g reen c hemistry by dr. kandikere ramaiah prabhu principal research scientist department of organic...
TRANSCRIPT
GREEN CHEMISTRY
By
Dr. Kandikere Ramaiah PrabhuPrincipal Research Scientist
Department of Organic ChemistryIndian Institute of Science
Bangalore – 560 012
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October 23, 2010, Bangalore
History…..Green Chemistry is born around 199oWhat is green chemistry or Sustainable
Technology
Traditionally - Chemical Yield was paramount
Green Chemistry Focuses on -Process efficiency in terms of eliminating wastes at source and avoid using or generating toxic substances
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PreventionIt is better to prevent waste than to treat or clean up waste after it has been created.
Atom EconomySynthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
Less Hazardous Chemical SynthesesWherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.
Designing Safer ChemicalsChemical products should be designed to effect their desired function while minimizing their toxicity.
Safer Solvents and AuxiliariesThe use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.
Design for Energy EfficiencyEnergy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.
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12 Principals of green chemistry
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Use of Renewable FeedstocksA raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.
Reduce DerivativesUnnecessary derivatization (use of blocking groups, protection/ deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.
CatalysisCatalytic reagents (as selective as possible) are superior to stoichiometric reagents.
Design for DegradationChemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.
Real-time analysis for Pollution PreventionAnalytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances.
Inherently Safer Chemistry for Accident PreventionSubstances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.
E-Factor??? Mass ratio of waste to desired product Higher e-factor – more waste and –ve
environmental impact Raw Materials-Product output
product
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The key to waste minimization is precision in organic synthesis,
where every atom counts!!!
Atom efficiency
Molecular weight of the product
Sum molecular weight of the
all products formed
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Atom efficiency of stoichiometric versus catalytic oxidation of alcohols
OH
+ 2CrO3 + 3 H2SO4
O
Cr2(SO4)3 + 6 H2O+3 3
Atom efficiency = 360/860 = 42%
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OH
+ 1/2 O2
O
+ H2OCatalyst
Atom efficiency = 120/130 = 87%
OH
+ 2CrO3 + 3 H2SO4
O
Cr2(SO4)3 + 6 H2O+3 3
Atom efficiency = 360/860 = 42%
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Additional questions!!?? Environmental impact of waste!!
Waste can be an useful output
What is the waste generated in manufacture of Organic compounds???
Fine chemicals and pharmaceuticals use stoichiometric amounts of reagents
Reductions – Metal hydrideOxidations - CrO3, KMnO4,etcSulfonation, Nitration, Friedel-Crafts reaction etc……!!!!
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R
OH NH2
O
Friedel Craft Reaction
Friedel Craft Reaction
H2SO4/SO3
NaOH
Nitration/reduction
The technologies used for the production of many substituted aromatic compounds have not changed in more than a century and are, therefore, ripe for substitution by catalytic, low-salt alternatives
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R
OH NH2
O
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HNO3/H2SO4
Fe/HCl MnO2
OOH
OH
OH
OOH
O2 H+
-2Me2CO
HCl
H+
Two routes to hydroquinones
Catalysts
Homogeneous catalyst & Heterogeneous
catalysts
Organocatalyst
Biocatalysts
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Homogeneous catalyst & Heterogeneous catalysts
Organocatalyst
DEVELOPMENT CATALYSIS IN ORGANIC SYNTHESIS
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If the solution to the waste problem in the fine chemicals industry is so obvious
Replacement of classical stoichiometric reagents with cleaner, catalytic alternatives
Why was it not applied in the past?
There are several reasons for this.
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First, because of the smaller quantities compared with bulk chemicals, the need for waste reduction in fine chemicals was not widely appreciated.
A second, underlying, reason is the more or less separate evolution of organic chemistry and catalysis.
Fine chemicals and pharmaceuticals have remained primarily the domain of synthetic organic chemists who, generally speaking, have clung to the use of classical “stoichiometric” methodologies and have
been reluctant to apply catalyticalternatives.
