Venugopal Rao VEERAMANENI, Ph.D.Venugopal Rao VEERAMANENI, Ph.D.Indus BioSciences (P) Ltd.Indus BioSciences (P) Ltd.

• Green Chemistry: Introduction– What is Green Chemistry?– Why we need to know? (Why Green Chemistry

is important?) – Where we can apply?– How many types of Alternatives?– Case Studies

• Green Chemistry – Water as a Solvent– Introduction– Applications

• Advantages & Conclusions

Green chemistry is the design of chemical products and processes that reduce or eliminate the generation of hazardous substances.

Green chemistry seeks to reduce the hazards associated with chemical process not just by preventing exposure or release, but by reducing the intrinsic hazards.

Green Chemistry Efficiently Utilizes (Preferably Renewable) Raw Materials, Eliminates Waste and Avoids the Use of Toxic and/or Hazardous Reagents and Solvents in Manufacture and Application of Chemicals Products.

To Introduce, Educate and Promote the Application of Green Chemistry in Colleges/Institutes

Key Philosophy: Voluntary Restraint is Better than Enforced Constraint

Green Chemistry Includes Protection of the Environment and Worker Safety

Information and Influencing the Green Chemistry Research Agenda

Cost of waste Cost of wasted reagents Cost of wasted energy Cost of waste disposal Cost of increased regulation

Green Chemistry: Addressing the Source

& Global Chemical

Production

Growing 3% per year Doubling every 25 years

Increasing Costs for Storing

Hazardous Substances

Increasing Costs of Waste

Disposal

Increasing Fines for Pollution

Increasing Energy Cots

Increasing Petrochemica

l Costs

Supply Chain Pressures and Uncertainties Increasing

Demands of Emerging Nations

Poor Public Image & Negative

Media Reporting

Reducing number of Chemistry Students

New Legistation

forcing testing of all

chemicals

Diminishing Supplies of

non-sustainable Resources

Increasing Producer

Responsibilities

Raw Materials Pre/Manufacturing

Chemical Manufacturing and

ProductionProduct use

DRIVERS

ACTIONS

BENEFITS

Diminishing fossil

Reserves &

Increasing Prices

Market Distortions due to new

Manufacturing Regions

Increasing Cost of Waste

Disposal & Storage of Hazardous

Increasing Energy

Cost

New Requirements

for Product testing

Recovery Recyclability

Reduce Dependence on

Traditional Resources.

Maximize use of Renewable Local

Resources

Employ Green Chemical

Technology to Improve Process

Efficiency & Reduce Waste

Build up Portfolio of Green and

Sustainable Chemical Products that can dominate

future World Markets

DATA GAP(Information)

TECHNOLOGY GAP(Capacity)

SAFTEY GAP(Accountability)

Business & Consumer Choice

Necessary & Available

Information

Evidence of Cause & effect

Slandered Evidence is Required for

Regulation

Intellectual & Technical

Capacity to Support Green Chemistry

MarketsBuyers: No Haz. Data

Sellers: No Case for GC

GovernmentInability to Assess Haz.Inability to Control Haz.

Subject Environmentally Thinking

Economically Thinking

Atom Economy

Minimal by Product Formation

More from Less - Incorporate Total Value of Materials

Solvent reduction

Less Solvent Waste Higher throughput, Less Energy

Reagent Optimization

Catalytic, Low Stoichometry, Recyclable Reagents, Minimize Us age

Higher Efficiency - Higher Selectivity

Convergency

Due to Increased Processed Efficiency

Higher Efficiency - Fever Operations

Energy Reduction

From Power Generation, Transport and Use

Reduced Energy , Increased Efficiency, Shorter Process and Mild Conditions

Safety Non-Hazardous Materials Reduce Risk of Exposure, Release, Explosions & Fire

Worker Safety and Reduced Down Time. Reduced Time on Special Control Measures

Prevent wastes

Renewable materials

Omit derivatization steps

Degradable chemical products

Use safe synthetic methods

Catalytic reagents

Temperature, pressure ambient

In-process monitoring

Very few auxiliary substances

E-factor, maximize feed in product

Low toxicity of chemical products

Yes, it is safea

Green Chemistry - 12 PrinciplesGreen Chemistry - 12 Principles

E-Factor= Total Waste (Kg)/Product (Kg)

Atom Economy = FW of Atoms Utilized/FW of all Reactants X 100

Atom Efficiency = % of Yield X Atom Economy

Effective Mass Yield = Product (Kg)/Hazardous Reagents X 100

Carbon Efficiency =Mass of Carbon in Product/Mass of Carbon in Reactants X 100

Reaction Mass Efficiency =Mass of Product/Mass of Reactants X 100

The first general metric for green chemistry remains one of the best, which proposed by Roger Sheldon

The E-factor calculation is defined by the ratio of the mass of waste per unit of product.

