A CONCISE AND REGIOSELECTIVE SYNTHESIS OF 1- AND 3-METHYL- BENZO[b]NAPHTHO[2,1-d]THIOPHENE

The two isomers 1and 3-methylbenzo[b]naphtho[2,1-d]thiophene (1and 3-Me-2,1BNT) are known alkyl thiaarenes belonging to the group of semi-polar PAH (heterocyclic or NSO-PAH). In particular, 1-Me-2,1-BNT is currently atracting much attention because it is one of the 15 priority substances, for which in Europe a need for regulatory steps under REACH regulation is potentially demanded (Schwarz et al. (2014) Integrat Environ Ass Manage, 10, 415). In order to investigate the occurrence of 1and 3-Me-2,1-BNT in environmental matrices, the synthesis of isomerically pure reference compounds was a prerequisite. Hitherto, these two isomers have been synthesized by a pathway including the oxidative photocyclization of diarylethylenes as a central step. but the subsequent separation of the obtained mixture of isomers was rather difficult and resulted in low yields, in particular for 1-Me-2,1-BNT (Tominaga et al. (1982) J Heterocyclic Chem, 19, 859). A new regioselective synthesis for both isomers 1and 3-Me-2,1-BNT was envisaged entailing overall 3 steps and a Suzuki coupling as the key reaction. In both syntheses 1-benzothiophene-2-boronic acid was used as buidling block, which was reacted with the trifluoromethanesulfonate of either 2-hydroxy-3-methylbenzaldehyde or 2hydroxy-5-methylbenzaldehyde using Pd(PPh3)4/(Et)3N as catalyst. For construction of the K-region in the target compounds the resulting 4’and 6’-methyl-2-(2’carbonylphenyl)thiophenes were applied to a Wittig reaction with triphenylsulfonium iodide and a subsequent in-situ cyclization of the intermediately formed styrene oxide derivatives to give 1and 3-Me-2,1-BNT, respectively. Overall both monomethyl 2,1BNT derivatives were obtained in more than 60% yield.