A third reason, which partly explains the reluctance, is the pressure of time. Fine chemicals generally have a much shorter lifecycle than bulk chemicals and, especially in pharmaceuticals, ‘time to market’ is crucial.
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Major points to be addressed
Catalysts
Solvents
Renewable Raw Materials – White
biotechnology
Risky Reagents
Process integration and catalytic cascades
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Catalysts
Solid catalystsBio catalystOrgano catalysts
Heterogeneous catalystsHomogeneous catalyst
Acid base catalyst
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Acid base catalyst
Montmorillonite clays
OHMontmorillonite clays
80 oC
Clayzic
80 oCPhH2C
PhCH2OH+
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Zeolites
(CH3CO)2O
O
140 oC
Zeolites
RCOOH
O
R
140 oC
Zeolites
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Reductions
Catalytic reductions
Hydrogen gasHydrogenation catalysts
Selectivity in hydrogenation
Chiral reductions
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oxidations
COOH
COOH
Na2WO4 (1 mol%)
H2O2
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Biocatalysts
Egs:
Yeast-ADH as alcohol dehydrogenaseHorse liver-ADH
O OH
O
O OH
OH
GlucoseLactobascillus kef ir
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Organocatalysis
Proline-catalyzed aldol reaction
O
OAminoacids
R
HO
R H
O
Transition Metal oxides Chemical transformations Academia & Industry.
Metal-oxo complexes Oxidations & reductions processes.
M Oxidized MReduced
Oxidation
X XO
XOReductionX
Our Research…!!!! Mo
O OS
S
S
SN N CH3
CH3H3C
H3C
Oxygen is transformed from Molecular Oxygen
N3
CHO
O O
H2O, O2
Reflux+ MoO2(X)2
10 mol%90%
M. Maddani, K. R. Prabhu, Tetrahedron Lett., 2008, 49, 4526
Oxidation of Alcohols to Carbonyls Catalysed by Molybdenum Xanthate
Heterogeneous catalysts Recovery, recycling and Stability.Liquid phases
NH2+ 1.5MHCl +
Amm.persulphate in 1.5MHCl
Aq AmmoniaPolyaniline
No reactionMoO2(Et2NCS2)2
CHOOH
Toluene/Water Reflux, 40h
Proposed polyaniline-supported MoO2(X)2 structure.
+ MoO2(X)2
Acetonitrile
RT, 50hMoO2(X)2
= Polyaniline3
MeO
OH Catalyst 3, O2
Toluene, Reflux, 20h MeO
O
H
Run Product (Yield %) Recovery of PASMOX
1.
2.
3.
98
95
92
>99 %
>98 %
>96 %
Efficiency of the catalyst
M. Maddani, K. R. Prabhu, Unpublished Results
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Disposal or decomposition protocols for hydrazine and its derivatives by using
user friendly protocols
Disposal or decomposition protocols for hydrazine and its derivatives by using
user friendly protocols
Convert surplus high energy materials to safer products
II
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R.A. BACK, Reviews of Chemical Intermediates, 5 (1984) 293—323C.Willis, R.A.Back, International Journal of chemical kinetics, 1977, 9, 787
R1
R
N2 +R1
RN NHH
N NH
H+ + N N
H
HH H
NH
R1R
H2N NH2
Mo(IV) or V(V)Catalytic N N
+ H2O
N2 + H2
N2 +
+
HHN N
H
H+
N NHH
N NH
H+ N N
H
H
H2N NH2
IN SEARCH OF CATALYST FOR HYDROGENATION USING HYDRAZINE
HYDRATE
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Mo
O
O OOVO O
OO
Vanadium acetylacetonate Molybdenum trioxide
Method for the generation of diimide
H2NNH2, CuSO4, air H2NNH2, CuSO4, H2O2 H2NNH2, CuSO4, O2
using metal Catalyst
Metals such as mercuric oxide and Hexacyanoferrate(III) are also used along with hydrazine hydrate
