1. Dr. Kandikere Ramaiah Prabhu
Green Chemistry By
Dr. Kandikere Ramaiah Prabhu
Principal Research Scientist
Department of Organic Chemistry
Indian Institute of Science
Bangalore –
October 23, 2010, Bangalore

2. History….. Green Chemistry is born around 199o What 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

3. 12 Principals of green chemistry
Prevention It is better to prevent waste than to treat or clean up waste after it has been created.
Atom Economy Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.
Less Hazardous Chemical Syntheses Wherever 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 Chemicals Chemical products should be designed to effect their desired function while minimizing their toxicity.
Safer Solvents and Auxiliaries The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.
Design for Energy Efficiency Energy 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.

4. Use of Renewable Feedstocks A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.
Reduce Derivatives Unnecessary 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.
Catalysis Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.
Design for Degradation Chemical 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 Prevention Analytical 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 Prevention Substances 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.

5. E-Factor???
Mass ratio of waste to desired product
Higher e-factor – more waste and –ve environmental impact
Raw Materials-Product output
product
The key to waste minimization is precision in organic synthesis,
where every atom counts!!!

6. Atom efficiency
Molecular weight of the product
Sum molecular weight of the
all products formed
Atom efficiency of stoichiometric versus catalytic oxidation of alcohols

8. 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 hydride
Oxidations - CrO3, KMnO4,etc
Sulfonation, Nitration, Friedel-Crafts reaction etc……!!!!

9. 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

11. Two routes to hydroquinones

12. Homogeneous catalyst & Heterogeneous catalysts
Organocatalyst
Biocatalysts

13. Homogeneous catalyst & Heterogeneous catalysts
Organocatalyst

14. Development Catalysis in Organic Synthesis

15. There are several reasons for this.
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.

16. First, because of the smaller quantities compared. with
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 catalytic
alternatives.
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.

17. Major points to be addressed
Catalysts
Solvents
Renewable Raw Materials – White biotechnology
Risky Reagents
Process integration and catalytic cascades

18. Catalysts
Acid base catalyst
Heterogeneous catalysts
Homogeneous catalyst
Solid catalysts
Bio catalyst
Organo catalysts

19. Acid base catalyst
Montmorillonite clays

20. Zeolites

21. Reductions Catalytic reductions Hydrogen gas Hydrogenation catalysts
Selectivity in hydrogenation
Chiral reductions

22. oxidations

23. Biocatalysts
Egs:
Yeast-ADH as alcohol dehydrogenase
Horse liver-ADH

24. Organocatalysis
Proline-catalyzed aldol reaction

25. Our Research…!!!! X XO M Oxidized MReduced
Transition Metal oxides Chemical transformations Academia & Industry.
Metal-oxo complexes Oxidations & reductions processes.
M Oxidized
MReduced
Oxidation X XO
Reduction

26. Oxygen is transformed from Molecular Oxygen
M. Maddani, K. R. Prabhu, Tetrahedron Lett., 2008, 49, 4526

27. Oxidation of Alcohols to Carbonyls Catalysed by Molybdenum Xanthate
No reaction
Heterogeneous catalysts Recovery, recycling and Stability.
Liquid phases

28. Efficiency of the catalyst
M. Maddani, K. R. Prabhu, Unpublished Results

29. II
Disposal or decomposition protocols for hydrazine and its derivatives by using user friendly protocols
Convert surplus high energy materials to safer products

30. R.A. BACK, Reviews of Chemical Intermediates, 5 (1984) 293—323
C.Willis, R.A.Back, International Journal of chemical kinetics, 1977, 9, 787

31. In search of catalyst for hydrogenation using hydrazine hydrate

32. Method for the Aerobic Hydrogenation of Olefins
Method for the generation of diimide
using metal Catalyst
H2NNH2, CuSO4, air
H2NNH2, CuSO4, H2O2
H2NNH2, CuSO4, O2
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,
S. Huitig, H. R. Miiller, W. Thier, Tetrahedron Lett. 1961, 353.

35. From Azodicarboxylates (acid catalyzed hydrolysis)
Thermal decomposition of arenesulfonyl hydrazides
E. E. van Tamelen, R. S. Dewey, J. Am. Chem. Soc
E.J. Corey, W.L. Mock .D.J. Pasto Tetrahedron Letters 1961,

36. Flavin-Catalyzed Generation of Diimide
Y. Imada, H. Iida, T. Naota, J. Am. Chem. Soc. 2005, 127,
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

37. Flavin-Catalyzed Generation of Diimide
Y. Imada, H. Iida, T. Naota, J. Am. Chem. Soc. 2005, 127,
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

42. Y. Imada, H. Iida, T. Naota, J. Am Chem. Soc. 2005, 127, 14544-14545
Mechanism For oxidative cleavage of Hydrazine hydrate using Flavin Catalyst
Y. Imada, H. Iida, T. Naota, J. Am Chem. Soc. 2005, 127,

43. Environmentally Benign Method for the Aerobic Hydrogenation of Olefins

44. Reduction of alkenes and alkynes

49. Drugs with chiral methyl group

50. Synthetic scheme

51. Enantioselective Reduction
Tehshik P. Yoon, Eric N. Jacobsen*, Science 2003:Vol no. 5613, pp
Andreas Pfaltz * and William J. Drury III, PNAS April 20, 2004 vol. 101 no

53. 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

54. Acknowledgements Dr. Mahagundappa Maddani Mr. Manjunath Lamani
Mr. GS Ravikumar
IISc, AMRB, RL Fine Chem