GREEN
CHEMISTRY
GREEN CHEMISTRY
CHI-501
By
Prof. Vandana Srivastava
Department of Chemistry
Indian Institute of Technology (BHU)
Varanasi, India
List Of Books
• Green Chemistry: Frontiers in Benign Chemical
Syntheses and Processes, Paul T. Anastas, Tracy C.
Williamson, Oxford University Press, 1998.
• New Trends in Green Chemistry, V. K. Ahluwalia
and M. Kidwai New Delhi, India, 2004.
• Green Chemistry: Environmentally Benign
Reactions, Editor: V. K. Ahluwalia, University of
Delhi, India .
Outline
Introduction :12 Principles of Green Chemistry with examples
Synthesis in benign solvents
(a) Water
(b) ScCO2 (c) Ionic liquids (d) PEG
Synthesis in solid state
Alternate Energy sources:
(a) MW
(b) US (c) Photo induced reactions
Synthesis using Green reagents
(a) Dimethylcarbonate (b) Polymer supported reagents (c) Polymeric
NBS
Synthesis using green catalyst: Types, Advantages and applications
(a) PTC (Phase transfer catalyst), (b) Crown ethers, (c) Green
Catalysts
(d) Polymer catalyst (e) Biocatalyst
Green synthesis of industrially important compounds
(a) Adipic acid, (b)Paracetamol, (c)Caprolatum, (d) Ibuprofen
(e)Methyl methacrylate,
Green transformations mechanism
Thalidomide
•
•
•
Definition
Green chemistry is defined as environmentally benign chemical
synthesis.
The synthetic schemes are designed in such a way that there is least
pollution to the environment.
Green chemistry is a fundamental approach to designing chemical
products in very environmentally friendly way without using toxic
chemicals and solvents.
Objectives:
• To minimize/eliminate the formation of hazardous substances. By
using this approach scientists have been able to reduce the harmful
impact of chemicals on environments
•
To create pollution free environment for the benefits of the
mankind
GREEN CHEMISTRY
Pioneers of Green Chemistry
Prof Paul Anastas and Prof John Warner gave twelve principles to
understand the concept of green chemistry.
Prof. John Warner
Prof. Paul Anastas
Director
Yale University
Center for Green Chemistry
President
Warner-Babcock Institute for
Green Chemistry
Nobel Prize Winners in 2005 and 2010 on Green Synthesis
The 2005 Nobel Prize in
Chemistry was awarded to
Yves Chauvin, Robert H.
Grubbs, and Richard R.
Schrock " Development of the
environmentally
benign
products metathesis method
using Ru based catalyst in
organic synthesis
Palladium-catalyzed cross-couplings in
organic synthesis
Richard F. Heck, Ei-ichi Negishi, and Akira
Suzuki were jointly awarded the 2010
Nobel Prize in Chemistry “for palladiumcatalyzed cross-couplings in organic
synthesis.” They have been employed to
make materials, pharmaceuticals, and
other biologically active compounds.
Green Chemistry Universities/Centers
• Green Chemistry Centre of Excellence, York
University, USA
• Centre for Green Chemistry, Australia
• McGill University, Canada
• Interuniversity Consortium — Chemistry for the
Environment (Italy
• Green and Sustainable Chemistry Network, Japan
• University of Nottingham, Green Chemistry
Network, UK
Awards
•
•
•
•
Green Chemistry Challenge Award: Genomatica company Green
Synthesis Butylene Glycol fermentation of Sugar by Ecoli of Bacteria in
one step.. Conventional synthesis, Acetaldehyde in multi steps using toxic
metal catalyst.
Royal Society Chemistry (RSC) Green Chemistry Award:
Presidential Green Chemistry Challenge: Pfizer, For Improvement in
manufacturing process of sertraline and Sildenafil Citrate
Nobel Prize Award: 2005 Richard Schrock, Yves Chauvin and Robert
Grubbs, for developing an environmentally friendly process (Metathesis)
using green catalyst for variety of products i.e. plastics to biofuels
8
Basic Principles of Green Chemistry
1. Prevention of waste/by-products.
2. Maximum incorporation of the reactants (starting materials and
reagents) into the final product.