E-Factor = Raw Materials (Kg) – Desired Product (Kg) /Product Out (Kg)

Environmental (E) Factor:Environmental (E) Factor:

Industry Segment

Product Tonnage

E Factor(Waste/Product)

Oil Refining 106 -108 <0.1

Bulk Chemicals 104 -106 <1-5

Fine Chemicals 102-104 5-50

Pharmaceuticals

10-103 25-100

E-Factors in the Chemical IndustryE-Factors in the Chemical Industry

Effective mass yield is defined as the percentage of the mass of the desired product relative to the mass of all non-benign materials used in its synthesis. Hudlicky et al. suggests the following equation

Effective Mass Yield (%) = Mass of Products x 100 /Mass of Non-Benign Reagents

Effective Mass YieldEffective Mass Yield

Carbon efficiency is a simplified formula developed at GlaxoSmithKline (GSK).iv The mathematical representation

Carbon Efficiency (%) = Amount of Carbon in Product x 100 /Total Carbon Present in the Reactant

This metric is a good simplification for use in the pharmaceutical industry as it takes into account the stoichiometry of reactants and products

Carbon Efficiency:Carbon Efficiency:

Atom economy was designed in a different way to all the other metrics; most of these were designed to measure the improvement that had been made. Barry Trost, conversely, designed atom economy as a method by which organic chemists would pursue “greener” chemistry. The simple definition of atom economy is a calculation of how much of the reactants remain in the final product.

% Atom Economy: Atoms Utilized/Atoms Used X 100

Atom EconomyAtom Economy

Developed by GSK, the reaction mass efficiency takes into account atom economy, yield and stoichiometryFrom a generic reaction where A + B → C Reaction Mass Efficiency = Molecular weight of product C X Yield

Reaction Mass Efficiency:Reaction Mass Efficiency:

Green Reagents Biocatalysis Aqueous Phase Reaction Polymer-Supported

Reagents Solvent free Reaction Use of protecting groups Solid Phase Organic Synthesis

Enzyme Mediated Reactions

Reactions in Ionic Liqueds

Ultrasound-Assisted Reactions

Renewable Feedstocks Microwave Induced Reactions

Biodegradable Products Microbial Oxidations Non-Covalent Derivatization

Supercritical Fluid Intermediates

Atom –Efficient Reactions

Ambient Processing

Sertraline-Active Ingredient in Zoloft (Treatment for Depression)

Pfizer’s Conventional 3 step process Reduced to a Single Step

OHCl

Cl

O

Cl

Cl

NMe

Cl

Cl

NMe

Cl

Cl

TiCl4/MeNH2

Tolene/Hexane

MeNH2EtOH

Isolated

NHMe

Cl

Cl Isolated

NHMe

Cl

Cl

Pd/C, H2D-Mandelic acid

Sertralinemandelate

NHMe

Cl

Cl

D-Mandelic acid

NHMe

Cl

Cl

Sertralinemandelate

Pd/CaCO3

EtOH

THF

Not Isolated

Solvent use reduced from 60,000 to 6,000 gallons per ton of sertraline Eliminated the use of 440 metric tons of titanium dioxide per year Eliminating the use 150 metric tons of 35% hydrochloric acid per year Eliminating the use of 100 metric tons of 50% sodium hydroxide per year

232 L/kgDiscovery Route

98 L/kg1st Commercial

81 L/kg2nd Commercial

26 L/kg3rd Commercial

8 L/kg Chiral Tetralone

Methanol

Ethyl acetate

Ethanol

THF

Hexane

Toluene

Methylene chloride

Sertraline Process – Solvent Waste/Kg

Sildenafil useful for the treatment male impotency Old synthetic route is having 10 linear steps Potentially toxic materials in the final reaction Multiple crystalizations are needed to get pure compound Difficulties in Scale up process.

