Industrial Organic Chemistry (CY181, 3

credit course)
Handled by

Dr. S. NAGARAJAN
ASSOCIATE PROFESSOR & Member, INYAS-INSA
Department of Chemistry
National Institute of Technology, Warangal
Warangal
Telangana, India

A Section, Chemical Engineering Branch

1
Syllabus:
• Current approaches to organic synthesis: Functional group interconversions, synthesis of value added chemicals based
on functional group inter conversions (synthon approach), alternative reaction media (water, ionic liquids, and deep
eutectic solvents), and alternative energy sources (microwave, sonication) for organic reactions. Homogeneous and
heterogeneous catalysis.Purification of organic compounds:Chromatography (Thin-layer, Column, Gas and high
performance liquid chromatography), Bulk separation

• Heterocyclic Compounds and Pharmaceutical chemistry: Structure and reactivity of pyrrole, furan, thiophene and
pyridine. Importance of heterocyclic molecules in pharmaceutical chemistry, Modern approaches of drug discovery,
strategies for bulk drug preparation.
• Stereochemistry: Introduction to stereochemistry, isomerism, enantiomers, diastereomers, CIP rules,relative and
absolute configuration (D, L and R, S-nomenclature), racemization, resolution techniques. Conformational analysis of
ethane, butane and cyclohexane.
• Chemistry of biomolecules: Structure and biological importance of carbohydrates, amino acids, peptide synthesis,
proteins structure, purification of proteins, structure and biological importance of nucleic acids (DNA and RNA).

2
• Polymer chemistry: Polymerization methods, conducting polymers, liquid crystalline materials, paints and colouring agents.
• Advanced Spectroscopy Methods of Analysis: 13C NMR spectroscopic methods, Coupling Constant, Lanthanide Shift
reagents, Mass spectrometry: EI, ESI, and structural elucidation small molecules (combined problems).
Learning Resources:
• Text Books:
• 1. Organic Chemistry, John E. McMurry, Brooks Cole, 2011, 8th Edition.
• 2. Organic Chemistry, T. W. Graham Solomons, Craig B. Fryhle, Scott A. Snyder –Wiley, 2013, 12th Edition.
• Reference Books:
• 1. Organic Chemistry by Francis A. Carey, Tata Mc Graw Hill Publishing Company Limited, 2011, 7th Edition.
• 2. Organic Chemistry by Francis A. Carey, Tata Mc Graw Hill Publishing Company Limited, 2011, 7th Edition.
• 3. Principles and Applications of Stereochemistry, Micheal North, Taylor&Francis, 2017, 2nd Edition.
• 4. Heterocyclic Chemistry, John A. Joule, Keith Mills, XX publishers, 2010, John Wiley & Sons, Ltd., 5th Edition
• 5. Introduction to Spectroscopy, Donald L. Pavia, Gary M Lanyman, Cengage Learning, 2015, 5th Edition.
• 6. The Organic Chemistry of Drug Design and Drug Action, Richard B. Silverman, Elsevier, 2013, 3rd Edition.
• 7. Introduction to Polymer Chemistry, Charles E Carraher Jr, CRC Press, 2017, 4th Edition
• Online Resources:
• 1. https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/intro1.htm
• 2. https://chem.libretexts.org/Bookshelves/Organic_Chemistry 3
Science in ancient history Advanced Science and Technology

4
1KG seed cost : Rs 200-250
1L oil price: Rs 120-150

5
 NATURE - SCIENCE

CRITICAL THINKING ON SOCIETIAL NEEDS→ PROBLEM SOLVING (Science, where we

play major role) →DEVICE/TECHNOLOGY DEVELOPMENT (Engineering) →BENEFIT
OF SOCIETY (INCLUSIVENESS)

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ANCIENT SCIENCE

7
E=hv = hc/λ
 12 Principles of Green Chemistry
1. PREVENTION: It’s better and easier to prevent waste than to deal with it after it’s formed.

2. ATOM ECONOMY: We should maximize the amount of material inputs that get
incorporated into the final product.

3. LESS HAZARDOUS SYNTHESES: We should minimize hazardous by-products created by

syntheses.

4. SAFER CHEMICALS: We should use design to preserve the efficacy of a function while
reducing its toxicity.

Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice, Oxfor University press, 1998
 12 Principles of Green Chemistry
5. SAFER SOLVENTS AND AUXILIARIES: We should minimize the use of auxiliary substances
wherever possible, or use ones that are non-toxic.

6. ENERGY EFFICIENCY: Energy requirements have environmental and economic impacts. We

should conduct syntheses at ambient temperature and pressure to minimize energy
costs.

7. RENEWABLE FEEDSTOCKS: Use renewable feedstocks

8. REDUCE DERIVATIVES: Unnecessary derivatization (using protecting or blocking groups

during synthesis) should be avoided whenever possible to reduce waste. Minimise the
number of steps in the reaction.

Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice, Oxfor University press, 1998
 12 Principles of Green Chemistry
9. CATALYSIS: Catalytic reagents are better than stoichiometric reagents in that they allow
for lower temperatures and energy costs, and are reusable and therefore generate less
waste.

10. DESIGN FOR DEGRADATION: Design products that are biodegradable at the end of their
use.

11. REAL TIME POLLUTION PREVENTION: We should encourage methodologies to monitor

the process of a reaction so as to detect the emergence of toxic by-products.

12. ACCIDENT PREVENTION: By minimizing the use of toxic substances and high energy
processes.

Anastas, P.T.; Warner, J.C. Green Chemistry: Theory and Practice, Oxfor University press, 1998
 Greening a chemical process
Catalysts
•play on activation Products and by-products
Feedstocks energy and do more •Minimize waste
•Use renewable with less •Produce by-products and
feedstocks. products that are less
• Maximize the amount Synthesis design toxic and biodegradable
of inputs that make it •Minimize number of steps
into final product in reaction

Energy Medium and reagents

•Use less •Conduct reaction in
Energy water if possible
•Conduct reactions at low • Use safer solvents
temperature and pressure
Natural monomers: A mine for functional and sustainable materials – Occurrence, chemical modification and
polymerization, Progress in Polymer Science, Volume 92, May 2019, Pages 158-209
 Green Technology in Action: Plastics from renewable material
• Nature Works “bio-based plastic resins”: Joint venture between Cargill Inc and Dow Chemical
• Received Presidential Green Chemistry Challenge Award in 2002
• Developed the first synthetic polymer class to be produced from renewable resources (corn), a
potential substitute for petroleum-based polymers
• Biodegradable (compostable)
• Manufacturing sequence reduced consumption of fossil fuels by 30%-50% compared to
conventional oil-based plastic resins
http://www.natureworksllc.com/The-Ingeo-Journey/Eco-Profile-and-LCA/Eco-Profile
 Greening the plastic production process
Catalysts
•play on activation energy
and do more with less Products and by-products
Feedstocks (enzymatic fermentation •Produce by-products and
•Use renewable process) products that are less
feedstocks (corn) toxic and biodegradable
Synthesis design

Medium and reagents

Many steps in the
Energy reaction are solvent
•Use less free
energy
Pre-Requisites for this course:
CY132 – Chemistry: 3 credit course
Basic organic chemistry: Reactive intermediates, types of reactions,
structural characterization techniques (UV, FTIR and NMR)
Course plan:

