nozzle
Part B Design of the Mini Spray Dryer B-290 75
The two fluid nozzle consists of a nozzle tip and a nozzle cap. This geometry
enables fine atomization of the liquid feed. The nozzle cap includes a ruby stone
with a precise opening to guarantee a sharp and reproducible spray cone. A
nozzle cleaning option provides the possibility to spray dry high viscosity suspen-
sions and solutions without nozzle clogging.
The outlet filter is made of a polyester textile and prevents environmental pol-
lution. It also protects the aspirator from corrosion damage caused by very fine
particles being carried through in the gas stream. The system can also be run
with a PTFE membrane filter. With this filter fine particles collected on the mem-
brane can be partially recovered by counter pulsing the inner side of the filter
with the spray gas. This results in the particle cake being dislodged from the
membrane’s surface and deposited in the bottom of the filter housing vessel.
3.2 Open and closed mode configurations

An open system configuration is typically used to spray dry aqueous solutions
with less than 20% organic solvent content. It is also used with oxygen stable
substances. Air is usually used as the drying gas. The air stream is heated up
electrically and exits the process as an exhaust gas either to the atmosphere or
into a fumed hood. For use in the open mode, the Dehumidifier B-296 is an ac-
cessory to enable drying under constant and reproducible humidity conditions at
a dew point of 3-5 °C. The drying air is passed through the chiller in the Dehu-
midifier B-296. The humidity in the ambient air condenses in the chiller and is col-
lected in a closed bottle. The dried air is than heated up by the heat exchanger.
Figure 10a:
Open loop Mini Spray Dryer
Open mode: Closed mode:
B-290 with Dehumidifier
B-296 for inlet air con
ditioning
Mini Spray Dryer B-290
Dehumidifier B-296 Mini Spray Dryer B-290
N
1 Ambient
2 air
à 2 Condensation
Ö
3 Cooling unit
á Å
4 Condensed water
Å 5 Product
6 Exhaust gas
7 Compressed air
8 Feed
É Ü Ç
Ñ Ö
Mini Spray Dryer B-290 I
N2
Ç
76 Part B Design of the Mini Spray Dryer B-290
Figure 10b:
Open mode:B-296 used in
Dehumidifier Closed mode:
closed mode
Dehumidifier B-296 Mini Spray Dryer B-290 Mini Spray Dryer B-290 Dehumidifier B-296
N2
1 Feed
2 Product
à Ö
3 á Å
ÅExhaust gas
4 Condensate Ü
5 External preheat
exchanger á
Ç
6 Condensation
7 Cooling unit
É Ü Ç
ÉÑ
Ñ Ö
Closed loop with the Inert Mini Spray Dryer B-290 Inert Loop B-295
N2
Loop B-295
Ö
1 Feed Å
2 Product
3 Exhaust gas Ü
4 Solvent á
5 Preheat exchanger
6 Condensation
7 Cooling unit
Ç É Ñ
Closed loop with the Inert Mini Spray Dryer B-290 Inert Loop B-295
N2
Loop B-295 and adsorption
column
Å
1 Feed
2 Product
3 Adsorption column
4 Exhaust gas
5 Solvent Ç Ñ Ö
É
To safely dry inflammable solvents, toxic products or oxygen sensitive sub-

stances, oxygen must be excluded from the gas train to prevent the formation
of ignitable gas mixtures. In this case, spray drying is therefore carried out under
inert gas conditions in a closed cycle mode. Here, nitrogen or another inert gas
is introduced into the system.
The Dehumidifier B-296 enables the safe use of a water-organic solvent mix-
ture in a closed loop with up to 50 % organic solvent content.
The inert gas is loaded with the water-solvent mixture from the spray drying
process in an external preheat exchanger. The solvent condenses in the De-
humidifier B-296 and is collected in a receiving bottle. The cleaned gas stream
flows back and is heated up again in the preheat exchanger.
The Inert Loop B-295 is an accessory for the Mini Spray Dryer B-290 which
enables it to work safely with organic solvent mixtures and pure organic sol-
vents. It comprises a cooling unit, and pressure control and oxygen monitoring
sensors. The inert gas is loaded with solvent from the spray drying process and
Part B Design of the Mini Spray Dryer B-290 77
after pre-cooling in a preheat exchanger, the solvent is condensed in a chiller

operating at –20 °C and recovered in a closed bottle. The cleaned gas stream
is then reheated in the preheat exchanger and returned back to the Mini Spray
Dryer B-290. Typical solvent recovery rates are around 70%, depending on the
boiling point of the solvent.
If mixtures of organic solvents and water are used, it is recommended that the
additional adsorption column is used in the closed loop system. The adsorption
column consists of molecular sieve material and prevents the water from freezing
in the Inert Loop B-295. The humidity in the gas is detected by a sensor and as
soon the molecular sieve in the column is saturated with water, a control signal
stops the feed pump. The molecular sieve is then exchanged and the saturated
unit regenerated by drying in a vacuum oven.
3.3 Spray chilling accessory

Spray chilling is used to form particles directly from a molten sample by gas
phase solidification with a cooled gas, typically air. The principle is shown in
Fig. 11. Applications are found in cosmetics or taste masking, such as vitamins
dissolved in fats, lypophilic active agents in glycerides or microcapsules made
from waxes.
When a hot melt is dispersed into a cold gas stream, the droplets are solidified
into particles and can thus be separated and collected. The matrix substance
and the active ingredient are heated above their melting points up to a maximum
of 70 °C. The nozzle is also heated to prevent any blocking. If the sample has a
low melting point, the inlet air is cooled down to about 10 °C with the Dehumid
ifier B-296 to increase the temperature gradient for solidification. Using a spe-
cially developed refrigeration unit the inlet air temperature can be cooled down
even further.
Figure 11:
Spray chilling principle,
1
1 Temperature sensor
2 Circulating heating liquid
to bath-nozzle-peristaltic
4 pump-bath
3 Cold gas
4 Heated feed sample
3
78 Part B Optimizing the spray drying process parameters
4 Optimizing the spray drying process parameters

Spray Drying is a method where the results are highly dependent upon the cor-
relation and interdependency of the process parameters. Thus, the instrument
settings, (namely inlet temperature, feed pump rate, gas spray flow and aspirator
flow) combined with the feed concentration system all influence the following
product parameters:
– Temperature load
– Particle size
– Final humidity
– Yield
The optimization of these parameters is usually made using a «Trial & Error»
procedure. Some initial conditions can be found in the application database
(www.buchi.com) for equal or similar products. Fig. 12 gives an overview over the
spray drying parameters and their influence on the final product properties [4].
Figure 12: para- aspirator air humidity inlet tem- spray air feed rate ↑ solvent concentra-
Influence of process meter rate ↑ ↑ perature ↑ flow ↑ instead of tion ↑
parameters on the product de- water
characteristics (from [4]) pendence
outlet tem- ↑↑ less ↑ more en- ↑↑↑ direct ↓ more cool ↓↓ more ↑↑↑ less ↑↑ less
perature heat losses ergy stored proportion air to be solvent to heat of water to be
baded on in humidity heated up be evap energy of evaporated
total inlet of orated solvent
energy
particle size – – – ↓↓↓ more (↑) more (↓) less ↑↑↑ more
energy for fluid to surface remaining
fluid disper- disperse tension product
sion
final ↑↑ lower ↑↑ higher ↓↓ lower – ↑↑ more ↓↓↓ no ↓ less water
humidity of partial pres- partial relative water leads water in evaporated,
product sure of pressure of humidity to higher feed leads lower partial
evaporated drying air in air particle to very dry pressure
water pressure product
yield ↑↑ better (↓) more (↑) – (↓↑) ↑↑ no hygro- ↑ bigger
separtion humidity eventually depends on scopic particles
rate in can lead dryer prod- application behaviour lead to
cyclone to sticking uct prevent leads to higher
product sticking easier drying separation
Guidelines for quick process optimization are:

– Larger temperature differences between the inlet and outlet temperature re-
sults in a larger amount of residual moisture
– A higher aspirator rate means a shorter residence time in the spray chamber
and results in a larger amount of residual moisture in the product
– A higher aspirator rate results in a higher degree of separation in the cyclone
– Higher gas spray flow tends to result in smaller particles
– Higher feed concentrations tend to result in larger particles
– Higher feed pump rates results in a lower outlet temperature
Part B Optimizing the spray drying process parameters 79
4.1 Inlet temperature

The inlet temperature is understood as being the temperature of the heated dry-
ing gas. The drying gas is sucked or blown into the system by the aspirator
and is heated up before it enters the spray chamber. The inlet temperature is
measured at the inlet of the drying chamber. The inlet temperature is set to a
value where temperature gradient between the wet droplet surface and the hot
saturated gas leads to an evaporation of the solvent. The outlet temperature is
determined by the heat and mass balance in the drying cylinder and is influenced
by the following parameters (shown in Fig. 6):
1. Inlet temperature
2. Aspirator flow rate (quantity of air)
3. Peristaltic pump setting
4. Concentration of the material being sprayed
Due to the intense heat and mass transfer and the loss of humidity, the par-
ticles approach the gas temperature at the outlet. Thus, as a rule of thumb,
the maximal temperature the product may experience is the measured outlet
temperature.
One of the most important considerations is the choice of the temperature
difference between the inlet and the outlet. Other points are product specific fac-
tors, such as the melting point or decay temperature. In spite of this, there is still
some room for adjustment and optimization.
Figure 13:
Evaporation capacity of the
1.2 70
water Mini Spray Dryer B-290 in
1.1
air spray flow 680 NI/H (40mm) 60 function of inlet and outlet
1.0 aspirator rate 35m3/h (100%) temperature
Water evaporation capacity
0.9
–– 50
Feed pump rate [%]
0.8 T out = 60 °C
T out = 80 °C
–
0.7 40
T out = 100 °C
[kg/h]
0.6
0.5 30
0.4
20
0.3
0.2 10
0.1
0 0
50 100 150 200 250
T in [°C]
Fig. 13 shows the interaction between the inlet and outlet temperatures and
the feed pump rate in terms of water evaporation capacity. From this data some
guidelines can be derived:
First, to achieve a final product with a very small amount of residual moisture,
the inlet temperature must be set as high as possible and the temperature differ-
ence must be as small as possible.
Secondly, increasing the temperature difference while holding the inlet tem-
perature constant increases the residual moisture content in the final product as
well as the spray flow rate.
80 Part B Optimizing the spray drying process parameters
4.2 Aspirator rate

The drying gas is sucked or blown through the device by the aspirator motor,
creating a little under- or over-pressure in the system. By regulating the aspirator
rate, the amount of heated drying gas is increased or decreased, which has a
significant effect on the drying performance.
The optimum setting must be determined experimentally using the guideline:
A higher aspirator rate leads to a higher degree of separation in the cyclone. A
lower aspirator rate results in a lower residual moisture content.
4.3 Feed pump rate

The peristaltic pump feeds the spray solution to the nozzle. The pump rate
affects the temperature difference between the inlet and the outlet. The pump
rate corresponds directly to the inlet mass. The higher the throughput, the more
energy is needed to evaporate the droplets into solid particles. Thus, the outlet
temperature decreases.
The selection of too high a pump rate leads to wet and sticky particles, which
adhere to the spray chamber wall. The optimal pump rate depends also upon
factors such as the viscosity of the spray solution and tubing diameter.
Guidelines related to the feed pump rate are: An increase of the feed pump
rate lowers the outlet temperature and increases the temperature difference be-
tween the inlet and the outlet. Reducing the pump rate, while holding the inlet
temperature and aspirator rate constant, leads to a drier final product.
4.4 Feed concentration

An increase in solid concentration in the feed results in larger and more porous
dried particles. This influence is obviously due to pure mass balance of input
and output of solid material. The solid concentration depends strongly on the
application (see Table 2).
4.5 Gas spray flow

The gas spray flow is the amount of compressed gas needed to disperse the
liquid solution, emulsion or suspension into a nice spray cone. In a closed mode
configuration, compressed nitrogen is used instead of air. The gas spray flow is
adjusted manually by a needle valve to between 300 and 800Nl/h. The rotameter
indicates the gas spray flow in a mm-height scale.
Figure 14:
Droplet and particle size
distributions as a function
of the gas spray flow in Droplet size distribution Particle size distribution
the two fluid nozzle (20% 16 100 16 100
14 90 14 90
maltodextrin solution, 100% 80 80
12 12
aspirator rate, 140 °C inlet 70 440 Nl/h 70
10 10 670 Nl/h
dQ3 [%]
dQ3 [%]
60 60
temperature)
Q3 [%]
Q3 [%]
8 50 8 1050 Nl/h 50
6 40 6 40
30 30
4 4
20 20
2 10 2 10
0 0 0 0
0 10 20 30 40 50 60 0 10 20 30 40 50 60
Mean droplet size [micron] Mean particle size [micron]

Part B Optimizing the spray drying process parameters 81
As a guideline, the gas spray flow is the key process parameter to adjust the
droplet size. A higher gas spray flow rate leads to smaller droplets and accord-
ingly to smaller dried particles. Fig. 13 illustrates this relationship, showing the
shift of the particle and droplet size distributions towards smaller droplets and
particles with a higher gas spray flow.
4.6 Procedure to run a spray drying experiment

To carry out a spray drying trial with the Mini Spray Dryer B-290, the following
procedure is suggested:
1. Switch on the instrument. The instrument carries out an automatic self check
and then switches automatically to the operating mode.
2. Adjust the spray gas flow to about 40 mm with the rotary valve.
3. Pre-select the desired inlet temperature with the push-button.
4. Turn on the aspirator. For standard applications, the aspirator rate should be
100 % to maximize the separation rate within the cyclone. If a small powder
humidity is required, the aspirator rate can be decreased.
5. Turn on the heater and wait until the system has reached steady condi-
tions.
6. Turn on and set the automatic nozzle cleaning option to prevent the sample
clogging the nozzle.
7. Switch on the peristaltic pump. Use pure solvent, e.g. distilled water in case
of aqueous solutions, at the beginning of a trial. Check if the spray cone is
symmetrical and located in the axis of the spray cylinder. If this is not the
case, the nozzle may be dirty or defective.
8. The feed pump rate can be adjusted by means of the push-buttons for the
peristaltic pump control. The pump rate strongly influences the outlet tem-
perature, since the water draws energy from the gas by evaporation. Thus,
the outlet temperature can be set to the desired value by varying the quantity
of liquid via the pump rate setting of the peristaltic pump.
9. The outlet temperature can be regarded as the upper thermal load on the
product. Make sure that the product is not damaged by an excessively high
outlet temperature.
10. As soon as the desired operating conditions are found and are stable, the
feed tube is changed from the pure solvent to the prepared feed solution.
The spray drying process starts.
11. After the solution is completely spray dried, switch back to the pure solvent
and continue spraying for a short time to remove product deposits in the
hoses and the nozzle. Occasionally take the feed tube out of the solvent
reservoir and allow some air to be sucked through. This will help ensure an
efficient cleaning process.
12. Pump the feed tubing empty, turn off the peristaltic pump and lower the
pump bed.
13. Turn off the nozzle cleaner and the heater. The system can now be allowed
to cool down.
14. As soon as the temperature in the instrument falls below 90 °C, the aspira-
tor can be turned off. The product collection vessel with the product can be
removed now.
82 Part B Spray drying applications
5 Spray drying applications
The following section is dedicated to the remarkable list of materials, which can
be successfully spray dried. In general, the applications for a spray dryer can be
divided into distinct areas: Spray Drying, Micronization, Micro encapsulation and
Englobing (Fig. 15).
Spray drying is suitable for most real or colloidal solutions, for emulsions and
dispersions so long as the dried product behaves like a solid. Practical applica-
tions are corn starch, pigments or dried milk.
An aqueous solution of the product (A) is dispersed into fine droplets (B) using
a two fluid nozzle. The solvent evaporates immediately and surrounds the prod-
uct in a vapor cloud that protects the product from thermal load. As soon as the
critical concentration is exceeded, nucleation starts which forms a solid shell.
After the solvent has dried from the surface, the interface moves into the core
(second step of drying). The final product (C) is a fine, amorphous or crystallized
material. Spray drying of highly concentrated solution results in a more porous
final product.
Figure 15:
Applications where a spray Spray Drying Micro encapsulation
drier is used
A
B D E F
A B C
Micronization or Structural Change Englobing
A
B D E F
C D E
B
C
The micronization or structural change is the change of morphology, for ex-

ample if a fine powder is required. This has a positive effect on the solubility or
measurability of the final product. Typical examples are salts or dyes. The main
advantage of micronization is that a very regular particle size is achieved. The
crystalline product (A) is dissolved in a solvent (B) and this solution (C) is dis-
persed into small droplets (D). The result is a final product (E) just like the final
product described in the section on spray drying.
In micro encapsulation, a liquid product is embedded in a solid matrix. Typical
examples are encapsulated perfumes, aromas or oils. An emulsion (D) is cre-
ated from the liquid product to be treated (A), a carrier substance (B) such as
maltodextrin and a filmogen solution (C) such as gum arabic in water. This emul-
sion is then sprayed into small droplets (E). The solvent evaporates leading to a
solid matrix around the dispersed second phase (F). The result is that the small
Part B Spray drying applications 83
droplets of the product (A) are stored in the carrier substance (B) and embedded
in the filmogen (C).
The englobing process is analogous to the micro encapsulation process,
whereby a solid material is embedded in another solid or liquid product. An ex-
ample is carotenoids in gelatine. A solution or dispersion (D) is created from the
product to be treated (A), a matrix (B) and water eventually with additional filmo-
gen (C). This solution is then sprayed into small droplets (E).The matrix and / or
filmogen leads to an agglomeration or coating of the suspended particles (F).
Over the years Büchi Labortechnik AG has provided a unique service of spray
drying customer’s samples to check the feasibilities of spray drying the selected
product. The collected experience of those trials are summarized in Table 2. The
application list is sorted into Spray Drying/Micronization and Englobing/Micro
encapsulation applications and the industrial sectors Foodstuff, Chemical prod-
ucts, Aroma/Cosmetics/Cleaners/Detergents and Medical/Pharmaceutical. The
given parameters can be used as «first guess» operation parameters for trials on
the Mini Spray Dryer B-290.
Product Tin °C Tout °C Conc. % Table 2:

