SYNTHESIS AND RESOLUTION OF YLALKYL-2-(TETRAZOL-5-YL)-N-ARYLALKYL-CARBOXAMIDES - A NEW CLASS OF CHIRAL STERICALLY HINDERED TETRAZOLE DERIVATIVES

Chiral, racemic rylalkyl-2-(tetrazol-5-yl)-N-arylalkylcarboxamides 3 w ere conveniently prepared from ethyl cyanoacetate in four steps. The s ynthetic methodology developed is a facile way of introducing bulky su bstituents into a peptide-like framework, affording intermediate alpha -arylalkyl-alpha-amiodonitriles. These nitriles were sufficiently acti vated to give, upon treatment with ammonium azide in dimethylformamide at 145-degrees for twenty-four to thirty hours, the corresponding tet razoles in good yields. It has been determined that an optically pure alpha-arylalkyl-alpha-amidonitrile epimerized to give diastereomeric p roducts under the above conditions. A procedure for the fractional cry stallization of the (S)-(-)-alpha-methylbenzylamine salts 4 of the tet razoles to give the optically enriched tetrazoles 5 was also developed .