Synthesis of N-(p-Aminobenzoyl)-1,2,3,4-Tetrahydroquinoline delivertives

Abstract

The present investigation was to study the synthetic routes of N-(p-aminobenzoyl)- 1,2,3,4-tetrahydroisoquinolines , the new series of organic compounds , designed by using N-(­ methylbenzyl)benzamide as the lead compound. These rigid analogues of N-(-methylbenzyl)­benzamide were expected to possess anticonvulsant activity. In this research, there were four synthezied target compounds such as N-(p­ aminobenzoyl)-1 ,2,3,4-tetrahydroisoquinoline, N-(p-aminobenzoyl)-1 ,2,3,4-tetrahydro-1-methyl isoquinoline, N-(p-aminobenzoyl)-1 ,2,3,4-tetrahydro- 3-methylisoquinoline, and N-(p- aminobenzoyl)-1 ,2,3,4-tetrahydro-1 ,3-dimethylisoquinoline. The synthetic pathway can be divided into 3 major steps; (1) The synthesis of 1,2,3,4-tetrahydroisoquinoline by Bischler­ Napieralski or Pictet-Spengler reactions . For 1-methyl and 1,3dimethyl substituted compounds , the Bischler-Napieralski reaction was used , N-acyl-2-phenylethylamine was cyclized by reflux with P2O5 and/or POCl3, as condensing agent in toluene or xylene to form 3,4 dihydroisoquinoline , then it was reduced by sodium borohydride reduction to give 1,2,3,4- tetrahydroisoquinoline . For 3-methyl analogue, the Pictet-Spengler reaction was used without success, amphetamine was condensed with formaldehyde to form imine, then it was cyclized by reflux with concentrated hydrochloric acid. (2) The synthesis of N-(p-nitrobenzoyl)-1,2,3,4- tetrahydroisoquinolines. Tetrahydroisoquinoline was refluxed in tetrahydrofuran with p­nitrobenzoylchloride in the presence of K2CO3, (3) The synthesis of N-(p-aminobenzoyl) - 1,2,3,4- tetrahydroisoquinoline. The starting nitro compounds were reduced by hydrogenation in the presence of (10%) Pd/C. The structures of the synthesized compounds were confirmed by infrared spectrometry, nuclear magnetic resonance spectrometry and elemental analysis techniques.