Examples of spray drying
Foodstuffs applications and process
Spray Drying/ Micronization parameters for Mini Spray
Dryer
Baby food 160 95 40
Beer 180 108 10
Casein 150 90 6
Yeast 95 55 60
Krill 180 80 10
Lactose 160 105 30
Low-fat milk 174 102 50
Corn starch 130 70 40
Milk 110 70 15
Whey 180 80 6-45
Soyabean extract 130 75 80
Englobing/ Micro encapsulation
Fruit concentrate, raspberry, in maltodextrin, 2:8 150 90 30
Fruit concentrate, orange, in maltodextrin, 2:8 150 90 40
Invert sugar (date pulp) in lactose, 1:1 100 80 20
Black currant juice in maltodextrin 170 100 47
Soyabean oil in maltodextrin/gelatin 150 90 30
Sugar/fat mixture in maltodextrin/
gum arabic 25:15:50:10 160 90 22
Product Tin °C Tout °C Conc. %

Chemical products
Spray Drying/Micronization
Acrylamide 125 70 50
Albigen 280 90 10
Ammonium chloride 180 75 20
Ammonium nitrate 180 100 20
Lead oxide 150 90 10
Calcium hydrogen citrate 200 110 50
Calcium carbonate 220 100 10
Calcium phosphate 190 100 10
Di-calcium phosphate 170 90 20
Di-sodium phosphate 200 140 50
Dispersion dyes 150 95 20
Iron oxide 170 125 10
Pigments 130 110 36
Glass powder 120 90 20
Latex rubber 120 70 20
Indigo-sodium sulfate 150 90 30
Potassium hydrogen citrate 200 110 50
China clay 180 130 33
Ceramics (various types) 150 120 46
Synthetic glues 100 70 20
Latex 160 90 31
Lignin 130 55 7-4
Magnesium phosphate 120 90 15
Melamine resin 120 80 30
Metal oxide 210 135 10
Sodium citrate 160 90 20
Sodium orthophosphate 180 110 40
Sodium sulfite 180 90 20
Ceramic oxide 100 80 26
Phenolic resin 135 105 50
Polyacrylamide 204 111 9

Aroma/Cosmetics, cleaners and detergents
Spray Drying
Valerian extract 150 100 25
Beer concentrate 150 110 30-40
Chicory extract 130 75 38
Pine bark extract 120 85 4
Chestnut extract 200 130 20
Metal soap 165 122 60
Microfoam beads 160 114 3
Sodium citrate 160 90 20
Sodium orthophosphate 180 110 40
Olive leaf extract 150 90 20
Liquorice extract 100 75 36
Detergent 200 110 40
Fabric softener 125 75 20
Xanthane mixture 130 70 2-3
Zeolite 180 120 10
Englobing/ micro encapsulation
Aroma, strawberry in maltodextrin/
gum arabic 1,5 : 1,5 : 3 150 90 35
Aroma, orange in maltodextrin/
gum arabic 1,5 : 1,5 : 3 150 90 17
Cardamon oil in maltodextrin/gum arabic 1 : 20 : 39 170 100 20
Date juice in maltodextrin/gum arabic 25 : 25 : 1 120 90 30
Caraway oil in maidex/gum arabic 140 100 50
Perfume oil in maltodextrin/gum Arabic 1 : 2 : 1 130 70 30
Peach oil in maltodextrin 150 100 20
Bubble bath in sodium chloride 1 : 2 160 100 15
Cinnamon oil in maltodextrin/gum arabic 1 : 3 : 6 170 100 20
Lemon oil in maltodextrin/gum arabic 130 90 20

Medical/Pharmaceutical
Spray Drying
Albumin 110 60 5
Lyophilized anti-progresterone serum 80 60 1
Blood plasma 180 100 5
Dextran 154 120 20
Enzymes / coenzymes 80 55 12
Fructose-amino acid compounds 180 80 37
Galactomannan 200 115 5
Gelatin capsule dispersions 105 80 20
Glucose / amino acid compounds 1 : 1 130 80 10
Mannitol with enzymes 100 55 15
Combination vaccines 190 140 -
Organ extracts with tetra-sodium
di-phosphate 1 : 0,43 150 88 11
Peptides 110 70 2
Vitamin A + E / gelatine-emulsion 100 55 -
Cell suspension (bacteria cultures) 90 60 50
Englobing/ micro encapsulation
Carotinoid in gelatin 40 : 60 170 100 25
Guajazulene in maltodextrin/gum arabic 1 : 2 : 1 120 70 30
Streptococci in low-fat milk
powder/glucose/gelatin 1 : 1 : 1: 3 90 70 40
6 Safety precautions
The Mini Spray Dryer has been and built as a laboratory instrument. It serves
to dry aqueous solutions or suspensions in a one-step process. In combination
with the B-295, it is possible to work with organic solvents. If the instrument is
used with toxic or hazardous substances, it has to be installed inside a closed
fume cupboard. Applications not mentioned in table 2 or in the Buchi application
database (www.buchi.com) have to be considered as improper. In particular no
gases with unknown chemical composition may be drawn off. The following uses
are expressly forbidden:
– Spray drying of organic solvents without the inert loop B-295 in open cycle.
– Use of the Mini spray dryer in rooms which require ex-proof instruments
– Use on samples which can explode or are inflammable (example: Explosives,
etc.) due to shock, friction, heat or spark formation
– Use on oxygen-producing substances
7 Literature
[1] K. Masters: Spray Drying in Practice, SprayDryConsult International ApS,
Denmark, 2002
[2] K. Masters, Spray Drying Handbook, 3rd edition, George Godwin Limited,
London, 1979
[3] Spray Drying Brochure, BNA 480/GB-09/00, GEA Niro A/S
[4] Training Paper Mini Spray Dryer B-290, order number 97758
[5] Operation Manual Mini Spray Dryer B-290, Version G, order number 93001
Generation of a vacuum
C
90 Part C Generation of a vacuum
1 Introduction
1.1 Overview
The purpose of this chapter is to provide the interested user of vacuum sources
with a theoretical and practical survey of the field of vacuum generation. The
theory applies to the entire field of vacuum generation, and our overview covers
different types of pumps. Nevertheless, the main emphasis here is on the pumps
produced by Büchi Labortechnik, which operate in a low vacuum.
A brief historical introduction and an assessment of the present state of the
art with regard to vacuum technology are followed by a chapter that deals with
the theoretical basis for generating vacuums. This includes an explanation of gas
theory and not only shows how to build up a vacuum, but also provides an insight
into how vacuums are measured. The next chapter is devoted to vacuum regula-
tion, showing how to produce a vacuum that will suit specific needs, the factors
that influence it, and how to hold those factors constant. A fourth chapter provides
an overview of the various types of vacuum pumps available, explaining briefly their
design and how they function. A chapter then follows with detailed information on
diaphragm and water jet, to assist in the understanding of such equipment. Finally,
the last chapter describes the correct way to work with vacuum systems. This
information starts with how to select the correct equipment and how to operate it,
followed by various practical applications, and then describes the precautionary
measures that must be taken, and the risks involved with the equipment.
1.2 History of the development of vacuum generation

While compressed air pumps and pumps for moving water had already been
in use long before the time of Christ, vacuum pumps were not developed until
well into the 17th century. The reason for this lay in the natural philosophy of
Aristotle, who postulated an abhorrence on the part of nature for a void, the
«Horror vacui». This premise was so generally accepted that even Galileo Galilei
(1564–1642), who had broken to a large extent with Aristotelian dogmas, con
tinued to postulate the «Horror vacui».
One of his pupils, the Italian mathematician and physicist Evangelista Tor-
ricelli (1608–1647) was the first to free himself from the old preconceptions and
to produce the first vacuum. He did this by filling a long glass tube closed off at
the top with mercury, sealing its bottom end with his thumb, and dipping it into a
mercury bath. When he then removed his thumb, the mercury level dropped and
a vacuum formed above it up to a level 760 mm above the level of the mercury
bath. This was the first barometer and, thanks to its accuracy, it can still be used
today. Torricelli used it to verify the pressure exerted by air and to demonstrate
fluctuations in that pressure.
At that time, the German physicist Otto von Guericke (1602–1686) was also
working independently of Torricelli in the field of vacuum technology. His pio-
neering role may be said to have started the age of vacuum research. When
he concerned himself with Kepler’s (1571–1630) laws of planetary motion, he
recognized that the planets had to be moving through airless space. Otherwise,
they would have to come to a standstill due to the resistance of the air surround-
ing them. Stimulated by this realization, he started tests to verify the existence of
this vacuum experimentally. Because air pumps were still unknown at that time,
he made use of a water pump used for emptying water from a drum, the devel-
Part C Introduction 91
Figure 1:
Guericke’s air pump.
opment of which is attributed to Greek physicist Ktesibios of (3rd centrury B.C.).

However, because the air could be heard intruding audibly into the drum through
leaks and through pores in the wood, he shifted his experiments to metal vessels.
These, of course, became crushed while being evacuated. Only when he took a
sphere and withdrew air from it instead of water did he obtain his first vacuum.
This experiment also represents the birth of the first air pump, which Guericke
kept refining up until the time of his death. Fig. 1 shows the construction of his
pump. This pump enabled Guericke to experiment at will with vacuums. He thus
developed a water barometer, measured the weight of the air, and demonstrated
that sound does not propagate in a vacuum, though magnetic waves do. Best
known of all was his Magdeburg hemisphere experiment in 1657. He evacuated
two copper hemispheres approx. 50 cm in diameter that were sealed off with
a leather belt, and hitched eight horses to each of the hemispheres. Despite all
their exertion, the horses could not pull the two hemispheres apart.
These experiments caused an enormous growth of scientific interest in va
cuums. New discoveries and developments followed one upon the other in rapid
succession. On the one hand, the basic concept of the atmosphere changed
– people began to understand that this is a sea of air and that there is a weight of
approximately 10 tons pressing down on every square meter of the ground. On
the other hand, people started building even better pumps. First of all, the British
physicist and chemist Robert Boyle (1627–1691) improved Guericke’s air pump
by replacing the pump lever with a gear drive, thereby reducing the amount of
physical effort required to a fraction of that formerly needed. However, despite
steady improvement, the problem remained with Guericke’s pump that there
was always a small space, the dead space, left empty. The resultant incomplete
expulsion of air meant that only moderate vacuums could be attained. Fleuss
filled this dead space with oil, thereby creating a pump with almost no dead
space that already could generate considerable vacuums (4.1). In 1857, Geissler
actually developed a pump with a mercury piston, and Töpler and Poggendorf
improved that further in 1862. Mercury pumps were never proved successful on
the market. The German chemist Robert W. Bunsen (1811–1899) developed the
water jet pump, which operates on a completely different principle, in 1870.
92 Part C Introduction
The German physicist Wolfgang Gaede (1878–1945) made the break-through

into the medium-high vacuum range with his vane-type pump. With its rotating
pistons and valves submerged under oil, this pump created the basis for rotary
vacuum pumps. In 1915 he also developed the diffusion pump (4.2) that enabled
the first break-through into the high-vacuum range. From that point on, things
moved very quickly. Such new types as molecular pumps, sorption pumps,
cryopumps, and ion getter pumps were developed, each of them operating on
totally new principles. The attainable end pressures kept getting lower and lower,
the vacuum kept becoming more and more important for industry and for re-
search. Reading the next chapter, you will realize how important this science that
was born only 300 years ago has become today.
1.3 Applications for vacuums

The first major application for vacuums was in the production of incandescent
light bulbs and at the turn of the century, in the production of radio tubes. As
vacuum research progressed, it was discovered that many processes ran more
quickly or more cleanly under a reduced pressure, or were even impossible with-
out it. The spectrum of possibilities broadened steadily, and vacuum technology
was carried out of the laboratory and into industry.
Vacuum is used today primarily for research and in industrial capacities. There
are various considerations that make the use of vacuums reasonable or neces-
sary, whether in processes, methods, or as a component of the product. For
example, a vacuum is used to keep the air and its reactive constituents away
from processes and materials, to remove enclosed gases and volatile liquids
from mixtures of materials, to build up pressure differentials for doing mechan
ical work, to reduce the amount of energy flow, to produce clean surfaces, or
to increase the length of unimpeded particle travel. Table 1.1. indicates several
typical applications.
The great variety of these applications shows clearly that vacuum technology
is no longer confined to laboratory applications, but has become strongly rooted
in our everyday life.
Traditional application of a vacuum in the laboratory.

Part C Introduction 93
Removal of air Vacuum packing, Melting and annealing of metals, Incan- Tab. 1:
descent light bulbs Typical applications for
vacuum
Removal of materials Vacuum distillation, Freeze-drying, Oil de-aeration
Pressure differentials Lifting and transporting systems (tube mail), Shaping of
plastics, Searching for leaks, Filtration
Reduction of energy flows Thermal insulation, Electrical insulation
Producing clean surfaces Surface investigations (corrosion, catalysis)
Increasing the length Metal coatings, Cathode ray, Picture screen and X-ray of
unimpeded travel tubes, Particle accelerators, Electron microscopes, Mass
spectrometers
Various applications of a vacuum down to 1 mbar in the chemical laboratory.

94 Part C Theoretical basis for the generation of vacuums
2 Theoretical basis for the generation of vacuums
2.1 Definition of a vacuum

A vacuum was originally viewed as a space free of gaseous material. However,
no one has yet been able to produce such a vacuum and it is suspected that
there are still approx. 4 molecules per cubic meter even in those points in the
universe that are freest of all material. A vacuum is therefore defined as follows
today:
A vacuum is a space in which the prevailing pressure is less than the atmo-
spheric pressure.
Nevertheless, a space free of all gas is used as the reference parameter – the
pressure scale starts from 0 bar, and all pressures, whether overpressures or
underpressures, are positive in value. Vacuums are further subdivided into four
vacuum ranges.
low vacuum p approx. 1000 – 1 mbar

medium-high vacuum p approx. 1 – 10–3 mbar
high vacuum p approx. 10–3 – 10–7 mbar
ultra-high vacuum p < 10–7 mbar
But what is pressure? Unlike solids and liquids, the molecules in gases can
move freely. As a result of this free mobility, the individual molecules strike con-
tinually against one another like tennis balls and take on new directions – the
gas expands. Whenever a molecule strikes a wall, it rebounds from it, thereby
affecting the wall with a very slight force. The more molecules there are within a
given space, the more often one of them strikes against the wall, and/or the more
particles impact on the wall per unit of time, each exerting a force which added
together, is their pressure.
p = F (2.1)
A
Pressure is therefore a force (F) acting upon a surface (A). The standard
international unit for pressure is the Pascal (Pa), but it is generally reported as
mbar (=100 Pa).
1 Pa = 1 N/m2
(2.2)
1 hPa = 100 Pa = 1 mbar
In addition to the Pascal, there are also several other units of measurement
in common use. Particularly worth noting are the Torr, named for Torricelli, the
inventor of the mercury barometer. Torrs indicate the height of the mercury col-
umn in mm. At atmospheric pressure, a mercury column assumes a height of
760 mm, i.e., 760 mmHg or 760 Torr. The American unit psi (pounds per square
inch) is not customarily used in the vacuum range.
Other units of pressure are the technical atmosphere defined with the old
unit of gravitational force, the kilopound (obsolete), and, similar to the mercury
column, the height of a water column in inches (in H2O). These, however, are not
included in Tab. 2.
Part C Theoretical basis for the generation of vacuums 95
Table 2:
Pa bar mbar Torr/mmHg psi atm
Conversion table for the
1 Pa 1 10-5 10-2 7.5 ·10–3 1.45·10–4 9.87·10–6 various units of pressure.
1 bar 105 1 103 750 14.5 0.987
1 mbar 102 10–3 1 0.75 14.5·103 9.87·104
Torr/mmHg 133.3 1.333·10 1.333
–3
1 1.93·10 1.316·10–3
–2
1 psi 6.895·103 6.895·10–2 68.95 51.71 1 6.805·10–2

1 atm 1.013·105 1.01325 1.013·103 760 14.696 1
2.2 Basic gas theory

A vacuum is a pressure below atmospheric pressure. In order to understand this
phenomenon, one must concern themselves with the laws of nature, particularly
with those governing gaseous materials. Unlike the molecules in liquid and solid
materials, those in gaseous material are not bound to one another and automati-
cally fill an enclosed space completely. The chapters that follow explain several
regularities that can be derived from these properties.
2.2.1 The laws of gases

The laws of gases describe the relationships between the conditions of state:
pressure (p), temperature (T) and volume (V) for a given amount of gas (mass m,
number of particles N, molar quantity n). These simple relationships have been
determined experimentally, based on an ideal gas. An ideal gas is a model gas,
the molecules of which are point-shaped spheres between which there are no
forces acting. These molecules collide elastically with one another and impact on
the limiting wall, i.e., losing no kinetic energy in doing this. The first relationship,
the Boyle’s or Mariotte’s Law states that at any constant temperature, the prod-
uct of pressure times volume remains constant:
T = const: pV= const (2.3)
If either the pressure or the volume is held constant, then:
p = const: V=V0 (1+αT) (2.4)

V= const: p = p0 (1κ+T) (2.5)
wherein V0 is the gas volume at T = T0 = 0 °C or 273.15 K, p0 the pressure at

T = T0 = 0 °C, α the coefficient of thermal expansion, and κ the stress coefficient
of the gas. Gay-Lussac’s Law was derived experimentally for ideal gases:
α = κ = 273.15 °K (2.6)
With this relationship, Equations (2.3) and (2.4) can be simplified to (2.6) and
(2.7) and combined into (2.8), which also eliminates the coefficients of stress and
expansion:
V=V0T/T0 (2.7)
p = p0T/T0 (2.8)
pV/T = p0V0/T0 (2.9)
Equation (2.8) points out a very interesting relationship, namely that regardless
of the amount of gas, pV/T is always a constant. If one now makes the substitu-
tions p0 = 1 bar, T0 = 273.15 K and V0 = (molar mass M)/(normal specific gravity
p) = the volume for 1 mol of the ideal gas, one obtains the universal molar gas
constant R:
p0V0
R= = 8.314 J · mol–1 · K–1 (2.10)
T0
Substituting (2.9.) into (2.8.), one obtains the general equation of state for
ideal gases:
pV= nRT (2.11)
This equation brings the amount of gas (mol), pressure, volume, and tempera-
ture into the general relationship and, when three of the four values are known,
this enables the calculation of the fourth.
Example:
If one removes 90% of the ideal gas that is filling a space with V= 1 m3,
T = 20 °C and p = 01.013 bar, how much pressure is left?
(1.) Calculation of the number of moles present:
pV 101300 Pa ⋅1 m 3
n= = = 41.56 mol
RT 8.314 J · mol–1 · K–1 · 293.15 K
(2.) Calculation of the number of particles after evacuation:

nvac = 0.1 · n = 4.16 mol
(3.) Calculation of the new pressure:
nvac RT 4.16 mol · 8.314 J · mol–1 · K–1 · 293.15 K

pvac = = = 10130 Pa = 1013
. mbar
V 1m 3
This example could also be solved more easily as a system of equations without
involving the initial number of particles, but that method would be less illustrative.
There are further variants of this gas equation. By dividing R by the molar
mass M of a given gas, one obtains its specific gas constant Ri, and the gas
equation becomes dependent on the mass:
pV= mRT (2.12)
Another form of the gas equation is obtained by using the Boltzmann constant
k = R/NA= 1.380662 10–23 J/K:
pV = N/NART = NkT (2.13)

from which comes pV= NkT (2.14)
NA = 6.023 1023 mol–1 is the Avogadro constant, N the number of particles.

