3-氰基吡啶与Grignard试剂的反应研究

3-取代酰基吡啶可由3-氰基吡啶与相应的卤代烷基镁加成,然后酸化水解来制备.我们曾用该法顺利地制备了一系列的3-取代酰基吡啶,另外还得到少量的4-烷基-3-取代酰基吡啶.但当用氯化苄基镁时,只得到少量的3-取代酰基吡啶,而主要产物却是4-苄基-3-氰基吡啶.为了探讨这两种反应中各组分的相对含量,用高压液相色谱分别对3-氰基吡啶与溴化丁基镁、氯化苄基镁的反应产物进行了分析.为了解释反应产物的异常现象,对反应物进行了量子化学计算,用前线轨道理论对以上反应进行了讨论.

Studies on the reaction of 3-cyanopyridine with grignard reagents

3-cyanopyridine with alkylmagnesium halides, but an unexpected product, 4-benzyl-3-cyanopyridine was formed in the reaction with benzylmagnesium chloride. In order to study the unusual result, the EHMO calculation on 3-cyanopyridine, butylmagnesium bromide and benzylmagnesium chloride was performed. The results indicated that there were two terms of competitive forces, the Coulombic force and the frontier orbital interaction, existing in these reactions. The cyano carbon atom in 3-cyanopyridine carried more net pos. charge and the C4 in the pyridine ring possessed higher AO coefficient The carbon atom adjacent to the magnesium atom in butylmagnesium bromide carried more net neg. charge, hence in the reaction with 3-cyanopyridine the Coulombic force was dominant and the reaction would occur at the cyano group to form 3-valerylpyridine. The carbon atom adjacent to the magnesium atom in the benzylmagnesium chloride possessed less net neg. charge, and in the reaction with 3-cyanopyridine, due to the presence of steric hindrance of the benzyl group to the cyano addition reaction, the frontier orbital interaction is the chief factor and the reaction would occur at the C4 of the pyridine ring to give 4-benzyl-3-cyanopyridine as the main product.