Study on the Condensation of Different Hydroxy Aromatic Aldehydes with 2-Substituted 2-Oxazolin-5-ones Generated in situ

Abstract

In view to synthesize some bioactive 2-Substituted 4-(hydroxybenzylidene)-2-oxazolin-5-ones through a disciplined route, a study on the condensation of 2-, 3- and 4- hydroxy aromatic aldehydes (6) with 2-Substituted 2-oxazolin-5-ones (5) was carried out. 2-Substituted 2-oxazolin-5-ones (5) which are also known as saturated azlactones and unstable, were generated in situ from α-N-Acylglycines (1) using various cyclising agents namely ethyl chloroformate (2), benzene sulphonyl chloride (3) and p -toluene sulphonyl chloride (4) in dry benzene in presence of triethylamine base. The hydroxyl group at 3- and 4- positions of aromatic aldehydes namely 4-hydroxy-3-methoxybenzaldehyde (6a), m -hydroxybenzaldehyde (6b)and p-hydroxybenzaldehyde (6c) produce 2-substituted 4-( p -hydroxy- m -methoxybenzylidene)-2-oxazolin-5-one (8a), 2-substituted-4 ( m -hydroxybenzylidene)-2-oxazolin-5-one (8b) and2-substituted-4 ( p -hydroxybenzylidene)-2-oxazolin-5-one (8c) respectively as their (Z)-isomers, whereas 2-hydroxy aromatic aldehyde namely salicylaldehydeproduces 3-N-acylaminocoumarins (9) on condensation with 2-Substituted 2-oxazolin-5-ones (5) in appreciable yields and good purity. The reaction seems to be initiated by the formation of an adduct ( E )-2-substituted 4-( o -hydroxybenzylidene-2-oxazolin-5-ones (7), followed by intramolecular 1,5- bond cleavage of the 2-oxazolin-5-one ring by the vicinal phenolic group and subsequent recyclization led to the formation of resultant 3-N-acylaminocoumarins (9). It is noteworthy that free hydroxyl group bearing benzylidene moiety at 4-position of 2-oxazolin-5-ones (8) were obtained. All the steps can be carried out in one flask.