Reaction of unsaturated azlactones with sulfur nucleophiles: some observations

Abstract

The reaction of thiols with unsaturated azlactones, for example, l a , d (1, and, for the synthesis of penicillamine, ref.2) and a,P-unsaturated acid derivatives (3), was reported to form adducts, but these additions do not seem to have been properly investigated. Compounds la-g can behave as bielectrophiles, undergoing cleavage of the 1,5 bond and (or) involvement of the olefinic centre. To probe regioselectivity of the reaction and stereochemistry of the products, the present work using sulfur nucleophiles was undertaken (see ref. 4 for a preliminary communication, and ref. 5).The required substrates l a , c, d, e were prepared by known methods (for a recent review on azlactones, see ref. 6). The condensation of hippuric acid with triethyl orthoformate and benzaldehyde by the Erlenmeyer procedure (1, 7) afforded 4-ethoxymethlene-and 4-benzylidene-2-phenyl-4,Sdihydrooxazol-5-ones ( l a ) and (Id), respectively, the (Z) isomer being the major product (6). The similar acetic anhydride-mediated condensation of hippuric acid with salicylaldehyde produced (8) 3-benzoylaminocoumarin (2a) and (Z)-4-o-acetoxybenzylidene-2-phenyl-4,5-dihydrooxazol-5-one (le). The separation was not only tedious but gave low yields of contaminated compounds. Pure l e was therefore prepared by the acetic anhydride-mediated cyclodehydration of (Z)-2-benzoylamino-ohydroxycinnamic acid 4a. The condensation of aniline with l a furnished 4-anilinomethylene-2-phenyl-4,5-dihydrooxazol-