INTERNSHIP REPORT

A report submitted in partial fulfillment of the requirements for the Award of Degree of

MASTER OF SCIENCE
in
CHEMISTRY
by
A.GNANAVEL
Regd. No.: 2113112049010

Under Supervision of
Dr. R. Anandhan M.Sc., Ph.D.,
Assistant Professor
Department of Organic Chemistry
University of Madras
Guindy Campus
Chennai 600 025.
(Duration: 8th May, 2017 to 7th June, 2017)

DEPARTMENT OF CHEMISTRY
Government Arts College for Men (AUTONOMOUS)
(AFFILIATED WITH UNIVERSITY OF MADRAS)
Annasalai, Nandanam, Chennai – 600 035.
 DEPARTMENT OF CHEMISTRY
Government Arts College for Men (AUTONOMOUS)
(AFFILIATED WITH UNIVERSITY OF MADRAS)
Annasalai, Nandanam
Chennai – 600 035.

CERTIFICATE

This is to certify that the “Internship report” submitted by A.GNANAVEL ,Regd. No.:

2113112049010 is work done by him and submitted during July 2022, in partial

fulfillment of the requirements for the award of the degree of MASTER OF SCIENCE

in CHEMISTRY, at Department of Organic Chemistry ,University of Madras, Guindy

Campus, Chennai 600 025.

Internship Coordinator Head of The Department

Dr.S.Selvaraj, M.Sc., Ph.D., Dr.R.Bhavani,M.Sc.M.Phil.,D.F.T.,Ph.D.,
Associate Professor Associate Professor
 OVERVIEW OF INTERNSHIP ACTIVITIES

S.No. NAME OF THE TOPIC/MODULE COMPLETED

1. Introduction to the chromatographic techniques

2. Introduction to the coupling reactions

3. Sonogashira coupling reaction

4. Deprotection of functional group

5. Separation of compounds using column chromatography

 Introduction to the Chromatographic techniques

Chromatography is an important biophysical technique that enables the

separation, identification, and purification of the components of a mixture for qualitative

and quantitative analysis. Proteins can be purified based on characteristics such as

size and shape, total charge, hydrophobic groups present on the surface, and binding

capacity with the stationary phase. Four separation techniques based on molecular

characteristics and interaction type use mechanisms of ion exchange, surface

adsorption, partition, and size exclusion. Other chromatography techniques are based

on the stationary bed, including column, thin layer, and paper chromatography.

Column chromatography is one of the most common methods of protein purification.

Principles of Chromatography

Chromatography is a separation method where the analyte is combined within

a liquid or gaseous mobile phase., which is pumped through a stationary phase.

Usually one phase is hydrophilic and the other is lipophilic. The components of the

analyte interact differently with these two phases. Depending on their polarity they

spend more or less time interacting with the stationary phase and are thus retarded to

a greater or lesser extent. This leads to the separation of the different components

present in the sample. Each sample component elutes from the stationary phase at a

specific time called as retention time. As the components pass through the detector

their signal is recorded and plotted in the form of a chromatogram.

Types of Chromatography

1. Adsorption Chromatography

In the process of adsorption chromatography, different compounds are adsorbed on

the adsorbent to different degrees based on the absorptivity of the component. Here

also, a mobile phase is made to move over a stationary phase, thus carrying the

components with higher absorptivity to a lower distance than that with lower

absorptivity. The main types of chromatographic techniques that are used in industries

are given as under.

2. Partition chromatography

In this process, a continuous differential partitioning of components of a mixture into a

stationary phase and mobile phase takes place. The example of partition

chromatography can be seen in paper chromatography. In this process,

chromatography paper is used as a stationary phase which is suspended in a mixture

of solvents that act as a mobile phase.

Here, we put a spot at the base of the chromatographic paper with the mixture to be

separated and as the solvent rises up this paper, the components are carried to

different degrees depending upon their retention on the paper. The components are

thus separated at different heights.

 Column Chromatography
Column chromatography is the adsorption technique used to separate the

components of a mixture using a column of suitable adsorbent packed in a glass tube,

as shown in the figure below. The mixture is placed on the top of the column, and an

appropriate eluant is made to flow down the column slowly.

Depending upon the degree of adsorption of the components on the wall adsorbent

column, the separation of the components takes place. The component with the

highest absorptivity is retained at the top, while the other flow down to different heights

accordingly
 Introduction to the Coupling reactions

A coupling reaction in organic chemistry is a general term for a variety of

reactions where two fragments are joined together with the aid of a metal catalyst. In

one important reaction type, a main group organometallic compound of the type R-M

(R = organic fragment, M = main group center) reacts with an organic halide of the

type R'-X with formation of a new carbon-carbon bond in the product R-R'. The most

common type of coupling reaction is the cross coupling reaction.

Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki were awarded the

2010 Nobel Prize in Chemistry for developing palladium-catalyzed cross coupling

reactions.

Broadly speaking, two types of coupling reactions are recognized:

• Heterocouplings combine two different partners, such as in the Heck

reaction of an alkene (RC=CH) and an alkyl halide (R'-X) to give a substituted

alkene, or the Corey–House synthesis of an alkane by the reaction of

a lithium diorganylcuprate (R2CuLi) with an organyl (pseudo)halide (R'X).

Heterocouplings are also called cross-couplings.

• Homocouplings couple two identical partners, as in the Glaser coupling of

two acetylides (RC≡CH) to form a dialkyne (RC≡C-C≡CR).

Homo-coupling types

Cross-coupling types
 General procedure A: Sonogashira coupling

Synthesis of aryl substituted 2-methyl-4-phenylbut-3-yn-2-ol compound

To the oven dried round bottom flask containing arylbromide (3 mmol) in

triethylamine (10 mL) was charged with CuI (1 mol%) and Pd(PPh3)2Cl2 (2 mol%)

under nitrogen atmosphere, and allowed to stir at rt for 10 minutes. Then alkyne (3.6

mmol) was added drop wise under nitrogen atmosphere then the reaction mixture was

allowed to stir at 80 oC for 4-6 hours. The reaction completion was monitored by thin

layer chromatography. After the completion of reaction, the reaction mixture was

passed through celite, washed with ethyl acetate and concentrated under reduced

pressure. The crude product was purified by column chromatography using silica gel,

hexanes and EtOAc as eluent to furnish the corresponding sonogashira coupled

product as oily liquids.

Synthesis of o-alkynylated benzaldehyde:

 General procedure B: Deprotection reaction
Synthesis of terminal alkynes:

To a solution of sonogashira coupled compound (2.1 mmol) in toluene was

added powdered KOH (6.4 mmol) in portion wise. Then the reaction mixture was

allowed to stir at 70 oC for 2-3 hours. After the completion of the rection was monitored

by TLC (Thin Layer Chromatography), the reaction mixture was allowed to cool to

room temperature, passed through celite and purified by column chromatography

using silica gel, hexanes and EtOAc as eluent to furnish the corresponding terminal

alkynes as a final product.

Conclusion

During the internship I learnt a concept live and I have gained the knowledge

of the coupling reactions and the laboratory techniques, which are all the chemistry

students should be knowing. During the internship I was enjoyed my sessions.