Pr

O

N

NHO

O

Pr

N

NHO

O

Pr

HNO3

O2N

N

NH2N

O

PrO2N

N

NH2N

O

PrH2N

SOCl2NH4OH

SnClEtOH

OEt

Cl

O

NN

H2N

O

PrNH

OEtO N

NHN

O

PrN

OEt NNHN

O

PrN

OEt

SO2Cl

NNHN

O

PrN

OEt

S

N

O O

N

Old Synthetic Route:

Pd/C & H2 Used for reduction of nitro to amine instead of SnCl/EtOH

During Sulfonation, thionyl chloride used to convert sulfonic acid (intermedite) to Sulfonyl chloride

Sulfonamide formation was performed in aq. NaOH CDI used in the formation of amide (coupling) instead of Oxalyl

chloride Cyclization reaction worked well in the presence of KOBut

Commercial/Convergent Route:

N

NH2N

O

PrO2N

N

NH2N

O

PrH2N

OEt OH

O

NNHN

O

PrN

OEt

S

N

O O

N

Pd-C/H2

ClSO3H

SOCl2

OEt

OH

O

SO2Cl

OEt

OH

O

SNaOH/H2O

N

O O

N

CDI

OEt O

SN

O O

N

NN

H2NO

Pr

NH

KOBut/tBuOH

1816 L/kg MedicinalChemistry

1990

139 L/kgOptimized

Med. Chemistry1994

31 L/kgCommercial Route

(1997)

10 L/kgCommercial Route following solvent

recovery

Pyridine

Toluene

t-Butanol

2-Butanone

Ethyl Acetate

Ether

Methanol

Ethanol

Acetone

Methylene Chloride

How the amount of waste produced in the manufacture (L of waste/kg of product) has decreased over the past 13 years.

Ibuprofen (Pain Killer,) discovered in 1961

Traditional Synthesis (by Boots) involves 6 steps.

And atom utilization is only 40%

Excess AlCl3 is used old process and which gave 20,000 tones of solid waste.

AlCl3/Ac2O

O

ClCH2CO2EtNaOEt

OCO2Et

H3O

CHO

CHNOH CN CO2H

BHC Redesigned in 1990 (after patent expire in 1984)

Catalytic Synthesis, completed in 3 steps

77% Atom Utilization

Catalytic amount of Hydrofluoric acid used instead of AlCl3.

Catalyst Reused in Next Batch.

Acetic acid is by product in first step, was converted to Ac2O (99% of recovered)

HF/Ac2O

O OH CO2H

H2

R-Ni

Pd

CO

Organometallics, 1997, 16, 4229

B(OH)2 CHO

Rh(acac)/CO2/dppf

50oC/Organic/Water

OH

SnCl3 CHO

Catalyst

100oC/Water

71%

OH

JACS., 2000, 122, 9538 & 2001, 123, 7451

J. Amer. Chem. Soc., 2003, 125, 2958

CHO

Br

a b

In, Water

OH OH

"a" Aduct"b" Aduct

DMF- 72h, 65%; 100:0; THF-72h, 20%; 100:0

MDC & Neat- No Reaction; Water -72h, 90%; 100:0; Water (more dilution) -24h,

85%; 1:99

Acc. Chem. Res., 2002, 35, 209

Angew. Chem. Int. Ed., 2001, 40, 2816

OSiMe3

OH

CHO

Cat. Yb(OTf)3

H2O/THF 91%Dry THF 10%

O

CHO OSiMe3

O

N N

O

Cu(OTf)2

OH O

H2O/THF: 81% Yield, 81% ee (Syn)Dry EtOH: 10% Yield, 41% ee (syn)MDC: 11% Yield, 20% ee (syn)

Acc. Chem. Res., 2002, 35, 209

CHO

Ph

OSiMe3 Ph2BOH

OH O

H2O: 90% Yield, 92:8 (Syn/Anti)Et2O: Trace; MDC: Trace; Neat: 24% Yield, 90:10 (Syn/Anti)

Carbanion Chemistry Carbocation Chemistry Addition of Boronic acid

Phenylation

Selective Alkylation

Mukaiyama Aldol Reaction

Lewis Catalyzed Asymmetric Reaction

Boron Catalyzed Reaction

AcO

N

O

O

N

Me

H

H

AcO

O

O

R,T

Acetonitrile – 17% ee; THF - 24% ee; EtOH – 39% ee; CHCl3 – 44% ee; Water – 74% ee

Angew. Chem. Int. Ed., 2005, 44, 3275

J. Amer, Chem, Soc. 1999, 121, 6798

O

Ph

N

O

Ph

N

Toluene -144hrs, 79% ; ACN -144hrs, 43%; MeOH – 48hrs, 82%; Neat – 10hrs, 82%; Water – 8hrs, 81%