16
https://www.honeywell.com/us/en/industries/overview

https://www.honeywell.com/us/en/industries/chemicals-materials
India is an attractive hub for chemical companies. Chemical
industry is one of the significant contributors to the growth and
development of any economy.
Read more at:
https://auto.economictimes.indiatimes.com/news/auto-
components/indias-growing-chemistry-with-the-
world/91267028

MAJOR INVESTORS IN CHEMICAL

INDUSTRY OF INDIA https://cen.acs.org/
Mitsubishi Chemicals
BASF
ADEKA
AkzoNobel
Dupont
Syngenta
DyStar
Henkel
Rhodia
WACKER
CRODA
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 Functional Group Interconversion
The functional group interconversion (FGI) reactions are among the most common synthetic
processes.
The synthesis of an organic compound must pay attention to ... Functional groups
Functional Group Interconversion (FGI)
1. Substitutions
2. Additions
3. Eliminations
4. Reductions
5. Oxidations

"the process of converting one functional group into another by substitution, addition,
elimination, oxidation or reduction, and the reverse process used in (retrosynthetic) analysis."
23
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Alcohols are one of the very important class of compounds for organic synthesis
28
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 -OH in ROH is not a good leaving group, hence the reactivity is moderate/slow.

1. FGI into the corresponding tosylate/mesylate makes the substrate more reactive.

2. FGI into the corresponding halides makes the substrate more reactive (SNi reaction).

Retention of configuration

Inversion of configuration, in
the absence of solvent/in the
presence of pyridine
Method involving sulfuryl
chloride is useful for
sterically hindered
substrates
 Zydus Cadila, Israeli generic major Teva
, GlaxoSmithKline, Johnson & Johnson

Carvedilol (COREG) is used to treat heart failure (condition in which the heart cannot pump enough
blood to all parts of the body) and high blood pressure. It also is used to treat people who have had a
heart attack. Carvedilol is often used in combination with other medications.
39
 Atomoxetine is used to treat attention-deficit hyperactivity disorder
(ADHD) in children, teenagers, and adults. Atomoxetine also significantly
reduced anxiety symptoms like excessive worry, sweating and trembling
by 32 percent

Apotex, Teva, Aurobindo and

Glenmark to make atomoxetine
Benzene is primarily used as a building block for producing derivatives like styrene,
cyclohexane, cumene, aniline, alkyl benzenes and chlorobenzenes. Among these
derivatives styrene, cumene and cyclohexane are the major chemical products produced
from benzene. More than half of the global benzene is used in making styrene.
Styrene Produced In One Step (chemical and engineering news, April 2015)
Industrial Organic Chemistry: New catalyst enables single-step synthesis of styrene from benzene
and ethylene

https://cen.acs.org/articles/93/i17/Styrene-Produced-One-Step.html
 Caprolactam and adipic acid prepared from benzene (reduction of
benzene using H2/Ni)

This report addresses the recent developments and improvements in the chemical technology for the
manufacture of caprolactam and nylon 6 since the issuance of those reports.

Caprolactam can be produced from cyclohexane, phenol, or toluene by the following four routes:

From cyclohexane via cyclohexanone by oxidation, oximation, and Beckmann rearrangement

From phenol via cyclohexanone by hydrogenation, oximation, and Beckmann rearrangement
From toluene via cyclohexane carboxylic acid by oxidation, hydrogenation, nitrosation, and
rearrangement
Adipic acid prepared from benzene/D-glucose
Chemical technology for the preparation of value added products
Chemical technology for the preparation of cumene and other value added products
Cumene is formed in the gas-phase Friedel–Crafts alkylation of benzene by propene. Benzene and
propene are compressed together to a pressure of 30 standard atmospheres at 250 °C in presence of a
catalytic Lewis acid. Phosphoric acid is often favored over aluminium halides.

The cumene process (cumene-phenol process, Hock process) is an industrial process for synthesizing
phenol and acetone from benzene and propylene. The term stems from cumene (isopropyl benzene),
the intermediate material during the process. It was invented by R. Ūdris and P. Sergeyev in 1942 and
independently by Heinrich Hock in 1944
Cumene is oxidized in air, which removes the tertiary benzylic hydrogen from cumene and hence
forms a cumene radical:

The cumene radical then bonds with an oxygen molecule to give cumene peroxide radical, which in
turn forms cumene hydroperoxide by abstracting a benzylic hydrogen from another cumene molecule.
This latter cumene converts into cumene radical and feeds back into subsequent chain formations of
cumene hydroperoxides. A pressure of 5 atm is used to ensure that the unstable peroxide is kept in
liquid state.
Cumene hydroperoxide undergoes a rearrangement reaction in an acidic medium (the Hock
rearrangement) to give phenol and acetone.

The resulting carbocation is then attacked by water, forming a hemiacetal-like structure. After
transfer of a proton from the hydroxy oxygen to the ether oxygen, the ion falls apart into phenol and
acetone.
In the petroleum refining and petrochemical industries, BTX refers to mixtures of benzene, toluene,
and the three xylene isomers. If ethylbenzene is included, the mixture is sometimes referred to as
BTEX.

The BTX aromatics are very important petrochemical materials..

Toluene is also a valuable petrochemical for use as a solvent and intermediate in chemical
manufacturing processes and as a high octane gasoline component
Ethylene oxide is industrially produced by oxidation of
ethylene in the presence of silver catalyst.
Ethylene oxide is prone to nucleophile attack

https://en.wikipedia.org/wiki/Ethylene_oxide#Chlorohydrin_pr
ocess_of_production_of_ethylene_oxide

https://www.chemengonline.com/ethylene-oxide-
production-ethylene/
 Production of Propylene Oxide from Propylene Using Patented Silver Based Catalyst

https://repository.upenn.edu/cgi/viewcontent.cgi?article=1082&context=cbe_sdr#:~:text=The%20proposed%20process
%20design%20is,to%20PO%20in%20high%20yeild.
 Production of 1,2-dichloroethane
Ethene is obtained from the cracking of ethane, propane, naphtha and gas oil. In practice, two processes for the overall
conversion of ethene to chloroethene are used in parallel.

(i) Direct chlorination

Ethene is reacted with chlorine in the liquid phase, using excess chloroethene as solvent. The catalyst, iron(lll) chloride, is
soluble in chloroethene. The reaction is exothermic, and no external heat is needed.

The reaction temperature is maintained at 320-350 K and with a pressure of ca 4 atm. Higher temperatures give unwanted
polychlorinated compounds.

(ii) Oxychlorination route

The cracking of 1,2-dichloroethane during stage (b) of the overall process forms hydrogen chloride as a by-product. It is
unwanted as hydrogen chloride and is very detrimental to the environment. However, it can be used in this second
method of making 1,2-dichloroethane.

Ethene is mixed with hydrogen chloride and air (enriched with oxygen). The gases are passed over a heated solid catalyst
in metal tubes, in a fluid bed reactor, maintained at ca 500 K and 5 atm.
The catalyst generally used is a mixture of copper(ll) and potassium chlorides,
deposited on alumina.
As the reaction is highly exothermic, the reactor vessel is cooled to give the optimum
reaction temperature and to reduce unwanted by-product formation of, for example,
chloroethane and 1,1,1,2-tetrachloroethane. 95% conversion of ethene to 1,2-
dichloroethane is obtained.
Unreacted hydrogen chloride is removed by scrubbing the gases with aqueous
sodium hydroxide solution. Impurities, such as unreacted ethene and unwanted
chlorinated hydrocarbons, are removed by distillation. Ethene is recycled.

