选择性串联合成功能化的苯并[b][1,4]二氮杂■化合物  

A Domino Reaction for the Selective Synthesis of Functionalized Benzo[b][1,4]diazepines

作　　者：孙悦玮 周来运 王兰芝[1] Sun Yuewei;Zhou Laiyun;Wang Lanzhi(College of Chemistry&Material Science,Hebei Normal University,Shijiazhuang,050024)

机构地区：[1]河北师范大学化学与材料科学学院

出　　处：《有机化学》2019年第12期3516-3523,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.21776060,21276064);河北省自然科学基金(No.B2016205165)资助项目

摘　　要：以取代的邻苯二胺、噻唑-2-甲醛和乙炔二甲酸二乙酯为原料,无水乙醇为溶剂,通过串联反应(亲核加成、脱水、环合和质子转移等)合成了12种新颖的取代的3,4-二乙氧羰基-2-(噻唑-2-基)苯并[b][1,4]二氮杂?化合物.由于化学/区域选择性,在同一反应不同条件下分别得到了烯胺型和亚胺型苯并[b][1,4]二氮杂?的异构体,通过考察反应条件对产物异构体选择性的影响,研究产物选择性的变化规律,为实现选择性合成苯并[b][1,4]二氮杂?化合物提供简便的合成思路.采用密度泛函(DFT)方法在B3LYP/6-31G基组水平上对反应原料和两种目标化合物进行量化计算,从原子布居电荷的角度,进一步对反应的选择性规律进行理论解释,并且在此基础上提出了合理的反应机理.12 novel substituted 3,4-diethoxycarbonyl-2-(thiazol-2-yl)benzo[b][1,4]diazepines were obtained via a domino sequence of a nucleophilic addition/dehydration/cyclization/H+ shift. These reactions were achieved by reacting substituted 1,2-phenylenediamines, 2-thiazolecarboxaldehyde with diethyl acetylenedicarboxylate in Et OH. Benzo[b]-[1,4]diazepines of the two structures of imine structure and enamine structure were found in this reaction process due to chem-/regio-selectivity. The influence of reaction conditions on the selectivity of target products was also studied in detail. The selectivity law of synthesis reaction was obtained, and the yield of single product was maximized. A simple synthesis strategy for the selective synthesis of benzo[b][1,4]diazepines was provided. To understand the reaction mechanism and further prove the conclusion, quantum chemical calculations were performed, and density functional theory(DFT) studies based on B3 LYP method and 6-31 G basis set were employed to carry out the study. Natural bond orbital(NBO) charge analysis of the substituted 1,2-phenylenediamine was carried out to justify the selective attack at the nucleophilic centers. NBO charge analysis of the target compounds was carried out to explain the stability of benzo[b][1,4]diazepine isomers with imine or enamine structure. Moreover, the plausible reaction mechanism was proposed.

关 键 词：苯并[b][1 4]二氮杂■ 合成 选择性 机理 密度反函数理论(DFT) 

分 类 号：O626.25[理学—有机化学] TQ460.1[理学—化学]