Green Chemistry & Green

Synthesis

by

Dr. (Mrs). B. Rama Devi

Introduction
Green Chemistry:
• The term green chemistry was coined by Anastas
• It is also called sustainable chemistry
• Cradle to grave approach changes to cradle to cradle
(sustainable) technology
• It is the need of the hour to shift to
• Sustainable development
• Environmentally compatible technology for conservation
• Adopt process to reduce use & production of hazardous
chemical
• development of environmental management system
• Green chemistry program supports invention of more
environmental process to reduce hazardous waste generation
GREEN
GREEN CHEMISTRY
CHEMISTRY

PREVENTING POLLUTION
SUSTAINING THE EARTH

3
Natural processes Chemical processes
(Lab)
Sun light (energy Source) Thermal / Electrical heating

Enzyme Catalyzed Catalysts are used

Highly specific Not specific

pH-7 pH- variable

Room Temperature Temperature Variable

Water is Used As Solvent Organic solvents are used

Exclusive and pure products are Mixture are obtained

formed

Environmentally Friendly producing Wastes formed Pollute the

no pollution environment

4
Forthcoming situation

5
Green Chemistry is About...
Waste

Materials

Hazard

Risk
Energy

Environmental Impact

COST
Some Aspects of Green Chemistry

Safer Reactions Catalysis

& Reagents Solvent

Replacement
Separation
Green Use of
Processes
Chemistry Renewable

Energy Feedstocks

Efficiency Waste
Process Minimisation
Intensification
Principles of
Green Chemistry
Anastas embodied the concept of Green Chemistry into 12 principles.

1. Waste prevention instead of remediation

2. Atom efficiency
3. Less hazardous/toxic chemicals
4. Safer products by design
5. Innocuous solvents and auxiliaries
6. Energy efficient by design
7. Preferably renewable raw materials
8. Shorter syntheses (avoid derivatization)
9. Catalytic rather than stoichiometric reagents
10. Design products for degradation
11. Analytical methodologies for pollution prevention
12. Inherently safer processes
• Green chemistry is about the utilization of set of principles that reduces &
eliminates the use & generation of hazardous substance in design,
manufacturing & application of chemical product
• E factor: The E factor is the actual amount of waste produced in the process,
defined as everything but the desired product. It takes the chemical yield into
account and includes reagents, solvents losses, all process aids and, in
principle, even fuel (although this is often difficult to quantify). There is one
exception: water is generally not included in the E factor. For example, when
considering an aqueous waste stream only the inorganic salts and organic
compounds contained in the water are counted; the water is excluded.
Otherwise, this would lead to exceptionally high E factors which are not useful
for comparing processes.
• A higher E factor means more waste and, consequently, greater negative
environmental impact.
• The ideal E factor is zero.
Kilograms (of raw materials) - kilograms of desired product
E factor = kilograms of product out
Atom Efficiency
 The atom utilization, atom efficiency or atom economy concept, first introduced by Trost.
 Is an extremely useful tool for rapid evaluation of the amounts of waste that will be generated by
alternative processes.
 Widely used to measure green ness of a process
 Should be as high possible improved by selecting suitable starting materials & catalyst
 It is the conversion efficiency of a chemical process in terms of all atoms in to desired products
 It is calculated by dividing the molecular weight of the product by the sum total of the molecular
weights of all substances formed in the stoichiometric equation for the reaction involved.
 For example, the atom efficiencies of stoichiometric (CrO3) vs. catalytic (O) oxidation of a
secondary alcohol to the corresponding ketone are compared below.
What is Atom Economy?

A+B P + U
Reactant Product Unwanted Material

Mass of Product
% Atom economy = 100  ----------------------
Mass of Reactants

11
Example

+ 4.5 O2 O + 2 CO2 + 2H2O

78 144
98 O

98
% Atom economy = 100  -------------- = 44.1%
78 +144

12
Atom Uneconomic Reactions
Example:-
• Substitution
• Elimination
• Wittig
• Grignard

13
Substitution Reaction (Atom Un-economic)

(CH2)4 OH (CH2)4
Cl
H3C C + SOCl2 H3C C + SO2 + HCl
H2 H2
64 36.5
102 119 120.5

120.5
% Atom economy = 100  --------- = 54.5%
102+119
SO2 and HCl are unwanted by products reducing the overall
atom economy.