3. Prevention or minimization formation of hazardous products.
4. Designing of safer chemicals.
5. Energy requirement for any synthesis should be minimum.
6. Selecting the most appropriate solvent.
7. Selecting the appropriate starting materials.
8. Use of the protecting group should be avoided whenever possible.
9. Use of catalysts should be preferred wherever possible.
10. Products obtained should be biodegradable.
11. The manufacturing plants should be so designed as to eliminate the
possibility of accidents during operations.
12. Strengthening of analytical techniques
1. Prevention of Waste/By-Products
We should design a synthesis in which minimum waste product should
be formed.
Disadvantages…
1.
Waste product causes Pollution of environment
2.
It involves expenditure for cleaning of the waste products
Therefore prevention is always better than cure.
2. Maximum Incorporation of the Reactants (Starting Materials
and Reagents) into the Final Product: Atom Economy
Synthetic process should be designed in such a way that output should be
maximum, i.e. maximum incorporation of reactants
Example:
A
+
B
desired

C
+
D
by-product
MW ( C )
% Atom economy (A.E.)= ----------------------------- x 100
MW ( A + B )
In calculation of Atom economy molecular weight of by-product is not considered
MW of desired product
% Atom economy = ----------------------------------- x 100
MW of reactants
Example 1
Consider the substitution reaction of ethyl propionate with methyl amine. In this
reaction, the leaving group (OC2H5) is not utilized in the formed amide. Also, one
hydrogen atom of the amine is not utilized.
Example 2
MW=102
MW=31
MW=87
MW=46
Therefore, the % atom economy =
This is a 100% atom economical reaction, since all the reactants are incorporated into the product.
Mw= 28
Mw= 54
Mw= 82
Example 3: Synthesis of Maleic anhydride
Benzene C6H6 + 4.5 O 2 
Maleic anhydride C4O3H2 + 2 CO 2 +2H2O
Mw= 78
Mw= 144
Mw= 98
Atom Efficiency = 98 / (78+144)* 100 = 44.1%
Butene C4H8 +
3O2 
Maleic anhydride C4O3H2
Mw = 56
Mw= 96
Mw= 98
Atom Efficiency = 98 / (56+96) *100 = 64.5%
Butane C4H10 + 2.5 O 2 
Maleic anhydride C4O3H2
Mw= 58
Mw= 80
Mw= 98
Atom Efficiency = 98 / (58+80) *100 = 71%
By calculating atom efficiency, better method of synthesis can be selected
Example 4
C6H5NH2 + C6H5COCl
MW = 93
 C6H5NH(CO) C6H5 + HCl
MW = 140
MW = 197
Benzanilidine
C6H5NH2 = C6H7N = (6*12)+1*7+ 14 = 93
C6H5COCl = C7H5OCl = (7*12) + 1*5 + 16+ 35.5 = 140.5
C6H5NH(CO) C6H5 = C13H11NO = 197
% Atom Economy = 197 / (140.5 + 93 ) * 100 = 84.26%
3. Prevention or Minimization of Hazardous Products
Polyurethane can be synthesised replacing toxic hazardous phosgene by Carbon dioxide.
Reactions involving use of safer reactants than the hazardous ones
RNH2 + COCl2  RNCO + HCl  RNHCOOR (polyurethane)
phosgene (toxic)
RNH2+ CO2  RNCO + H2O  RNHCOOR
non-toxic
Non-hazardous chemical synthesis of Indigo-Dye
ROH in presence of enzyme as Aniline is a
Replacing aniline by non hazardous amino acid tryptophan
hazardous chemical. Indigo blue dye can be synthesised by replacing aniline by Typtophan (amino
acid).
ROH
Aniline / Tryptophan
Indigo Dye
Tryptophanase
4. Designing Safer Chemicals
Example of an unsafe drug is thalidomide (introduced in 1961) for
lessening the effects of nausea and vomiting during pregnancy
(morning sickness). The children born to women taking the drug
suffered birth defects (including missing or deformed limbs).
Subsequently, the use of thalidomide was banned. It was replaced
by a safer drug perinorm.
thalidomide (unsafe)
perinorm (safer)
5. Energy Requirements for Synthesis
•
In any chemical synthesis, the energy requirements should be kept to a
minimum.