Diels-Alder Reactions

O

O

H2O

Tetrahedron Lett, 39, 1239

OH2O

O2N

O

N

N

O2N

Acetonitrile – 17% ee; THF - 24% ee; EtOH – 39% ee; CHCl3 – 44% ee; Water – 74% ee

Tetrahedron Lett, 36, 2645

CO2HH2O

CO2HCO2H

CO2H

J. Am. Chem. Soc. 1980, 102, 7816

Bull. Chem. Soc. Jpn., 2001, 74, 225

J.Am. Chem. Soc., 2000, 122, 11041

O

I

O

Et3B

3hrsO O

IMDC (0%); THF (0%)MeOH (6%); EtOH (3%)ACN (13%); DMF (13%)DMSO (37%); H2O (78%)

J.Am. Chem. Soc., 2000, 122, 11041

O

O

Et3B

3hrs

Hexane (10%); Benzene (23%)MeOH (0%); H2O (69%)

OI

O

O

O

I

OR

I

H3PO4, NaBCO3

AIBN, H2O

OR

98% Yield

Radical Reactions

Atom transfer Radical Cyclization

Radical Reductions

Pure Applied Chem, 2000, 1327

Textbook of Practical Organic Chemistry,

Radical Coupling

OHWater Drop

&Grind

OH

OH

FeCl3

N

NHCOCF3

N2

BF4S

S

S

S

Acetone/Water N

F3COCHN

OH

OH

Ru(OH)x/Al2O3

Oxygen/Water/100oC/98%

OH

OH

J.Am. Chem. Soc., 2005, 127, 6632

Angew. Chem. Int. Ed., 2003, 42, 194

R

OH

ARP-Pd (cat.0

O2/H2OR=H (97%); R=Me (99%)

R

O

Angew. Chem. Int. Ed., 2004, 43, 6731

R

OH

RuCl2 Cat.

aq. NaCO2H90% Yield & 77% ee

OH

Oxidations & Reductions

Reduction of Ketones

Oxidative Coupling of 2-Naphthol

BrominationsBromination of trans-stilbene

Method 1: HBr in H2O

Method 2: NaBr/NaBrO3/H2OBr

Br

Bromination of acetanilide)NHCOCH3

CAN/KBr

H2O/EtOH

NHCOCH3

Br

Journal of Chemical Education. 1996, 173, 267

85%

Synthesis of tetrabutylammonium tribromide (TBATB) and application:

O

TBATB

Water, 15 min

OBr

Br

US Patent No. 7005548, February 28, 2006

Angew. Chem. Int. Ed., 2004, 43, 1576

J.Am. Chem. Soc., 2001, 123, 5358

R NRu(OH)x/Al2O3

R NH2

O

WaterR=Alkyl, Aryl, Vinyl; 80-99%

B(OH)2

Rh Cat.TPPDS

Na2CO3/H2O80% Yield

J. Am. Chem. Soc., 2002, 124, 5638

N R

Cu(OTf)

H2O, 93% Yield

96% ee

R

NH

N

Cl B(OH)2 Na2PdCl4

Phosphine LigandWater, K2CO3 N

Cl B(OH)2 K3PO4

CatalystWater

R

R

Appl. Organometal Chem, 2008, 233

J.Am. Chem. Soc., 2003, 125, 6653

Cl NH2

Phoshine Ligand

Pd2dba3/KOH, H2O

HN

91% Yield

Transition Metal Catalytic Reactions

Copper Catalyzed Reations

Olefins with Boronic Acids

Amides from Nitrile Using RuOH Sujuki-Maiyura Coupling

Green Chem. 2009, 9, 1287

Sujuki Coupling

Pd Catalyzed C-N bond formation

Chem. Comm., 2000, 2049

J. Braz. Chem. Soc., 2001, 12, 135

Adv. Synth. Catal. 2006, 2057

OHO

HO

OH

OH

OH

OHO

HOOH

OH

NaHCO3/H2O96%

OO

O

NO2 SH

S

NO2Ph

Ph S

NO2Ph

PhAnti Syn

ACN/TEA - 1hr, 85% yield; 34:66 (anti/syn)H2O/NaHCO3 - 30min, 95% yield; 73:27 (anti/syn)