14
Substitution Reaction
(Atom Un-economic)
(CH2)4 OH (CH2)4
Cl + SO
H3C C + SOCl2 H3C C 2 + HCl
H2 H2
119 120.5 64 36.5
102

120.5
% Atom economy = 100  ----------- = 54.5%
102+119
SO2 and HCl are unwanted by products reducing the overall atom
economy.

15
Elimination Reactions

122
H H2
H3C C C CH3 t-BuOK KBr t-BuOK
H3C C C CH3
Br H H
-HBr
136 56

56
% Atom economy = 100  ----------- = 45.9%
122

16
Atom Economic Reactions
Example:-
• Rearrangement
• Addition
• Diels-Alder
• Other Concerted
reactions.
( Pericyclic)
17
Rearrangements
Ex. Claisen Rearrangement
O O OH
H
200OC

Phenyl allyl ether Product

( Reactant ) 134 134

134
% Atom economy = 100  ------ = 100 %
134
18
Addition Reactions

R H R Br
+ HBr CH3
R H R

% Atom Economy =
100%

19
Diels Alder Reactions

+ h

Atom Economy = 100%

20
TYPES OF GREEN CHEMICAL REACTIONS
 Solvent free/ Solid phase reacctions
 Ionic liquids
 Microwave assisted synthesis
 Sono Chemistry
Solvents and Green
Chemistry…

22
Why Are Reactions Performed Using
Solvents?
 Used for dissolving substances

 Increase rate of reaction- heat transfer agent

 Evaporated for their recovery

 Coating 1. Paints, adhesives

2. coating removal
 Cleaning- dry cleaning- poly chloro ethylene ( a carcinogenic also contaminates ground water
supplies)
 Extraction- Coffee ( De caffination- benzene, CH2Cl2 selection of solvents should be based on hazard
that the chemical may process, but also on existing environmental problems that its use may enhance

Risk= hazard x exposure

 Green solvents:
 H2O, CH3OH, CH3NO2, CH3-CO-CH3, Et-OH, DMF, DMSO,
HMPA, CAN, Py, NH3
Issues with Organic Solvents
 Organic solvents are of concern to the chemical industry

because of the sheer volume used in synthesis, processing,

and separation.

 Organic solvents are expensive

 Organic solvents are highly regulated.

 Many organic solvents are volatile, flammable, toxic, and

carcinogenic.

25
Solvent alternatives

Use of solvent less reactions

Use of “non-organic” solvents

Processing technology

26
Advantages to Solvent less
Organic Reactions

 There is no reaction medium to collect, purify, and recycle.

 Reaction times can be dramatically shortened.

 Lowered energy usage.

 Considerable reduction in batch size volume.

 Less expensive.

27
Ways to be Solvent-Free
Neat – reagents react together in the liquid
phase in the absence of a solvent.
Solid-state synthesis – two macroscopic
solids interact directly and form a third,
solid product without the intervention of a
liquid or vapor phase.

28
Solvent free reactions
A.Solid phase reactions or Physical grinding reactions

B. Solvent free microwave organic synthesis

C. Solid support reactions

Solid-phase synthesis
• In chemistry, solid-phase synthesis is a method in which molecules are
bound on a bead and synthesized step-by-step in a reactant solution;
compared with normal synthesis in a liquid state, it is easier to remove
excess reactant or byproduct from the product.
• This method is used for the synthesis of peptides, deoxyribonucleic acid
(DNA), and other molecules that need to be synthesized in a certain
alignment.
• More recently, this method has also been used in combinatorial
chemistry and other synthetic applications. The process was originally
developed in the 1950s and 1960s by Robert Bruce Merrifield in order to
synthesize peptide chains, and which was the basis for his 1984 Nobel Prize
in Chemistry.
• Solid-phase reactions are usually meant reactions in which both the
reagents and reaction products are solids.
• The specificity of solid-phase processes is a weak transport mobility of the
components of the system and, consequently, as a rule, a low rate of
chemical reactions. The time in which a solid-phase chemical reaction is
completed generally ranges from several hours to tens and in some cases
hundreds of hours at temperatures close to or exceeding the Tamman’s
temperature TT ~ 2/3Tm (Tm is the melting point, K).
Chemical reactions (including phase transitions)

