Some thiophen and benzo [b] thiophen derivatives of potential biological interest

Abstract

In an introductory section, the chemotherapeutic activity of thiophens, benzo[b]thiophens, and guanidine and related compounds is briefly surveyed, and the pharmacological activity of alkylamines derived from the the first two groups of compounds is considered. Methods for the preparation of arylthiophens and venzo[b]thiophens are then reviewed, and the electronic structure and electrophilic aromatic substitution of these compounds are discussed. The synthesis of a series of 5-halogenobenzo[b]thien-3-ylalkylguanidines and biguanides from the corresponding 5-halogenobenso[b]thien-3-ylalkylanines is described, and the preparation of some N-methyl-substituted 5-halogenobenzo[b]thien-3-ylacetamidines is also reported. Four methods for the preparation of 2-arylthiophens have been investigated and these compounds have been converted to the corresponding 5-arylthiophen-2—carboxylic acids from which a series of primary and tertiary amides has been prepared. Reduction of certain 5-arylthien-2-ylamides ( aryl = phenyl, p-chlorophenyl, p-tolyl ) with an excess of lithium aluminium hydride has been found to give the corresponding 5-arylthien-2-ylmethylamines, but reduction of the 5-p-bromophenylthien-2-ylamides under similar conditions is accompanied by hydrogenolysis of the aromatic bromine. The required 5—p-bromophenylthien-2-ylmethylamines have therefore been prepared either by reduction of the amide with the calculated quantity of lithium aluminiun hydride, or by treatment of 5-p—bromopheny1-2-chloromethylthiophen with the appropriate secondary amine. Some preliminary work on the synthesis of a related series of 2-(5-arylthien-2-yl)ethylamines is discussed. The required intermediate 5-arylthien-2-ylacetic acids have been prepared by two methods, and 2-(5-phenylthien-2-yl)ethylamine itself has been prepared by the reduction of 2—cyanomethyl-5—phenylthiophen. Certain 5—p-halogenophenylthien-2-ylaldehydes and their thiosemicarbazone derivatives have been synthesised, and the preparation of two 5—phenylthien-2-ylmethylamidines has been accomplished. The i.r. and n.m.r. spectra of many of the new compounds are recorded. The mass spectra of a selection of S-halogenobenzo[b]thien-3-ylalkylguanidines, 5-arylthien-2-ylamides, 5-arylthien-2-ylmethylamines, and 5-arylthien-2-yl acid hydrazides have been measured and possible fragmentation pathways for these compounds have been suggested.