Whenever dealing with a gas mixture made up of several ideal components, the
gas equation can easily be expanded by adding together their conditions of state.
p tot =
( ∑ n ) ⋅ R ⋅T
i
(2.15)
∑p i =
V
The equations discussed above are valid for ideal gases and/or for all gases
at low pressures and with temperatures far above the boiling point. The situation
becomes difficult at high pressures and temperatures close to the boiling point
because other mechanisms then come into play. At any rate, there are the equa-
tions for conditions of state for real gases available for such cases, among which
Van-der-Waals’ equation of state is of particular significance. This is a modifica-
tion of the equation for an ideal gas into which two constants dependent on the
material, a and b, have been introduced.
Vm is the molar volume Vm = V/n, pi are the partial pressures, and ni the
amounts of material, in mols.
)
p+
V m2
a
)(
⋅ V m − b ) = R ⋅T (2.16)
This equation is of no practical importance in the vacuum range.
2.2.2 Transport processes within the gas

In addition to the laws of gases and gas kinetics, several transport processes
within the gas are also of importance. The most important transport processes
include diffusion (the transport of material) and thermal conductance (the trans-
port of heat). We will deal briefly with these below.
Diffusion occurs whenever two different gases are present within the same
space. A gas that is put into a space filled with another gas tries to distribute
itself evenly. To do this, the zig-zag course of its particles takes place in a directed
movement until a balanced concentration is achieved. This directed movement is
a diffusion flow extending from the source to the most distant point in the space.
Whenever the non-equilibrium is maintained, e.g., in distillation processes, this
phenomenon can be used for gas transport.
Whenever a gas connects two locations that differ in temperature, it can con-
duct heat from the location with the higher temperature to that with the lower
temperature in a heat flow Q̇. This heat flow functions in a manner analogous
to electrical conductance. At the source, the heat energy is transferred to the
degrees of freedom of the molecules when they strike the wall. The molecules
then give the energy from their degrees of freedom off to the wall at the location
with a lower temperature. Between these two points, the particles pass the heat
along from one collision to the next, driven by the thermal gradients. Heat that
is transferred to the translatory degrees of freedom increases the velocity of the
molecule, and thereby the likelihood of a collision. It therefore produces a more
rapid heat transport. Heat imparted to the rotational and vibrational degrees of
freedom does not affect the velocity of the molecule. No acceleration takes place
and the energy is not transported more quickly.
The fewer the particles there are within a given volume, the lower the rate of
impact and the poorer the thermal conductivity will be. This is why a vacuum
provides a good thermal insulation.
2.3 Measurement of vacuum

The pressure range of attainable vacuum from today’s state of the art equip-
ment ranges from 1,013 mbar ambient pressure down to 10-12 mbar. As a result,
no single instrument can cover all needs. On the other hand, there are a large
number of different instruments available for measuring them, each covering a
specific range of pressures.
Pressure meters or gauges can be classified into four groups:
– mechanical vacuum meters
– liquid manometers
– heat-conductance vacuum meters
– ionization vacuum meters
The pressure is measured either directly, by measuring the force exerted by

the pressure on a surface, or indirectly, by measuring a parameter that is propor-
tional to that pressure, such as the density of the particles.
Figure 4:
Operating principle of a
mechanical vacuum meter.
D = diaphragm.
P1 P2
Mechanical vacuum meters work by direct measurement of the pressure.

These meters contain a diaphragm separating two chambers from one another.
The pressure levels prevailing in the two chambers are different, and the differ-
ence in pressure causes the diaphragm to bend. This bending can be transmit-
ted mechanically to a scale. The pressure prevailing in the one chamber is the
pressure to be measured, that in the other is a reference pressure, which is either
a vacuum or the current atmospheric pressure. In bourdon-tube vacuum meters,
the space within a bent tube is connected to the pressure that is to be measured.
The pressure used for comparison is the atmospheric pressure pressing the tube
together when there is a vacuum present. This bending is transmitted to the
needle of a gauge, indicating the pressure.
The method of measurement used by Büchi Labortechnik also works by di-
rect measurement. The electrical properties of the piezo-electric diaphragm built
Figure 5:
Operating principle of the P1 P2
liquid manometer. In a U-
tube manometer, pressure
p2 would be 0 bar.
h
h2
h1
into the sensor change as the diaphragm bends. This change in resistance is
measured, converted into a pressure, and shown on the display.
Liquid manometers also work by direct measurement. These are further de-
velopments of Torricelli’s mercury column. An open liquid manometer has two
chambers in which differing pressures prevail. These are connected by a tube
filled with a blocking liquid, usually mercury. Whenever the pressures in the two
chambers are the same, the levels in both chambers are the same. If they differ,
the difference in pressure between the two chambers can be calculated from the
difference in height ∆h and the specific gravity of the blocking fluid:
∇ ∇
p = ρ ⋅ g⋅ h (2.35)
The U-tube manometer, also referred to as a closed liquid manometer, is an-

other type of liquid manometer. Here, one arm of a U-tube is melted shut and
filled with a blocking liquid. At the end melted shut, a space forms that has an
internal pressure p = 0. Here, too, Equation 2.35 is used to calculate the pressure
at the other end of the tube. The advantage of the U-tube manometer is that it is
absolute, i.e., it does not depend upon calibrations. Liquid manometers can be
used to measure vacuums down to 1 mbar.
The heat-conductance vacuum meter is one type of vacuum meter that mea-
sures the pressure indirectly. In these meters, a wire is stretched through a cyl
indrical tube in which the pressure to be measured prevails. The wire is heated,
and heat starts to flow from the wire, through the gas, to the edge of the cylinder.
A conclusion as to the pressure present can be derived from measuring the
amount of heat that has been supplied to the wire.
Ionization vacuum meters are the instruments used to measure the lowest pres-
sures. These also measure pressure indirectly. Here the gas being measured is ion-
ized, and the resulting current charge proportional to the number of particles pres-
ent is measured. In hot-cathode ionization vacuum meters, a flow of ions (I–) going
to the anode meets the gas and partially ionizes it. This produces a flow of positive
ions (I+) to the collector that is proportional to the pressure present. The best of
these instruments can measure pressures from 1 mbar down to 10–11 mbar.
Figure 6:
Design of a hot-cathode
ionization vacuum meter.
200 V
if
A H C
+ 200 V + 30 V
More detailed literature on this topic:

– H.D. Baehr: Thermodynamik
This book provides a great deal of information on the laws of gases, kinetics,
and other thermodynamic relationships. Knowledge of the fundamentals of
thermodynamics can be obtained here.
– Nigel Harris: Modern Vacuum Practice
This offers a clear, short introduction to the theory of vacuum technology. It
presents its material in a very understandable form, but leaves gaps. It de-
scribes vacuum measurement very well. Generally speaking, the book is suit-
able for obtaining a quick overview.
– M. Wutz, H. Adam, W. Walcher: Theorie und Praxis der Vakuumtechnik
This is «the» book for vacuum technology. It provides well-founded theoreti-
cal background and brings thermodynamics into a concrete relationship with
vacuum technology. However, it requires a certain amount of prior knowledge
of the physics and procedures involved. This book is very suitable for con-
tinuing research of vacuum technology after one has once obtained a general
overview of it.
Part C Vacuum regulation 101
3 Vacuum regulation
A vacuum is not a fixed quantity, but refers to the entire range of pressures
less than atmospheric pressure. Due to this difference in pressure, the system
is constantly seeking to equalize itself. In an absolutely sealed system, such an
equalization process would never come about. But because no such system
exists, air is drawn in through every leak, regardless of how small it is. Distilla-
tion equipment, incandescent light bulbs, television tubes, etc. always leak. But
because they operate under a vacuum, the amount of leakage must be kept as
small as possible. This problem has been solved well enough in the case of light
bulbs, but not in the case of distillation equipment. The many cocks, lapped-in
joints, gaskets, etc. are in fact quite well sealed off but still allow a little air to get
in, so that the pressure inside them is continually rising. These losses are called
leakage air. The increase in pressure can become problematic in practical ap-
plications. For example, in vacuum distillation, a vacuum is used to lower the
boiling point of the liquid being extracted far enough so that the distillation can be
carried out at a low temperature. If the pressure rises, it suddenly reaches a point
where the boiling point is higher than the point to which the material is heated.
Distillation stops. The vacuum must be monitored and adjusted continually to
prevent this. In addition, stable pressure relationships reduce the risks of foaming
and retarded boiling.
The amount of vacuum is also of importance in vacuum applications and re-
quires regulation. When a pump is connected to a vacuum tank, it will keep with-
drawing air from that tank until it reaches the ultimate vacuum. For most vacuum
applications, however, there is no sense in doing this, because what these appli-
cations need is not the lowest pressure possible, but a vacuum appropriate to the
application at hand. In a distillation process, if the pressure is set too low, the am-
bient temperature may become higher than the boiling point of the components
being separated, and the entire solution will then be drawn out of the system
through the pump because no condensation is taking place any longer.
3.1 Changes in pressure

The closed vessel in which a vacuum is built up is never perfectly sealed. The
causes of such leakage and how to search for leaks are described below.
Figure 7:
Possible leak locations in a
rotary evaporator.
102 Part C Vacuum regulation
3.1.1 Leakage air

A leak is an opening in the wall, a container, a gasket, or a seal. These are not
holes that allow an audible intrusion of air, but extremely fine defects a few µm in
thickness, such as a scratch on a polished surface or a hair-line crack at a weld
seam. These leaks act as ducts between two different pressure zones, i.e., gas
flows through them from the outside to the inside.
In a laboratory rotary evaporator, a leakage rate of 1 to 2 mbar per minute is
considered to be very good.
There are two categories of leaks. Pore leakages are small channels, gener-
ally in polycrystalline materials. They are always there. They result from thermal
or mechanical processing, and do not present a problem until there are enough
present to produce a critical leakage rate. The other category, leaks at joints,
generally results from improper use or manufacture. This can ocur when flanged
joints are incorrectly greased, or gaskets are either incorrectly installed or brittle.
3.1.2 Leak detection

Depending on the application in question, it can be important to check the sys-
tem for leaks. A picture tube would be completely useless if it were to fill with air
within a short time. On the other hand, in distillation equipment, corrections can
be made for quite a large amount of leakage air by withdrawing that air at regular
intervals. No search for leaks would be necessary here except in the case of very
large leaks that would make it very difficult to build up any vacuum.
There are many methods available for leak detection. These extend from very
simple methods that can be used at any time to complicated leak detection
equipment. Generally leak detection techniques can be classified into vacuum
and overpressure procedures.
The simplest of the vacuum procedures is probably measurement of the pres-
sure rise. The vessel is evacuated at different pressures and the way in which the
pressure changes is observed. If it rises steadily to high levels, one must assume
there is a leak. Whether or not the leak has to be located and sealed depends
on the application in question and how high the leakage rate is. If, however, the
pressure rises only at the beginning and the rise then diminishes gradually, ceas-
ing altogether while the pressures are still quite low, it may be assumed that rem-
nants of liquids have been evaporated or that the vessel wall has given off gas.
This method is very easy to use, but it cannot be used to locate the leak.
A high-frequency vacuum tester is a brush-shaped high-frequency electrode
that causes colored discharges inside vacuum zones. Whenever it comes close
to a leak, a bright capillary discharge occurs in the leak. The advantage of this
method is that it locates the leak.
The simplest method in the overpressure range is measurement of the pres-
sure drop. Another simple procedure is bubble test. Here the equipment filled
with an overpressure is dipped into a water bath and watched for bubbles ris-
ing. Leaks may be located with this method. In the soap bubble test, locations
suspected of leaking are coated with a soapy solution and the apparatus is then
checked with overpressure. Any leak present reveals itself with the formation of
a bubble. Leak detectors operate on a different principle. Here the apparatus is
filled with a gas containing a halogen or with helium. The work here is done with
a sniffer, an instrument that uses mass spectrometry. Whenever the mass spec-
trometer reveals traces of helium or the halogen, a leak has been discovered.
Part C Vacuum regulation 103
3.2 Maintaining a constant pressure

Even when a vacuum application is not absolutely leak-free, it is necessary that
the pressure always remain approximately constant. It is therefore advantageous
to monitor pressure within the system continuously so as to enable drawing air
off to compensate for deviations from the prescribed pressure. In order to reduce
the costs of this very expensive task, instruments are available that keep measur-
ing the pressure until they reach the desired setpoint and then hold it constant
over a period of time by controlling pumps and valves.
One such device is the Büchi Vacuum Controller. This maintains the desired
pressure by controlling an in-line valve between the vacuum and the pump.
Here, the control parameter used to regulate pressure is the hysteresis, the
value higher than the setpoint for pressure below which the pressure is not al-
lowed to fall. The pump evacuates the system down to the setpoint, and the
Controller then closes the valve. Leakage air causes the pressure to rise slowly
until it reaches the hysteresis value, whereupon the Controller reopens the valve.
Pumping starts, reducing the vacuum to its prescribed value. The hysteresis to
be set depends on the application intended. If a very precisely defined vacuum
is required, the hysteresis selected must be small. If no precision vacuum is
necessary for the intended application, a larger hysteresis is permissible.
Figure 8:
example Regulating pressure with the
p setpoint 400 mbar,
Hysteresis 7 mbar
Vacuum Controller.
1. the pump evacuates to

the setpoint of 400 mbar
407 2. the pressure increases
mbar by 7 mbar (leakage rate)
400 3. the pump evacuates
mbar again back to the setpoint
1 2 3
* pump running
t * pump off
This Controller also performs other important functions. In addition to control-

ling valves, the device can also be used to regulate the supplying of cooling water
and the operation of the vacuum pump. The Controller also offers a possibility for
supplying the pump with power only when needed. This results in shorter operat-
ing times, less power consumption (or water consumption in a water-jet pump),
a longer service life for the pump, and less noise in the laboratory.

An overview of leakage detection technology and the equipment used for it.
The information presented is rather brief.
This presents a very detailed explanation of the theory of leakage air and how
to calculate it. The description of leakage detectors is also especially good.
– A great deal of information on the use of a Vacuum Controller can be obtained
from the training documents and the operating instructions for the B-720
Vacuum Controller, the diaphragm pumps, and the rotary evaporators from
Büchi Labortechnik AG.
104 Part C Survey of types of pumps
4 Survey of types of pumps

There are several different types of pumps available for building a vacuum. This
chapter provides a survey of the most important types. Special attention is given
here to the most common types, namely oil-sealed rotary pumps, oil-free mech
anical pumps, and vapor pumps.
4.1 Oil-sealed rotary pumps

Oil-sealed rotary pumps are a type of displacement pump and can be classified
into two groups, rotary vane pumps and rotary piston pumps.
Rotary vane pumps are very widely used today in vacuum generation. They
are suitable for vacuums down to 10–3 mbar. Their pumping capacities differ
widely and, in large industrial plants, may range up to several 100 m3 per hour.
A motor drives an eccentric shaft to which two or more vanes are attached.
These are movable and are pressed against the wall of the cylinder by centrifugal
force or by springs. The vane always pushes a pool of oil ahead of itself to form
a seal between the expansion chamber and the compression chamber. The gas
is drawn through the intake duct into the space between the two vanes which,
due to the eccentricity of the rotor, continually grows larger. After the expansion
chamber reaches its maximum volume, it again grows smaller and gas is driven
out through the outlet valve. To provide a further seal, the outlet valve is placed
Figure 9:
Principle of suction in a under a pool of oil above which there is an open space to ensure separation of
rotary vane pump. the gas and the oil being carried along.
outlet valve inlet nipple
pool and oil
4.2 Oil-free displacement pumps

Among oil-free displacement pumps, a distinction is made between rotary
pumps and oscillating displacement pumps. The oscillating displacement pump
also includes the diaphragm pumps described in detail later.
Liquid-ring pumps and roots pumps are worth mention when discussing ro-
tary pumps. A liquid-ring pump consists of a cylindrical casing enclosing an ec-
centric paddlewheel that rotates to fill with water. Empty chambers form between
the paddles. At first these expand, producing a suction on the gas being sup-
plied. As they turn further, the empty chambers again compress to atmospheric
pressure, releasing the gas into the exhaust. The liquid here functions both as
a piston and as a seal. Since this method results in heating the water, the water
must continually be refreshed with cooler water. If it becomes too hot, the vapor
pressure of the water becomes too high and the suction capacity becomes too
Part C Survey of types of pumps 105
Figure 10:
Design of a liquid-ring
pump.
Figure 11:
Operating principle of the
Figure 10 Figure 11 roots pump.
low. These pumps can be used to attain final pressures down to 33 mbar. Their
maximum suction capacity can reach 25,000 m3 per hour.
In a roots pump, two pistons shaped like a figure eight run counter to one
another within an oval casing. Fig. 11 shows how they operate. The roots pump
operates completely without oil, the disadvantage being that the gap with a di-
ameter of approx. 0.1 mm between the piston and the stator wall is not sealed
off. Nevertheless, due to high speeds (1,400 to 4,000 rpm), a final pressure of
below 10–3 mbar can be attained. Their suction capacity can reach 50,000 m3
per hour. Because a tight seal does not exist they are unable to handle any great
differences in pressure, and they therefore are usually used in conjunction with
a fore-pump.
Figure 12:
reciprocal pump.
Oscillating pumps are probably the most important type of pumps for this
book, since the diaphragm pumps produced by Büchi Labortechnik are of this
type. Their principle of operation can be explained most clearly using by the
example of a reciprocating pump. Here, there is a piston driven by a motor oscil-
lating within a cylinder. The piston has an inlet and an outlet valve attached to its
upper end. When the piston moves downward, air is drawn in. Diaphragm pumps
differ from reciprocal pumps in that instead of driving a piston, the connecting
rod raises and lowers an elastic diaphragm stretched between the cylinder and
the pump head. This type of pump is described in more detail in Chapter 5.1.
106 Part C Survey of types of pumps
4.3 Vapor pumps

Vapor pumps forward the gas through a quick-moving working fluid – a liquid,
steam, or a gas. The most familiar representative of this type of pump is the jet
pump described in more detail in Chapter 5.2.
The operating principle of the water, steam, and gas injector pump is provided
by Bernoulli’s Law. Relaxation of the working fluid, steam, or gas from the high
pressure p0 within the pressure chamber to the low pressure p in the jet, directs a
jet with a given speed through the mixing chamber. There it mixes with the gas that
is to be drawn off, accelerating it. This mixture of working fluid and air then reaches
a pitot tube, where it is braked back down to a high pressure by compression and
drawn off by the fore-vacuum stage. The quicker the flow of the working fluid, the
greater the difference in pressure between the pressure chamber and the jet, and
the greater the suction capacity. Steam and gas injector pumps differ from water
injector pumps mainly in the higher speeds of their jets. In addition, the working fluid
is already present in the form of steam or a gas, which means that there is no limita-
tion due to steam pressure, making a significantly lower final vacuum possible.
Figure 13: PQ

jet pump.
PA
Steam injector pumps are generally connected in series. Intermediate con-

densers are used with such pumps to prevent the working fluid (steam) from
being drawn off. For economical reasons, gas injector pumps are frequently run
in combination with mechanical pumps as an end stage. Such pumps can attain
ultimate pressures of 10–3 mbar and can pump up to 14,500 m3 per hour.