(b) Production of chloroethene (vinyl chloride)

1,2-dichloroethane is then passed rapidly through metal tubes heated to ca 650 K. It is cracked to eliminate hydrogen chloride:

Polymerization of chloroethene (vinyl chloride)

This is an example of addition polymerization. PVC is made by
free-radical polymerization in suspension

https://www.essentialchemicalindustry.org/polymers/polychloroethene.html
Carbon dioxide hydrogenated to methanol on large scale
https://cen.acs.org/articles/94/i13/Carbon-dioxide-
hydrogenated-methanol-large.html
Scientists had shown earlier that indium oxide catalyzes the
direct hydrogenation of CO2 to CH3OH on a lab scale. Javier
Pérez-Ramírez of ETH Zurich and coworkers now demonstrate
that zirconium oxide-supported In2O3 catalyzes the process
under conditions similar to those required for industrial
production

reverse water gas shift (RWGS)

 THE HABER PROCESS
The catalyst

The catalyst is actually slightly more complicated

than pure iron. It has potassium hydroxide added to
it as a promoter - a substance that increases its
efficiency.

The pressure

The pressure varies from one manufacturing plant

to another, but is always high. You can't go far
wrong in an exam quoting 200 atmospheres.

Recycling

At each pass of the gases through the reactor, only

about 15% of the nitrogen and hydrogen converts to
ammonia. (This figure also varies from plant to
plant.) By continual recycling of the unreacted
nitrogen and hydrogen, the overall conversion is
about 98%.
59
 The Haber-Bosch process, which converts hydrogen and nitrogen to ammonia, could be one of the most important
industrial chemical reactions ever developed. The process made ammonia fertilizer widely available, helping cause a world
population boom as yields from agriculture increased rapidly in a short time.
According to the Institute for Industrial Productivity’s Industrial Efficiency Technology Database, between 75 and 90% of thi s
ammonia goes toward making fertilizer, and about 50% of the world’s food production relies on ammonia fertilizer.
The reaction, which runs at temperatures around 500 °C and at pressures up to about 20 MPa, sucks up about 1% of the world’s
total energy production. It emits up to about 451 million t of CO2 in 2010, according to the Institute for Industrial Productivity.
That total accounts for roughly 1% of global annual CO2 emissions, more than any other industrial chemical-making reaction
https://cen.acs.org/environment/green-chemistry/Industrial-ammonia-production-emits-CO2/97/i24
Chemical plant for production of ammonia and nitrogen fertilization on day time.
Preparation of Sulphuric Acid by Contact process
Sulphuric Acid is world’s most produced chemical because of its widespread use in not only in Chemical, Metallurgical,
Process, Petrochemical, Fertilizer industries but also in electrical and electronics, Semiconductor industries and also in
variety of labs all around the world. The most important use is in phosphate industry and also in metal extraction industries.
They also find important uses in Paint and Pigment, Explosive, Detergent, Plastic and Synthetic Fiber industries.

Sulphuric Acid is a colourless liquid which has an appearance similar to that of water. It has a molecular weight of about
98. It is heavier than water. The sulphuric acid can be diluted by water to get acids in various strengths for different
purposes. During the mixing process, sulphuric acid should be added to water.

Reason being that since sulphuric acid is heavier than water it will move to the bottom due to gravity and the mixing will
be much uniform. In case we add water to sulphuric acid, since the water is lighter than sulphuric acid, it will stay at the
top.

Hence, we will have water in the top layer and sulphuric acid in the bottom layer. At the interface the sulphuric acid will
absorb water and release heat. This released heat will evaporate a fraction of water near the interface. It will convert it
into steam. The steam will expand and the mixture will be splashed everywhere in an exploding fashion.

Almost all the sulphuric acid around the world is manufactured by Contact Process.
Raw Materials used in Contact Process
Sulphuric acid is made up of Sulphur, Oxygen and Hydrogen. So naturally the sources which are rich in these elemental
compositions are chosen for the task of production of Sulphuric Acid. The raw materials used can be elemental sulphur
by itself or Sulphur Dioxide or Pyrite. Also, air and water are used.

Sulphur can be found from mines, Sulphur and Sulphur Dioxide can be found from stack gases which are obtained from
coal or oil industries. Sulphur or Hydrogen Sulphide can be obtained from petroleum desulphurisation. Sulphur dioxide
can be obtained from smelting of metal silicide ores or it can be isolated from pyrite.

Sulphuric Acid Manufacturing Process

Production of Sulpur Dioxide Gas (SO2)
Production of Sulpur Trioxide Gas (SO3)
Production of Sulphuric Acid (H2SO4)
 Bio-based syn gas production

Gasification is a process that converts organic or fossil-based carbonaceous materials at high temperatures (>700°C), without
combustion, with a controlled amount of oxygen and/or steam into carbon monoxide, hydrogen, and carbon dioxide. The
carbon monoxide then reacts with water to form carbon dioxide and more hydrogen via a water-gas shift reaction. Adsorbers
or special membranes can separate the hydrogen from this gas stream.
Simplified example reaction Water-gas shift reaction
C6H12O6 + O2 + H2O → CO + CO2 + H2 + other species CO + H2O → CO2 + H2 (+ small amount of heat)

http://biomassmagazine.com/articles/1399/syngas-101
https://www.energy.gov/eere/fuelcells/hydrogen-production-biomass-
gasification#:~:text=Gasification%20is%20a%20process%20that,%2C%20hydrogen%2C%20and%20carbon%20dioxide.
Challenges in Hydrogen gas production
Key challenges to hydrogen production via biomass gasification involve reducing costs associated with capital equipment
and biomass feedstocks.
Research to lower capital costs:
1. Replacing the cryogenic process currently used to separate oxygen from air when oxygen is used in the gasifier with
new membrane technology.
2. Developing new membrane technologies to better separate and purify hydrogen from the gas stream produced
(similar to coal gasification).
Intensifying the process (combining steps into fewer operations).
We have already studied the conversion of syn gas to methanol and other value added product
Carbon dioxide hydrogenated to methanol on large scale
https://cen.acs.org/articles/94/i13/Carbon-dioxide-
hydrogenated-methanol-large.html
Scientists had shown earlier that indium oxide catalyzes the
direct hydrogenation of CO2 to CH3OH on a lab scale. Javier
Pérez-Ramírez of ETH Zurich and coworkers now demonstrate
that zirconium oxide-supported In2O3 catalyzes the process
under conditions similar to those required for industrial
production

reverse water gas shift (RWGS)

Route A, traditional and direct route based on a single catalyst. Route B, indirect route including three processes, i.e., methanol
synthesis, methanol carbonylation with CO and acetic acid (AA) hydrogenation. Route C, indirect route including three
processes, i.e., syngas to dimethyl ether (DME), DME carbonylation with CO and methyl acetate (MA) hydrogenation. Route D,
Tandem catalytic route of this work.
 The Fischer–Tropsch process is a collection of
chemical reactions that converts a mixture of
carbon monoxide and hydrogen or water gas into
liquid hydrocarbons. These reactions occur in the
presence of metal catalysts, typically at
temperatures of 150–300 °C (302–572 °F) and
pressures of one to several tens of atmospheres.
In the usual implementation, carbon monoxide
and hydrogen, the feedstocks for FT, are
produced from coal, natural gas, or biomass in
a process known as gasification. The Fischer–
Tropsch process then converts these gases into
synthetic lubrication oil and synthetic fuel.

