26-00055 Flow Chemistry III - NW

Why using a Fluitec flow calorimeter?
A report presented by
Fluitec mixing + reaction solutions AG,
Alain Georg, Dipl. Ing. HTL, Research and Development
CH-8413 Neftenbach
30.5.2023
Overview of Topics
• Fluitec mixing + reaction solutions AG

• Flow chemistry
• GMP flow chemistry
• Flow Calorimeter
• Process understanding
• Process safety
• Assemblies with safety concept
Fluitec mixing + reaction solutions AG
Page 3
Flow calorimeter
Calorimetry without calibration
Calorimetry with calibration
Continuous reaction calorimeter set-up at Fluitec. F. Mortzfeld, J. Polenk, B. Guélat, F. Venturoni, B. Schenkel, P.
Filipponi, Org. Process Res. Dev., 2020, 24, 10, 2004-2016.
DOI: 10.1021/acs.oprd.0c00117.
6
Flow Calorimeter
TIR
0003
Pressure 2 - 8 bar
Sampling
TIR
0019 TIR
TIR 0001
0018
Feed 1
3 - 100 ml/min TIR
1 - 200 mPas 0017
.... kg/m3
.... J/kg/K TIR
... W/m/K 0016
TIR
0015
TIR WT001
0014 TG001
Feed 2 TIR Article-no. 55626

Laboratory Bottles
V = 2 Liter 0013
TIR
0012
TIR FIRC
TIR
0002 0001
PIR FIRC TIR 0011
Temperature 1000 1000 1000 TIR
Tmax = 50 °C 0010
Option
Dosing pressure
Solvent Pmax = 15 bar
Laboratory Bottles
V = 5 Liter Calibration valve
M Gearpump ZRP-200-15-3
PIR FIRC TIR

Temperature
Tmax = 50 °C
2000 2000 2000
P&ID diagram
Fluitec Reaction Calorimeter
Dosing pressure
Feed 1 Pmax = 15 bar
Laboratory Bottles
V = 2 Liter Calibration valve
M
Gearpump ZRP-200-15-3
Feed 2
3 - 100 ml/min
1 - 200 mPas
Page 7
.... kg/m3
.... J/kg/K
... W/m/K
Flow Calorimeter
10 sensors in one capillary

Flow Calorimeter
Equation of the heat transfer balance for
continuous ideal tubular reactors.
𝑄̇ !"# + 𝑄̇ "# = 𝑄̇ $%&' = 𝑚̇ ()*+,-. & Q ) & 𝑋/!.&01 with 𝑄̇ "# = 𝑘 & 𝐴 & ΔT2
𝑆𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒 𝑑𝑎𝑡𝑎
𝑁𝑢!"#!$% 𝑁𝑢&'(#!$%
𝛼!"#!$% 𝛼&'(#!$% Segmental Anlaysis
𝑘 Page 9
Flow Calorimeter
Simulation PDF-Report
Analysis
10
Flow Calorimeter
Page 11
Flow Calorimeter
https://microinnova.com/2022/10/17/continuous-flow-reaction-calorimetry-a-novel-
tool-for-industrial-flow-chemistry/
Page 12
Flow Calorimeter
Why using a Fluitec flow calorimeter?
Process understanding
Process safety
Scale-up
Page 13
Selective, fast and exothermic neutralization
reaction of acetic acid and sodium hydroxide.
Marlies Moser, Alain G. Georg, Finn L. Steinemann,

David P. Rütti, Daniel M. Meier
Journal of Flow Chemistry, 2021
DOI: 10.1007/s41981-021-00204-y
Selective, homogeneous exothermic
hydrolysis of acetic anhydride with half-lives
from a few seconds to a few minutes.
Finn L. Steinemann, Marlies Moser, Alain G. Georg,

David P. Rütti, Daniel M. Meier
Journal of Flow Chemistry, 2022
DOI: 10.1007/s41981-022-00237-x
Nonselective, fast and exothermic deprotonation
of ethanol (EtOH) with hexyllithium (HexLi).
F. Mortzfeld, J. Polenk, B. Guélat, F. Venturoni, B.

Schenkel, P. Filipponi,
Org. Process Res. Dev., 2020, 24, 10, 2004-2016.
DOI: 10.1021/acs.oprd.0c00117.
Non selective, fast and exothermic deprotonation
of ethanol (EtOH) with hexyllithium (HexLi).
Scale-up
F. Mortzfeld, J. Polenk, B. Guélat, F. Venturoni, B.

