Control of Selectivity in Acylation OF Glucosides

我们已经证明酸酐也是一种很好的酰化试剂，迄今为止报道的低选择性是由于吡啶催化剂，而不是酸酐固有的，基于各种脂肪叔胺催化的4,6- o -苄基- α - d -葡萄糖吡喃苷(1)与苯甲酸酐的苯甲酰化的结果。研究了环和非环脂肪族叔胺在50℃的温度下在乙腈中对1的苯甲酰化反应。相对速率——2-苯甲酰化与3-苯甲酰化的速率之比——在4.4到23的范围内变化，比吡啶催化的苯甲酰化要大得多。选择性2-苯甲酰化是实现时，空间较少阻碍环胺的使用，与最大的n -甲基吡咯烷。在n -甲基啉的情况下，由于碱性较弱，选择性较低，反应较慢。以三乙胺、吡啶和n -甲基哌啶为原料，在拟一阶条件下进行了动力学研究。结果发现：(1)反应物的时间过程(1)浓度变化对于1和苯甲酸酐是一级的，另一方面(2)在脂肪胺催化的情况下，速率对胺浓度的依赖曲线表现出相当复杂的特征，(3)基于上述曲线的分析，1:1和1：(4)在吡啶催化反应中，1与胺类催化剂形成1∶1络合物，而胺类催化剂是选择性2-苯甲酰化反应的关键中间体。这将导致观察到的低选择性。总之，当反应由脂肪族叔胺催化时，酸酐的选择性并不亚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固有的，而是由于吡啶的催化作用。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