Cl

O

Ph(CHOH)CH3methylimidazole

TEMDA, KOH, H2O92% O

O

OR in presence of DBSA/Water 81% yield

Adv. Synth. Catal., 2002, 344 (3+4), 370

O

RX, Catalyst

aq. NaOH10hrs/70-94%

O

R

OH R1X, Catalyst

aq. NaOH10hrs/22-85%

OR1

R R

Adv. Synth. Catal., 2002, 344 (3+4), 370

ARKIVOC 2008 (XV), 88-89

N

X

NH2

O

BrB-CD/H2O

50-55oC5-25min/65-85%

N

X N

Ph

Miscellaneous Reactions

One pot synthesis of C-glycosidie Ketone Alkylations in the presence of Butylcalix[n]arenes:

Micheal Addition

Esterification Synthesis of bridgehead azaheterocycles

Formation of ethers

O

CO2Et

Pd(PPh3)4 Cat.

Triton X-100 Cat.K2CO3/H2O

OAcO

CO2Et

DBSA=Dodecabenzenesulfonic acid

Triton X 100=4-octylphenol polyethoxylate

HSSH

CHO DBSA Cat.

Water/4hrs/40oC

96% Yield

S

S

Green Chemistry, 2000, 2, 272

J. Am. Chem. Soc., 1990, 112, 9436

ONH2

NPh

Benzene/Acid Cat./Several hrs; 47-95% Water/Neat/1-3 hrs; 86-98%

OMe

O

CHO

H CO2Na

OMe

OH

CHO

CO2Et

H

Benzene/80oC/72hrs/67%; Water/R.T/5hrs/75%

O BrCH2CO2Et

Ph3P/LiOH/LiClWater/15min-120min

86-99%

CO2Et

Ph3P/LiOH/LiClWater/5min-120min

71-97%

BrCH2CNNC

Syn. Comm. 2006, 36 (20), 2939

Miscellaneous Reactions

Synthesis of Chapraninone

One Pot Wittig Reactions

Dehydration Reaction

C-C Bond Formation Aldehyde-Amine Condensation

Green Chemistry, 2008, 10, 939

Adv. Synth. Catal., 2003, 345, 576

ARKIVOC 2008 (XV), 1-8

Asymmetric Dihydroxylation

OH

OH

Water

CHO

O O EAA, NH4OAc

Water NH

O

CO2Et

Ph

Miscellaneous Reactions

Anti Hepatitis C Virus; J. Org, Chem, 2005, 70, 10765

N

O

HN

O

Ph

HN

O

O

O

O

O

Catalyst

N

O

NH

OPh

NH

OO O

OO

WaterRCM

Chem. Com, 2003, 1977-1986

Br Br

PhCHO

In/WaterBr

Ph

OH PhCHO

In/Water Ph

OH

HO

Ph

HOOH

O

O

O

OH

HNO3 H2O2

H2O

O

HO

OProline Cat.

Water/THF

OH

OH O OH O

OH

89-99%ee (~90% Yield) Traces or No Product

Chem. Eur. J. 2007, 13, 689 – 701

Miscellaneous Reactions

Toluene -120h; ACN – 84h; MeOH – 18h; DMSO – 36h; Neat – 48h; Water – 10 min

Cl

O

Cl

OH

R.T, 120hrs

Toluene -16% ; ACN -27% ; MeOH – 56%

Neat – 73%; Water – 100%

N

NMeO2C

CO2Me

N

N

CO2Me

CO2Me

Angew. Chem. Int. Ed., 2005, 44, 3275

3,4-dihydro-2H-benzo[b]thiazine-3-3,4-dihydro-2H-benzo[b]thiazine-3-onesones

Used as Key Ingredient in NCE’sUsed as Key Ingredient in NCE’sGrowth Hormone Releasing Activity

US20060142264

N

S

O

HN

O

NH2

O

Anti Bacterials

US20070004710NH

S

ON

N

OH

N

N

O

Treatment for CNS Damage

US2005009733

NH

S

OO

OMe

NH

O

O

O

Anti Bacterial

US20050197326

N

SHN

O

OH

O

HN N

Treatment of HyperUricemia

US20080305169

N

S

O

Cl

Cl

NH

S

O

OMe

1,2,3,4-tetrahydro-2-quinoxalinones1,2,3,4-tetrahydro-2-quinoxalinonesUsed as Key Ingredient in NCE’sUsed as Key Ingredient in NCE’s