– Martyn Drost: Pumpen – Arten, Arbeitsweisen, Verwendung
One can learn a great deal about the design and operating principles of
pumps. The main focus is on the forwarding of liquids and bulk materials.
– W. Frank, D. Kutsche: Buchreihe Verfahrenstechnik: (2) Die schonende Destil-
lation
A brief, but informative treatment of pumps suited for vacuum distillation.
The design, operating principles, and performance of various pumps are well-
and well-illustrated. Unfortunately, a few types of pumps have been omitted.
Various types of pumps are described in detail here, with emphasis placed on
calculation and optimization of their process characteristics. There is a limited
presentation of their design and function. Very interesting for the conceptual
planning of a large industrial vacuum plant.
Part C Vacuum pump technology 107
5 Vacuum pump technology
5.1 The diaphragm pump
5.1.1 Design and operation of the diaphragm pump
Figure 14:
Principle of operation of the
diaphragm pump. (1) dia-
phragm, (2) eccentric drive,
1 (3) connecting rod.
back-and-forth
movement
3
driving shaft
oscillating movement
Diaphragm pumps are one type of oscillating displacement pumps. They operate
on the same principle as the reciprocating pump, the main difference being that,
instead of a piston, the connecting rod raises and lowers an elastic diaphragm
that is stretched pressure-tight between the cylinder and the pump head. The
forwarding chamber is thus stretched between the diaphragm and the pump
head. The eccentric drive, which enables a good transfer of forces from torque
to the pumping movement, produces a tipping movement that must be taken
into consideration when designing the pump head so as to prevent a crushing
of the diaphragm. In multi-stage versions, final pressures down to 0.5 mbar are
possible, with suction capacities up to 20 m3 per hour.
Figure15:
Büchi diaphragm pump
V-710.
3
4 2
Figure 16:
Secondary condenser:
(1) cooling water inlet,
(2) outlet, (3) inlet for
1
exhaust gases (4) outlet for
exhaust gases.
108 Part C Vacuum pump technology
The diaphragm is the most important structural element in this pump. Its main
task is to draw in the gases and to compress them, but it must also satisfy other
requirements. Unlike a reciprocating pump where the connecting rod is con-
nected to the piston, the diaphragm must keep the rod lined up. It is particularly
important that the diaphragm be stable enough to keep the rod in line at its upper
dead point. The diaphragms used by Büchi Labortechnik are made of natural
rubber and coated with polytetrafluorethylene (PTFE, Teflon®). This material has
both excellent chemical resistance and very high heat resistance.
The valves are another important structural component. Those used here are
mainly self-activated tongue valves made of heat-resistant elastomers (neoprene,
perbunan) or PTFE. They open and close due to the difference in pressures. Heat
resistance is important because the high velocities of the gas being transported
heats the valves considerably. It should be noted that the speed of the valve
opening and closing must remain in phase with the speed of the pump.
Two or more stages are usually used in order to improve the performance of
diaphragm pumps. How the stages are connected depends on what is required:
parallel connections increase the suction or pumping capacity, series connec-
tions improve the final pressure.
The main wearing parts of the diaphragm pumps are the diaphragms and the
valves. The limiting factors are the mechanical load, pressure, and temperature
of the gas, the motor, and the aggressivity of the gas being forwarded. Often
it is a combination of several factors that render diaphragms unusable. Thus
despite the coating, a large number of gas components can permeate into the
diaphragm, causing it to swell and produce increased wear on the pump head.
Generally, a service life of 2,000 to 5,000 service hours per diaphragm can be
expected. If handled sparingly, the mechanical parts of the pump have a very
long service life. The ball bearings must be replaced occasionally (after 15,000 to
20,000 hours in operation).
The vacuum pump built by Büchi Labortechnik is a 2-stage diaphragm pump
with its two stages connected in series across a hose with two valves. The pump
heads are made of glass, allowing any fouling to be identified and removed be-
fore it causes any damage. In addition, the inert glass neither reacts with solvents
nor allows them to diffuse inward. The diaphragms are made of rubber, with a
particularly thick coating of PTFE that prolongs their service life. This pump can
attain a suction capacity of 1.7 m3 per hour and a final pressure of less than
10 mbar.
There are various accessories available to enable optimum use of this pump.
The Vacuum Controller is one of the most useful of these accessories. Its primary
function is to maintain a constant pressure across the transfer valve (refer to 3.2).
In addition, it can – across a relay – regulate operation of the pump and control
the cooling water via a cooling water valve. It also allows for automatic distillation
(refer to the topic Distillation with the rotary evaporator / drying oven).
In order to prevent the environmentally harmful emission of solvents in the
exhausts, the system should include a secondary condenser. With this unit, the
gases from the pump enter a gas coil that is placed in cooling water. Even low-
boiling solvents can be held within emission limits with tap water. The use of this
condenser becomes particularly important whenever it is impossible to select
optimum conditions for a distillation.
Figure 17:
Valve unit: (1) connection
5 to the first recipient, (2)
connection to the second
valve unit, (3) connection to
the vacuum sensor on the
Controller, (4) connection
4 to the suction pipe of the
3 pump, (5) control cable for
the valve.
The valve unit is an important element for the protection and operation of the
pump. This is where the hose from the suction pipe and the hose from the ap-
plication come together. This is why, once the setpoint has been attained, the
in-line valve that interrupts the connection to the vacuum application is installed
here. Two connections with non-return valves enable the carrying out of two
vacuum applications at the same time. The connection to the pressure gauge on
the Vacuum Controller is also located here. In addition, the valve unit functions
as a Woulff bottle, separating out the liquid and thereby preventing harmful sub-
stances from getting into the pump and damaging the diaphragms.
5.1.2 Economic and ecological considerations

Due to their construction, diaphragm pumps are the ideal pumps for laboratory
operation. Because they are operated without oil, no gas comes into contact
with the sealing oil. There is no contamination of the gas being forwarded, and
no contamination of the oil by aggressive gases which can cause operating mal-
functions. The expense of preventive maintenance disappears. Another advan-
tage is their high sealing capacity to gas, with leakage rates down to 5 · 10–9
mbar per second. This means that the diaphragm pump is well-suited for trans-
porting dangerous and poisonous gases. The simple design of these pumps
makes it easy to remove any impurities and condensates that might be drawn
in. The low procurement costs, the infrequent preventive maintenance, and the
small external dimensions make the diaphragm pump an optimum pump for the
laboratory.
The diaphragm pump also has several advantages from an ecological stand-
point. Environmentally harmful fumes can be removed in suitable secondary con-
densers before they enter the environment, while water injector pumps direct
their exhausts into the sanitation and sewage system. After use, the PTFE coat-
ing can be removed from the diaphragm and recycled.
110 Part C Vacuum pump technology
5.2 The water jet pump
5.2.1 Design and operation of the water jet pump

A water jet pump uses a quick-moving liquid to forward the gas being pumped
off. The jet is accelerated by relieving it within the nozzle from the pressure p0
in pressure chamber A (water line, 2 to 5 bar) to the pressure p in the jet in ac-
cordance with Bernoulli’s Law. The jet coming from the nozzle enters mixing
chamber B, where it comes into contact with the gas being pumped off and then
mixes with it. The intake suction pressure pA prevails in this mixing chamber.
The mixing accelerates the gas being pumped off and forwards it into the fore-
vacuum chamber, where it is relieved to approx. 1 bar and directed off into the
sanitation and sewage system. The law driving the jet is Bernoulli’s Law of Flow:
2 ( p 0 − p)
v2 = (5.1)
ρ
in which p0 is the pressure in the line, p the current pressure in the jet, v the cur-
rent jet velocity, and ρ the specific gravity of the water. It can be seen from this
formula that the greater the difference in pressure is, the faster the jet becomes.
There is frequently a swirler built into the nozzle to improve weak pump output
somewhat. This improves the mixing of air and water. The final vacuum is limited
by the saturation vapor pressure and, depending on the operating temperature,
can range from 20 to 30 mbar. The material and size of the pump play an impor-
tant role in its suction capacity. The stronger the material and the larger the size,
the more water can be forwarded and the greater the pump’s suction capacity.
The water jet pumps offered by Büchi Labortechnik are made of plastic and
are equipped with a solenoid valve. A Vacuum Controller switches the water on
only when needed, thereby reducing water consumption. One model also has a
controlled cooling water valve. The advantage of this is that one water connec-
tion can serve for both the cooling water and the water jet pump.
5.2.2 Economic and ecological considerations

Water jet pumps are widely used because they are very economical to procure
and take up scarcely any room. Their insensitivity to chemically active substanc-
es is also valued in chemical laboratories. But they do have considerable disad-
vantages. For example, they attain only a slight final vacuum that is dependent
on fluctuations in temperature and water pressure. They are relatively noisy, have
only a modest ultimate pressure, and result in high operating costs due to their
enormous water consumption.
Ecological disadvantages are also of importance. In addition to water high
consumption, they can also direct poisonous residues of solvents into the sanita-
tion and sewage system.
For these reasons, the use of a water jet pump must be given careful consid-
eration. They represent a sensible solution in situations where a vacuum is only
rarely used, e.g., in school laboratories.

– The available literature on water injector an diaphragm pums is limited.
– Erich Becker: Membranpumpen mit mechanischem Membranantrieb für Gase
An informative book about diaphragm pumps. Clearly written and well-illus
trated. Provides an overview and a basic understanding of diaphragm pumps.
– Büchi Labortechnik: Training documents, Vakuumerzeugung und -regelung
and operating manuals for vacuum pumps.
A brief overview of the operation and theory of water injector pumps. Unfortu-
nately, it does not go very far.
– Offers a quick introduction to the design and applications of diaphragm and
injector pumps.
112 Part C Applications of vacuum systems in the laboratory
6 Application of vacuum systems in the laboratory
6.1 Selection of vacuum systems

The chapter below is restricted to the water jet pump, the diaphragm pump,
and the rotary vane pump since these are the pumps most frequently used to
produce vacuums in a laboratory.
The following points must be taken into consideration when selecting the
vacuum source:
– the suction output needed
– the final vacuum needed
– user-friendliness
– financial aspects
– the prevention of contamination in exhaust air and waste water
It is necessary to consider a combination of specification to meet your appli-

cation requirements, rather than to focus upon one parameter.
6.1.1 Suction output

This depends primarily on the volume and on the speed of extraction. A large vol-
ume does not always mean that one unit with a large volume need be involved. It
may require several small devices connected to one another around a ring-circuit
with a vacuum, under some circumstances simultaneously. The table below pro-
vides a rule of thumb as to what vacuum source can be the correct choice for
the laboratory with regard to suction output.
Table 3:
> 30 L/min PTFE-diaphragm pumps, rotary vane pumps, rotary piston pumps
Comparative suction output
of various types of pumps. < 30 L/min Water jet pumps
6.1.2 Final vacuum

Naturally, the final vacuum required depends on the application. If a distillation
can be carried out even with a vacuum of 500 mbar, a water jet pump will work.
On the other hand, extracting the remnants of solvents requires a far lower final
vacuum. The table below attempts to clarify selection of the correct vacuum
source based on the ultimate attainable vacuum.
Table 4:
Final vacuum Water jet pump Diaphragm pumps Rotary vane pumps
Pressure ranges for various
types of pumps. 1013 – 25 mbar • • •
25 – 1 mbar • •
< 1 mbar •
6.1.3 User-friendliness
Pumps also differ in their user-friendliness. Oil-free pumps have an advantage
over pumps with an oil seal. The oil seal requires frequent preventive mainte-
nance, and carries with it the risk that the rotor will fret into the stator. The sealing
oil and the carrier gas may also contaminate one another, which might result in
operating malfunctions or environmental pollution due to the exhaust gases.
Part C Applications of vacuum systems in the laboratory 113
With regard to noise pollution, a water jet pump produces more noise than
any other pump. Rotary vane pumps and diaphragm pumps feature a low-noise
operation, depending on the type of motor used.
6.1.4 Financial aspects

A simple water jet pump represents only a fraction of the procurement costs
needed for a diaphragm or even a rotary vane pump. However, operating costs
stet must be considered along with procurement costs. A water jet pump can
have high water consumption rate of 500 L/hr.
The costs of the water and the waste water disposal fees have to be consid-
ered.
In contrast, the primary requirement of a diaphragm pump is electrical pow-
er. In the Büchi V-500, for example, this means an electrical take-up of 180 W
(= 3 light bulbs V-700). Maintenance costs are negligible.
Table 5:
Water jet pump Diaphragm pump Rotary vane pump
Costs of various types of
Procurement pumps.
price low medium high
Annual operating
costs high low medium
6.1.5 Reduction of emissions into the exhaust air and waste water
Vacuum Controller
With a Vacuum Controller, it becomes possible to ensure reproducible and con-
trolled vacuum conditions. From an ecological point of view, a Vacuum Controller
also ensures that the pump will not run to the full final vacuum, where the sol-
vent fumes can no longer be condensed out. The use of additional switchboxes
ensures that the pump connected to it will only run when its output is actually
needed. For example, a distillation with a rotary evaporator will not have the
pump running 90% of the time, which represents a massive reduction in the risk
of solvent emissions.
Secondary-condenser
As already described in detail in Chapter 5.1, a secondary-condenser reduces
emissions of solvents. This type of secondary-cooler is used only in connection
with diaphragm pumps, mainly in cases where the user has decided not to use
a Vacuum Controller or is working with the wrong conditions despite his having
a Vacuum Controller.
Woulff bottle
This supply reservoir is installed in the intake line between the pump and the con-
tainer being evacuated. It protects the pump, and the exhaust air or waste water,
from the fumes of solvents or the chemicals leaving the system.
6.2 Comparison of the PTFE diaphragm pump

and the water injector pump
Table 6:
In most cases, the user in the laboratory has to decide on one of these two
Advantages and disadvan-
tages of diaphragm and vacuum sources. The table below shows the most important features in which
water jet pumps. they differ.
Diaphragm pump Water jet pump

high procurement price low procurement price
low operating costs high operating costs
low maintenance costs no maintenance costs
requires more space requires little space
low noise levels high noise levels
low electrical consumption no electrical consumption
no water consumption water consumption
no environmental burden due to poisonous gases possibility of contamination of water systems
(with a secondary-condenser) with poisonous gases
high suction capacity low suction capacity
ultimate vacuum <10 mbar ultimate vacuum approx. 20 mbar
ultimate pressure independent of external factors ultimate pressure dependent on fluctuations
in water pressure and temperatures
6.3 Design of a complete vacuum system based

on a PTFE-diaphragm pump
The structure of a vacuum system normally depends on its intended application.
As a general rule, there should be an extractor installed bet-ween the application,
e.g., a rotary evaporator or a filter, and the source of the vacuum so as to protect
the pump and an in-line valve should also be installed for purposes of regulation.
Because it is not possible to describe every application for a vacuum, shown
below is a typical design and operation of a vacuum system based on a detailed
example (Fig. 19). We have deliberately chosen a somewhat more complicated
system so that we can point out more complex problems as well. For other ap-
plications, the other appropriate end unit may essentially be substituted for the
rotary evaporator.
The structure of a vacuum system differs for each application. The accesso-
ries, pressure, etc. have to be adapted to the intended application. The location
of the vacuum system is also of importance: it should lie in the open to provide
protection from the dangers involved. Chemicals and other equipment represent
possible hazards and should therefore be kept as far as possible from the sys-
tem. There should not be any open fire in proximity to the system. When select-
ing accessories, attention must be paid to appropriatness for use with a vacuum.
Glassware in particular must not be cracked or otherwise damaged. Although
the requirements for a tight seal are relatively slight in the low vacuum range,
care should nevertheless be taken to see that all connections are sealed as well
as possible. Lapped-in glass connections must always be greased. This will also
ensure that they can be taken apart again more easily at a later time. Hoses can
be drawn over connecting pieces more easily if glycerin is used, but they must be
secured in place with hose clips. Screw-in connections must be well-tightened,
No. Unit Description

