Control of Selectivity in Acylation OF Glucosides

根据4，6-O-亚甲基-α-D-吡喃葡萄糖苷(1)与苯甲酸酐在不同脂肪族叔胺催化下的苯甲酰化反应的结果，我们证明了酸酐也是一种很好的酰化试剂，并且迄今报道的低选择性是由于吡啶催化剂，而不是酸酐所固有的。我们研究了在50ﾟC乙腈中环状和非环状脂肪族叔胺催化1的苯甲酰化反应。相对速率--2-苯甲酰化速率与3-苯甲酰化速率之比--在4.4到23的范围内变化，远大于吡啶催化的苯甲酰化反应。当使用位阻较小的环胺时，可以实现选择性的2-苯甲酰化，其中N-甲基吡咯烷是最大的。在弱碱性条件下，N-甲基吗啉的选择性较低，反应速度较慢。在t…的作用下，对三乙胺、吡啶和N-甲基哌啶的反应动力学进行了研究更多的是伪一阶条件。结果表明：(1)在脂肪胺催化下，反应物(1)的浓度变化是一级反应，(2)在脂肪胺催化下，反应速率随胺浓度的变化曲线表现出相当复杂的特征；(3)根据上述曲线的分析，1与胺催化剂形成了1：1和1：2的络合物，后者是选择性2-苯甲酰化反应的关键中间体，(4)在吡啶催化的反应中，只有1：1的络合物。这将导致观察到的低选择性。总而言之，当脂肪族叔胺催化反应时，酸酐获得的高选择性不低于更复杂的酰化试剂，如酰氯、氰化物或咪唑。迄今为止观察到的低选择性不是酸酐所固有的，而是由于吡啶催化。较少

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 … More 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