Homogeneous Heterogeneous
• Homogeneous catalysis is a sequence of reactions that involve
a catalyst in the same phase as the reactants. In solid phase homogeneous
reactions, both reactants are solid.
• Heterogeneous catalysis refers to the form of catalysis where the phase
of the catalyst differs from that of the reactants. Phase here refers not only
to solid, liquid, vs gas, but also immiscible liquids, e.g. oil and water. The
great majority of practical heterogeneous catalysts are solids and the great
majority of reactants are gases or liquids.
• Generally three main stages are distinguished in solid-state chemical
reactions in heterogeneous systems:
(1) the transport of reagents to the reaction zone and the increase in the area of
their contact,
(2) nucleation of a new phase, and
(3) growth of its nuclei.
• A solvent-free or solid state reaction may be carried out using the reactants
alone or incorporating them in clays, zeolites, silica, alumina or other
matrices.
• Thermal process or irradiation with UV, microwave or ultrasound can be
employed to bring about the reaction. Solvent-free reactions obviously
reduce pollution, and bring down handling costs due to simplification of
experimental procedure, work up technique and saving in labour. These
would be especially important during industrial production.
• Often, the products of solid state reactions turn out to be different from
those obtained in solution phase reactions. This is because of specific spatial
orientation or packing of the reacting molecules in the crystalline state.
• This is true not only of the crystals of single compounds, but also of co-
crystallized solids of two or even more reactant molecules. The host-guest
interaction complexes obtained by simply mixing the components
intimately also adopt ordered structure.
• The orientational requirements of the substrate molecules in the crystalline
state have provided excellent opportunities to achieve high degree of stereo
selectivity in the products. This has made it possible to synthesize chiral
molecules from prochiral ones either by complexation with chiral hosts or
formation of intermediates with chiral partners.
Physical Grinding reactions
If two or more substrates are involved in the reaction, they are thoroughly
ground together in a glass mortar or co-crystallized, and allowed to stay at
room temperature or transferred to a suitable apparatus and heated
carefully in an oil bath or exposed to appropriate radiation until the
reaction is complete.
Examples:
Thermal Solid State Reactions:
Historically significant organic synthesis of Urea, achieved by WOhler in
1828 belongs to the class of solid state reaction.
solid
NH4NCO NH2-CO-NH2
Pyrolytic distillation of barium or calcium salts of carboxylic acids to
prepare ketones is even now a commonly used procedure.

(Ph-CH2-COO)2Ba Ph-CH2-CO-CH2-Ph + BaCO3

CO2
O + BaCO3
CO2Ba
Physical grinding of reactants
using Pestle and Mortar
Work from our Laboratory

Synthesis of Benzimidazoloyl coumarins under grinding Conditions

Physical grinding, rt, 30 mins

R
O
H H
N O OHC R N
Acetic anhydride,
CH3 +
N HO triethylamine, rt, 5h N O
O
(31) (28) (30)

DMF, piperidine, Microwave-60 %

• Reactions of 2-cyanomethylbenzimidazoles
with Heterocyclic aldehydes

OHC

H N H
N CN R N or N
(33) N R
N N CN R
(34, a-d) and (36, a-d)
(3)
OHC N (R=H, -CH3, -C2H5,-C5H7 PhCH2-
R
(35)

Physical grinding, L-proline,

rt, 5-10 mins

Reactions of 2-mercapto-6-methylpyrimidin-4-one
with 2-(chloromethyl)-4,5-disubstitutedpyridine
hydrochloride under green conditions

R1 O R1
Physical grinding / K2CO3 /
R2
HN 10-15 mins R2

Cl
+ S
H
N O
HS N CH3 (81%) N
N
.HCl N
(43) (44)
44a= R1, R2=OCH3 CH3
44 b= R1, R2=OCF3
• Certain Friedel-Crafts reactions or the related Fries reaction are carried out
in the absence of a solvent. O
C CH3
O O AlCl3, Solid
H3C C O O C CH3 HO OH

Michael Addition: NO2

O
O Al2O3
O2N CH3 Ph Ph
Ph Ph µv
O CH3

O COOMe K2CO3/H2O O COOMe

Ph Ph O CH3 rt Ph Ph

X
H3C CH3 X
50-60 oC, solid phase H3C O

OH O CH3 O

H3CO H3CO
K2CO3/H2O
Ph-SH
O rt S O
Ph
Aldol condensation is an important reaction of aldehydes and
Aldol reaction: Ketones in forming carbon-carbon bonds.