8 CO + 17 H2 → C8H18 + 8 H2O

Methyl tert-butyl ether-MTBE: increases octane and oxygen levels in gasoline and reduces pollution emissions.
Direct-methanol fuel cells or DMFCs are a subcategory of proton-exchange fuel cells in which methanol is used as the fuel.
Dimethyl ether (DME) CH₃OCH₃: The simplest ether, it is a colorless gas that is a useful precursor to other organic compounds
and an aerosol propellant that is currently being demonstrated for use in a variety of fuel applications
https://www.basf.com/global/en/who-we-are/sustainability/we-drive-sustainable-solutions/circular-economy/mass-
balance-approach/biomass-balance/biomass-balance.html
Why chemical engineering: https://www.ceb.cam.ac.uk/undergraduates/prospective-students/why-study-chemical-
engineering
77
 Solvents and Alternate Reaction Media
• Chemical reactions are often carried out in media - organic solvents or water - to provide a medium in reactants can
dissolve and come into close, rapid contact at the molecular level.
• A good solvent for chemical synthesis is one that enables facile product separation and is amenable to purification and
reuse with minimum loss.
• Substances dissolved in a solvent are solvated by binding of the solvent to the molecules or ions of the dissolved
substance, the solute.
• Solvation of reactants and products often plays an important role in determining the kinds and rates of reactions.
• Many organic reactants are not soluble in water or are getting decomposed, so organic solvents including
hydrocarbons, chlorinated hydrocarbons, and ethers have to be used as reaction media.
• Organic solvents cause several problems in chemical synthesis. Particularly because of problems associated with their
containment, recovery, and reuse
• organic solvents especially are major contributors to undesirably high E factors (E factor (environmental factor) is
another simple metric of how “green” a reaction is, It is defined as the ratio of the mass of waste per mass of product).
• Many of the environmental and health problems associated with making chemicals are the result of the use of organic
solvents as media.
• Hydrocarbon solvents will burn and hydrocarbon vapors in air are explosive. Although many hydrocarbon solvents are
not particularly toxic, some can cause the condition of peripheral neuropathy (damage to peripheral nerves such as
those in feet and legs), and benzene is regarded as a carcinogen thought to cause leukemia.
• Released to the atmosphere, hydrocarbons can also participate in photochemical processes leading to the formation of
photochemical smog
A batch reactor (left) involves mixing a large amount of reactants, often with a homogeneous catalyst, and allowing the
reaction to take place for the required amount of time with the result that if anything goes wrong a large amount of
material is spoiled and a considerable hazard may develop. In a continuous-flow reactor (right) only a small amount of
material is reacting at any given time, heterogeneous catalysts can be used, energy input can be accurately regulated,
and the process can be stopped at any time if something goes wrong.
One approach to making chemical synthesis processes greener is to replace specific solvents with less hazardous ones.
For this reason, toxic benzene solvent is replaced by toluene wherever possible.
As shown by their structural formulas below, toluene has a methyl group,−CH3, that benzene does not possess. The methyl
group in toluene can be acted upon by human metabolic systems to produce a harmless metabolite (hippuric acid) that is
eliminated in the urine, whereas metabolic processes acting upon benzene convert it to a toxic intermediate that can react
with cellular DNA.

As another example of solvent replacement, n-hexane, which can cause peripheral neuropathy in exposed individuals, can
be replaced with 2,5-dimethylhexane, which does not cause this condition, for reactions where the higher boiling
temperature of the latter compound is not a problem.

There is significant interest in reaction media other than organic solvents. The ultimate approach to eliminating problems
with solvents in chemical synthesis is to do reactions without solvents of any kind. Some reactions can be performed in
which the reactants are simply mixed together or are held on solid supports, such as clays. Microwave heating of such
reaction mixtures has proven effective in providing energy to enable reactions to occur rapidly. However, in many cases
that is not possible and solvents are required. Some alternative solvents are discussed below.
Water Solvent
• The greenest solvent for green chemical processes is water.
• Water is abundant, cheap, not toxic, and does not burn.
• Because of its polar nature and the ability to form hydrogen bonds, water is an especially good solvent for ionic
compounds — acids, bases, and salts.
• Water is particularly useful as one of the solvents in biphasic catalysis
• Normally the catalyst is held in the water phase and the product in a water-immiscible organic solvent, which allows
facile separation of the catalyst after the reaction is complete.
• Because of water’s many advantages, significant efforts have been made in replacing organic solvents used for reaction
media with water.
• Although water does not appreciably dissolve many nonpolar organic compounds, in some cases these materials may
be suspended as very small colloidal particles in water, enabling close enough contact of organic materials to undergo
reactions.
• Water is a good solvent for some of the biological materials, such as glucose, now favored as chemical feedstocks
where they can be used.
On-water reactions are a group of organic reactions that take place as an emulsion in water and have an unusual reaction
rate acceleration compared with (i) the same reaction in an organic solvent, or (ii) the corresponding dry media reaction.

The rate acceleration is found in certain Claisen rearrangements ([3,3]-sigmatropic rearrangement). In one typical example
of this reaction at room temperature the chemical yield was found to be 100% on water after 120 h compared with 16% for
the same reaction in toluene and 73% in the neat reaction.

Enhanced reactivity is also found in cycloadditions. The reaction of quadricyclane with DEAD (diethylazodicarboxylate) is a 2σ
+ 2σ + 2π cycloaddition that on water takes place within 10 minutes at room temperature with 82% yield. The same reaction
in toluene takes 24 hours at 80 °C with 70% yield. An emulsion reaction in fluorinated cyclohexane takes 36 hours and the
neat reaction takes even longer (48 hours).
 On-water reactions

Fischer indole synthesis in aqueous medium

Synthesis of 2-phenylbenzimidazole in water

83
Novartis scientists in 2016 compared two processes for making an undisclosed API, using organic solvents (red) and micellar
chemistry (yellow).
https://www.novartis.in/ (Our talented, diverse and driven teams work collaboratively to bring our pipeline of innovative
medicines to life. With close to 8000 associates in the country, Novartis has a vision of a better today and tomorrow for
patients – a vision that drives our growth and success. The greatest job satisfaction for our associates is the knowledge that
they improve the quality of life for patients through breakthrough science and innovation.
 Chemical reactions in supercritical fluid

Matter can be pushed to temperatures and pressures beyond those of its critical point. This stage is characterized by the
inability to distinguish whether the matter is a liquid or a gas, as a result, Supercritical fluids (SCF) do not have a definite phase.
Critical Points of Common SCFs
Critical Temperature
Liquid Critical Pressure (atm)
(K)
Hydrogen (H) 33.3 12.8
Neon (Ne) 44.4 26.3
Nitrogen (N) 126 33.5
Argon (Ar) 151 48.5
Methane (CH4) 191 45.8
Ethane (C2H6) 305 48.2
Carbon Dioxide (CO 2) 305 72.9
Ammonia (NH3) 406 112
Water (H2O) 647 218