E.J. Corey, W.L. Mock .D.J. Pasto Tetrahedron Lett. 1961, 347-352
S. Huitig, H. R. Miiller, W. Thier, Tetrahedron Lett. 1961, 353.
METHOD FOR THE AEROBIC HYDROGENATION OF OLEFINS
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OH
O
O NH2NH2.H2O+ + V(acac)2EtOH / Air
RT, 23h
OH
O
O
>99%20mol%5 equiv
OH
O
O NH2NH2.H2O+EtOH / Air
RT, 23h
OH
O
O
>99%5 eq
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H2N NH2+ + H2O.RT
EtOHMoO3
<5%
From Azodicarboxylates (acid catalyzed hydrolysis)
Thermal decomposition of arenesulfonyl hydrazides
E. E. van Tamelen, R. S. Dewey, J. Am. Chem. Soc. 1961 83 3729 .
E.J. Corey, W.L. Mock .D.J. Pasto Tetrahedron Letters 1961, 347-352
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NN
O
-O
O
O-
2K+
+ 2H+ 2CO2 + NH=NH
NH=NHArSO2NHNH2100-150 oC
Flavin-Catalyzed Generation of Diimide
Y. Imada, H. Iida, T. Naota, J. Am. Chem. Soc. 2005, 127, 14544-14545
Reduction of Carbon-Carbon Double Bonds Using Diimide genearted by using
C. Smit, M. W. Fraaije, A. J. Minnaard, J. Org. Chem. 2008, 73, 9482–9485
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R1
R2R3
R4
N
N
N
N
Me
O
Me
Et NH
Me
MeClO4
NH2NH2. H2O (1-2eq) O2 (1atm)
H
R2R3
R4
H
R1
NNH
O
N
OH
HOOH
OH
N O
H2N NH2
HN NH
O2Flcat
N2
R2R1R2R1
Flavin-Catalyzed Generation of Diimide
Y. Imada, H. Iida, T. Naota, J. Am. Chem. Soc. 2005, 127, 14544-14545
Reduction of Carbon-Carbon Double Bonds Using diamide generated by an Organocatalyst
C. Smit, M. W. Fraaije, A. J. Minnaard, J. Org. Chem. 2008, 73, 9482–9485
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R1
R2R3
R4
N
N
N
N
Me
O
Me
Et NH
Me
MeClO4
NH2NH2. H2O (1-2eq) O2 (1atm)
H
R2R3
R4
H
R1
NNH
O
N
OH
HOOH
OH
N O
H2N NH2
HN NH
O2Flcat
N2
R2R1R2R1
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O N
N
N
N
O
H2N NH2
NH H
Cl
CaffineGuanidine hydrochloride
H2N NH2
NH H
CH3C(O) H2N NH2
NH H
NO3
Guanidine acetate Guanidine Nitrate
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O N
N
N
N
OO
OHO
+ NH2NH2 . H2O+
O2, EtOH
4h
O
OHO
>95%
OH
O N
N
N
N
O
+ NH2NH2 . H2O+
O2, EtOHOH
+
OH
30 hr
1:1 Mixture
O
OHO
NH2NH2 . H2O+
O2, EtOH
4h
O
OHO
>95%
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H2N NH2+ H2O.EtOH , O2
1.2 100%1
H2N NH2
NH H
CH3C(O)
Guanidine acetate
H2N NH2++
H2O.EtOH , O2
10 -40 mol% 100%1
RT , >30h
H2N NH2
NH H
NO3
Guanidine Nitrate
H2N NH2+ H2O.EtOH , O2
100%1 10 -40 mol%
RT , >30h
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H2N NH2H2N NH2
NH H
Cl+ + H2O.EtOH , O2
10 mol% 1.2 100%1
Y. Imada, H. Iida, T. Naota, J. Am Chem. Soc. 2005, 127, 14544-14545
MECHANISM FOR OXIDATIVE CLEAVAGE OF HYDRAZINE HYDRATE USING FLAVIN CATALYST
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R1
R2R3
R4
N
N
N
N
Me
O
Me
Et NH
Me
MeClO4
NH2NH2. H2O (1-2eq) O2 (1atm)