NaOH/r.t/solid phase
Ar-CHO + Ar'-CO-CH3 Ar-CHOH-CH2-CO-Ar' + Ar-CH=CH-CO-Ar'
5 min, 97%
Tishchenko reaction:

CaO or BaO or SrO

O CHO O CH2O O
C
solid phase
O
Robinson annulation:

O R O R O
R (S)-Proline

O O solid phase O O
OH
opt. active

(S)-Proline
CHOH
O
O O
solid phase
O
opt. active
Condensation of Amines with Carbonyl Compounds
Oxidations:
Binapthol has played an important role in asymmetric synthesis
that led to 2001 chemistry Nobel Prize.
Reductions:
Pericyclic reactions:
Pericyclic reactions are concerted inter­ or intra-molecular reactions
involving a cyclic transition state formed by the reorganization of 4n+2
electrons. The rules governing such reactions are called Woodward­Hoffmann
rules.

1. Diels-Alder reactions quite easily occur in the absence of solvents. Just

mixing the reactive dienes and dienophiles is enough to bring about a number
of these [4+2] addition.
2. Related ene-reactions or sigmatropic rearrangements also occur under
neat conditions.

Rearrangement reactions:
•The foregoing short discussion shows that a variety of organic reactions, which
are traditionally conducted in solvent media, can be carried out more profitably
in the absence of solvents.

•The organic chemist will certainly continue his endeavor to bring more and
more reactions into the fold of the solvent-free synthetic methodology.
Work from our Laboratory
(1)

(2)
(3)
(4)
(5)
Highly Efficient [3 + 2] Cycloaddition: Click Synthesis of Novel 1H-indol3-yl-
benzo[d]imidazole Bis-triazoles

B. Mahesh Goud, T. Ashok Kumar and B. Rama Devi.

R1

O H N
R Br
H R1 NH2 R + 2eq.
N
Ethanol
+
N Na2S2O5
NH2
H Reflux,120°C N
H CH3CN
90 min
47 TBAB,
1(a-c) 43(a-c)
57(a- i) K2CO3
R.T,
H 120 min
N R1
N R1
N

N
R N
N t-BuOH:H2O R N
2eq.NaN3
CuSO4.5H2O +
N Sodium ascorbate
11 N
N R.T
N
N
H
55(a-i)
56(a-i)
A Facile synthesis of Novel (Z)-ethyl-3-(5-substituted-1-alkyl/aryl-1H-indol-
3-                        yl)-2-(1H-tetrazol-5-yl)acrylate
B. Mahesh Goud*, T. Ashok Kumar B. Rama Devi
Microwave assisted synthesis
• Extremely used in solvent free synthesis
• Product recovery difficult in PTC (H2O evaporated for
recovery product, energy efficiency is lost)
• Polarity of molecule is essential, there four H2O abs. MW &
convert to heat energy
• H.C. solvents are not suitable there four of less dipole
moment. They poorly absorb M.W
• M.W.I are mainly employed in heterocyclic compound
synthesis
• M.W reactions involve selective ab. of e.m.r. by polar molecule.
• Molecule with μ are subjected to electric field, they become
aligned. As the field oscillates, their oriental changes. This
reorientation produces internal heating
• In M.W heating- core & homogeneous heating
• In M.W classical heating- heat transfer by pre-heated molecule
• Advantages: Quick reaction time
No need of prolonged heating
For the reaction solvent need not be used
Small volume of solvent decreases waste disposal
• Classification:

