Homogeneous Catalysis.pptx

Homogeneous catalysis, hydrogenation, hydroformylation, hydrocyanation, Ziegler-Natta catalyst, Wilkinson catalyst, chiral ligands and chiral induction.

M.Pharm (2nd Semester- Pharmaceutical Chemistry/Medicinal Chemistry), B.Pharm, B.Sc., M.Sc. (Chemistry)

1. Homogeneous Catalysis Advanced Organic Chemistry - II Prepared by: Chandni Pathak 2208212120001 M.Pharm (Pharmaceutical Chemistry) - 2nd Sem Parul Institute of Pharmacy

2. Catalysis Catalysis is an action by a catalyst which takes part in a chemical reaction process and can alter the rate of reactions, and yet itself will return to its original form without being consumed or destroyed at the end of the reactions . A catalyst typically increases the rate of reaction by lowering the activation energy by opening up pathways with lower Gibbs free energy of activation (G). ‹#›

3. Catalysis ‹#›

4. Classification of Catalysts ‹#›

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6. Homogeneous Catalysts Homogeneous catalysis is a reaction in which the catalyst is in the same phase as the reactants in the solution. Most often, homogeneous catalysis involves the introduction of aqueous phase catalyst into an aqueous solution of reactants. In such cases, acids and bases are often very effective catalysts, as they can speed up reactions by affecting bond polarization . E.g. : Hydrolysis of sugar is catalysed by H + ions furnished by sulfuric acid. ‹#›

7. Homogeneous Catalysts ‹#›

8. Selectivity of Catalysts 1] Chemoselectivity When two chemically different functionalities are present such as an alkene and an aldehyde which both can be hydrogenated, the chemoselectivity tells us whether the aldehyde or the alkene is being hydrogenated; or when more than one reaction can take place for the same substrate. E.g.: Hydrogenation ‹#›

9. Selectivity of Catalysts 2] Regioselectivity The formyl group can be attached to either the primary, terminal carbon atom or the secondary, internal carbon atom, which leads respectively to the linear and branched product. E.g.: Hydroformylation ‹#›

10. Selectivity of Catalysts 3] Diastereoselectivity The substrate contains a stereogenic centre and this together with the catalyst can direct the addition of dihydrogen in the example to give two diastereomers, the selectivity for either one is called the diastereoselectivity. ‹#›

11. Selectivity of Catalysts 4] Enantioselectivity The substrate is achiral in this instance, but the enantiopure or enantio-enriched catalyst may give rise to the formation of one specific product enantiomer. ‹#›

12. Important Reaction Types Oxidative Addition Reductive Elimination Migratory Insertion 𝝱-Hydride elimination ‹#›

13. Oxidative Addition ‹#›

14. 2. Reductive Elimination ‹#›

15. 3. Migratory Insertion ‹#›

16. 3. Migratory Insertion ‹#›

17. 3. Migratory Insertion ‹#›

18. 4. 𝝱-Hydride Elimination ‹#›

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20. Hydrogenation It is a chemical reaction between molecular hydrogen (H 2 ) with unsaturated organic compound (alkene or aldehyde) in presence of a catalyst such as Rh or Co. The process is commonly employed to reduce or saturate organic compounds (alkane or alcohol). E.g.: ‹#›

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23. Applications of Hydrogenation Reaction Homogeneous catalysts are useful for selective hydrogenation of the C-C double bond without hydrogenolysis of other susceptible groups. E.g.: Benzyl cinnamate is converted into the dihydro compound without hydrogenolysis of the benzyl group . C 6 H 5 CH=CHCOOC 6 H 5 E.g.: Allyl phenyl sulfide on reaction gives 93% phenyl propyl sulfide . CH 2 =CHCH 2 SC 6 H 5 H 2 , PPh 3 RhCl C 6 H 6 C 6 H 5 CH 2 CH 2 COOC 6 H 5 H 2 , PPh 3 RhCl C 6 H 6 CH 3 CH 2 CH 2 SC 6 H 5 ‹#›

24. Hydroformylation Synthesis of aldehydes from terminal alkenes with cobalt and rhodium catalysts. Hydroformylation, popularly known as ‘ oxo ’ process. The reaction is catalyzed by organorhodium or organocobalt compounds and adds a hydrogen atom to the C=C to form a C-C bond and a formyl group to the molecule, creating an aldehyde. The metal hydride complexes namely the rhodium based HRh(CO)(PPh 3 ) 3 and the cobalt based HCo(CO) 4 complexes catalyzes the hydroformylation. ‹#›

25. Hydroformylation Hydroformylation is also used in specialty chemicals, relevant to the organic synthesis of fragrances and natural products. Comparative study of three commercial homogeneous catalytic processes for the hydroformylation reaction: Though most long-chain, branched chain and cyclic olefins can be hydroformylated, the most common starting chemicals are ethylene and propylene, which yield propionaldehyde, n-butaraldehyde and iso-butaraldehyde. ‹#›

26. Rhodium-catalysed Hydroformylation The high selectivity and mild conditions make the rhodium process more attractive than the cobalt one for the manufacture of n-butyraldehyde. In this process, rhodium was recovered. ‹#›

27. Cobalt -catalysed Hydroformylation ‹#›

28. Cobalt-catalysed Hydroformylation Cobalt catalysts operate at 150 C and 250 atm pressure whereas rhodium catalysts operate at moderate temperature and 1 atm pressure. Propylene coordination followed by olefin insertion into the metal hydrogen bond in a markovnikov or anti-markovnikov fashion gives the branched or the linear metal alkyl complex. ‹#›