Supercritical fluids are useful for various purposes ranging from

the extraction of floral fragrance from flowers
the process of creating decaffeinated coffee,
applications in food science and functional food ingredients, pharmaceuticals, cosmetics, polymers, powders,
bio- and functional materials, nano-systems, natural products, biotechnology, fossil and biofuels,
microelectronics and environment
Carbon Dioxide Solvent
At a high pressure above 73.8 atm (73.8 times > normal atmospheric pressure at sea level) and a
temperature exceeding 31.1 ̊C, carbon dioxide becomes a supercritical fluid, a relatively dense state
of matter in which there is no longer a distinction between liquid and gas.
Supercritical carbon dioxide can be used as a reaction medium for organic chemical reactions.
An advantage of supercritical carbon dioxide in this application is that its viscosity is only about 1/30
that of common liquid organic solvents, which enables reactant species to move much faster
through the fluid, thus speeding the reactions that they undergo.
At temperatures and pressures somewhat below those at which carbon dioxide becomes critical, it
exists as separate gas and liquid phases while retaining many of the solvent properties of supercritical
carbon dioxide. Under these conditions carbon dioxide is called a dense phase fluid, a term that also
encompasses supercritical fluids.
Adjustment of the composition and conditions under which dense phase fluid carbon dioxide is maintained can provide
significant variations in its solvent properties and adjustment of its ability to act as a reaction medium. In addition to
variations in temperature and pressure, dense phase fluid carbon dioxide may be mixed with small quantities of other
solvents (modifiers), such as methanol, to further vary its solvent properties.

In addition to its solvent properties, dense phase fluid carbon dioxide offers the advantage of low toxicity and low potential for
environmental harm (the small amounts of greenhouse gas carbon dioxide released from its application as a solvent are
negligible compared to quantities released from combustion of fossil fuels). A big advantage of dense phase fluid carbon
dioxide is its volatility, meaning that it separates readily from reaction products when pressure is released. Furthermore,
carbon dioxide released from a reaction mixture can be captured and recycled for the same application. Carbon dioxide can be
obtained at low cost from biological fermentation processes.
Applications of supercritical carbon Comparison of conventional organic solvent and
dioxide extraction supercritical carbon dioxide extraction and pretreatment
Field Material Purpose
methods
Coffee beans Decaffeinated
Tea Flavor ingredient Organic solvent Disadvantages
Hop Hop extract Soxhlet extraction &
Red pepper Spicy extract, pigment Uses harmful organic solvents
Food Fish meal Fish oil
purification
Fish oil EPA, DHA Process is complicated and time-
Essential oils, pigments,
Plant consuming
medicinal ingredients Solvent extraction &
Vegetable oil Vitamin E Long pre-processing time
purification
Natural products
Medicinal ingredients, Higher sample concentration required
Pharmaceutical bioactive substances
Trace residual solvent
Tablet Residual solvent
Low boiling point
component Supercritical carbon
Advantages
Polymerization solvent dioxide
Coal, oil, energy Monomer
Plastic, rubber, polymer
Oligomer
Carbon dioxide Uses safe carbon dioxide
Metal
Chemical
Inorganic compounds Impurities Simple process that can be
and ceramics Nasty smell
Aerogel
automated
Developing agent
Electrical / electronic
Degreasing Fast pre-processing and extraction
parts Carbon dioxide & ethanol,
Dehydration Selective extraction possible
etc.
Solvent removal Online SFE-SFC
Washing
Prevention of sample oxidation,
Cigarettes Nicotine
Others
Soil Organic matter
operation at low temperature
 Ionic Liquid Solvents (ILs)
• An ionic liquid (IL) is a salt in the liquid state. In some contexts, the term has been restricted to salts whose melting poi nt
is below some arbitrary temperature, such as 100 °C.
• Ordinary liquids such as water and gasoline are predominantly made of electrically neutral molecules, ionic liquids are
largely made of ions.
• These substances are variously called liquid electrolytes, ionic melts, ionic fluids, fused salts, liquid salts, or ionic glasses
Ionic liquids present another alternative to organic solvents for use as media for
chemical synthesis. Inorganic salts consisting of ions, such as NaCl composed of
Na+ and Cl- ions, are normally hard, high-boiling solids. However, when one or
both of the ions are composed of large charged organic molecules behave like
ionic liquid

In ILs, substances can be dissolved and undergo reactions, and active research is underway to explore this possibility.
An interesting possibility that has been tried experimentally is to use a mixed ionic liquid/supercritical carbon dioxide single
fluid phase in which the reaction proceeds with a homogeneous catalyst followed by reduction of pressure that causes the
supercritical carbon dioxide and ionic liquid to separate into two phases with the catalyst remaining in the ionic liquid —
hence available for reuse — and the product in the supercritical carbon dioxide.
 Many applications have been considered, but only one is commercialized. ILs are used in the production of gasoline
by catalyzing alkylation.

https://www.chevron.com/ IL-catalyzed route to 2,4-dimethylpentane

(gasoline component) as practiced by Chevron.

chevron headquarters
6001 Bollinger Canyon Road
San Ramon, CA 94583, USA
 Deep eutectic solvent

Deep eutectic solvents or DESs are solutions of Lewis or Brønsted acids and bases which form a eutectic mixture.

Deep eutectic solvents are highly tunable through

varying the structure or relative ratio of parent
components and thus have a wide variety of potential
applications including catalytic, separation, and
electrochemical processes.
The parent components of deep eutectic solvents
engage in a complex hydrogen bonding network
which results in significant freezing point depression
as compared to the parent compounds

Example: a mixture of choline chloride and urea in a 1:2 mole ratio. Choline
chloride and urea are both solids at room temperature with melting points of 302°C
(decomposition point) and 133°C respectively, yet the combination of the two in a
1:2 molar ratio forms a liquid with a freezing point of 12°C. DESs share similar
properties to ionic liquids such as tunability and lack of flammability yet are distinct
in that ionic liquids are neat salts composed exclusively of discrete ions. In contrast
to ordinary solvents, such as Volatile Organic Compounds (VOC), DESs are non-
flammable, and possess low vapour pressures and toxicity. Choline chloride-urea mixtures at 303 K. (Mole fraction
urea from left to right: 0, 0.33, 0.5, 0.66, and 1
Hendry reaction followed by Michael addition
 ALTERNATIVE ENERGY SOURCES FOR A CHEMICAL PROCESS/REACTION

1. Microwave irradiation
2. Sonication
3. Photochemical source UV/visible light

1. Microwave irradiation
• Microwave induced chemical process is the science of applying microwave radiation to chemical reactions
• Microwaves act as high frequency electric fields and will generally heat any material containing mobile electric charges,
such as polar molecules in a solvent or conducting ions in a solid.
• Polar solvents are heated as their component molecules are forced to rotate with the field and lose energy in collisions.
• Semiconducting and conducting samples heat when ions or electrons within them form an electric current and energy is
lost due to the electrical resistance of the material.