 M.W. reactions in water

 M.W reactions in organic solvents in very small

quantity

 M.W reactions in solvent free condition with out

catalyst
 Microwaves have wavelengths between 1cm to 1 meter, located between IR
and Radio/Radar frequencies.
 The mechanism of how energy is impacted to a substance under microwave
irradiation is complex.
 Microwaves may be considered a more efficient source of heating than
conventional source of heating, the energy is directly imparted to the
reaction medium rather than through the walls of a reaction vessel.
55
Applications of Microwaves in organic Chemistry:

1. Solvent free organic synthesis:

a. MW synthesis is an ideal procedure for solvent free organic synthesis.

b. It is a clean, safe, efficient and economic method with an increase in easy of
work-up processes.
c. Due to solid phase, MW directly interact with the reagents.
d. Reusable and recyclable catalysts can be used in the same vessel for next cycles.
e. Highly useful fort he reactions in which we use catalysts like Alumina or
KF on alumina or montmorillonite clays.
Green chemistry:
Microwave assisted reactions can be performed using green solvents such as
Water, glycerol etc.

Enzyme catalysis:
Benefits of Microwave
 Very rapid reactions ( few minutes)

 Higher degree of purity achieved due to short residence time at high

temperature
 No local Overheating

 Yields often better.

 Pure Products

58
Limitations of Microwave

 The boiling points of solvents are reached

rapidly, leading to fire and explosions.

 Absence of measurement and control of

temperature.

59
Microwave Induced Synthesis of 3-methyl-4-[(Chromon-3-yl)-methylene]-1-
Phenyl Pyrazolin-5(4H) ones with Alumina Support and in Solvent free
Conditions
Ph
O O
O MW, Al2O2 N
R R N
N
O N
O O Ph O H
Exclusive product

One Pot Synthesis of Substituted [1,2,4]-Triazolo [1’,2’:1,2]pyrimido [6,5-

b]-quinoline and Its Antibacterial Activity
Thiamine hydrochloride (VB1) promoted one-pot synthesis of
2,4,5-triphenyl-1H-imidazole using microwave irradiation

O H
O N
or VB1 Ar
Ar-CHO NH4OAc
O OH MW N

Microwave Induced Synthesis of Flavones

OH O
DMSO/ I2

DMSO/ CuCl2 R
O MW O

R=H
R = Cl
Microwave Assisted Improved Method for the Synthesis of Pyrazole Containing
2,4,-Disubstituted Oxazole-5-one

O H
O N
or VB1 Ar
Ar-CHO NH4OAc
O OH MW N
Work from our Laboratory
Synthesis of Benzimidazoloyl coumarins under M.W Conditions

R1
CH3
N

N O
(30a-g)
O

H3C O CH3
Microwave Irradiation (60 %) R1 CHO O N
+
5-10 mins OH N

(28) (31a)
• REACTIONS OF 2-MERCAPTO-6-METHYLPYRIMIDIN-4-ONE WITH
2-(CHLOROMETHYL)-4,5-DISUBSTITUTEDPYRIDINE
HYDROCHLORIDE UNDER GREEN CONDITIONS

R1 O R1

R2 HN R2

Cl
+ S
H
N O
HS N CH3 N
N
.HCl N
(43) (6) (44)
44a= R1, R2=OCH3 CH3
44 b= R1, R2=OCF3

Microwave irradiation / 2min (82%)

70%
What is Sonochemistry?

Study of chemical changes that occur in

presence of sound or ultra-sound.

66
Some properties of Sonochemical /
Ultrasound radiations
 Frequency ranges from 20 KHz to 10 MHz

(Human hearing upper limit is 18 KHz)

 Region 20-100 KHz is best for chemical transformation

 Frequency range 1-10 MHz are suitable for ultrasound imaging of

body organs

67
Classification of sonochemical
Radiations
 Low frequency – high power ultra sound (20-
100 KHz)
 High frequency - medium power ultrasound
( 100 KHz –1MHz)
 High frequency- low power ultrasound

(1-10MHz)
68
Applications of Sonochemistry

Emulsification
Refining
Pasteurization
Soldering
Dispersion
Degassing of Liquids
Organic Chemical transformations
69
• Source- electrochemical transducer- quartz based on piezo electric
effect
• When equal & opposite electric changes are applied to opposite
faces of a quartz- expansion or contraction occurs
• Application of rapidly reversing changes setup a vibration that emit
ultrasonic waves
• Yield will be very high
• Combination of sonication with other techniques-PTC, M.W gives
best results
Ultrasound assisted green synthesis of bis(indol-3-yl)methanes catalyzed
by 1-hexenesulphonic acid sodium salt

