Anchimeric Assistance

The well-known facilitation1,2 of nucleophilic displacement reactions (particularly solvolytic reactions) resulting from a suitably positioned neighboring group. This functional group may help in directing the nucleo-phile to the electrophilic center or it may increase reactivity by stabilizing a reaction intermediate. Jencks3 provides the following example of the importance of intramolecular assistance: Hydrolysis of tetramethylsuc-canilic acid at pH 5 has a half-time of 30 minutes, whereas the hydrolysis of acetanilide at the same pH has a halftime of around 300 years.

Anchimeric assistance may also explain slight changes in mechanism resulting from the presence of a neighboring group. One likely case is the acid-catalyzed hydrolysis of phenylglycosides. Raftery's group4 found that the secondary kinetic isotope effect (kH/kD) was 1.13 for acid hydrolysis ofphenyl-4-O-(2-acetamido-2-deoxy-fi-d-glu-

copyranosyl)-fi-d-glucopyranoside, but kH/kD was later determined to be only 1.08 for phenyl-4-O-(2-acetamido-2-deoxy-fi-d-glucopyranosyl)-2-acetamido-2-deoxy-fi -d-glucopyranoside5. Such a result suggests that the kinetics for forming the likely oxocarbonium ion intermediate are influenced by the neighboring acetamido group. Interestingly, the value of kH/kD for lyzozyme-catalyzed hydrolysis are 1.11 and 1.14, respectively, suggesting that substitution of the acetamido group for a hydrogen has little effect on the enzymic process. See also Neighboring Group Mechanism

1C. K. Ingold (1953) Structure and Mechanism in Organic Chemistry, p. 511 Cornell University Press, Ithaca. 2S. Winstein & E. Grunwald (1948) J. Am. Chem. Soc. 70, 828. 3W. P. Jencks (1969) Catalysis in Chemistry and Enzymology, p. 211, McGraw-Hill, New York. [Also available as Jencks, W. P. (1986) Catalysis in Chemistry and Enzymology, Dover Publications, New York] 4F. W. Dahlquist, T. Rand-Meir & M. A. Raftery (1969) Biochemistry 8, 4214.

5L. H. Mohr, L. E. H. Smith & M. A. Raftery (1973) Arch. Biochem. Biophys. 159, 505.

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