Deviation of 80% Schenkel, P. Filipponi,
Org. Process Res. Dev., 2020, 24, 10, 2004-2016.
DOI: 10.1021/acs.oprd.0c00117.
Comparison of reaction calorimeter

Heat flow calorimeter - Fluitec Flow Calorimeter
Sequen&al reac&on?
-. -/
𝐴 𝑅 𝑆
𝑃𝑎𝑟𝑎𝑙𝑒𝑙𝑙 𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛?
-.
𝐴 + 𝐵 𝐶 desired
-/
𝐴 + 𝐶 𝐷 not desired
- Specific heat of reaction Qr (HFC) = 159 kJ kg-1 The screening shows:

- Adiabatic temperature rise DTad = 89 °C - Conversion is approx. 100%.
- Temperature TONSET = 74 °C - The side reaction is visible.
- Reaction control is reproducible
- Concentration X = 0.36
- Fast reaction with viscosity ratio h1/h2 = 2
Page 19
Page 20
RTD, polytropic profile
Page 21
- The accurate temperature profile of the liquid 𝑇3 − 𝑇34 (°C. K) is measured.
- The specific heat of reaction 𝑄 (kJ kg-1) is calculated.
- The enthalpy of reaction Δ𝐻) (kJ mol-1) is determined.
- The adiabatic temperature rise Δ𝑇"+ (°C, K) is defined.
- The time t 564% (s), the time at which 50% of the specific heat of reaction 𝑄 will be
calculated. It corresponds to an approximation of the half-life.
5
- The maximum specific heat transfer capacity (W K-1 per liter) is determined.
89:;
- The error calculation for substance value deviations (+/- %) will be calculated.
- The mole ratio (-) is specified.
- The rough degree of conversion 𝑈/ can be estimated from the curves.
- The enthalpy of mixing Δ𝐻' is very well represented and can be determined.
- It is also possible to detect non-selective reactions with very different kinetics.
- The creation of simplified safety kinetics is possible.
- From the diagram, the safety relevant temperatures 𝑇< , 𝑇( , 𝑇' , 𝑇=>< and 𝑇<?@=;
can be determined, so that the classification of the reaction can be done quickly
and efficiently.
Fluitec Flow Calorimeter, unlock the full potential of flow chemistry

Process safety
Set with the flow calorimeter Definition of safety

classes
Temperature
TDEC MAX TDEC MAX TDEC MAX TDEC MAX TDEC MAX Maximum possible Classification according
to EN12100
TS decomposition temperature
Determination of SIL
TDEC MAX protection layers
TONSET T0 + Tad according to EN61511
TONSET Decomposition temperature (DSC)
TONSET
T0 + Tad
TS TS TS TS TS Maximum allowable Temperature (PED)
TONSET T0 + Tad TONSET
TONSET Tm =T0 + Tad Maximum temperature of the
T0 + Tad T0 + Tad synthesis reaction
TEXO TEXO TEXO TEXO TEXO TEXO Temperature at which the
Safety Purge System is triggered
TP TP TP TP TP TP Temperature range of the process

T0 T0 Start temperature of the synthesis reaction
Safety
Class 1 Class 2 Class 3 Class 4* Class 5* Class
* Effects on high liquid vapour pressure, gassy or hybrid

reactions systems are taken into account in the risk analysis.
Page 23
Process safety
- Specific heat of reaction Qr(HFC) = 366.5 kJ kg-1 The rapid screening shows:
- Adiabatic temperature rise DTad = 202 °C - The reaction needs a certain time until it ignites.
- Temperature TONSET = 118 / 128 °C - The TONSET temperature is clearly exceeded.
- There is no decomposition.
- Concentration X = 0.11
- Medium fast reaction with viscosity ratio h1/h2 = 2
Page 24
Fluitec safety concept
Definition of safety
classes
Classification according
to EN12100
Gas or
Can the gas protection layers

according to EN61511
steam Yes be Measures

generation? discharged?
Gas or
Severity
steam No reduced Severity 1
generation?
Page 25
Process safety
classes
to EN12100
protection layers
Determine TDEC
Page 26
Process safety
classes
to EN12100
protection layers
Novartis, CHIMIA 2019, 73, No. 10
Risk assessment (ISO 12100, 2011-03)
Risk Risk Risk Residual risk

analysis evaluation reduction
Page 27
Process safety
classes
to EN12100
protection layers
Setting the protection layers
Page 28
Assemblies with safety concept
Page 30
Assemblies with safety concept
Page 31
Page 32

26-00055 Flow Chemistry III - NW

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Why using a Fluitec flow calorimeter?

• Fluitec mixing + reaction solutions AG

Calorimetry without calibration

Calorimetry with calibration

Feed 2 TIR Article-no. 55626

PIR FIRC TIR

10 sensors in one capillary

𝛼!"#!$% 𝛼&'(#!$% Segmental Anlaysis

Why using a Fluitec flow calorimeter?

Marlies Moser, Alain G. Georg, Finn L. Steinemann,

Finn L. Steinemann, Marlies Moser, Alain G. Georg,

F. Mortzfeld, J. Polenk, B. Guélat, F. Venturoni, B.

F. Mortzfeld, J. Polenk, B. Guélat, F. Venturoni, B.

Comparison of reaction calorimeter

- Specific heat of reaction Qr (HFC) = 159 kJ kg-1 The screening shows:

RTD, polytropic profile

Fluitec Flow Calorimeter, unlock the full potential of flow chemistry

Set with the flow calorimeter Definition of safety

TP TP TP TP TP TP Temperature range of the process

* Effects on high liquid vapour pressure, gassy or hybrid

Can the gas protection layers

steam Yes be Measures

Novartis, CHIMIA 2019, 73, No. 10

Risk assessment (ISO 12100, 2011-03)

Risk Risk Risk Residual risk

Setting the protection layers

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