|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1994 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1993 : ¥1,700,000 (Direct Cost : ¥1,700,000)
We have demonstrated that acid anhydride is also a good acylation reagent and that the hitherto reported low selectivity is due to pyridine catalyst, not intrinsic to acid anhydride, on the basis of the results in benzoylation of 4,6-O-benzylidene-alpha-D-glucopyranoside (1) with benzoic anhydride catalyzed by various aliphatic tertiary amines.
We have investigated the benzoylation of 1 catalyzed by cyclic and acyclic aliphatic tertiary amines at 50ﾟC in acetonitrile. The relative rate--the ratio of the rate for 2-benzoylation to that for 3-benzoylation--varies in 4.4 to 23 ranges, much larger compared with that of the pyridine-catalyzed benzoylation. Selective 2-benzoylation is achieved when sterically less hindered cyclic amines are used, with N-methylpyrrolidine the largest. Relatively low selectivity as well as slow reaction in the case of N-methylmorpholine would be due to the weak basicity.
A kinetic study was carried out with triethylamine, pyridine, and N-methylpiperidine under t
he pseudo-first-order conditions. As a result, it was found that (1) the time course of the reactant (1) concentration change is first order with respect to 1 and benzoic anhydride, on the other hand, (2) the profiles of the dependence of the rate on amine concentration show a rather complex feature in the case of aliphatic amine catalysis, (3) based on the analysis of the above profiles, the 1 : 1 and 1 : 2 complex formation was suggested between 1 and the amine catalysts, and the latter would be the key intermediate in selective 2-benzoylation, and (4) in pyridine-catalyzed reaction only 1 : 1 complex was suggested. This would result in the observed low selectivity.
In conclusion, acid anhydrides would achieve no less high selectivity than more sophisticated acylation reagents, such as acyl chlorides, cyanides, or imidazoles, when the reaction is catalyzed by aliphatic tertiary amines. The hitherto observed low selectivity is not intrinsic to the acid anhydride, but due to the pyridine catalysis. Less