•
Use of a catalyst has the great advantage of lowering the energy
requirement of a reaction.
•
By replacing conventional means energy to a reaction can be supplied
by UV light, microwave (MW) or sonication.
•
These processes involve less energy and time.
6. Selection of Appropriate Solvent
•
Many solvents are volatile, that may damage human health and the
environment. If possible, the reaction should be carried out in aqueous
phase or without the use any of solvent.
•
Replacement of CCl4, CHCl3 by water and other safer solvents like:
PEG (polyethylene glycol) and Inorganic Liquids (ILs)
7. Selection of Starting Materials
•Petrochemicals are mostly obtained from petroleum, which is a non-renewable source
in the sense that its formation take millions of years from vegetable and animal
remains.
•Petroleum reactants must be replaced by natural compounds
•Substances like carbon dioxide and methane gas (obtained from natural sources such
as marsh gas) are available in abundance. These are considered as renewable starting
materials.
•Synthesis of Succinic acid
7 Glucose + 6 CO2  12
(C6H12O6)
Succininc Acid
renewable starting
material
•Synthesis of Adipic acid
Replace Benzene (carcinogenic) by Glucose
Benzene
Glucose
oxidation
E.coli
Adipic Acid
Adipic Acid
8. Use of Protecting Groups
•
Protecting the functional group in organic reactions should be avoided.
•
In case an organic molecule contains two reactive groups and you want
to use only one of these groups, the other group has to be protected, the
desired reaction completed and the protecting group removed.
•
Since protecting groups are not incorporated into the final product,
their use is less atom-economical. Hence the use of protecting groups
must be avoided whenever possible.
Example
Penicilin gives 6APA in three steps using protecting and de-protecting
groups. Therefore the atom economy is considerably reduced.
However 6APA can be obtained in presence of Penacylase in Room
temperature without using any protecting group.
9. Use of Catalyst
•
It is well known that use of a catalyst facilitates transformation without the catalyst being consumed
in the reaction and without being incorporated in the final product.
•
•
•
Therefore, use of catalyst should be preferred whenever possible. Advantages:
Better yields.
Shorter reaction time
No reaction occurs without the PTC catalyst
without the catalyst the yield is 30%
10. Products Designed Should be Biodegradable
•
It is possible to have a molecule (e.g. insecticide) which may possess
functional groups that facilitate its biodegradation. The functional groups
should be susceptible to hydrolysis, photolysis or other cleavage.
(non-biodegradable)
dibenzoylhydrazines
(biodegradable)
Fenozides
Bz – NH – N- Bz
Design and synthesis of safe product
DDT can be replaced by safe pesticides which are mostly derived from neem plants
24
11. Designing of Manufacturing Plants
.
• The hazards posed by toxicity, explosions,
fire etc. must be looked into.
• The manufacturing plants should be so
designed to eliminate the possibility of
accidents during operation.
12. Strengthening of Analytical Techniques
To monitor and control generation of hazardous by products during
chemical reaction by placement of accurate sensors.
•
Analytical techniques should be so designed that they require minimum
usage of chemicals, like:
Recycling of some unreacted reagent (chemical) for the completion of a
particular reaction.
GREEN SOLVENTS
WATER
POLYETHYLENE GLYCOL
SUPERCRITICAL CO2
IONIC LIQUIDS
WATER
• H 2O can also be used as a solvent
• Properties
–Abundantly available
–Cheap
–Non-volatile
–Readily recycled
–Non Toxic
Aqueous Phase Reactions
Diels-Alder Reaction
Pinacol Coupling
• KnoevenageI Reaction
Benzoin Condensation
• Claisen-Schmidt Condensation
POLYETHYLENE GLYCOL
•
•
•
•
•
•
Low toxicity, low volatility
Biodegradable
Stable in acid/ base
Not effected by O2 and H2O
Can be recycled
Used in oxidation reactions
• Diels-Alder Reaction
PEG
• Williamson’s Ether Synthesis
PEG
Glucan Enzyme
cellulose
PEG
glucose
What is Supercritical CO2
When CO2 is compressed at 73 bar pressure and 310 C
temperature it is converted to supercritical state.
It exists both as gaseous and liquid state.
