TRYPTAMINES, CARBOLINES, AND RELATED COMPOUNDS .2. A CONVENIENT SYNTHESIS OF TRYPTAMINES AND BETA-CARBOLINES
TRYPTAMINES, CARBOLINES, AND RELATED COMPOUNDS .2. A CONVENIENT SYNTHESIS OF TRYPTAMINES AND BETA-CARBOLINES
复制标题
DOI：
10.1039/jr9560004589
复制
发表时间：
1956-01-01
期刊：
影响因子：
--
通讯作者：
SHAPIRO, D
中科院分区：
文献类型：
--
作者：
ABRAMOVITCH, RA;SHAPIRO, D
4590 A bramovitch and Shapiro: Tryptamines, Carbolines, becomes readily available; it was hydrolysed by aqueous-alcoholic alkali to tryptamine-2-carboxylic acid (IV; R= H), which was decarboxylated to tryptamine (V; R= H) by boiling 5% hydrochloric acid. 10 When absolute-ethanolic potassium hydroxide was used for hydrolysis of the amide, most of the amide was recovered: these or similar conditions may have been used by Nishikawa, Perkin, and Robinson, ll who were unable to effect the ring opening of 1: 2: 3: 4-tetrahydro-7-methoxy-l-oxo-~-carboline by alcoholic potassium hydroxide. The same sequence of reactions was carried out with diazotised p-anisidine in the Japp-Klingemann reaction, to give the methoxyphenylhydrazone (11; R= OMe). The nature of the product obtained in this and similar Japp-Klingemann reactions was found to depend mainly on the pH of the reaction mixture. At pH> 7 only a tar was formed, whereas at pH 6-7 a compound was obtained whose properties (instability on attempted purification, formation of a small amount of the phenylhydrazone accompanied by extensive decomposition on quick recrystallisation from water, and transformation into the carboline with ethanolic hydrogen chloride) point to a phenylazo-structure. At pH 3-4 and at 0-5" the required phenylhydrazone was obtained. This could not be cyclised with polyphosphoric acid as tar formation occurred, but 90% formic acid gave the required carboline (111; R= OMe)(previously prepared by Barrett, Perkin, and Robinson by a seven-stage synthesis 12), which was hydrolysed and decarboxylated as above. Decarboxylation could also be effected with toluene-9-sulphonic acid. Since 5-methoxytryptamine has already been demethylated to serotonin 4a this constitutes a new and convenient synthesis of this compound.To avoid the final demethylation it was thought of interest to use the benzyloxyderivative, as 5-benzyloxytryptamine can be smoothly debenzylated to serotonin. l* Again, the success of the JappKlingemann reaction depended on the pH (optimum ca. 4-5). The product (I1; R= O* CH, Ph) was cyclised in 70% formic acid, and the amide (I11; R= O* CH, Ph) hydrolysed as before to the amino-acid (IV; R= O* CH, Ph). The last, however, could not be decarboxylated to the required base under a variety of conditions, so that this route was abandoned. The oxocarbolines (111) are convenient starting materials for the synthesis of 1: 2: 3: 4-tetrahydro-b-carbolines. Attempts to reduce the amide linkage with lithium aluminium hydride failed, probably owing to formation of an insoluble complex before reduction, and the amide was recovered. Similar difficulties with secondary cyclic amides have been reported l3 in connection with the synthesis of morphine. 1: 2: 3: 4-Tetrahydro-1-0x0-pcarboline had been reduced with sodium and butan-1-01 by Ashley and Robinson, 14 and substitution of propanol for butanol did not lead to an increased yield. 1: 2: 3: 4-
