ALPHA-EFFECT NUCLEOPHILES - A NOVEL AND CONVENIENT METHOD FOR THE SYNTHESIS OF DIBENZO[A,D]CYCLOHEPTENIMINES
ALPHA-EFFECT NUCLEOPHILES - A NOVEL AND CONVENIENT METHOD FOR THE SYNTHESIS OF DIBENZO[A,D]CYCLOHEPTENIMINES
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DOI：
10.1021/jo00243a031
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发表时间：
1988-04-15
影响因子：
3.6
通讯作者：
WEINSTOCK, LM
中科院分区：
文献类型：
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作者：
LAMANEC, TR;BENDER, DR;WEINSTOCK, LM
提出了一种合成具有重要药用价值的5-甲基-和5 H-二苯并[a，d]环庚烯亚胺的新方法。通过向甲醇3中新加入表现出α-羟基的各种物质，为了达到这一效果，在叔C-5位引入胺等价物，得到衍生物9a-d。甲醇3的Ritter反应得到了二聚和重排的衍生物以及亚胺桥物种[5，10-（腈基亚甲基）衍生物]。在中等酸性条件下，获得高产率的C-5衍生物9a-d，而没有竞争消除或二聚化。在碱性条件下，这些化合物与相应的杂环10a-d的闭环速率大大提高。观察到与亲核性的增加平行的增加的反应性顺序（9a ≥ 9a）。9c > 9b > 9d > 9e）。5-去甲基闭环羟胺14的合成也通过该途径加速。的13 C NMR光谱性质的闭环杂环的调查表明，通过在氮桥反转，顺式和反构象之间的平衡。10a-c和14的氢解分别完成了5-甲基-和5 H-二苯并[a，d]环庚烯亚胺1a和1b的合成。
A new approach to the medicinally important 5-methyl- and 5H-dibenzo[a,d]cycloheptenimines is presented. Through the novel addition to carbinol 3 of various species exhibiting an .alpha.-effect, amine equivalents were incorporated at the tertiary C-5 position, giving derivatives 9a-d. Ritter reactions of carbinol 3 gave a dimerized and rearranged derivative as well as an imine-bridged species [a 5,10-(nitrilometheno) derivative]. Under moderately acidic conditions, high yields of the C-5 derivatives 9a-d were obtained without competing elimination or dimerization. The rate of ring closure of these compounds to the corresponding heterocycles 10a-d was greatly enhanced under basic conditions. An increasing reactivity order paralleling an increase in nucleophilicity was observed (9a .gtoreq. 9c > 9b > 9d > 9e). The synthesis of the 5-desmethyl ring-closed hydroxylamine 14 was also expedited by this route. Investigation of the 13C NMR spectral properties of the ring-closed heterocycles showed an equilibration, via inversion at the nitrogen bridge, between syn and anti conformers. Hydrogenolysis of 10a-c and 14 completed the synthesis of the 5-methyl- and 5H-dibenzo[a,d]cycloheptenimines 1a and 1b, respectively.