29. Hydrocyanation Hydrocyanation of olefins refers to the transition-metal-mediated or -catalysed addition of hydrogen cyanide across a carbon-carbon 𝞹 bond. This reaction may be used to synthesize nitriles from olefins in a Markovnikov or anti-markovnikov fashion. The common catalysts used to effect hydrocyanation are Ni(0) and Pd(0) complexes. The industrial development of nickel-catalyzed hydrocyanation was motivated by the need to mass produce adiponitrile (1,4-dicyanobutane) for nylon synthesis . ‹#›

30. Hydrocyanation A key step in hydrocyanation is the oxidative addition of HCN to low-valent metal complexes. In hydrocyanation of unsaturated carbonyls addition over the alkene competes with addition over the carbonyl group. It is basically used in steroids synthesis . ‹#›

31. Ziegler-Natta Catalysts The German chemist “ Karl Ziegler ” discovered in 1953 that when TiCl 4 and Al(C 2 H 5 ) 3 are combined together, they produce an extremely active heterogeneous catalyst for the polymerization of ethylene at atmospheric pressure. “ Giulio Natta ” , an Italian chemist, extended the method to other olefins like propylene and developed variations of the Ziegler catalyst based o his findings on the mechanism of the polymerization reaction. The Ziegler-Natta catalysts family includes halides of titanium, chromium, vanadium and zirconium, typically activated by alkyl aluminium compounds. Ziegler-Natta received the Nobel prize in chemistry for their work in 1963. ‹#›

32. Ziegler-Natta Catalysts The titanium chloride compound has a crystal structure in which each Ti atom is coordinated to 6 chlorine atoms. On the crystal surface, a Ti atom is surrounded by 5 chlorine atoms with one empty orbital to be filled. When ET 3 Al comes in, it donates an ethyl group to Ti atom and the Al atom is coordinated to one of the chlorine atoms. Meanwhile, one Cl atom from titanium is kicked out during this process. Thus, the catalyst system has an empty orbital. ‹#›

33. Ziegler-Natta Catalysts ‹#›

34. Ziegler-Natta Catalysts 1] Regioselectivity For propene polymerization, most ZN catalysts are highly regioselective, favouring 1,2-primary insertion due to electronic and steric effects. 2] Stereoselectivity The relative stereochemistry of adjacent chiral centers within a macromolecule is defined as tacticity. Three kinds of stereochemistry are possible: isotactic, syndiotactic and atactic. ‹#›

35. Ziegler-Natta Catalysts ‹#›

36. Wilkinson’s Catalysts Wilkinson’s catalyst is the common name for chlorotris(triphenylphosphine)rhodium (I) [(C 6 H 5 ) 3 P] 3 RhCl. It is red brown colored solid that is soluble in hydrocarbon solvents such as benzene, and more so in THF or DCM. The compound is widely used as a catalyst for hydrogenation of alkenes . The catalyst is sensitive to the steric influence of the alkene substrate. Terminal alkynes are hydrogenated more rapidly than terminal alkenes. Conjugated dienes are reduced more slowly than isolated alkenes . For disubstituted alkenes, cis are more reactive than trans. Trisubstituted alkenes are more reactive than tetra-substituted alkenes. ‹#›

37. Wilkinson’s Catalysts Preparation: Reaction: It is used in the selective hydrogenation of alkenes and alkynes without affecting the functional groups like C=O, CN, NO 2 , aryl, CO 2 R, etc. ‹#›

38. Wilkinson’s Catalysts ‹#›

39. Chiral Induction and Chiral Ligands Most chiral ligands combine with metals to form chiral catalyst engages in a chemical reaction in which chirality is transferred to the reaction products. Chiral induction is also known as asymmetric induction . Substrate has to be prochiral . Catalyst has to be chiral . Homogeneous catalysts are also used for the manufacture of chiral molecules. Depending on the number of asymmetric centres, chiral molecules have two or more optical isomers. ‹#›

40. Chiral Induction and Chiral Ligands ‹#›

41. Chiral Induction and Chiral Ligands ‹#›

42. Chiral Induction and Chiral Ligands ‹#›

43. Chiral Induction and Chiral Ligands Chiral ligands are no different from the general categories of ligands that we have already encountered. They, however, have one or more chiral or asymmetric centres and can be broadly classified into two types: The first type has ‘hard’ donor atoms such as nitrogen and/or oxygen and can be monodentate or chelating depending upon the nature of reaction. The second type is almost exclusively based on chelating phosphines. ‹#›

44. Chiral Induction and Chiral Ligands First Category ‹#›

45. Chiral Induction and Chiral Ligands 2) Second Category ‹#›

46. Homogeneous Catalysis in Drug Synthesis Contribution of homogeneous catalytic process in chemical industry is significantly smaller compared to heterogeneous catalytic process, it is only about 17-20% . But importance of homogeneous catalysis is increasing significantly. Some of the important industrial processes include: Oxidations of alkenes such as production of acetaldehyde, propylene oxide, etc. Polymerization such as production of polyethylene, polypropylene or polyesters. ‹#›

47. A] Synthesis of l-DOPA The asymmetric hydrogenation of cinnamic acid derivatives involves the synthesis of L-DOPA. The carbon atom bonded to the -NH 2 group is the chiral centre. The enantiomer D-DOPA is inactive. The reaction is carried out in presence of rhodium complex having asymmetric diphosphine ligand which induces enantio-selectivity. The main step in L-DOPA synthesis is the hydrogenation of prochiral alkene to a specific optical isomer. ‹#›

48. B ] Other Examples ‹#›

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