STERIC INHIBITION OF INTRAMOLECULAR CYCLIZATIONS BY ORTHO SUBSTITUENTS . SYNTHESIS OF 1H,3H-THIENO[3,4-C]THIOPHENE ITS 2,2-DIOXIDE AND 5-ETHYL-5,6-DIHYDRO-4H-THIENO[3,4-C]PYRROLE

During our study of the synthesis of anellated five-membered rings on thiophene, we discovered that some intramolecular cyclizations are adversely affected by ortho substituents in the aromatic ring. Reaction of 2,5-dibromo-3,4-bis(bromomethyl)thiophene with sodium sulfide furnished 4,6-dibromo-1H,3H-thieno [3,4-c] thiophene and ring closure of 2,5-dichloro-3,4-bis(chloromethyl)thiophene with sodium sulfide gave the 4,6-dichloro derivative. On the other hand, reaction of 2,5-dichloro-3,4-bis(chloromethyl)thiophene with ethylamine in acetonitrile does not form a thienopyrrole derivative, while cyclization to 5-ethyl-5,6-dihydro-4H-thieno[3,4-c]pyrrole was successful when the chlorine atoms on the thiophene nucleus of the tetrachloride were removed prior to the reaction with ethylamine. Our explanation of the steric inhibition of intramolecular cyclization by ortho substituents is given. © 1969, American Chemical Society. All rights reserved.