Properties
•
•
•
•
•
Non-toxic environmentally benign solvent
It is used for dry cleaning of clothes and dying
Used in extraction of caffeine
Solvent for many organic reactions
Very good solvent for organic, inorganic and
polymeric reactions
Reactions
• Diels-Alder Reaction
Sc CO2
+
CO2Me
CO2Me
Carboxilation
Sc CO2
• Fridel crafts reaction
Sc CO2
Versatile Ionic Liquids
What are ionic liquids
• They are low melting point salts. M.Pt. < 100 0C.
Properties
• No vapour pressure
• Reduced toxicity
• They dissolve wide range of organic compounds
• They are designer solvents, means they can be designed for
particular application. Their properties can be changed by
changing anionic or cationic part.
[I.L.] BF4 ------------------- hydrophilic
[I.L.] PF6 ------------------ hydrophobic
• They can be recycled.
Synthesis of Ionic liquids
• Acetylation
, [emin]Cl-ALCl3
5 min, 0°C,
I.L.
• Diels-Alder Reaction
I.L.
Hydrogenations
Ru catalyst/ H2
I.L.
• Heck Reaction
Synthesis of Pharmaceutical compound
Pravadoline
Ist-Alkylation of 2-methylindole
2nd-Friedel Craft alkylation
Advantages of reactions
in Solid State
Organic Synthesis in Solid
State
• Simply by grinding
• Without solvent
• On solid support (Al2O3 / silica)
Beckmann Rearrangement
Usually, Beckmann rearrangement of oximes of ketones are
converted into anilides by heating with acidic reagents like PC15,
HCOOH, SOCl2 etc. However, solid-state Beckmann
rearrangement has been reported. In this method oxime of a
ketone is mixed with montmorillonite and irradiated for 7 min
in a microwave oven to give corresponding anilide in 91% yield.
However, conventional heating gives only 17% yield.
Benzil-Benzilic Acid Rearrangement
Normally Benzil-Benzilic Acid rearrangement
has been carried out by heating benzil and
alkali metal hydroxides in aqueous organic
solvent. It is found that the rearrangement
proceeds more efficiently and faster in the solid
state. The reaction takes 0.1 to 6 hr and the
yields are 70-93%.
Reformatsky Reaction
Treatment of aromatic aldehydes with ethyl
bromoacetate and Zn-NH4C1 in the solid
state give the corresponding Reformatsky
reaction products.
Wittig Reaction
The well known Wittig reaction has been reported to
occur in solid phase. In this procedure a 1:1 mixture of
the
finely
powdered
inclusion
compound
of
cyclohexanone or 4-methyl cyclohexanone and (-)-b
(derived from tartaric acid and a catalytic amount of
benzyltrimethyl ammonium hydroxide) was heated at 70
°C
with
Wittig
reagent
carbethoxymethylene
triphenylphosphorane to give optically active 1(carbethoxymethylene) cyclohexane or the corresponding
4-methyl compound.
Aromatic Substitution Reactions
Nuclear
bromination
of
phenols
with
Nbromosuccinimide (NBS) in the solid state.
The reaction of 3,5-dimetylphenol with 3 mol equivs
of NBS in the solid state for 1 min gave the tribromo
derivative in 45% yield. However, if the reaction is
conducted in solution a mixture of mono and
dibromo derivatives are obtained
Nitration
The nitration of aromatic compounds with stoichiometric
quantity of nitric acid and acetic anhydride (in absence of
solvent) at 0-20°C in presence of zeolite catalyst gave the
nitration product as given.
Solid Supported Synthesis
The solid supported synthesis of azoles and diazines
by using K2C03 as a solid support has been reported.