H
R2R3
R4
H
R1
ENVIRONMENTALLY BENIGN METHOD FOR THE AEROBIC HYDROGENATION OF OLEFINS
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H2N NH2
H2N NH2
NH H
Cl
O2
N N
R
H
H
N NHH +
R1
RR1
N N
HH
R R1
N N+
REDUCTION OF ALKENES AND ALKYNES
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O
O
BnO
HO
O
O
OH
Br
O
SubsrateEntry
1
2
3
4
5
6
7
Time(h)
8
4
3
4
12
12
3
Yield(%)
99
95
91
93
97
99
87
Product
O
O
BnO
HO
O
O
OH
Br
O
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S
O2N
O
O2N NH
O2N N
OH
SubsrateEntry
8
9
10
11
13
Time(h)
7
30
16
14
24
Yield(%)
94
95
96
92
93
Product
S
O2N
O
O2N NH
O2N N
OH
N3
O
ON3
O
O
14
O2N N12 O2N N
4 95
1886
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SubsrateEntry Time(h) Yield% Product
HO
N
N
HO1
2
N
N
HO
HO
4
8
93
97
O O
24
24
3
4
OH
O
O
O
5
6
OH
O
O
O
98
98
12 93
24 55
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SubsrateEntry Time(h) Yield% Product
O
OH
O16 98
O
OH
O
24 83a
N O
O
N O
O
24
24
1
2
3
4
99
99
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O OH
Br
O
Na2CO3 NH2NH2 . H2O+H2N NH2
N+
O OH
Br
O
+Water 12h
Reflux
H H Cl
10 mol%
O
ONa
Br
O
NH2NH2 . H2OH2N NH2
N+
H H Cl
O
ONa
Br
O
1. dil.HClNa2CO3
DRUGS WITH CHIRAL METHYL GROUP
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RO
OH
RO
OH
Chiral ligand
OO
OH
OO
OH
O
OH
F
(S)-Ibuprofen
(S)-Flurbiprofen(S)-Fenoprofen
(S)-Naproxen
RO
OH
SYNTHETIC SCHEME
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BrO
OO
O
O
O
O
O
1 2
2 3
O
OH
OO
OH
OO
OH
O
OH
F
4 5 6
ENANTIOSELECTIVE REDUCTION
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O
OH
O
OHNH2NH2.H2O
H2N NH2
NH H
ClO2
Chiral ligands
N
N
HO
NH2
NH2
PPh2
PPh2
P
P
R
RR
R
NH2
NH2
O
N N
O
R R
OH
OH
Ligands
Tehshik P. Yoon, Eric N. Jacobsen*, Science 2003:Vol. 299. no. 5613, pp. 1691 - 1693
Andreas Pfaltz * and William J. Drury III, PNAS April 20, 2004 vol. 101 no. 16 5723-5726
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NHAc
OH
O
HO
OH
NHAc
OH
O
HO
OH
H2N NH2
NHH
Cl NH2NH2.H2O
AcHN
O
OH
H2N NH2
NHH
Cl NH2NH2.H2O AcHN
O
OH+ +
+ +
Chiral Ligand
Chiral Ligand
(R)-2-acetamido-3-(3,4-dihydroxyphenyl)propanoic acid
(R)-2-acetamidopropanoic acid
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Conclusion
P Prevent waste
R Renewable raw material
O Omit derivatization steps
D Degradable Chemical Product
U Use of safe synthetic methods
C Catalytic reagents
T Temperature, Pressure ambient
I In – process monitoring
V Very few auxiliary substrates
E E-factor, atom efficiency
L Low toxicity of chemical products
Y Yes, it is safe
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Dr. Mahagundappa Maddani
Mr. Manjunath Lamani
Mr. GS Ravikumar
Acknowledgements
IISc, AMRB, RL Fine Chem
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