Control of Selectivity in Acylation OF Glucosides

糖苷酰化选择性的控制

• 批准号: 05640618
• 负责人: ITO Masato
• 金额: $ 1.41万
• 依托单位: Soka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05640618/
• 关键词: Glucoside; Acylation; Amine catalyst; Selectivity; Kinetics; Reaction Intermediate; Basicity; Steric Effect; NMR

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

我们已经证明酸酐也是一种良好的酰化试剂，并且迄今报道的低选择性是由于吡啶催化剂，而不是酸酐固有的，基于4，6-O-亚苄基-α-D-吡喃葡萄糖苷（1）在各种脂肪族叔胺催化下与苯甲酸酐反应，研究了环状和无环脂肪族叔胺催化1的苯甲酰基化反应，胺在50 ℃的乙腈中。相对速率-2-苯甲酰基化速率与3-苯甲酰基化速率之比-在4.4至23的范围内变化，与吡啶催化的苯甲酰基化相比大得多。当使用空间位阻较小的环胺时，实现选择性2-苯甲酰化，其中N-甲基吡咯烷最大。以三乙胺、吡啶和N-甲基哌啶为原料，在碱性条件下，研究了N-甲基吗啉的选择性和反应速度，结果表明，在碱性条件下，N-甲基吗啉的选择性较低，反应速度较慢。 ...更多信息 伪一阶条件。结果发现，（1）反应物（1）浓度变化的时间过程相对于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性曲线显示出相当复杂的特征，（3）基于对上述曲线的分析，1：1和1：在吡啶催化的2-苯甲酰化反应中，胺催化剂与1形成1：2络合物，后者是选择性2-苯甲酰化反应的关键中间体。总之，当反应由脂肪族叔胺催化时，酸酐将实现不低于更复杂的酰化试剂（如酰氯、氰化物或咪唑）的高选择性。迄今观察到的低选择性不是酸酐固有的，而是由于吡啶催化。少