1 Pump Evacuates the system
2 In-line valve Separates the pump from the system once the desired pressure has been reached
3 Woulff bottle Acts as extractor to protect the pump from the liquid particles drawn in, allows installation
of a pressure measurement device and a second vacuum recipient, acts as a volume
buffer to break the peak fluctuations within the vacuum
4 back pressure valve Prevent an equalization of the pressures
5 Vacuum Controller Has a built-in pressure gauge. Based on that measurement, it opens the In line valve until
the desired pressure has been reached. It also controls the flow of cooling water and
monitors the distillation temperature
6 Rotary evaporator This is where the vacuum is used
7 Secondary condenser Condenses out the last remnants of solvent from the rotary evaporator condenser
8 Second rotary Functions analogously to Nos. 2 to 6
evaporator, with its
associated vacuum
controls
Figure 19:
Process flow diagram for
1. valve unit a vacuum system using a
Vacuum
Controller PTFE-diaphragm pump with
2 3
two rotary evaporators as
V recipients.
v. cont pump
CW
AS
vacuum hose R1 R2 vacuum hose
5 B - 721
6
1. rotary
evaporator
vacuum hose
control cables
Vacuum 2. valve unit
Controller
2 3 vacuum hose
V
v.cont pump
CW
AS
R1 4 R2
vacuum vacuum hose

5 B - 721
hose
8
2. rotary
evaporator
vacuum pump
and sealed where necessary with an O-ring. It is especially important that all
glass parts be fixed in position. The apparatus should not stand too close to the
edge of the laboratory table. Hoses should not be crimped or subjected to loads.
There should always be a hose connected to the exhaust in order to direct the
exhaust gases into an exhaust fan.
Once the vacuum system has been built, it can be put into use by merely
switching on the pump. The Vacuum Controller is of special assistance here: It
can be used for the quick and easy setting of all important adjustments such as
those for pressure and hysteresis. If a Controller has not been installed, the pres-
sure should always be checked with a pressure gauge or meter. When operating
the vacuum system, care should be taken to ensure that the pressure does not
drop below the vacuum resistance of the glassware. When taking the unit out of
operation, the valve between the pump and the application must be closed first.
Only then may the pump be switched off and the system aired. Otherwise liquid
from the pump may intrude into the system (water injector pump).
6.4 Instructions, parameters, and special features of

several laboratory applications
6.4.1 Vacuum for distillation

Vacuum distillation is probably the most widely used application of vacuum in the
laboratory. Lowering the boiling point allows the distillation to be performed at the
lowest possible temperatures, sparing the material being distilled and preventing
it from taking part in any reactions.
6.4.2 Vacuum for filtration

Filtration represents the simplest application of a vacuum. In this process, a suc-
tion filter is set on top of a vacuum flask and the difference in pressures draws the
substance off through the filter. Since filtration always produces strong foaming,
the installation of a secondary extractor downstream from the vacuum flask to
draw off this foam is recommended, especially when using a diaphragm pump.
If a water jet pump is being used, it is important that the pump be disconnected
from the flask by closing the transfer valve before shutting the pumps off, or to
wait until the pressure within the flask has risen to the atmospheric level. Other-
wise, water from the pump will be drawn into the flask.
Figure 20:
Design of a vacuum system
for filtering mixtures of
liquids and solid.
6.4.3 Vacuum for drying

Because a vacuum lowers the boiling points of liquids, vacuum is often used to
dry substances or to keep them free of water. An exsiccator is frequently used
to do this. The substance being dried gives off water, which is immediately taken
up by the drying agents in the unit. This procedure thus maintains a state of non-
equilibrium that favors water being given off. The exsiccator remains connected
to the vacuum source until it has been as fully evacuated as possible. Then the
supply line to the pump is interrupted, and the exsiccator is left to stand in its
evacuated state.
There are also drying cabinets that operate under a vacuum. The drying pro-
cess here is sped up by both the high temperatures and the lowered boiling
point.
Figure 21:
Design of a vacuum system
for drying in an exsiccator.
6.5 Precautionary actions and dangers involved

Whenever using vacuum, it is necessary to remain conscious of the potential
for danger that this technology carries with it. The majority of accidents occur
because the users have not had enough training or because they do not under-
stand what they are working with.
The main danger arises from the difference in pressure between the atmo-
sphere and the system. Whenever a part breaks, an implosion takes place.
Whenever an apparatus made of glass implodes, it results in splinters of glass
and the chemicals that were present in the apparatus flying through the area
and possibly causing serious injuries. Often implosions occur because the glass
equipment used had been damaged, was unsuitable for use with a vacuum, or
because it was broken by external mechanical factors. Damaged glassware can
be identified from cracks, splinters, or starring. Most suitable for use in a vacuum
are round flasks and thick-walled vessels. Erlenmeyer flasks, glass beakers, and
reagent glasses must never be used for vacuum applications. Care must also be
taken to see that all glassware is fixed in position, e.g., by clamping it to a stand
to ensure that it cannot fall over. Also make certain that no objects can fall onto
the apparatus.
It is important to follow certain basic rules when using a vacuum:

• Before using a vacuum system, let someone who is familiar with handling
it give you instructions, and read through the Operating Instructions for the
equipment and apparatus.
• Always build the vacuum system carefully and correctly.
• Always fix all glass parts in position so that they cannot fall over or get broken.
• Never exert any further mechanical force on the system while it is standing
under a vacuum (tightening bolts, straightening it, etc.).
• Always check the pressure and make sure it does not drop too low.
• Always wear protective eyewear and a laboratory coat.
• Always use only parts designed for a vacuum, if necessary, even extra-strength
glassware («Plastic + Glas»).
• Never use damaged parts. Above all, never use damaged glassware.
• Keep sources of ignition far away from the exhaust.
• Always direct the exhausts into a fume cabinet.
• Always keep yourself informed of the possible toxic, biological, and chemical
risks involved in your application and take all necessary safety precautions.
• Always make sure, that a system is no longer under a vacuum before opening
it. Always aerate it.
• Certain classes of solvents tend to form peroxides. There is a considerable
risk of explosion here, particularly when doing work with a rotary evaporator.

• Büchi Labortechnik: Operating instructions for vacuum pumps and rotary
evaporators, and training documents.
Very informative with regard to the operation of the pumps and the sources of
danger associated with it. The interaction and design of systems using Büchi
Products, particularly with the rotary evaporator, are presented in a clear and
easily understandable form.
• N.T.M. Dennis, T.A. Heppell: Vacuum System Design
The optimum book on the design of a vacuum system. The presentation is
very technical.
• German Standards Committee: Fliessbilder verfahrenstechnischer Anlagen
Rules and figures for standardized representation of plants for process tech-
nology. Interesting.
• Nigel Harris: Modern Vacuum Practice
Both system design and safety precautions are presented in an easily under-
standable form here. Unfortunately, there are no illustrations.
• Andreas Pfalz, Reinhard Keese: Grundoperationen der präparativen orga
nischen Chemie
Description of applications for vacuums in the laboratory. Very brief, and with
no presentation of the theoretical background.
• M. Wutz, H. Adam, W. Walcher: Theorie und Praxis der Vakuumtechnik
The structural elements for vacuum technology and the work procedures
when using a vacuum are described in great detail here, and are presented in
a very technical manner.
• Teflon® is a registred trademark of E.I DuPont (see page 105)
Melting point
D
120 Part D Melting point
1 Introduction
1.1 What is a melting point?

There are several material constants that can be used to describe a material,
for example, its specific gravity, light refraction, adsorption capacity, or chroma
tographic behavior. The melting point is also one of these constants. Along with
the boiling point and the solidification point, it is one of the important thermal
characteristics that describe a material. The melting points of many pure ma
terials can be measured with great accuracy.
Crystalline materials consist of extremely fine particles that form a certain reg-
ular 3-dimensional structure. These 3-dimensional arrangements are referred to
as lattice structures or (crystalline) lattices. The particles within the lattice are held
together by lattice forces.
Whenever this solid structure, the lattice, is heated, the particles in it begin to
move more strongly, until finally the forces of attraction between them are no lon-
ger strong enough to maintain the crystalline structure. The lattice is destroyed
and the solid material melts.
At the melting point a material shifts from its ordered, solid state to an unor-
dered, liquid state. The stronger the forces of attraction between the particles
within the lattice, the greater the amount of energy that must be used to over-
come them. The melting temperature of a crystalline solid is thus an indicator for
the stability of its lattice. The higher the temperature, the more strongly the lattice
structure in question holds together.
1.2 Why measure melting points?

There are various methods of chemical and physical analysis used to differenti-
ate, identify, and classify materials. Measurement of the melting point is, among
other things, one of these standard laboratory procedures. It is an experimental
and easily performed method of physical analysis used to find out about the
identity, the purity, and the thermal stability of a material.
Identification
Pure materials have exactly defined melting points, the values for which can
be obtained from reference tables. Thus, the identity of a material can be de-
termined by measuring its melting point: One need only compare the melting
point of the substance as determined in the test with the values in the technical
literature.
Of course, determination of its melting point alone is not yet enough for the
clear identification of a substance. There may be several substances with the same
melting point. In such cases, the shift in the mixed melting point (refer to Sect.
2.6.2) can provide an indication of the definitive identification of the material.
Purity
Even slight impurities in a material cause a lowering of its melting point or at least
a widening of its melting range (the material melts within a range of temperatures
instead of at a precisely definable melting point).
This phenomenon is used to obtain indications of the purity of a material: The
closer the melting point of a substance lies to the melting point shown in the
tables and the narrower its melting range, the purer the material is.
Part D Introduction 121
Thermal stability
Many materials change at high temperatures, e.g., decomposition or discolor-
ation. Measurement of the melting point is one method that can be used to de-
termine how high the temperature is to which a material can be heated without
causing chemical changes. This value is useful as an indicator for the thermal
stability of a substance and can be used to suggest a possible temperature for
drying.
1.3 Who measures melting points?

Various groups of users use melting point determination in their daily work with
chemical substances. Their priorities and their specific requirements for how the
melting point is to be determined may differ. The needs of users are different, es-
pecially with regard to accuracy of measurement and the ability to observe how
the substance behaves during the measurement process.
Synthesizing laboratories
A traditional research laboratory continually produces new types of chemical
compounds. In order to find out how these new compounds behave, the re-
search scientists observe the melting process closely.
Often, these researchers are dealing with different substances: They receive
about 1 to 4 samples each week for investigation. Thus, having a high degree of
automation for the measurement of melting points is only of secondary impor-
tance for them. Far more important is their ability to observe the sample comfort-
ably during the melting process.
Analytical laboratories
Analytical laboratories perform the tests done on the receipt of goods (raw prod-
ucts) and when examining the end products of a production process. Their main
interest here is checking the purity of the products. Their measurements must be
as precise as possible. These laboratories analyze from 10 to 50 samples each
week, whereby determination of the melting point is part of their daily routine.
Because they are examining the same materials over and over, a high degree of
automation is an important advantage for them.
For the most part, these researchers do not need to observe the samples
while measuring the melting point. Frequently, the substances they have to in-
vestigate are discolored or decomposing so that no automated determination of
the melting point is possible. In this case, visual melting point determination may
be considered.
Pharmacies
A mistaken identification of medication in pharmacies can become a danger for
the health of patients. It thus becomes extremely important to verify the identity
of the medications and agents.
Measurements of melting points done in pharmacies therefore require both
maximum accuracy and an opportunity to observe the melting process when
necessary.
122 Part D Introduction
Area of Use Situation surrounding and requiring Features needed in the instrument
measurement of melting points used for measuring melting points
Synthesizing – Creation of new, unknown compounds – The possibility of observing the sample
laboratories – A need to obtain knowledge of how while it is melting
the compounds behave when melting
– Few samples (1 to 4 per week)
Analytical – Checking the purity of raw or finished – The possibility of observing the sample
laboratories products while it is melting
– Examination of the same kind of samples – Maximum precision
over and over again – A high degree of automation
– A large number of samples
(10 to 50 per week)
Pharmacies – Verifying identities – The possibility of observing the sample
– Examination of the same kind of samples while it is melting
over and over again – Maximum precision
– A medium number of samples
(5 to 10 per week)
Table 1:
Situation of various user groups requiring determination of melting points, and the necessary features of measurement
methods that result.
1.4 The boiling point

All elements and many inorganic and organic compounds have characteristic
boiling points. The values for these can be obtained from reference tables.
Mixed liquids do not have a precisely defined boiling point. Instead, they boil
over a fairly wide range of temperatures within clearly defined boiling limits. Ac-
cordingly, observation of their boiling behavior is an easily measurable experi-
mental criterion for determining their purity. Whenever the boiling temperature
changes during the boiling process, the material you are investigating cannot be
a single pure material.
However, it must be noted that impurities basically have less of an effect on
the boiling point than on the melting point. For that reason, the boiling point is
not quite as informative a criterion for purity or for the description of materials as
is the melting point.
Part D Theoretical basis for the measurement of boiling points and melting points 123
2 Theoretical basis for the measurement of boiling

points and melting points
2.1 Physical states

The «physical state» of a material is the state in which the material exists
under the given external conditions (pressure/temperature). A distinction is made
here between «solids», «liquids», and «gases».
Solids Liquids Gases

• Defined volume • Defined volume • No defined volume
• Defined shape • No defined shape • No defined shape
• Particles have a defined position • Particles can shift positions with • Particles can move freely;
within the lattice respect to one another there is no longer any reciprocal
attraction present
Generally speaking, a material may be present in any of these three physical Table 2:
states provided, first, that the necessary conditions (pressure/temperature) can Comparison of properties of
the physical states «solid»,
be realized in the experiment and, second, that the material is also stable at high «liquid», and «gaseous». The
temperatures. kinetic energy of the small-
When the external conditions change, materials can go from one physical est particles, the compress-
ibility of the material, and
state to another. This process is referred to as «phase transition». A change in
diffusion within the material
physical state always entails taking up or giving off a considerable amount of increases as you go from
energy. left (solids) to right (gases).
Figure 1:
Changes in state: Transi-
gaseous tions between the various
physical states.
evaporation condensation
sublimation liquid solidification

Particle energy of motion
melting solidification
solid
124 Part D Theoretical basis for the measurement of boiling points and melting points
Most materials are crystalline when solid, i.e., in that state, their smallest par-
ticles (atoms, molecules, or ions) form an orderly, 3-dimensional arrangement – a
crystalline lattice. The stability of the lattice depends not only on how great the
forces between two components of the grid are in themselves, but also on how
uniformly these forces act in all directions in space.
In addition to crystalline solids, there are also amorphous solids, whose par-
ticles are in a random arrangement when in a solid state. Glass, resin, and many
synthetic plastics are examples of amorphous materials.
2.2 Phase transitions

The «phase» or physical state refers to material that is homogeneous in chemical
composition and in a spatially constant physical condition. As already mentioned,
materials may transform from one phase into another by means of phase transi-
tion. A phase transition always takes up or gives off energy (the heat of melting
or evaporation, and/or the heat of condensation or solidification, cf. Sect. 2.3)
and always occurs at the same pressure for any given temperature. The density
of materials also changes during phase transitions.
During the actual transition, the two physical states (phases) of the mate-
rial always exist side-by-side, and the temperature remains constant until the
change in phase has been completed. A temperature/energy diagram shows
these relationships.
Figure 2:
temperature
Temperature/energy diagram.
evaporation/ heat of evaporation

condensation
heat of condensation
heat of melting
melting/
solidification
heat of solidification
energy
2.2.1 Phase diagrams for 1-material systems (state diagrams)

The phase transition point is where the different phases, or physical states, of a
material, interchange depending on external driving forces.
The vapor pressure of a material indicates the number of molecules per unit of
volume that are present in the gas zone in a state of equilibrium. It therefore indi-
cates the tendency of the particles to pass over from a liquid or a solid phase into
the gas phase, and is an indicator for the strength of the intermolecular forces of
attraction within the liquid or the solid. The lower the vapor pressure, the stronger
the forces of attraction between the particles.
Figure 3:
Vapor pressure curves for
vapor pressure (kPa)
various liquids.
Diethylether Ethanol Water
101,3
75
50
25
0 20 34,6 60 78,3 100

temperature ( 0 C)
The vapor pressure of a material depends on temperature, and it increases as

the temperature rises. Fig. 3 shows the vapor pressure curves for various liquids
in comparison with one another.
Figure 4:
vapor pressure Vapor pressure curve for a
vapor pressure
material in its solid and in
its liquid phases (1-material
critical point system).
liquid liquid
solid
gaseous
solid
triplepoint
temperature
Figure 5:
temperature
State or phase diagram of a
Figure 4 Figure 5 1-material system.
Fig. 4 shows the vapor pressures for the solid and the liquid phases of a ma-
terial. At the pressure where the vapor pressures for these two phases are the
same, the equilibrium for melting (or freezing) is present. Expanding this diagram
to include the other transitions between the three physical states produces what
is referred to as a state or a phase diagram.
The phase diagram for a material is a pressure-temperature diagram showing
under what conditions a material is a solid, a liquid, or a gas. The zones are di-
vided from one another by phase boundaries that represent pairs of values (p,T)
at which the two phases are in equilibrium with one another (melting point, vapor
pressure, and sublimation curves). For given pressure-temperature conditions,
one can determine from a phase diagram the phase or phases in which the given
material may exist (cf. Fig. 5).
At the so-called «triple point» – that is, at that point where the three curves
meet – the three physical states (solid/liquid/gaseous) can coexist. The location
of the triple point cannot be altered. There is only one characteristic pair of values
(pressure/temperature) for any given material. The best known triple point is that
for water, which lies at 273.16 K (0.01 °C).
The vapor pressure curve ends at the critical point. Above this critical temper-
ature, a material can no longer exist as a liquid. There is therefore no longer a limit
surface between the liquid phase and the gaseous phase. The conditions at this
transition point (pressure/temperature) can be obtained from reference tables.
2.3 What happens during melting?

