Synthesis and antimicrobial activity of new (4,4,4-trihalo-3-oxo-but-1-enyl)-carbamic acid ethyl esters, (4,4,4-trihalo-3-hydroxy-butyl)-carbamic acid ethyl esters, and 2-oxo-6-trihalomethyl-[1,3]oxazinane-3-carboxylic acid ethyl esters

Abstract

This work presents a three-step synthesis of a new series of 4-substituted 2-oxo-6-trihalomethyl-[1,3]oxazinane-3-carboxylic acid ethyl esters, from β-alkoxyvinyl trihalomethyl ketones of general formula X 3C–C(O)–CH C(R)–OR 1, where R = H, Me, Ph, and 4-Me-Ph; R 1 = Me and Et; and X = F and Cl. The Michael addition–substitution of the ethyl carbamate on β-alkoxyvinyl trihalomethyl ketones furnished the corresponding (4,4,4-trihalo-3-oxo-but-1-enyl)-carbamic acid ethyl esters. These compounds underwent reduction with NaBH 4 leading to the respective (4,4,4-trihalo-3-hydroxy-butyl)-carbamic acid ethyl esters. The 3-hydroxy-butyl carbamates were submitted to cyclization reaction with triphosgene to give a series of 4-substituted 2-oxo-6-trihalomethyl-[1,3]oxazinane-3-carboxylic acid ethyl esters. The in vitro antimicrobial activity, of some of the three new series of the title compounds, was assessed against a panel of microorganisms including yeast like fungi, bacteria, and algae, and their minimal inhibitory concentration and minimal fungicidal, bactericidal, and algacidal concentrations were determined. Some of the analyzed carbamates exhibited significant in vitro antimicrobial activity.