2 CuICl C2H4 – II 2 Cl + 2 Cu Cl2 II 2– Pd Cl4 Cl– O Pd0 H3C H PdIICl – + HCl 3 Mechanistic Studies on H2O the Wacker Oxidation H O + – II H , Cl Pd Cl Pamela Tadross H3C H Stoltz Group Literature Presentation OH December 8, 2008 8 PM, 147 Noyes PdIICl – HO 2 OH PdIICl H3C Cl– PdIICl Cl Cl – Pd Cl Cl + H2O Pd H2O HO Origins of the Wacker Oxidation F. C. Phillips, 1894: 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Origins of the Wacker Oxidation F. C. Phillips, 1894: 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl Smidt, Wacker Chemie, 1959: – 2– Pd(0) + 2 CuCl2 + 2 Cl 2 CuCl + PdCl4 2 CuCl + 1/2 O2 + 2 HCl 2 CuCl2 + H2O Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Origins of the Wacker Oxidation 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl – 2– Pd(0) + 2 CuCl2 + 2 Cl 2 CuCl + PdCl4 2 CuCl + 1/2 O2 + 2 HCl 2 CuCl2 + H2O Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Origins of the Wacker Oxidation 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl – 2– Pd(0) + 2 CuCl2 + 2 Cl 2 CuCl + PdCl4 2 CuCl + 1/2 O2 + 2 HCl 2 CuCl2 + H2O C2H4 + 1/2 O2 CH3CHO Net Result: Air oxidation of ethylene to acetaldehyde! Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Origins of the Wacker Oxidation 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl – 2– Pd(0) + 2 CuCl2 + 2 Cl 2 CuCl + PdCl4 2 CuCl + 1/2 O2 + 2 HCl 2 CuCl2 + H2O C2H4 + 1/2 O2 CH3CHO Net Result: Air oxidation of ethylene to acetaldehyde! ! First organopalladium reaction applied on industrial scale. ! First rendered commercial in 1960. ! At one point was responsible for the production of over 2 billion pounds per year of acetaldehyde! Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Origins of the Wacker Oxidation 2– – PdCl4 + C2H4 + H2O Pd(0) + CH3CHO + 2 HCl + 2 Cl – 2– Pd(0) + 2 CuCl2 + 2 Cl 2 CuCl + PdCl4 2 CuCl + 1/2 O2 + 2 HCl 2 CuCl2 + H2O C2H4 + 1/2 O2 CH3CHO Net Result: Air oxidation of ethylene to acetaldehyde! ! First organopalladium reaction applied on ! Prior acetaldehyde production: industrial scale. a) Oxymercuration of acetylene b) Dehydrogenation of ethanol ! First rendered commercial in 1960. ! Wacker process eventually replaced ! At one point was responsible for the because of more efficient ways of production of over 2 billion pounds per producing acetic acid (i.e. Monsanto year of acetaldehyde! process). Phillips, F. C. Am. Chem. J. 1984, 16, 255-277. Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, S.; Sabel, A. Angew. Chem. Int. Ed. Engl. 1962, 1, 80. Early Kinetic Studies Conditions: ! First order in PdII 2– –d[C2H4] k [PdCl ] [C H ] [PdII] = 0.005 - 0.04 M Rate = = 4 2 4 – – 2 + ! Second order Cl inhibition [Cl–] = 0.1 - 1.0 M dt [Cl ] [H ] + [H ] = 0.04 -1.0 M ! First order acid inhibition Henry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. Dokl. Akad. Nauk. SSSR 1963, 153, 140. Early Kinetic Studies Chloride Inhibition Conditions: ! First order in PdII 2– –d[C2H4] k [PdCl ] [C H ] [PdII] = 0.005 - 0.04 M Rate = = 4 2 4 – – 2 + ! Second order Cl inhibition [Cl–] = 0.1 - 1.0 M dt [Cl ] [H ] + [H ] = 0.04 -1.0 M ! First order acid inhibition Source of Chloride Inhibition: 2– – 1 Cl Cl Cl – inhibition Pd + C2H4 Pd + Cl – Cl Cl Cl Cl [Cl ] – 1 Cl + H O Cl + Cl– inhibition Pd 2 Pd [Cl–] Cl Cl Cl OH2 Henry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. Dokl. Akad. Nauk. SSSR 1963, 153, 140. Early Kinetic Studies Proton Inhibition Conditions: ! First order in PdII 2– –d[C2H4] k [PdCl ] [C H ] [PdII] = 0.005 - 0.04 M Rate = = 4 2 4 – – 2 + ! Second order Cl inhibition [Cl–] = 0.1 - 1.0 M dt [Cl ] [H ] + [H ] = 0.04 -1.0 M ! First order acid inhibition – – OH Outer-sphere hydroxide attack: Cl Cl CH CH OH Pd Pd 2 2 Predicted to be 103 times faster Cl OH2 Cl OH2 than diffusion controlled process Henry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. Dokl. Akad. Nauk. SSSR 1963, 153, 140. Early Kinetic Studies Proton Inhibition Conditions: ! First order in PdII 2– –d[C2H4] k [PdCl ] [C H ] [PdII] = 0.005 - 0.04 M Rate = = 4 2 4 – – 2 + ! Second order Cl inhibition [Cl–] = 0.1 - 1.0 M dt [Cl ] [H ] + [H ] = 0.04 -1.0 M ! First order acid inhibition – – OH Outer-sphere hydroxide attack: Cl Cl CH CH OH Pd Pd 2 2 Predicted to be 103 times faster Cl OH2 Cl OH2 than diffusion controlled process H2O – Cl Cl CH CH OH Outer-sphere water attack: Pd Pd 2 2 + H+ Predicted to occur by an anti Cl OH2 Cl OH2 hydroxypalladation mechanism Henry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. Dokl. Akad. Nauk. SSSR 1963, 153, 140. Early Kinetic Studies Proton Inhibition Conditions: ! First order in PdII 2– –d[C2H4] k [PdCl ] [C H ] [PdII] = 0.005 - 0.04 M Rate = = 4 2 4 – – 2 + ! Second order Cl inhibition [Cl–] = 0.1 - 1.0 M dt [Cl ] [H ] + [H ] = 0.04 -1.0 M ! First order acid inhibition – – OH Outer-sphere hydroxide attack: Cl Cl CH CH OH Pd Pd 2 2 Predicted to be 103 times faster Cl OH2 Cl OH2 than diffusion controlled process H2O – Cl Cl CH CH OH Outer-sphere water attack: Pd Pd 2 2 + H+ Predicted to occur by an anti Cl OH2 Cl OH2 hydroxypalladation mechanism – – Inner-sphere hydroxyl Cl Cl Cl CH CH OH Pd Pd + H+ Pd 2 2 attack: Predicted to Cl OH Cl OH Cl OH occur by a syn 2 2 hydroxypalladation mechanism Henry, P. M. J. Am. Chem. Soc. 1964, 86, 3246. Jira, R.; Sedlmeier, J.; Smidt, J. Liebigs Ann. Chem. 1966, 693, 99. Moiseev, I. I.; Vargaftik, M. N.; Syrkin, Ya. K. Dokl. Akad. Nauk. SSSR 1963, 153, 140. Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn Hydroxypalladation Mechanism D D O 2– – + PdCl4 + H2O + Pd(0) + 2 HCl + 2 Cl D D D3C D kH = 1.07 k H H O D 2– – + PdCl4 + H2O + Pd(0) + 2 HCl + 2 Cl H H H3C H Henry, P. M. J. Org. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461. Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn Hydroxypalladation Mechanism D D O 2– – + PdCl4 + H2O + Pd(0) + 2 HCl + 2 Cl D D D3C D kH = 1.07 k H H O D 2– – + PdCl4 + H2O + Pd(0) + 2 HCl + 2 Cl H H H3C H KIE for decomposition step determined by competitive isotope effect experiment: H-shift O DH2C D D D D D – k 2– H + PdCl4 + H2O HO Pd(OH2)Cl2 = 1.70 k H H H H D O D-shift HD2C H Henry, P. M. J. Org. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461. Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn Hydroxypalladation Mechanism KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs outer-sphere anti hydroxypalladation before decomposition. – Cl Cl Cl Cl Pd Pd + + H2O + H H2O H2O CH2CH2OH O +H+ –H+ H3C H – – Cl Cl Cl Cl Pd + H O Pd HO 2 H2O CH2CH2OH inner-sphere syn hydroxypalladation Henry, P. M. J. Org. Chem. 1973, 38, 2415. Kosaki, M.; Isemura, M.; Kitaura, K.; Schinoda, S.; Saito, Y. J. Mol. Catal. 1977, 2, 351. Saito, Y.; Schinoda, S. J. Mol. Catal. 1980, 9, 461. Kinetic Isotope Effects Early Evidence for an Inner-Sphere Syn Hydroxypalladation Mechanism KIE 1.07 and competitive KIE of 1.70 indicates that the slow step occurs outer-sphere anti hydroxypalladation before decomposition. – Cl Cl Cl Cl Pd Pd + + H2O + H H2O H2O CH2CH2OH fast slow O +H+ –H+ H3C H fast – slow – Cl Cl Cl Cl Pd + H O Pd HO 2 H2O CH2CH2OH inner-sphere syn hydroxypalladation anti pathway has decomposition as the slow step syn pathway has hydroxypalladation as the slow step Henry, P.