Catalysis preassociation

Pre-association by a proton donor or electron acceptor can be a novel catalytic component in decarboxylation reactions. The mechanism is readily available in biochemical systems but is difficult to achieve in solution as the preassociation requires specific interactions. As instances are found, they provide important information on the mode of catalysis. 

Rebek and his co-workers have shown that replication - autocatalysis based on molecular recognition - best accommodates the facts observed in the reaction of 42 with 43, and that under the published conditions 44 is responsible for the autocatalysis. The results indicated template-catalyzed replication as the source of autocatalysis, where recognition surfaces and functional groups interact to form a productive termolecular complex. The mechanism demands that catalysis would be absent with esters that lack hydrogen-bonding sites. One complication of this system is that the initial product of this bimolecular preassociative mechanism is postulated to be a cw-amide, which isomerized to the frani-amide, the active form of template. This appears to be one major background reaction for product formation (Scheme 14). 

However, general acid catalysis is observed for the (1375 times slower) cyclization of the C-methyl compound 4.3 (R = CH3, Scheme 2.32) evidently methyla-tion destabilizes the vinyl carbanion to the point where it no longer has a significant lifetime in water, and the preassociation-concerted mechanism is enforced once more [67]. 

This is a particular case of general Lewis base catalysis of a substitution reaction. It may be troublesome for other studies because of the ease with which some phosphines are oxidized to phosphine oxides. This type of preassociation and catalysis is favored by the low-polarity solvents used in this area and may be unobserved in more polar and hydroxylic solvents. 

Kinetic studies of the iV-methyUmidazole-catalysed reactions of X-phenyl isothiocyanates (124 X = 4-Me, 3-Me, H, 4-Cl, 4-Br, 3-Br, 4-NO2) with diphenylphosphinic hydrazide (125) in benzene at 25 °C have provided further evidence for a preassociation general base mechanism of catalysis for this reaction type. Thiosemicarbazides (126), the products of reaction, formed only slowly in the absence of the catalyst, but the catalytic reaction was ca 10 times faster and was found to be more sensitive than the non-catalytic reaction to electronic effects of substituents in the aryl isothiocyanates. ... 

Cox, M.M., Jencks, W.P. Catalysis of the methoxyaminolysis of phenyl acetate by a preassociation mechanism with a solvent isotope effect maximum. J. Am. Chem. Soc. 1981,103(3), 572-580. 

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