NH

N

O

O

HN

OO2N

S

Histone Deacetylase Inhibitors

US 20070155730

N

HN

O

Treatment for Breast Cancer

US20080255109

O

N

NNH

S

O

O

N

N

O

Cardio Vasculor Agent

US20060247244

O

NH

O

NH

NH

HN

OAnti Cancer Agent

US20060019959

N

N S

O

O

Anti Cancer Agent

US20050148586

N

HN

O

HN

O

HN

N O

S.NoS.No Conditions

1.1. CH3CH(Br)COOH, Zuletzt, 150 oC

2.2. CH3CH(Br)COOEt, in AcOH; Con. HCl

3.3. RCH(X)COOEt; DMF, 90 – 95 Oc; R = CH3, Ph

4.4. CH3CH(Br)COOH; 120 – 125 oC

5.5. CH3CH(Cl)CONH2; K2CO3, Acetone, Refluxed for 16.0 hrs

6.6. i) SmI, THF; ii) RCH(Br)COOH; R = CH3, Ph

7.7. KOH, Methanol, 2,2,2 – trichloro-1-phenyl

8.8. CH3CH(Cl)CO2H; NaOH, Water; Refluxed for 4.0 hrs

9.9. PhCH(Br)COOH,; Zuletzt, 150 oC

10.10. i) PhCH(Br)COOMe, KI; ii) NaOMe, C6H6, 80 ° oC

11.11. PhCH(Cl)COOH,; NaOH.

12.12. (CH3)2C(Br)COOH; KOH, EtOH

3,4-dihydro-2H-benzo[b]thiazine-3-3,4-dihydro-2H-benzo[b]thiazine-3-onesones

Known Methods to Prepare Known Methods to Prepare

Entry Product R Yield (%)

A B C11 2a2a HH 9494 9696 969622 2b2b MethylMethyl 6060 6565 777733 2c2c DimethylDimethyl 6262 6565 717144 2d2d EthylEthyl 6868 6767 737355 2e2e PropylPropyl 5353 5959 616166 2f2f IsopropylIsopropyl 5151 6262 656577 2g2g HexylHexyl 3939 4242 575788 2h2h Phenyl Phenyl 6363 6969 7474

NH

S

ONH2

SHBrCH(R)CO2Et, NaOHBrCH(R)CO2Et, NaOH

1 2

R

NH

S

O

R

Water, MW, 4 - 5 minWater, 80 0C, 1.0 hr

2

A: Conventional, B: Using Parallel synthesizer, C: Microwave irradiation. A: Conventional, B: Using Parallel synthesizer, C: Microwave irradiation.

3,4-dihydro-2H-benzo[b]thiazine-3-ones3,4-dihydro-2H-benzo[b]thiazine-3-onesMW Assisted Aqueous Phase Synthesis MW Assisted Aqueous Phase Synthesis

Entry Product R Yield (%)

A B1 4a H 74 792 4b Methyl 69 753 4c Dimethyl 49 734 4d Ethyl 65 735 4e Propyl 68 766 4f Isopropyl 59 687 4g Phenyl 63 75

A: Parallel synthesizer, B: Microwave irradiation. A: Parallel synthesizer, B: Microwave irradiation.

NH

HN

ONH2

NH2 BrCH(R)CO2Et, DMFBrCH(R)CO2Et, NaOH

3 4

R

NH

HN

O

4

R

Water, MW, 4 - 5 minWater, 80 0C, 1.0 hr

1,2,3,4-tetrahydro-2-quinoxalinones1,2,3,4-tetrahydro-2-quinoxalinonesMW Assisted Aqueous Phase Synthesis MW Assisted Aqueous Phase Synthesis

Synthesis Must be Fine Tuned to the Nature Procedures are not only Green but Often also Better and Cheaper Competitive Advantage Beneficial in Reducing Costs/Risks and

Provide Greater Manufacturing Flexibility Green Chemistry Reducing Local Pollution and Can Make Your

Community A Cleaner, Safer Place Water is Cheapest, Safe and Green Solvent No inflammable, Explosive, Mutagenic, Carcinogenic Synthetic Utility:- Simple operation and Efficiency Would Be The 21st Century Be A Century of Organic Reaction in

WATER???!!! Every Chemist’s Wish….But A Strive To Fulfill It Is Compulsory Only in this Way can Chemists Pride Themselves as Human

Benefactors A Decline of the Public Anxiety and Improvement in Public Image

Towards Chemistry, Chemicals and Related Items.