R
O 1-Hexenesulphonic
acid sodium salt
2
N R H Water, )))))) N N
H H H
Ultrasound promoted greener approach to synthesize α-hydroxy
phosphonates catalyzed by potassium dihydrogen phosphate
under solvent-free condition

O EtO OEt HO O
P KH2PO4
R H P
OEt ))))))), r.t. OEt
R EtO

71
Tetrabutylammonium Fluoride (TBAF) Catalysed Synthesis of 2-Arylbenzimidazole in
Water under Ultrasound Irradiation

An efficient synthesis of 3,4-dihydropyrimidin-2(1H)-ones catalyzed by thiamine

hydrochloride in water under ultrasound irradiation

O EtO OEt HO O
P KH2PO4
R H P
OEt ))))))), r.t. OEt
R EtO

72
Development of practical methodologies for the synthesis of novel 3(4-oxo-4H-
chromen-3-yl)acrylic acid hydrazides

73
Ultrasonic Promoted Synthesis and Antibacterial Screening of Some Novel Piperidine
Incorporated α-Aminophosphonates 

74
An efficient synthesis of some novel 3-(5-phenyl-1,3,4-oxadiazol-2-yl)pyridine
derivatives catalyzed by ammonium metavanadate in ethanol under ultrasound
irradiation

Synthesis of 1-(2-Hydroxy-phenyl)-3-piperidin-1-yl-propenone by Ultrasonic

Irradiation

O OH
EtOH
N
))))))) R
R N
O O H O

75
Work from our Laboratory
Ultrasound promoted N-Alkylations of 2-Substitutedbenzimiazoles

H3C
H
N O )
Ultrasound Irradiation ))))) ,
N O

N CH3 N CH3
(88) TBAB, K2CO3, ACN, rt, 6-15 mins (88b)
Work from our Laboratory
• These ions are poorly coordinated, solvents being liquid below 100⁰C (or) at room temperature.
• Characteristics:
• Designer solvents
• High ionic conductivity
• Less toxic
• High thermal stability
• No vapor presser, non-volatile, non-coordinating but polar
• Non-inflammable
• Exists in liquid states over entire range of temperature
• Low solubility in water, hence can be recovered & reused after extracting product with organic
solvents
• Easily recycled. Reused after extraction
• They are called designer solvents- helps in separating water soluble by-products by simple extraction
• Good solvents for Pd-catalyzed reactions, C-C, C-O bond
formation
• Use of room temperature ionic liquids
• Disadvantages:
• Loss due to evaporation
• Toxic & O3 depleting
• Fire hazards, explosive
• Monitory cost is more
• Super critical fluids
• Super critical CO2 in place of Vocs
• For dry cleaning of clothes
• Extracting PCBs
• Extracting DDT in water, soil, sediments
• Use of microorganism-for synthetic drugs
• Disposal of chemicals with the help of genetically manipulated living system
• Green insecticides-pheramones (sex hormes)
• Genetically engineered crops- Bt-cotton
Bt-maize
Bt-potato
It has self defence mechanism to battle insects, pests which attack cotton balls
• This defence artillery is created by fusing genes of naturally occurring bacteria Bacillus
Thuringiensis (B.t)
• Green & eco friendly solvents
Water
PEG
ILs
Super critical water, CO2
• Best solvent- no solvent but problem of heat, mass transfer, mixing of reactants
• To over come- grinding
M.W.I
Solid support- clay, silica etc.
Soil fumigant- CH3-Br is replaced by protein Harpin
CFCs is refrigeration replaced by CO2
Chitin- waste management
• Replacing hazardous chemicals by safer chemicals
• AlCl3 in Friedel-craft’s by zeolite (reversible, recoverable)
catalyst
• Poly carbonate synthesized by phosgene, DCM by- solid stage
polymerization

Green starting material

Green catalyst

Green reagent Green product

Green reaction
green solvent

green methodology
• Green chemistry is not a solution to all
environmental problems but the most
fundamental approach to preventing
pollution