Studies related to penicillins. Part XII. Reactions of (1R,5S)-3-benzyl-7-(2-methylprop-1-enyl)-2-oxa-4,7-diazabicyclo[3.2.0]hept-3-en-6-one with alcohols and with acids

Abstract

(1R,5S)-3-Benzyl-7-(2-methylprop-1-enyl)-2-oxa-4,7-diazabiyclo[3.2.0]hept-3-en-6-one (12) is converted into (3S,4S)-4-ethoxy-1-(2-methylprop-1-enyl)-3-phenylacetamidoazetidin-2-one (4) by ethanol containing toluene-p-sulphonic acid. The oxazoline (12) undergoes an analogous reaction with acidic methanol and with acidic 2-mercaptoethanol to give the derivatives (5) and (6), respectively. Reagent-grade chloroform and toluene-p-sulphonic acid transform the derivatives (12) and (4) into (2S)-3,3-diethoxy-N-(2-methylprop-1-enyl)-2-phenylacetamidopropionamide (15).

The oxazoline (12) is also converted into (2R,4S)-4-acetylthio-1-(2-methylprop-1-enyl)-3-phenylacetamidoazetidin-2-one (8) by thioacetic acid; a corresponding reaction occurs with 2-mercaptoacetic and with trifluoroacetic acid to give the derivatives (9) and (10), respectively. The azetidinone (9) rearranges to (2R)-N-(2-methylprop-1-enyl)-2-(5-oxo-1,3-oxathiolan-2-yl)-2-phenylacetamidoacetamide (16) when chromatographed on silica gel, and the azetidinone (10) yields 2-benzyl-4-[(2-methylprop-1-enyl)aminomethylene]-Δ²-1,3-oxazolin-5-one (19) when left in the presence of trifluoroacetic acid. Derivative (19) is also obtained from S-chloromercurio(II)benzylpenicillenic acid (22) and dimethyl sulphoxide.