In order to melt a solid, you must break its lattice structure by supplying energy
to counteract the forces of attraction holding the particles together. The greater
the effective forces between the particles, the more energy you need to destroy
the lattice structure.
The particles in a crystalline lattice do not exactly stand still, but vibrate slightly
about their spatially fixed position (thermal movement). For each particle, the
mean kinetic energy is
m: mass of 1 1

W k = m v 2 or, in other terms, Wk = kT
the particle 2 2
v: velocity
k: Boltzmann The higher the temperature, the more energetic the particles become and the
constant more strongly they vibrate. As a result of their stronger movement, the particles
(=1.3806 *
require more space as the amount of warming increases – the material expands.
10–23 J/K)
T: temperature Finally, at the melting point, the vibrations of the particles are strong enough so
that the lattice forces can no longer maintain the orderly arrangement – the solid
material melts.
The melting point of a material is defined as that temperature at which, under
normal atmospheric pressure (101.3 kPa), the solid/liquid equilibrium sets in.
At the melting point, then, the solid substance is in a state of equilibrium with
its molten state. Or, in other terms: At the melting point, the liquid and the solid
both have the same vapor pressure (cf. Fig. 1).
The molecules of a substance do not have to be separated completely from
one another during melting (as during boiling), and the resultant change in vol-
ume is relatively slight. This means scarcely any volume works in opposition to
the atmospheric pressure that needs to be exerted. Because a small change in
pressure has only a slight effect on the melting point of a substance, external
pressure may be neglected when determining the melting point.
The heat supplied to a material during the melting process does not cause
any change in temperature because the total amount of (heat) energy supplied
is needed to overcome the forces of attraction between the particles (cf. Fig. 2).
The energy used to accomplish this is referred to as the melting heat or the melt-
ing enthalpy ∆Hmelt.
E.g., for water:

H2O (s) → H2O (l) ∆H = + 6.01 kJ mol–1
The same amount of energy that was needed to melt a material is released when
freezing it. That means that the enthalpy change when the phase transition runs
in the opposite direction has the opposite mathematical sign:
H2O (l) → H2O (s) ∆H = – 6.01 kJ mol–1
Table 3:
Substance Melting point (K) Molar melting heat
Melting point and molar
(kJ/mol) ∆Hf
melting heat for several
H2O 273.15 6.01 important substances.
H2S 187.61 2.38
NH3 195.3 5.96
CH4 90.5 0.95
2.4 The boiling point, or «What happens during evaporation»?

The boiling point is defined as that pair of values for pressure and temperature
identifying the condition of a chemically homogeneous substance at which the
substance passes from a liquid state to a gaseous state by boiling.
The boiling point is reached when the vapor pressure of a liquid becomes
equal to the external pressure. The forces of attraction between the particles are
then no longer strong enough to hold the particles together – the liquid boils.
The process of evaporation does not start suddenly at the boiling tempera-
ture. Even at lower temperatures, there is already a state of equilibrium pres-
ent between the liquid and the gaseous phases. At the boiling point, however,
the vapor pressure becomes so great that the atmosphere is pushed back and T1 and T2:
evaporation can take place freely. two different temperatures
The boiling temperature of liquids is determined by the external pressure upon of the liquid
the liquid and the forces of cohesion between the liquid particles. The vapor
p1 and p2:
pressure curve (cf. Fig. 3 and Fig. 4) shows the boiling points of a liquid under vapor pressures of the
various different external pressures. Liquids with a very high normal boiling point liquid at the temperatures
can be brought to boil at a lower temperature by reducing the pressure upon T1 and T2
them. ∆Hv:
Unlike the melting point, the boiling point is strongly pressure-dependent. molar evaporation heat of
The Clausius-Clapeyron equation describes the relationship between the vapor the liquid (= the amount of
heat required to evaporate
pressure and the temperature of a liquid:
1 mol of the liquid)
∇
p2 Hv T2 − T1 R:
log = ⋅ ideal gas constant =
p1 2.303 ⋅ R T1 T2
8.314 J · mol–1 · K–1
The Clausius-Clapeyron equation can also be written in a general form as

a straight line equation in which «p» again stands for the vapor pressure of the
liquid and «T» its temperature:
∇
Hv 1
log p = − · + constant
2.303 R T
This equation is now in the form of the general equation for a straight line,
y = a x + b. Thus, graphing the logarithm of the vapor pressure against the recip-
rocal values for temperature produces a straight line on which the vapor pressure
of the liquid at various temperatures can be read. The evaporation heat of the
liquid can be calculated from the slope of the straight line.
Because the boiling points of liquids as shown in the tables are always those
for a standard pressure of 1.013 bar (mean atmospheric pressure at sea level),
these values – the so-called «normal» values – can be used as direct indicators
of the cohesive forces within the liquid (cf. Tab. 4).
Substance Formula Boiling point Molar evaporation enthalpy

in °C (1.013 bar) ∆Hv in kJ · mol–1
Water H2O 100.0 40.7
Benzene C6H6 80.1 30.8
Ethanol C2H5OH 78.5 38.6
Chloroform CHCl3 61.3 29.4
Table 4: When the increase in heat is constant, the temperature of the liquid increases
Normal boiling points and evenly prior to boiling. Then, at the boiling point, the temperature remains con-
molar evaporation enthalpy
of several substances.
stant until all of the liquid has been evaporated: the energy supplied during the
boiling process is being utilized (cf. Fig. 2). The greater the amount of heat sup-
plied, the faster the liquid goes into the gaseous phase, but its temperature does
not rise while this is happening.
While pure materials (elements and compounds) have a constant boiling pres-
sure at any given pressure, mixtures of several materials (e.g., solutions of solids,
gasolines) behave differently when boiling: They have a so-called boiling range,
i.e., their boiling pattern extends between defined boiling limits.
Dissolving a solid in a liquid always reduces the vapor pressure of the liquid.
More energy is then needed before the vapor pressure of the liquid equals the
∆p/p: relative external pressure. This raises the boiling temperature of the liquid (cf. Fig. 2).
lowering of
vapor pressure
Raoult’s Law describes this relationship. The relative lowering of vapor pressure
Ns: number of here depends only on the number Ns of particles dissolved. The nature of the
particles dissolved material makes no difference.
dissolved
N1: number of
∇ p Ns
particles of
= Raoult’s Law
p N s + N1
the solvent
2.5 The range between the boiling point and the melting point
Pure materials (molecular compounds, salts) have «sharp», i.e. precisely defined,
melting points: The change in temperature between the solid and the liquid takes
place within a very small temperature range of 0.5 to 1 °C.
Below the melting point, the material remains solid; above it, it is in liquid
form.
The melting temperature of a crystalline material depends on its lattice stabil-
ity. The greater the forces of attraction between the particles in the lattice struc-
ture, the higher the melting temperature.
Amorphous solids do not have one single defined melting temperature, but
melt over a broad range of temperatures within which the amorphous body grad-
ually softens and liquefies.
The phase transition from solid to liquid for contaminated solids likewise takes
place over a range of temperatures that may be as much as several degrees.
As a rule, a broad range of melting temperatures indicates contamination of
the substance. But it may also be an indication that the substance is decompos-
ing during the melting process.
Thus, the way in which a material melts provides some first indications of its
purity, and the location of the melting point is used for purposes of identifying it.
2.6 Melting point depression and the mixed melting point
2.6.1 Melting point depression

Even minimal amounts of impurities cause a change in the melting behavior of
a pure substance (melting point depression) and usually result in a considerable
broadening of its melting range as well.
The theory of melting point depression can be explained based on the vapor
pressure phenomenon: The displacement of the vapor pressure curve due to the
contamination of a substance lowers its melting point. A soluble contaminant
therefore weakens the lattice forces within a solid. The graph in Fig. 6 shows this
relationship.
Figure 6: Lowering of the

pressure p
melting point and rais-
equilibrium equilibrium ing of the boiling point.
contaminated solid liquid solid liquid
Contaminants weaken the
lattice forces within a solid,
bringing with it a depres-
l atm.
sion of the melting point.
The vapor pressure in a
liquid is reduced whenever
a substance is dissolved
in it. As a result, its boiling
temperature rises.
solid liquid gaseous
temperature T
melting point melting point boiling point

of mixtures of pure substance
2.6.2 Mixed melting point

The phenomenon of melting point depression can be used for the determination
of unknown pure substances. For example, when you measure the melting point
of an unknown substance A at a temperature 180 °C, you will find from the refer-
ence tables that this is the right melting point for 10 different substances.
Substance A can be identified by determining its mixed melting point: A is
mixed one-by-one with small amounts of the other substances, and the mixed
melting point is determined in each case. Whenever the melting point of A is
reduced by mixing a small amount of another substance B with it, the two sub-
stances cannot be identical. If, however, the melting point of A does not change,
the substance B that was added was identical to A: A has been identified.
2.6.3 The eutectic point

Two or more materials that form a homogenous molten product with one another
(but are not miscible in their solid state, because one is dealing in each case with
pure components) behave eutectically when mixed in certain proportions with
one another. This means that there is a certain mixing ratio for these materials at
which they act like a pure material when melting, i.e., the mixture has a sharply
defined melting point.
Figure 7:
pure compound A pure compound B
Mixing diagram for a
eutectic product.
liquid liquid
and solid and solid
A B B melting point of B,
temperature
Tb
melting interval
melting point of A, Ta A
C
melting point
of the eutectic
solid mixture solid mixture
of of
A + eutectic B + eutectic
1,0 eutectic 1,0

portion of point C portion of
A with sharp B
melting point
The melting points for the pure components A and B are shown on the ordi-
nates. These are joined by the melting diagram of the mixtures. The melting
curve drops off from Ta and Tb to the melting point of the eutectic product, the
eutectic point.
When the mixing ratio of the substances differs from the eutectic mixture, the
mixture melts at the beginning in eutectic proportions. The remaining molten
eutectic and the crystals of the two pure substances in it melt over a range of
melting temperatures.
Part D Principles and methods of melting point determination 131
3 Principles and methods of

melting point determination
3.1 Methods of melting point determination

The procedural rules for melting point determination are defined in the pharma-
copoeias (Medical Handbooks/cf. Chap. 5.1). These agree in describing the cap-
illary method as the basic method for melting point determination. The medical
handbooks even explain minimum requirements for the design of the apparatus
and for carrying out the determination. In addition to the capillary method, the
pharmacopoeias also describe other possible methods that may be called upon
in special cases for melting point determination.
3.1.1 Determining the melting point in the capillary tube

Melting temperature determined using the capillary method is that temperature
at which the last solid particle from a compact column of the substance in the
melting point tube goes over into the liquid phase. The determination thus uses
the so-called «clear» melting point since this represents an unmistakable criterion
for recording the melting point.
Figure 8:
3 Melting point determination
4 in the glass beaker and in
the Thiele apparatus.
2
5 1. substance
2. capillary
1
3. thermometer
4. rubber plug with notch
6 7 5. opening receiver
in the capillary
6. bath liquid
7. sheet metal protective
front view side view liner
melting point determination

in glass beaker
The standard capillary method described in the pharmacopoeias starts with a

heated liquid bath equipped with a thermometer for measuring the temperature.
A glass capillary tube containing the substance to be determined is introduced
into this liquid in such a way that the substance in the capillary tube is located
close to the mercury reservoir on the thermometer. At the clear melting point, the
temperature reading on thermometer is taken.
132 Part D Principles and methods of melting point determination
The capillary method described in the pharmacopoeias starts from visual de-
tection of the melting point. More modern instruments for melting point deter-
mination enable detection of the melting point not only in the traditional way,
visually, but also automatically (cf. Chapter 4.1.1).
In addition to the capillary method, the medical handbooks also provide an-
other method that can be called upon «in certain exceptional cases» for deter-
mining the melting point – the so-called «open capillary method» (rising tube
melting point).
This method is of importance mainly for the investigation of solid greases (e.g.,
mixtures of various glycerides) because what is observed here on heating is not
really a melting point in the strictest sense of the word, but rather a gradual soft-
ening and liquefying of the substance.Fig. 8 shows two possible instruments that
operate using the «bath method» described in the pharmacopoeias.
3.1.2 Immediate melting point

Some materials decompose during the melting process or show a tendency
toward polymorphous modifications. The capillary method is not suitable for use
with such substances, which is why the pharmacopoeia provides for using the
flash melting point in such cases. In this method, the temperature does not affect
the substance at all prior to its reaching its melting point.
This method uses a heatable metal block (e.g., of brass) that is heated up
evenly. A few crystals of the substance to be determined are scattered on this
block at regular intervals. The first temperature at which the substance melts
immediately on contact with the metal block is read off as T1. The heating of the
block is discontinued, and while it is cooling down, small samples of the sub-
stance are again scattered on the block at regular intervals. T2 is the temperature
at which the substance stops melting immediately on contact with the metal.
The immediate melting point is then obtained from the formula:
T1 + T2
2
Mainly, there are two variants of such a metal block that have worked out well
in practice: the rectangular Bloc Maquenne that is used predominantly in France,
and the metal block of the DAB7 that is commonly used in Germany. The Kofler
heating stand is particularly well-suited for series measurement of the immediate
flash point where no special requirements are made with regard to accuracy of
measurement. Fig. 9 shows the various instruments available.
a) Block Maquenne
Block with thermometer
cool end
b) Kofler, heating stand
metal plate
hot end
scale
pointer
temperature
Determination of temperature with pointer
molten solid
substance crystal
pointer
Figure 9:
Metal block instruments for determining the immediate melting point: Block Maquenne and the Kofler heating stand.
3.2 Principles of melting point determination
3.2.1 Melting point determination according to the pharmacopoeia

The instructions for melting point determination in the pharmacopoeias call for
an increase of heat in the «liquid bath» (or in the heating stand) of approximately
1 °C per minute in the range close to the expected melting temperature. This
slow increase of heat and the continual stirring of the liquid bath are used to en-
sure that the sample will reach the same temperature as the bath. Nevertheless,
in most cases it is difficult to prevent a temperature difference of approximately
1 °C remaining between the sample and the liquid bath.
In determining the melting point as described in the pharmocopeia – the tem-
perature on the thermometer at the clear melting point (cf. Chap.3.1.1) is read.
This is not the temperature of the sample, but that of the liquid bath (or the heat-
ing stand) measured at the clear melting point.
Table 5 shows dependance Rate of heat rise °C/min Melting point determined, in °C
of melting point and rate of (acc. to the pharmacopoeia)
heat rise.
0.2 82.5
0.5 82.8
1 83.3
2 83.6
When different rates of heat increase are used for determining the melting
point of a sample, the values obtained for the melting point are dependent on the
temperature gradient: the quicker the heat rises, the higher the temperatures are
found to be. Table 5 shows this dependency.
What is being measured when determining the melting point is not the effec-
tive temperature of the sample itself but that of the heating bath / heating block.
Because the heat transfer from the bath liquid (or the heating block) to the sam-
ple cannot be increased proportionally to rate of heat increase, the temperature
in the bath liquid (or the heating block) rises to a higher level with faster rates of
heat increase than it does with slower rates.
Due to the dependence on the rate of heat increase, measurements taken
for melting points are comparable with one another only if they were taken using
the same rates. Any variance from the rates of heat increase called for in the
specifications during the determination of a substance (e.g., the instructions in
the pharmacopoeia) must be properly documented.
3.2.2 Thermodynamic determination of melting points

The melting of a substance does not take place instantaneously: it requires a
certain amount of time. The melting process starts at that point where the first
particles of the substance go over into liquid (the start of melting), and the end of
melting has been reached when the last solid particles have gone over into the
liquid phase (clear melting point). During this period while the sample is melting,
a certain amount of heat, the «melting heat», is supplied to it.
When determining the melting point using the method in the pharmocopeia,
the temperature of the liquid in the bath (or of the heating furnace) at the end of
the melting is read. While that temperature depends on the rate of heat increase
in the system (cf. 3.2.1), it also neglects a certain difference in temperature be-
tween the start and the end of the melting.
In order to obtain the correct melting temperature, it is therefore reasonable
to subtract a thermodynamic correction factor from the temperature detected.
This calculates back to the temperature of the sample at the start of melting, so
that the value detected then includes practically no effect arising from the rate of
heat rise used.
Table 6 shows thermody-

Rate of heat increase °C/min Melting point detected, in °C
namically detected melting
(thermodynamically)
points at various rates of
0.2 81.9 heat increase.
0.5 81.9
1 82.0
2 81.8
Procedure for calculating the thermodynamic correction factor:
Figure 10:
Calculation of the thermo
temperature oven temperature dynamic correction factor.
temperature
at detection thermodynamic
temperature
correction
of sample
h F
melting point g
start of melting detection time

(end of melting)
The amount of thermodynamic correction depends on the rate of heat rise select-
ed (ramp gradient): The smaller the gradient, the less the correction required.
The temperature detected is thus corrected by the height h of the triangle
(cf. Fig. 10). The area of the triangle F corresponds here to the melting heat
of the sample, which is proportional to the amount of heat needed to melt the
substance. This is not dependent on the rate of heat increase selected, and may
therefore be considered as constant.
g: Base of the triangle (time interval between the start and the end of melting)
h: Altitude of the triangle (the value being sought)
F: Area of the triangle (a constant, dependent on the substance)
1
F= ( g· h)
2
g
r: Ramp slope selected r =
h

r=
g
h
g=
h
r
entered into
1
F = ( g· h)
2
→ F= ()
1 h
2 r
⋅h =
1 h2
2 r ( )
solving for h: h= 2⋅ F ⋅ r = 2⋅ F ⋅ r =K⋅ r
Theoretically, the value for K depends, among other things, both on the melt-
ing heat and the thermal conductivity of the substance, and on how the sample
has been prepared (densely or loosely filled). The geometry of the oven and the
properties of the liquid bath also affect the value for K.
Empirical measurements have shown that, for example, in most cases a good
calculation is obtained with the Büchi B-545 for a K-value of 1.0.
Instruments with automatic detection already have available the electronics
needed for analysis, so that this thermodynamic correction of the melting point
being measured can easily be programmed in.
3.3 Melting point determination yesterday and today – an overview
3.3.1 Instruments for melting point determination over the course of the years
A glance into the «ancestral gallery» of today’s instruments for determining melt-
ing points shows that these instruments have undergone considerable devel-
opment within the past few years. Various examples of Büchi instruments are
presented below to demonstrate this.
Instrument BÜCHI 510 BÜCHI 530 BÜCHI B-540 BÜCHI B-545

Medium Silicone oil Silicone oil Metal block Metal block
Thermometer Thermometer Pt-100 resistor Pt-100 resistor
Melting point Visual Visual Visual Visual +
determination automatic
Applications • Determination of • Boiling point • Boiling point • Boiling point
boiling point and • Determination of
molar weight drop point
• Determination
of flow point
3.3.2 From silicone oil to the metal block