This novel technique involves aqueous work up
Synthesis of substituted pyrrole over silica gel
under microwave irradiation has been reported
Synthesis of Furans
Naturally occurring, pharmacologically important
2-aroyl-benzofurans are easily obtainable in the
solid state from a-tosyloxyketones and
salicylaldehydes in the presence of a base such
as KF doped alumina using microwave
irradiation
Microwave Induced Green
Synthesis
Advantages
•
•
•
•
•
•
•
•
High yield
High purity of compound
Shorter reaction time
Moderate reaction conditions
Selectivity
Cost effectiveness
Eco-competibility
Conventional heating is slow through
conduction, while Microwave heating is
direct
Applications
Microwave Assisted Reactions in
Water
Hydrolysis of Benzyl Chloride
Conventional 1 hr
Oxidation of Toluene
Conventional 10-12 hr
Hofmann elimination
conventional 30 mins
Microwave Assisted Reactions in
Organic Solvents
Esterification: Reaction of Carboxylic Acid and
Alcohol
Synthesis of Chalcones
Microwaves have been used for the synthesis of
Chalcones and related enones. Considerable rate
enhancement is observed, bringing down the reaction
time from hours to minutes in improved yield
Diels Alder Reaction
under microwave conditions diglyme is used as a solvent
it gave 80% yield of the adduct is obtained in 90 sec
Microwave Solvent Free Reactions (Solid State
Reactions)
 Deacetylation
Ultrasound Assisted Green
Synthesis
Advantages
• Excellent yields
• High purity of compound
• Shorter reaction time
• Moderate reaction conditions
• Esterification
• Saponification
94%
Conventional yield 15%, 90 mins
• Hydrolysis
• Substitution Reactions
• Cannizaro Reaction
Coupling Reactions
PHOTO INDUCED ORGANIC SYNTHESIS
A. Some time it is possible to carry out a reaction
1). by direct mixing of the reactants in the solid state.
2). by slightly warming.
3). Besides direct heating this energy can be supplied by
MW, US (Sonication), photo chemically.
B. The energy for a chemical reaction can be supplied
photo chemically.
This involves absorption of electromagnetic radiation in
the visible or ultraviolet region
B. The energy for a chemical reaction can be supplied photo chemically.
1) This involves absorption of electromagnetic radiation in the visible
or ultraviolet region
2) Under these conditions, a molecule absorb a quantum of light, the
energy of which depends on the frequency of the radiation.
3) In a photochemical reactions the absorption of light raises an
indivisible molecule to an excited electronic state.
Advantages of Photochemical Reactions
 Used in highly strained thermodynamically unstable compounds.
 Highly stereospecific.
 The product obtained by thermal and photochemical process
normally differ in stereochemistry.
1) Photolysis of Benzophenone
Photolysis of benzophenone (in sunlight) in the
presence of an alcoholic solvent gives
benzopinacol in quantitative yield. This reaction
is
also
known
as
photo
reduction
dimerization
O
Sun light
C6H5
C
Benzophenone
C6H5
Isopropyl alcohal
CH3CH3CHOH
C6H5
C6H5
C6H5
C
C
OH
OH
Benzopinacol
C6H5
2) Isomerization
3)Photoisomerization of cis and transstilbene
4)Photochemical cycloaddition
reaction
5)Paterno-Buchi Reaction
Photochemical cycloaddition reaction is the addition of
carbonyl compounds to olefins to yield oxetanes (oxacyclobutanes).
6)Free radical chlorination
Photochlorination of toluene to
benzyl chloride, benzylidene
dichloride and benzotrichloride.
Synthesis of Adipic Acid
Conventional Synthesis of Adipic Acid
Green Synthesis of Adipic Acid
An environmentally benign (or green) synthesis of adipic acid
starting with glucose and using a biocatalyst (genetically altered E.
coli bacteria)
Synthesis of Ibuprofen
Conventional Synthesis of Ibuprofen
Synthesis of Ibuprofen
Green Synthesis of Ibuprofen
• Synthesis of Catechol
Conventional synthesis of Catechol
Green Synthesis of Catechol
An environmentally benign (or green) synthesis of
catechol has been developed, starting with glucose and
using a biocatalyst (genetically altered E. coli bacteria)
Green Synthesis of 3-phenyl Catechol
The 3-substituted catechols are important
building
blocks
for
the
chemical
and
pharmaceutical
industries.
Their
chemical
synthesis
is
cumbersome,
requiring
organometallic reagents, HBr etc.
An industrial green synthesis of 3-phenyl
catechol consist in the transformation of 2-phenyl
phenol
into
3-phenylcatechol
by
a
2hydroxybiphenyl 3-monooxygenase.
Conversion of Penicillin into 6-APA by
the enzyme ‘Penacylase’