The Catalytic Hydrogenation of Indolylethylpyridines. 4-(Indolylethyl)-1-aralkylpiperidines as Potent Analgesics
The Catalytic Hydrogenation of Indolylethylpyridines. 4-(Indolylethyl)-1-aralkylpiperidines as Potent Analgesics
复制标题
吲哚乙基吡啶的催化氢化。
DOI：
10.1021/jo01067a084
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发表时间：
1961
影响因子：
3.6
通讯作者：
H. Kraus
中科院分区：
文献类型：
--
作者：
A. Gray;H. Kraus
吲哚乙基吡啶碱在酸性溶液中催化加氢得到相应的吲哚乙基胡椒类化合物。它们与芳基取代的烷基化试剂反应，得到吲哚乙基-L-芳烷基哌啶衍生物。通过初始定量可以得到相同的产品。在中性条件下，吡啶的三元化，然后加氢。这些实验室最近的一份报告指出，在酸性条件下，吲哚取代的吡啶的催化氢化首先在两个环系不共轭的情况下导致吡啶环饱和。本文件记录了这方面的一些证据，特别是关于吲哚乙基吡啶碱2 3氢化成相应的哌啶类化合物。某些衍生产品，即。4-(吲哚乙基)-L-芳烷基哌啶类化合物在小鼠和兔身上的镇痛活性与吗啡相当。·‘1’4这些化合物具有明显不同于吗啡的中枢神经系统抑制特性。在铂催化下，4-(3-吲哚乙基)吡啶、4-(1-甲基-3-吲哚乙基)-吡啶和2-(吲哚乙基)吡啶在冰醋酸或含醇盐酸中氢化得到了哌啶衍生物I、XIV和XVII，产率分别为60-80%。在更强的矿物酸介质中，氢的吸收更快。表III的紫外吸收数据清楚地证明了吲哚核在这些条件下没有被还原。5此外，I与苯乙基溴的烷基化反应得到了80%的产率
Catalytic hydrogenation of indolylcthylpyridine bases in acidic solutions afforded the corresponding indolylethylpiperi-dines. These reacted with aryl substituted alkylating agents to give indolylethyl-l-aralkylpiperidine derivatives. The same products could be obtained by initial qua. ternization of the pyridine followed by hydrogenation under neutral conditions. Several of the derived compounds proved to be as effective as morphine in producing analgesia in animals.A recent report1 from these laboratories indi-cated that catalytic hydrogenation of indolesubstituted pyridines under acid conditions leads first, when the two ring systems are not conjugated, to saturation of the pyridine ring. The present paper documents some of the evidence for this and, in particular, is concerned with the hydrogenation of indolylethylpyridine bases2 3to the corresponding piperidines. Certain of the derived products, viz. 4-(indolylethyl)-l-aralkylpiperidines, have been found to possess analgesic activity equivalent to morphine when tested in mice and rabbits.·'1'4 These compounds display a profile of central nervous system depressant properties which dis-tinctly differs from that of morphine. Platinum-catalyzed hydrogenation of 4-(3-indol-ylethyl) pyridine, 4-(1-methyl-3-indolylethyl)-pyridine and 2-(indolyIethyI) pyridine in either glacial acetic acid or aqueous alcoholcontaining hydrochloric acid provided the piperidine deriva-tives, I, XIV, and XVII, respectively, in yields of 60-80%. Uptake of hydrogen was more rapid in the stronger, mineral acid medium. That the indole nucleus was not reduced under these conditions is clearly evidenced by the ultraviolet absorption data given in Table III. 5 Further, alkylation of I with phenethylbromide afforded an 80% yield of