The pharmacopoeias describe the capillary method as the standard method for
melting point determination (cf. 3.1.1). In this method, the glass capillary tubes
containing samples of the substance are introduced into a liquid bath that is
continuously being heated up.
In principle, various substances could be used as the bath liquid for this type
of equipment. Because the sample is observed through the bath, the primary
features required for the liquid are that it must have a high boiling point and be
water-clear.
As a rule, silicone oil is used for the bath. Even after it has been frequently
reheated, it takes on a brownish color very slowly and it can be stet up to more
than 350 °C , depending on the grade selected. Liquid paraffin or dibutylphthlate
can also be used for temperatures up to approx. 300 °C.
Formerly, sulphuric acid was also used as the bath liquid, but this possibility
has been rejected for safety reasons.
The use of silicone oil brings with it various problems, such as a general risk of
contamination in the laboratory and problems in waste disposal. For that reason,
a dry thermal block (metal block) has proven to be a good alternative to a liquid
bath consisting of silicone oil. In addition to its clean operation, this block also
offers the possibility of detecting the melting point automatically.
In addition to the elimination of the bath liquid, another advantage of a metal
block instrument is that it operates without a mercury thermometer. Instead of
the traditional thermometer, a built-in Pt-100 resistor is used to measure the
temperatures.
3.3.3 Data Processing

The inspection done on the receipt of goods and in the monitoring of production
charges makes great demands on the automation and documentation of melting
point determinations. For that reason, a modern instrument should offer the pos-
sibility of storing various measurement programs. Because GLP regulations (cf.
Chap. 5.3) demand verifiable documentation of the results of analyses, the ability
to transfer the data to a printer and a PC is also a desirable feature.
Modern instruments are equipped accordingly today. The Büchi B-545, for
example (refer to Chapter 4) has a working memory for ten methods and also
calculates the standard deviation and mean values for every measurement of
melting points. With its RS-interface, the instrument enables outputting the pa-
rameters and the results of the determination (including a melting curve) to a
printer or to a PC.
138 Part D Melting point determination using the Büchi B-545
4 Melting point determination using the Büchi B-545
The Büchi Melting Point B-545 is used to determine melting temperatures and
ranges and boiling points ranging from room temperature up to 400 °C.
Unlike conventional instruments, this instrument combines automatic and
visual methods for melting point determination. Values can be detected auto-
matically, and when necessary, the user can perform visual determination of
immediate melting points. The Büchi B-545 offers a possibility for performing
determinations on three different samples at the same time.
In addition to determination of the melting point, it can also carry out two
measurements of boiling points. The boiling point is determined here visually
(cf. Chapter 4.5).
4.1 Operating Principle of the Büchi B-545
4.1.1 Automatic Determination of melting points

The Büchi Melting Point B-545 enables automatic determination of melting points
by utilizing the principle of permeability to light (measurement of transmission). To
do this, the samples are placed in a light barrier. A source of IR light illuminates
the glass capillary tubes from the front. Three photodiodes (photoelectric cells)
located behind the samples measure the remaining light passing through (cf.
Fig. 11).
Figure 11:
Automatic detection of transmission %
melting points by measuring
light transmission.
transmission curve
during melting
capillary temperature
light source detector
sample solid = non transparent sample liquid = transparent

low transmission high transmission
Part D Melting point determination using the Büchi B-545 139
Printout of a melting point determination
What Entry/change
Name of company Configuration menu 2

Date of the determination Configuration menu 2
Name of method Main menu 2
Identification of the determination Main menu 2
Start temperature of the determination Main menu 1

Heating rate for the determination Main menu 1
Final temperature of the determination Main menu 1
Manually (visually) determined melting points for each capillary
Automatically determined melting points for each capillary

Factory setting of thermodynamic compensation
Transmission threshold for the
automatic melting point detection Configuration menu 1
Average value of the three melting point determinations
Standard deviation of the three melting point determinations
Diagram of the transmission

in the first capillary Configuration menu 3

in the second capillary Configuration menu 3

in the third capillary Configuration menu 3
Signature of the person executing the calibration

Date of last calibration
Manufacturer's number and software version
Figure 12:
Transmission curves for automatic detection of the melting point with the Büchi B-545.
At the start of the measurement, the sample is crystalline: no light passes

through. Transmission is practically 0%. When it reaches the melting point, the
optical character of the sample changes from opaque to translucent and the
transmission of light increases suddenly. The photoelectric cell detects the in-
crease in radiation, thereby indicating that the melting point has been reached.
The Büchi B-545 defines the melting point as a translucence of 40%. Upper and
lower transmission thresholds of 1% and 90% translucence have been defined for
the detection of a melting range. The user can adjust both the values for determin-
ing the melting point and the thresholds for the melting range to fit his needs.
Fig. 12 shows two typical transmission curves as recorded by the Büchi
B-545 for automatic detection of the melting point.
4.1.2 Metal heating block

Since a heatable block is absolutely required for automatic detection of the melting
point, a metal heating block in the Büchi B-545 replaces the silicone oil bath used in
earlier apparatus (cf. Chapter 3.3.2). This enables exceptionally quick heat-up and
cool-down times, and the samples can be heated to clearly higher temperatures.
The heating block method conforms to the current pharmacopoeia, and has
the advantage that no waste silicone oil need be disposed of. In addition, by
replacing the traditional liquid bath with a metal heating block it has become
possible to determine the melting point automatically.
Chapter 3.2 explains the differences between thermodynamic determination
of the melting point and recording the melting point as called for in the pharma-
copoeia. In its standard configuration, the Büchi B-545 supplies thermodynami-
cally corrected values of the melting points determined automatically. The users
can, however, switch off this thermodynamic correction. The unit then supplies
the melting point values as called for in the pharmacopoeia, i.e., the values cor-
responding to the oven temperature at the melting point.
Introduction of the dry heating block has also done away with the mercury
thermometer. In its place, a built-in platinum resistor (a Pt-100 resistor) takes over
the digital measurement of the temperature.
4.2 Structure of the BÜCHI Melting Point B-545

The Büchi B-545 is a compact, space-saving unit that is ready to run without
requiring additional accessories. If desired, the instrument can be augmented
with a printer for documenting measurements or a mini-PC keyboard to simplify
entering the parameters.
Figure 13:
BÜCHI Melting Point B-545.
The main unit has a front panel with an LCD monitor. A large magnifying glass
on the front of the instrument enables comfortable observation of the samples
during the process of melting or boiling (cf. Fig. 6).
The upper section of the oven is ceramic and includes the blocks for holding
the glass capillaries (two for detection of the boiling point, and three for determin-
ing the melting point). These can be seen at the top of the instrument. The metal
heating block with electrical heater is located underneath this ceramic unit.
4.3 Melting point determination procedure with the Büchi B-545
4.3.1 Preparation of the samples

The substance being investigated must be fully dry, homogeneous, and in pow-
dered form. Moist samples must be dried first (the pharmacopoeias prescribe
that the substance be dried in a vacuum for 24 hours over silica gel R). Coarse-
crystalline and non-homogeneous samples are finely ground in a mortar.
To fill the capillary tubes with the sample, the open ends of the tubes are
pressed into the substance. The substance is moved to the bottom of the
tubes by repeatedly pounding the tubes against a hard base. The same effect
is achieved by letting the tube drop onto the table through a larger glass tube
approximately 1 meter long.
Enough substance must be filled into the glass capillary to form a compact
column 4 to 6 mm in height. (A height of 5 mm is recommended for precision
measurements.) To ensure comparable results, it is important to fill all three capil-
lary tubes to the same height and to compact the substance well in the tubes
(using a packing wire as an aid if necessary).
For the investigation of hygroscopic substances, the open end of the capillary
is melted shut.
4.3.2 Temperature settings and rate of heat rise

Three temperature values must be selected for determining the melting point
with the Büchi B-545: the Setpoint, the rate of heat rise (the Gradient), and the
maximum point (Maxpoint).
Setpoint Gradient Maxpoint

The temperature at which The rate of heat rise The maximum
the sample capillaries are between the Setpoint and temperature to be reached
introduced into the the Maxpoint. The following in the determination.
instrument, which serves Gradients may be selected:
as the starting temperature 0.1/ 0.2/ 0.5/ 1.0/ 2.0/ 3.0/
for the preset temperature 5.0/ 10.0/ 20.0 °C
program. per minute.
Figure 14: 25.0 °C While the determination is in progress, a graph on the

Graph, with explanation of 136 °C LCD monitor shows the range in which you are currently
the various heating profiles.
working (cf. Fig. 14).
The Setpoint selected is usually 5 to 10 °C below the
135.6 °C expected melting point.
The Gradient selected depends on the accuracy
2.0 °C
145 °C
desired in the determination of the melting point (refer
also to 3.2.1). Rates of heat increase of up to 2 °C/min.
140 °C
are reasonable. If the gradients are higher than that, the
determination loses precision and is suitable only for pur-
2.0 °C
145 °C poses of quick information about substances with an un-
known melting point.
145 °C
The Büchi B-545 automatically sets the Maxpoint
15 °C higher than the Setpoint. This can, however, be
adjusted by the user when necessary.
100 °C Moreover, the parameters for Setpoint, Gradient, and
Maxpoint can be changed on short notice while the mea-
surement is in progress should they prove unsuitable.
4.3.3 Calibration
Before the unit is put into operation, it must be calibrated using appropriate sub-
stances with melting points that are known exactly. In addition, the calibration
should be rechecked periodically to verify that the instrument is still supplying
correct melting point values even after having been in operation for a long time.
Table 7: Substance Clear melting point, in °C

Reference substances for
melting points, from the Azobenzene 69
WHO. Vanillin 83
Benzil 96
Acetanilide 116
Phenacetine 136
Benzanilide 165
Sulfanilamide 166
Salophene 192
Sulfapyridine 193
Dicyanidamide 210
Saccharine 229
Caffeine 237
Phenolphthalein 263
These references are basically substances whose melting points can be de-
termined exactly. The pharmacopoeia recommends the substances listed by the
WHO (World Health Organization) for this purpose.
The following three WHO reference substances are used for calibrating the
Büchi B-545:
Vanillin Defined melting point: 83 °C

Phenacetine Defined melting point: 136 °C
Caffeine Defined melting point: 237 °C
The reference substances must be stored over a desiccant in an exsiccator

before being used to check the instrument.
To perform the calibration, the melting point of the reference substance is de-
termined (with the capillary filled to 4 mm; Gradient: 0.5 °C/min) and the results
are compared with the defined melting point. If the deviation found between the
melting point as measured and as defined is more than 0.3 °C, the user must
recalibrate the instrument by entering an appropriate correction factor into the
calibration menu.
In addition to calibrating the instrument using calibration substances, the
transmission should also be calibrated to ensure correct adjustment of transmis-
sion measurements.
4.4 Flow charts for a melting point determination with the Büchi B-545
The work flow for a melting point determination depends on whether or not the
melting point of the substance being measured is known. If not, it must first be
determined roughly to ascertain the approximate melting point of the substance.
For both cases, the work flows for a melting point determination (with melting
points known/unknown) are presented below in schematic form.
Visual determination of the melting point is shown shaded in gray on the sche-
matics. The boxes framed in broken lines describe steps that may be taken or
omitted, depending on the needs of the user.
4.4.1 Substances with a known melting point or range

Melting point determination with the Büchi B-545
Flow diagram for a substance with a known melting point
has a pr ogram for this melting point

determination already been stored?
Yes No
call up the pr ogram from determination: melting point or

memory melting range?
approx. 10 °C below
define the S ETPOINT the melting point
define the G RADIE NT e.g. 1°C/min
automatically : 15 °C
prepare the define the MAXPOINT
above the S ETPOINT
sample of the sub-
stance and fill
1 capillary tube
possibly store the parameters
as a program
START the program
unit heats up to the SETPOINT; accustic signal

on reaching the SETPOINT
introduce the sample and

press START
the program between the S ET- and MAXPOINT

starts with the corr ect gradient
observe the
sample thr ough
the magnifying
possibly c hange for parameters
glass
MAXPOINT or G RADIENT
hold the melting

point by pr essing
the SAMPLE
keys 1/2/3
read the values on

completion of detection
forward the data to

print out the results
the computer
4.4.2 Substances with an unknown melting point or range

Whenever the approximate melting point of a substance is unknown, the ap-
proximate location of the melting point must be found in a rough determination
prior to doing the actual melting point determination. The actual determination of
the melting point can then be carried out as described in Chapter 4.4.1.
Melting point determination with the Büchi B-545

Flow diagram for a substance with an unknown melting point
define the SETPOINT as low as possible
prepare the define the GRADIE NT as high as possible

sample of the sub-
stance and fill must with cert ainty be higher
1 capillary tube define the MAXPOINT
than the estimated melting point
START the program
unit heats up to the SETPOINT; accustic signal

on reaching the SETPOINT
introduce the s ample and

press START
the program between the SET- and MAXPO INT

starts with the corr ect gradient
observe the
sample thr ough
the magnifying possibly c hange for parameters
glass MAXPOINT or GRADIENT
hold the melting

point by pr essing
the SAMPLE
keys 1/2/3
read the values on

completion of detection
carry out an exact melting point determination as shown in the flow diagram in chapter 4.4.1
4.5 Boiling point determination with the BÜCHI Melting Point B-545
In addition to determining melting points, the Büchi B-545 can also be used to
determine the boiling points of small amounts of liquid. The heating block has
two inserts available for boiling point tubes (on the outside, left and right, in the
block for holding the samples). The moment of boiling is determined visually.
In preparation, sample tubes with an inside diameter are filled 5 to 10 mm
deep with the sample liquid. We recommend using a syringe to simplify filling.
Then a so-called boiling capillary (see fig. 15) is inserted into the sample tube with
its open/thick end down, and the sample is put into the holding block.
The process for boiling point determination is analogous to that for determin-
ing a melting point:
• The setpoint is set 5 to 10 °C lower than the expected boiling point.
• Starting from that setpoint temperature, the sample is heated at a temperature
gradient of 1 °C per minute, watching the sample while this is taking place.
• As the temperature rises, small bubbles of gas rise slowly and regularly from
the immersed end of the boiling capillary.
• The boiling point of the liquid has been reached when the flow of steam bub-
bles («chain of pearls») at the end of the capillary is very fast and continuous.
Whenever the boiling point of a liquid is unknown, a measurement is taken

for purposes of orientation before doing the actual determination. This is done
to find the approximate boiling point – analogous to the method for melting point
determination where the melting point is unknown.
Figure 15:
Boiling point determination:
Schematic presentation in
three steps.
20 °C 95 °C 100 °C
4.6 Troubleshooting
Sometimes again, problems arise during the determination of melting points.
Often these can be attributed to unsuitable instrument settings or incorrect han-
dling of the samples, and can be eliminated by simple corrective actions. For that
reason, frequently found problems are explained below.
Problem Cause Solution

No value and no • The sample is unstable, decomposing, • e.g., select a higher Maxpoint
transmission curve is browning, or is not melting • Observe visually
are found in the homogeneously
automatic melting • The temperature parameters have been
point determination entered incorrectly and the sample
is not melting at all
A melting point has Preparation of the samples • Good compaction of the substance in
actually been • Poorly filled capillaries (can lead to the capillaries (by pounding the tube
measured, but is bubbling, with the result that against a hard base) to a depth of 5 mm.
not correct the melting point is detected too early) • Use of standard capillaries with correct
• Use of incorrect capillaries dimensions
Causes specific to the sample
• The sample is not dry or has been • Drying the samples beforehand
contaminated with another substance
• The sample is decomposing during
the melting process
(bubbling, turning brown, etc.)
Instrument parameters
• The instrument has not been calibrated, • Regular calibration of the instrument
or has been poorly calibrated using WHO reference substances
• The setpoint is too close to the melting • Select a setpoint 5 to 10 °C below
point the melting point
• Incorrect adjustment of the transmission • Adjust the gradient selection
• The gradient selected is too large (≤0.5 °C/min. for exact measurements)
• Incorrect selection of the modes • Change the parameter in question
«by pharmacopoeia» or «thermodynamic
melting point determination»
Basically, many problems can be identified by observing the sample during the
measurement process. The use of a control or reference substance is recom-
mended whenever you get the impression that there is something wrong with
the instrument itself.
148 Part D Data quality – accuracy control
5 Data quality – accuracy control
5.1 Pharmacopoeia
The pharmacopoeia – or «Medicinal Handbook» – is a volume containing official
regulations. It provides data on the nature and storage of medicines and their
ingredients, and how they are to be tested and issued by the pharmacist.
In 1964, eight European countries took part in the convention for prepara-
tion of a European medicinal handbook. The objective of this convention was to
achieve an international harmonization of specifications and standards in the field
of pharmaceuticals.
National pharmacopoeias have been retained as supplements to the Euro-
pean pharmocopeia. These have been designed to enable a quick and flexible
introduction of new pharmaceutical standards on a national level.
The European Pharmacopoeias are structured in the same fashion. A first
section describes specifications for equipment, performance, and calibration of
the various methods of analysis. For example, the provisions governing the de-
termination of melting points are also found here in the sub-chapter «Methods of
Physics and Physical Chemistry» (cf. Chapter 3.1).
Another chapter is devoted to reagents (reagents, reference and standard so-
lutions, buffer solutions, titration substances, etc.). The so-called «monographs»
present data on effective agents, adjuvants, pharmaceutical preparations, and
other products. The use of the title or sub-title of a monograph thus implies that
the product conforms to the specifications of that monograph.
5.2 Avoiding errors in melting point determination

The observance of a few basic rules can help avoid errors in the determination of
melting points. Above all else, the way in which the sample is prepared and the
settings of the equipment have the greatest impact on the accuracy of melting
point determinations.
Preparation of samples
Careless preparation of the sample can lead to inexact results, which is why
special attention must be paid to this point.
In every case, the substance to be investigated must be dry and in powdered
form. Accordingly, the substance must be dried and finely pulverized in a mortar
beforehand.
The filling of the sample tube may be called the «alpha and omega» of an
exact measurement. The substance is moved to the base of the tube and com-
pacted there by pounding the capillary against a hard base. (This method should
be given preference over the use of a packing wire). In addition to packing, main-
taining a given level in the fill is another criterion. An exact height of 5 mm is
recommended here.
Settings equipment parameters