Conventional heating: heating a large sample of ceramic bricks

microwave radiation is able to heat the target compounds without
heating the entire furnace or oil bath, which saves time and energy

Microwave heating can have certain benefits over

conventional ovens:
• reaction rate acceleration • higher chemical yield
• milder reaction conditions • lower energy usage
• different reaction selectivities
 Friedel-Crafts benzylation

Claisen rearrangement

The rates of these reactions were dramatically enhanced using microwave heating compared with conventional heating.
The Friedel-Crafts benzylation (top) sped up without an increase in bulk temperature, a surprising result proposed to
occur from selective heating of the ionic reactant. The catalytic Claisen rearrangement (bottom) proceeded more quickly
without any loss of enantioselectivity, a surprising result that defies accepted thermodynamics and remains unexplained.

https://cen.acs.org/articles/92/i4/Microwave-Chemistry-Remains-Hot-Fast.html
 MICROWAVE CHEMICAL AT A GLANCE
Headquarters: Osaka, Japan

Main business: Production of

fatty acid esters and sugar esters
via microwave heating;
technology licensing

Could industrial-scale microwaves transform chemical manufacturing?

Developed a new process to produce sugar-ester-based emulsifiers. The process employs

microwaves to selectively heat water in a solution primarily containing oil and sugar. It does
away with nonedible solvents that would otherwise have to be removed from the final
product at high expense,
2. Sonication

• The process in which sound waves are used for agitating the particles in the solutions.

It converts an electrical signal into a physical vibration to break substances apart.

• These disruptions can mix solutions
• accelerate the dissolution of a solid into a liquid, such as sugar into water
• remove dissolved gas from liquids.
• In DNA testing, sonication breaks apart molecules and ruptures cells, releasing proteins for testing.
Sonication typically uses ultrasound waves with frequencies of 20 kHz (20,000 cycles per second) or higher. These
frequencies are above what you can hear, but ear protection is still recommended during sonication because the process
creates a loud screeching noise. The greater the frequency, the stronger the agitation of particles.
Parts of Sonicator
• A generator
• A transducer
• A probe
1. The generator is used for transforming the input electrical power into an electrical signal that drives the
transducer.
2. The transducer is used for converting the electrical signal into vibration. This vibration is used in the probe tip by
amplifying it into a longitudinal vibration causing a cavity in the sample. (The transducer converts the electric signal
using piezoelectric crystals – crystals that respond directly to electricity by creating a mechanical vibration)
3. The ultrasound energy is the creation of cavitation which causes the disruption of the sample and makes it easy to
break down the particles into smaller ones.
 During sonication,
• cycles of pressure form thousands of microscopic vacuum bubbles in the solution.
• The bubbles collapse into the solution in a process known as cavitation.
• This causes powerful waves of vibration that release an enormous energy force in the cavitation field, which disrupts
molecular interactions such as interactions between molecules of water, separates clumps of particles, and facilitates
mixing.

The energy from sound waves creates friction in the solution, which creates heat. To stop a sample from heating up and
degrading, keep it on ice before, during and after sonication.
Direct Sonication Method Indirect Sonication Method

https://www.hielscher.com/information-about-
sonochemistry.htm
Description of mechanism of ultrasonic assisted synthesis
 4.I6 Green Chemistry
Catalysis
• A catalyst is a substance that increases the rate of a reaction without being consumed
• A heterogeneous catalyst is in a different phase from the reaction mixture
• A homogeneous catalyst is in the same phase as the reaction mixture

Energy

Eact uncatalysed

Eact catalysed

reactants

products
Why is Catalysis green?

Using catalysts should reduce: Materials

including
plant
• energy
Energy Waste

• the use of stoichiometric reagents

Cost

• by-products (particularly if the catalyst is highly selective) Impact on the Risk and
environment Hazards
• waste.
Toxicity

Recall the 12 principles of green chemical process:

1. It is better to prevent waste than to treat or clean up waste after it is formed.

6. Energy requirements should be minimized. Synthetic methods should be

conducted at ambient temperature and pressure.

9. Catalytic reagents are superior to stoichiometric ones.

4.I6 4 - 4
Potential disadvantages of catalysis

Many catalysts are based on heavy metals and may be toxic (e.g. the Cr(VI) oxidation
catalyst mentioned in lecture 2). Therefore the following factors should also be considered
when assessing a catalyst:

• separation of catalyst residues from product

• recycling of the catalyst
• degradation of the catalyst
• toxicity of the catalyst, of the catalyst residues and of catalyst degradation
products.

In general, it is greener to use catalysts than to not use them

4.I6 4 - 5
Case study: Boots synthesis of Ibuprofen

AcOH, HCl,
Al waste HCl

AcOH

NH3
Case study: Hoechst synthesis of Ibuprofen

All three steps

are catalytic

AcOH

Less waste 99 % conversion

generated 96 % selectivity

4.I6 4 - 7
Some definitions

Homogeneous catalysis
Reagents and catalyst are all in the same phase (typically all are in
solution).

Heterogeneous catalysis ('surface catalysis')

Reagents are in a different phase from the catalyst - usually the
reagents are gases (or liquids) and are passed over a solid catalyst (e.g.
catalytic convertors in car exhausts).

Biocatalysis
Using enzymes to catalyse a reaction

4.I6 4 - 8
Heterogeneous versus Homogeneous

General features:

Heterogeneous Homogeneous

Readily separated ✓ Difficult to separate 

Readily recycled / regenerated ✓ Difficult to recover 
Long-lived ✓ Short service life 
Cheap ✓ Expensive 
Lower rates (diffusion limited)  Very high rates ✓
Sensitive to poisons  Robust to poisons ✓
Lower selectivity  Highly selective ✓
High energy process  Mild conditions ✓
Poor mechanistic understanding  Mechanisms often known ✓

Ultimate goal: to combine the fast rates and high selectivities

of homogeneous catalysts with the ease of recovery /recycle of
heterogeneous catalysts

4.I6 4 - 9
 Heterogeneous Catalysis

Used in refining / bulk chemical syntheses much more than in fine chemicals and
pharmaceuticals (which tend to use homogeneous catalysis).
• Many transition metals can adsorb gas
molecules onto their surface
• This involves the formation of a weak
“bond” using metal d electrons
Seven stages of surface catalysis:
• The molecules can then react and the
1. Diffusion of the substrate(s) towards the surface. products desorb
2. Physisorption - i.e. physical absorption via weak
interactions, e.g. van der Waals, adhering the
• The metal provides an alternative
substrate(s) to the surface. path, with a lower activation energy
3. Chemisorption - formation of chemical bonds between • Example: catalytic converters
the surface and the substrate(s).
4. Migration of the bound substrate(s) to the active
catalytic site - also known as surface diffusion.
5. Reaction.
6. Desorption of product(s) from the surface.
7. Diffusion away from the surface.
4.I6 4 - 10
Heterogeneous Catalysts

Stage
Stage
Stage
Stage
Stage
Stage
4:3:
2:Surface
Chemisorption
6:
Physisorption
1:
5:
7:Desorption
Diffusion
Reaction
Diffusion
diffusion

A B C C

A C B C

Surface
Heterogeneous Catalysts

Active sites
are in pores

Surface
Heterogeneous Catalysts

Typical features:

Metal or metal oxide impregnated onto a support (typically silica and / or alumina).