Along with proper sample preparation, the settings on the instrument are also
essential for the exact determination of a melting point. Correct selection of the
setpoint, the gradient, and the maximum point is absolutely necessary to prevent
inaccuracies due to a heat increase in the sample that is incorrect or too fast. A
gradient of no more than 0.5 °C per minute is recommended for an exact de-
Part D Data quality – accuracy control 149
termination of the melting point, and the setpoint selected should lie 5 to 10 °C
below the expected melting point.
For substances with a broad melting range, the Büchi B-545 has the ability
to measure that range. For substances of this type, the function «melting range»
should be activated, since the value measured otherwise is likely to be some-
what of a random measurement.
None of the above-mentioned parameters for correct measurement can lead
to success unless the instrument has been calibrated correctly. Regular calibra-
tion of the instrument is a basic prerequisite for an exact determination of the
melting point.
Visual checking
Along with the advantages that automatic melting point determination (e.g.,
using the Büchi B-545) can provide, a high degree of automation also creates
the risk that one will simply rely on numbers coming from the computer whose
accuracy cannot be checked. We therefore recommend doing visual checks on
a random sample basis in addition to the automatic melting point determinations.
Particularly in the case of problematic substances that are tinted or that tend to
bubble. That way, possible errors can be discovered by watching the sample
during the melting process.
5.3 GLP (Good Laboratory Practice) regulations

The GLP regulations originated in the pharmaceutical industry in the USA. At
that time, various irregularities in the conducting and reporting of laboratory tests
led to the establishment of rules to provide a quality standard for laboratory in-
vestigations. The first legal regulations covering GLP were issued in the USA in
1979.
The concept of quality assurance rapidly found increasing acceptance in the
rest of the western world and in Japan, so that the Organization for Economic
Cooperation and Development (OECD) published an internationally coordinated
version of the GLP testing methods in 1981. GLP regulations are of importance
mainly in analytical laboratories and developmental laboratories. All GLP regula-
tions include chapters on the structure of equipment (principles of design) and
the maintenance of laboratory equipment. Instruments used to produce, mea-
sure, or recheck data must be installed, tested, and calibrated/standardized ac-
cording to prescribed guidelines, and written documentation must be prepared
for all inspections performed.
One of the most important principles of the GLP is the requirement for reproduc-
ible documentation of the results of the analyses. The so-called «5-W-Rule» ap-
plies here: Who did What, When, With what, and Why?
150 Part D Data quality – accuracy control
5.4 GMP (Good Manufacturing Practice) regulations

GMP regulations are applicable in production, and in analysis associated with
production. They were developed at a later date than the GLP regulations, and
were focused at producing medicinal (pharmaceutical) products in accordance
with a quality standard in line with their intended use. In the USA, these GMP
regulations are referred to as cGMP (current Good Manufacturing Practice)
to point out that these guidelines must be adapted constantly in accordance
with the current state of knowledge and changing requirements. For pharma-
ceutical products, FDA regulations have set an international standard for GMP
regulations. Like the GLP regulations, they put major emphasis on the design
of the equipment used, the measurement and rechecking of data, and written
documentation of all the relevant intervention and checking procedures. Various
methods of qualification and validation are used for this purpose. A detailed de-
scription of the various qualification procedures, such as design and installation
qualification, functional or performance qualification, or the validation of analytical
processes and procedures, would go beyond the scope dealt with here, and has
been treated extensively in the technical literature of the field.
Part D Technical terminology 151
6 Technical terminology
Physical state The form of occurrence and condition in which a material exists under the given
external conditions (pressure and temperature). One distinguishes three physical
states: solid, liquid, and gaseous.
Amorphous materials Materials whose atoms or molecules are not arranged in a crystalline lattice.
Clausius-Clapeyron A thermodynamic equation showing the dependency of the boiling point of a

equation liquid on pressure
Vapor pressure The vapor pressure of a material indicates the number of molecules per unit of
volume that are in the gas zone when the material is in a state of equilibrium. It
therefore shows the tendency of the particles to pass from the liquid or the solid
phase into the gas phase. The vapor pressure depends strongly on temperature.
Eutectic A fine-crystalline mixture that contains two or more materials in the proportions
having the lowest melting point of all conceivable mixtures of those materials.
Capillary method Standard method described in the pharmacopoeia for melting point determina-
tion. The temperature at which the last solid particle of a substance in a compact
column within a melting point tube goes over into the liquid phase (See: clear
melting point).
Crystalline lattice The periodic, 3-dimensional arrangement of atoms, molecules, or ions in solid
materials.
Crystalline materials Solid materials that have a crystalline structure.
Critical point (See: Triple point)
Mixed melting point Method for identifying a substance: Whenever the admixture of a second sub-
stance B causes a reduction in the melting point of a given substance A, the two
substances are different. If the melting point of A remains unchanged when B is
added, the two substances are identical.
Pharmacopoeia Volume of official regulations governing the preparation, properties, storage, stock-
(Medicinal Handbook) ing, testing, and issuance of medications and their basic ingredients by the phar-
macist.
Phase diagram A pressure-temperature diagram showing the conditions under which a material
is a solid, a liquid, or a gas.
Melting point The temperature at which a substance passes from its solid state into its liquid
state at a constant pressure of 1.013 bar.
152 Part D Technical terminology
Melting point deter- When using the capillary method for melting point determination:
mination, as prescribed Determination of the temperature of the bath liquid (or the heating oven)
in the pharmacopoeia at the clear melting point.
Clear melting point The temperature at which the last solid particle of the substance in a compact
column in a melting point tube goes over into the liquid phase (See: capillary
method)
Melting point deter- Subtraction of a thermodynamic correction factor from the melting temperature
mination, thermo- as determined by the method in the pharmacopoeia. This calculates back to the
dynamically temperature of the sample at the start of melting.
Melting point A lowering of the melting point of a pure substance due to the admixture of one
depression or more other materials (or to a reduction in external pressure).
Melting heat The amount of heat needed to transform a material from its solid into its liquid
physical state without increasing its temperature.
Boiling point Pair of values for pressure and temperature that identifies the condition of a
chemically homogeneous material which, when boiling, passes from its liquid
into its gaseous state.
Silicone oil A synthetic polymeric silico-organic compound with short chain molecules (gen-
eral formula: RnSiO(4-n)/2 –R = organic remainder, n = 1,2,3); thermally very stable
and non-hygroscopic; Used as the bath liquid for melting point determination
using the capillary method (Additional uses for silicone oil: as hydraulic fluid,
lubricant, or defoaming agent, and for impregnation of textiles and paper).
Immediate Method of melting point determination procedure described in the pharmacopoeias

melting point for materials that discolor or tend to exhibit polymorphous modifications during
the melting process. In this method, the temperature has no effect at all on the
substance before it reaches its melting point.
Transmission The passage of light rays through a medium without a change in their frequency.
Triple point The point clearly defined by pressure and temperature for a given chemically
(3-phase point) homogeneous material where its solid, liquid, and gaseous physical states occur
simultaneously in a state of equilibrium (intersection of the vapor pressure, melt-
ing, and sublimation curves).
Evaporation heat The amount of heat energy that must be supplied to a body to transform it from
its liquid into its gaseous physical state without increasing its temperature.
Appendix A 153
Appendix
Bibliography A
Anderegg, G., Nägeli, R., Fässler, T. F.: Praktikum in allgemeiner Chemie I und II.
1995. Laboratorium für anorganische Chemie der ETH Zürich, Zurich.
Baehr, H. D.: Thermodynamik. 7th Edition, 1989. Springer Verlag, Heidelberg.
Bertele, E., Humbel, F. A.: Neukonzeption eines Ofens zur Beheizung kleiner
Mengen – insbesondere für die K-R-Destillation. G-I-T Fachzeitschrift für das
Laboratorium, Juni 1973. G-I-T Verlag, Darmstadt.
Billet, R.: Grundlagen der thermischen Flüssigkeitszerlegung. 1st Edition, 1961.
Bibliographisches Institut, Mannheim.
Büchi Labortechnik: Training documents «Grundlagen der Destillation», «Des-
tillation mit dem Rotationsverdampfer», «Umweltschonendes Destillieren»,
«Trocknen, Destillieren und Sublimieren im Glasofen B-580». Büchi, Flawil.
Büchi Labortechnik: Various Operating Instructions. Büchi, Flawil.
Büchi Labortechnik: Der automatische Vakuum Kontroller – ein Beitrag zum ak-
tiven Umweltschutz. Büchi, Flawil.
Frank, W., Kutsche, D.: Buchreihe Verfahrenstechnik, (2) Die schonende Destil-
lation. 1st Edition, 1969. Otto Krausskopf Verlag, Essen.
Kirschbaum, E.: Destillier- und Rektifiziertechnik. 4th Edition, 1969. Springer Ver-
lag, Heidelberg.
Krell, E.: Handbuch der Laboratoriumsdestillation. 3rd Edition, 1976. Deutscher
Verlag der Wissenschaften, Berlin.
Matissek, R., Schnepel, F. M., Steiner, G.: Lebensmittelanalytik. 2nd Edition, 1992.
Springer Verlag, Heidelberg.
Pfalz, A., Keese, R.: Grundoperationen der präparativen organischen Chemie.
5th Edition, 1994. Institut für Organische Chemie der Universität Bern, Berne.
Sattler, K.: Thermische Trennverfahren. 1st Edition, 1977. Vogel Verlag, Würzburg.
Schlünder, E.U., Thurner, F.: Destillation, Absorption, Extraktion. 1st Edition, 1995.
Friedrich Vieweg & Sohn Verlagsgesellschaft, Braunschweig.
Society of German Chemists: Sicheres Arbeiten im chemischen Labor. 2nd Edition,
1988. Bundesverband der Unfallversicherungsträger der öffentlichen Hand eV.
(BAGUV), Germany.
154 Appendix B
Bibliography B
K. Masters: Spray Drying in Practice, SprayDryConsult International ApS,
Denmark, 2002
K. Masters: Spray Drying Handbook, 3rd edition, George Godwin Limited, Lon-
don, 1979
Spray Drying Brochure, BNA 480/GB-09/00, GEA Niro A/S
Training Paper Mini Spray Dryer B-290, order number 97758
Operation Manual Mini Spray Dryer B-290, Version G, order number 93001
Appendix C 155
Bibliography C
Baehr, H. D.: Thermodynamik. 1984. Springer Verlag, Heidelberg.
Becker, E.: Membranpumpen mit mechanischem Membranantrieb für Gase.
1st Edition, 1998. Vulkan Verlag, Essen.
Büchi Labortechnik: Training documents: Vacuum generation and control. Büchi,
Flawil.
Büchi Labortechnik: Various operating instructions. Büchi, Flawil
Dennis, N. T. M., Heppell, T. A.: Vacuum System Design. 1st Edition, 1968. Chap-
man and Hall.
Drost, M.: Pumpen – Arten, Arbeitsweisen, Verwendung. 1998. Institut für Lebens
mittelwissenschaft, ETH Zürich, Zurich.
Frank, W., Kutsche, D.: Buchreihe Verfahrenstechnik: (2) Die schonende Destil-
lation. 1st Edition, 1969. Otto Krausskopf Verlag, Essen.
German Standards Committee: Fliessbilder verfahrenstechnischer Anlagen, DIN
28 004. Edition of April 1, 1975.
Harris, N.: Modern Vacuum Practice. 1st Edition, 1989. McGraw-Hill Book Com-
pany, London.
KNF Neuberger GmBH: Laborport, Betriebsanleitung für chemiefeste Labor-
pumpen mit modularem Zubehör.
O’Hanlon, J. F.: A User’s Guide to Vacuum Technology. 2nd Edition, 1989. John
Wiley.
Pfalz, A., Keese, R.: Grundoperationen der präparativen organischen Chemie.
5th Edition, 1994. Institut für Organische Chemie der Universität Bern, Berne.
Wutz, M., Adam, H., Walcher, W.: Theorie und Praxis der Vakuumtechnik. 2nd Edition,
1981. Friedrich Vieweg & Sohn Verlagsgesellschaft, Braunschweig.
Teflon® is a registered trademark of E. I. Dupont de Nemours (see p. 106).

156 Appendix D
Bibliography D
Physical states, phase transitions, melting point, and boiling point
Anisfeld, H.: International Biotechnology, Buld Chemical, and Pharmaceutical
GMPs. 5th Edition, 1998. Interpharm Press, Inc., Buffalo Grove, IL, USA.
Atkins, P. W.: Kurzlehrbuch Physikalische Chemie. Spektrum, Akademischer Ver-
lag, Heidelberg; Berlin; Oxford 1993, 60 – 65.
Atkins, Peter W.: Pysikalische Chemie. 2nd Edition, 1996. VCH, Weinheim,
174 – 177.
Brown, Theodore L.: Chemie: ein Lehrbuch für alle Naturwissenschaftler. VCH,
Weinheim-New York, 1988.
Campbell, J. A.: Allgemeine Chemie: Energetik, Dynamik und Struktur chemischer
Systeme. 2nd Edition, 1985. VCH, Weinheim-Basel, 974-977.
Ciba-Geigy: Laborpraxis 2, Messmethoden. Birkhäuser, Basel, 1996, 51 – 69.
Falbe, J., Regitz, M.: Römpp Chemie Lexikon. 9th Edition. Georg Thieme Verlag,
Stuttgart, New York.
Gmehling, J., Kolbe, B.: Thermodynamik. 2nd Edition, 1992. VCH, Weinheim,
Chapter 2: Reinstoffeigenschaften, Chap. 2.1.
Hellenthal, W.: Physik und ihre Anwendung in der Praxis für Pharmazeuten, Me
diziner und Biologen. 4th Edition, 1988. Georg Thieme Verlag, Stuttgart, New
York, 91 – 98.
http://www.chemistry.mcmaster.ca/~chem2o6/labmanual/expt1/expt1b-i.html –
Recrystallization and Melting Point Determinations.
http://www.wpi.edu/Academics/Depts/Chemistry/Courses/CH1010/Stream1/
concept7.html – The Solid and Liquid Phases.
Huber, L.: Validation and Qualification in analytical laboratories. 1999. Interpharm
Press, Inc., Buffalo Grove, IL, USA.
Mortimer, C. E.: Chemie, Das Basiswissen der Chemie. 5th Edition, 1987. Georg
Thieme Verlag, Stuttgart, New York, 162 – 169.
Reich, R.: Thermodynamik – Grundlagen & Anwendungen in der allgemeinen
Chemie. 2nd Edition, 1993. VCH, Weinheim, 67 – 69; 273 – 279.
Stricker, H. (Edit.): Physikalische Pharmazie, Pharmazeutisch angewandte physi-
kalisch-chemische Grundlagen. 3rd Edition, 1987. Wissenschaftliche Verlags
gesellschaft mbH, Stuttgart, 11 – 28; 35ffg.
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rule, 1979. U.S. FDA, Rockville, Md., USA, Title 21 CFR, Part 58.
Wedler, G.: Lehrbuch der physikalischen Chemie. 4th Edition, 1997. Wiley-VCH,
Weinheim, Chap. 5.7.
Appendix D 157
Methods for melting point determination

Davidson, M.: Avoiding Errors in Melting Point Determinations. International Lab-
mate, July 1998.
Deutscher Apotheker Verlag Stuttgart: Europäische Pharmakopöe – Swiss Edition.
3rd Edition, 1997.
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1998. Deutscher Verlag für Grundstoffindustrie, Leipzig, pp. 281 – 286.
Hartke, K., Mutschler, E. et al: DAB10-Kommentar, Wissenschaftliche Erläute
rungen zum Deutschen Arzneibuch, Vol. I, Allgemeiner Teil (Methoden und
Reagenzien). 10th Edition, 1991. Wissenschaftliche Verlagsgesellschaft mbH
Stuttgart, Chap. V. 6.11.
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158 Notices
Notices 159
160 Notices

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The Laboratory

Project/ Technical editing

Büchi Labortechnik AG, CH-9230 Flawil

Design by Cavelti AG, Druck und Media, CH-9201 Gossau

Bound by Brülisauer Buchbinderei AG, CH-9201 Gossau

Copyright © 2007 by Büchi Labortechnik AG,

Further publications: Laboratory Chromatography Guide,

Dr. Reinhardt Büchi

Part A  eparation of mixtures using a rotary evaporator,

5 Design of the glass oven

6 Glass oven applications

Part B Spray Drying

2 Theoretical basis of the spray drying process. . . . . . . . . . . . .  70

2 Theoretical basis for the generation of vacuum

4 Survey of types of pumps

5 Vacuum pump technology

6 Application of vacuum systems in the laboratory

Part D Melting point

2 Theoretical basis for the measurement of boiling points

3 Principles and methods of melting point determination

4 Melting point determination using the Büchi B-545

6 Technical terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  151

1.3 Historical development of the rotary evaporator

For more detailed information on this topic:

2 Theoretical basis for distillation

2.1 Thermodynamic basis

2.1.1 Conditions of state, phase transitions

wet steam zone

2.1.2 Boiling point, vapor pressure, and evaporation heat

The Clausius-Clapeyron equation shows how vapor pressure depends on

p is the vapor pressure, T the temperature, R the universal gas constant

Raoult's law: p1 = p1* · x1

The heat of evaporation is a very important parameter in connection with boil-

2.1.3 Vapor pressure curves

2.1.4.1 Retarded boiling (bumping)

2.1.7 Transport of gas through the equipment

above, boiling produces up to a 20,000-fold increase in volume. A local overpres-

In order to maintain a balanced difference in dynamic pressure, it is important

2.2 Separation of mixtures

2.2.1 Separation by distillation

solvents) or the residue (cleaning of a product of reaction) that is to be regained.

2.2.1.1 Separation effect

The relative volatility α, i.e. the evaporability of a material 1 in comparison to

2.2.1.2 Ideal mixtures

With it comes (for ideal mixtures)

x1 [Mole %] Figure 15:

2.2.1.3 Non-ideal and azeotropic mixtures

2.2.1.4 Improvement of the separation effect

A further improvement can be attained by working in a vacuum. The vapor

For more detailed information on this topic:

3 Design of the rotary evaporator

3.1 Schematic design of a rotary evaporator

3.2 Heat supply

3.2.1 The heat source

3.2.2 Heat transfer media

3.3 The drive and the support frame

3.3.1 The motor

3.3.2 The jack

3.3.4 The sealing system

3.4 The glassware

3.4.1 The evaporation flask

3.4.2 The glass assembly

Glass assembly V is a vertical condenser. Cooling here is also provided by a

Part A eparation of mixtures using a rotary evaporator,

2 Theoretical basis of the spray drying process. . . . . . . . . . . . . 70

2 Theoretical basis for the measurement of boiling points

6 Technical terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151

The boiling point is at 29.7 °C. Parameters: 10/30/50 °C

1 Acetic acid 118 °C 8 Dioxan 101° C 15 n-Propylalcohol 97 °C