Three dimensional highly porous structure with very high surface area

A B Reactants
Products C C
A C
1. Diffusion to surface
2. Physisorption
B C 3. Chemisorption
1-3
1-3
6,7

4,5
6. Desorption 4. Surface diffusion
7. Diffusion out of pore M
5. Reaction
porous support
4.I6 4 - 11
Heterogeneous acid-base catalysis

Around 130 industrial process use solid acid-base catalysts

• Mainly found in bulk/ petrochemicals production e.g. dehydration,

condensation, alkylation, esterification etc.

• Most are acid-catalysed processes.

Around 180 different catalysts employed

• 74 of these are zeolites, ZSM-5 is the largest group.

• Second largest group are oxides of Al , Si , Ti , Zr.

4.I6 4 - 12
Zeolites - crystalline, hydrated aluminosilicates

Crystalline inorganic polymer comprising SiO 4 and AlO4- tetrahedra (formally derived from
Si(OH)4 and Al(OH)4- with metal ions balancing the negative charge).

Lattice consists of interconnected cage-like structures featuring a mixture of pore

(channel) sizes depending upon the Al : Si ratio, the counter-cation employed, the
level of hydration, the synthetic conditions etc.

Hydrated nature of zeolites allows them

to behave as Brønsted acids

4.I6 4 - 13
e.g. ZSM-5

Td Channels cross in three dimensions

- a highly porous material

Top-view Side-view

● = Si / Al
5.5 Å
●=O
NB: Cations
not shown!

4.I6 4 - 14
Zeolites - Asahi Cyclohexanol process

Traditional synthesis

225 °C
10 atm

For selectivity reasons, the reaction is run at low conversions (approx 6% per tank) and
the hot cyclohexane stream is continuously recycled.

Zeolite catalysed process:

98 % selectivity

100 °C

4.I6 4 - 15
Why is the Asahi process important?

Flixborough disaster in England 1974 - 28 deaths

225 °C Tank 5 removed

10 atm 1 2 3 4 6
for repairs

Tanks 1, 2 and 3

Temporary pipework between tanks 4

and 6 ruptured and cyclohexane cloud
exploded

4.I6 4 - 16
Zeolites - shape selective alkylation of toluene

H-ZSM-5 catalyses: H-ZSM-5

• toluene alkylation (acidic ZSM-5)
• xylene isomerisation

Channel size only allows para-xylene to emerge

Only para-xylene is required for PET synthesis:

poly(ethylene terephthlate) - PET

4.I6 4 - 17
 Homogeneous catalysis - principles

Well-defined active site allows rational catalyst development.

• Most homogeneous catalysts
join in the reaction
• A reaction intermediate is
Typical single-site catalyst: formed
• The reaction intermediate
decomposes to give reaction
X products and regenerating the
catalyst
Ln M

sterically bulky ligand(s) e.g. Cp2ZrMe+ for the

controls stereochemistry polymerisation of ethene

substrate approaches
vacant coordination site
and may then react with X

4.I6 4 - 19
 Homogeneous asymmetric catalysis

Most of the industrially important homogeneous catalysed processes are

found in asymmetric syntheses - e.g. pharmaceuticals.

e.g. Monsanto synthesis of L-DOPA (Parkinson's disease):

L* =

28 % e.e. 60 % e.e. 85 % e.e. 95 % e.e.

0.1% catalyst loading; Rh readily recovered (some L* is lost)

4.I6 4 - 20
Points to remember

• explain how catalysis may be considered green

Catalysis may reduce materials, waste and energy

• identify the characteristics of heterogeneous and homogeneous catalysis

Heterogeneous are easily recycled and long-lived but ill-defined
Homogeneous are more active and selective but expensive and hard to recover

• describe three examples of green heterogeneous catalysis

Asahi Cyclohexanol process
H-ZSM-5 alkylation of toluene/ isomerisation of xylene
Sumitomo base-catalysed isomerisation of vinylnorbornene

•describe one example of green homogenous catalysis

Asymmetric hydrogenation - e.g. Monsanto L-DOPA synthesis
4.I6 4 - 21
Model question

The traditional synthesis of ethylbenzene is a Friedel-Crafts alkylation, such as that shown below:

The modern industrial synthesis involves mixing ethylene and benzene in the presence of a zeolite (ZSM-5). In
what ways would you consider this method to be greener than the Friedel-Crafts reaction?

Suggest a suitable starting material for the following drug molecule. Suggest a economical and green
synthesis process for the following drug molecule

4.I6 4 - 22
Among these two methods, which is economical process

Maleic anhydride may be prepared using two routes:

Oxidation of benzene:

Oxidation of but-1-ene:

The benzene oxidation route typically occurs in 65 % yield and produces 35 g

non-benign waste for every 100 g benzene used, while the but-1-ene route only
gives yields of 55 %, and produces 45 g waste per 100 g but-1-ene.

(a) Assuming that each reaction is performed in the gas phase only, and that no
additional chemicals are required, calculate (i) the atom economy and (ii) the
effective mass yield of both reactions. You should assume that O2, CO2 and
H2O are benign chemicals.

(b) Which route would you recommend to industry? Outline the factors which might
influence your decision.
Answer

Benzene Oxidation

RMM of reactants = 78 + (4.5 x 32) = 222

RMM of desired product = 98 ∴ Atom economy = 44 %

But-1-ene Oxidation

RMM of reactants = 56 + (3 x 32) = 152

∴ Atom economy = 64 %
RMM of desired product = 98
 Answer

There are several ways of tackling this question - this is one way…

Benzene Oxidation
100 g benzene (1.28 mol) would give 81.5 g maleic anhydride (0.83 mol, 65 %).
mass of maleic anhydride
effective mass yield EMY = x 100 %
mass of non-benign reagents
= [81.5 / 100] x 100 %

= 81.5 %
But-1-ene Oxidation
100 g but-1-ene (1.79 mol) would give 96.3 g maleic anhydride (0.98 mol, 55 %).
mass of maleic anhydride
EMY = x 100 %
mass of non-benign reagents

= [96.3/ 100] x 100 %

= 96.3 %
Answer (b), recommendation to industry

The butene oxidation route would appear to be slightly greener (higher atom
economy and a higher effective mass yield). It also avoids the use of the toxic reagent
benzene (we would therefore expect its wastestream to be less hazardous). However,
the percentage yield is higher for the benzene oxidation route.

However, without a full life cycle analysis (which would take into account the
environmental impact of producing both benzene and butene) a definitive answer is
clearly not possible.

Recommendation: Butene route is possibly better -

but only if raw material costs are acceptable.
Answer (b), recommendaton to industry

The butene oxidation route would appear to be slightly greener (higher atom
economy and a higher effective mass yield). It also avoids the use of the toxic reagent
benzene (we would therefore expect its wastestream to be less hazardous). However,
the percentage yield is higher for the benzene oxidation route.

However, without a full life cycle analysis (which would take into account the
environmental impact of producing both benzene and butene) a definitive answer is
clearly not possible.

Recommendation: Butene route is possibly better -

but only if raw material costs are acceptable.
Physisorption is caused by the intermolecular force that exists between adsorbates
and adsorbents
Chemisorption, is a process resulting from a chemical bond between adsorbate
molecules and specific surface locations on a material, known as active sites.

Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or

dissolved solid to a surface.

Absorption is a chemical or physical phenomenon in which the molecules,

atoms and ions of the substance getting absorbed enters into the bulk phase
(gas, liquid or solid) of the material in which it is taken up. Absorption is the
condition in which something gets mixed or absorbed completely in another
substance.

Polarity Index. Burdick & Jackson solvents are arranged in order of

increasing polarity index, a relative measure of the degree of interaction of
the solvent with various polar test solutes.

Solubility: Based on the concentration of solute dissolves in a solvent,

solutes are categorized into highly Soluble, sparingly Soluble or insoluble.

127
 Thin Layer Chromatography

❖ technique used to separate the components of a mixture using a thin stationary phase supported by an inert backing.
❖ monitoring the progress of a reaction, or on the preparative scale to purify small amounts of a compound.
❖ Tool is simple, relative low cost, high sensitivity, and speed of separation.
❖ a compound will have different affinities for the mobile and stationary phases, and this affects the speed at which it
migrates. The goal of TLC is to obtain well defined, well separated spots.
Retention Factor
After a separation is complete, individual compounds appear as spots separated vertically. Each spot has a retention
factor (Rf) which is equal to the distance migrated over the total distance covered by the solvent. The Rf formula is
Rf=distance traveled by sample/distance traveled by solvent

Relative retention value

If it is desired to express positions relative to the position of another substance, x, the Rx (relative retention
value) can be calculated:
Rx=distance of compound from origin/distance of compound x from origin

While Rf can never be greater than 1

Thin Layer Chromatography- Model question Given:

#1=1.4 cm

#2= 1.5 cm

#3= 3.1 cm

#4= 3.6 cm

Using only the given information and the above

figure, answer the problems listed below.

1. What is the Rf value for component #2?

2. What is the Rf value for component # 3?
3. What is the relative retention value for
components #1 and # 4, with # 4 being
compound x?
4. Using the answers from questions 1 and 2
and assuming that components 2 and 3 are
different compounds, which component
would be considered more polar? Explain.
 Column Chromatography

• It separates substances based on differential adsorption of

compounds to the adsorbent as the compounds move through
the column at different rates which allow them to get separated
in fractions.
• This technique can be used on a small scale as well as large scale
to purify materials that can be used in future experiments. This
method is a type of adsorption chromatography technique.
 Elution: extracting an adsorbed substance from a solid adsorbing media using a solvent.
Eluent: is the solvent or mobile phase that passes through the column. When the polarity of the eluent matches
the polarity of the molecules in the sample, the molecules desorb from the adsorbent and dissolve in the eluent.

Mobile phase – This phase is made up of solvents and it performs elution

Stationary phase – It is a solid material which should have good adsorption property

Column Chromatography Applications

• Column Chromatography is used to isolate active ingredients.
• It is very helpful in separating compound mixtures.
• It is used to determine drug estimation from drug formulations.
• It is used to remove impurities.
• Used to isolate metabolites from biological fluids.

Types of Column Chromatography:

1. Adsorption column chromatography –components of the mixture are adsorbed on the surface of the adsorbent.
2. Partition column chromatography – The stationary phase, as well as mobile phase, are liquid in partition chromatography.
3. Gel column chromatography –separation takes place through a column packed with gel. The stationary phase is a solvent
4. Ion exchange column chromatography –stationary phase is always ion exchange resin.
 Gas Chromatography

• It is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that
can be vaporized without decomposition
• sample is dissolved in a solvent and vaporized in order to separate the analytes by distributing the sample between
two phases: a stationary phase and a mobile phase.
• The mobile phase is a chemically inert gas that serves to carry the molecules of the analyte through the heated
column.
• Gas chromatography is one of the sole forms of chromatography that does not utilize the mobile phase for
interacting with the analyte.
• The stationary phase is either a solid adsorbant, termed gas-solid chromatography (GSC), or a liquid on an inert
support, termed gas-liquid chromatography (GLC).

Scientists use GC for both qualitative and quantitative analysis of volatile analytes.
The instrument, called a gas chromatograph, employs a mobile phase and a stationary phase. That is, a moving
gas carries the sample across a stationary support (a piece of glass or metal tubing called a column) inside the
instrument.
 Time t

Carrier gas flow

Separation tr2-tr1

Peak width Wb1,2

Compounds are separated by their different affinities to the column during the
stationary phase. Compounds with less affinity will elute from the column sooner;
compounds with greater affinity will elute later.
 Instrumental components
Carrier gas
The carrier gas must be chemically inert. Commonly used gases include nitrogen, helium, argon, and carbon dioxide. The choice
of carrier gas is often dependant upon the type of detector which is used. The carrier gas system also contains a molecular sieve
to remove water and other impurities.
Sample injection port
For optimum column efficiency, the sample should not be too large, and should be introduced onto the column as a "plug" of
vapour - slow injection of large samples causes band broadening and loss of resolution.
Columns

There are two general types of column, packed and capillary (also known as open tubular). Packed columns contain a
finely divided, inert, solid support material (commonly based on diatomaceous earth) coated with liquid stationary phase.
Most packed columns are 1.5 - 10m in length and have an internal diameter of 2 - 4mm.
Capillary columns have an internal diameter of a few tenths of a millimeter. They can be one of two types; wall -coated
open tubular (WCOT) or support-coated open tubular (SCOT).
Wall-coated columns consist of a capillary tube whose walls are coated with liquid stationary phase. In support-coated
columns, the inner wall of the capillary is lined with a thin layer of support material such as diatomaceous earth, onto
which the stationary phase has been adsorbed. SCOT columns are generally less efficient than WCOT columns. Both types
of capillary column are more efficient than packed columns.

https://www.chem.ucla.edu/~bacher/General/30BL/gc/theory.html
What Happens Inside the Column?
Gas chromatography uses a gaseous mobile
phase to transport the sample through the
column, which can be packed or coated on
its inside surface. In most cases, GC columns
have smaller internal diameters and are
longer than HPLC columns.
GC columns
As the GC column is heated, the compounds
begin to separate based on boiling point.
Changing the column to polar stationary
phase will change the separation
capabilities. Compounds will separate by
both boiling point and polarity
characteristics.
HPLC columns
Introduction
What Happens Inside the Column?
tr2-tr1 tr2-tr1

Superior separation vs Inferior separation

Wb1 Wb2 Wb1 Wb2

Superior separation vs Inferior separation

 High-performance liquid chromatography

It is used to separate, identify, and quantify each component in a mixture.

It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid
adsorbent material. Each component in the sample interacts slightly differently with the adsorbent material, causing
different flow rates for the different components and leading to the separation of the components as they flow out of
the column.
Injection of the sample: Automated
Retention time: The time taken for a particular compound to
travel through the column to the detector. Different
compounds have different retention times. For a particular
compound, the retention time will vary depending on:
• the pressure used (because that affects the flow rate of the
solvent)
• the nature of the stationary phase (not only what material
it is made of, but also particle size)
• the exact composition of the solvent
• the temperature of the column

The detector: UV
 Contact: snagarajan@nitw.ac.in
https://www.nitw.ac.in/faculty/id/16902/
https://orcid.org/0000-0003-2233-4872
https://scholar.google.co.in/citations?user=bjsFwPEAAAAJ&hl=en

138