Studies related to dihydro-1,4-thiazines. Part VI. Thermal racemisation of sulphoxides

Abstract

Oxidation of the dihydrothiazine lactone (17) and the ester (2) with m-chloroperbenzoic acid yields the respective (R)-oxides (18) and (10); the analogous (S)-oxides (33) and (30) are obtained from the dimethyl derivatives (31) and (28). The foregoing sulphoxides undergo thermally induced racemisation under mild conditions; deuterium-incorporation experiments implicate the sulphenic acids, e.g.(23), as the reaction intermediates.

The hydroxymethylthiazine ester (7), prepared from the ester (2) and formaldehyde in the presence of an acid catalyst, is converted into the ethoxymethylthiazine ester (8) by ethanolic hydrochloric acid. Oxidation of the derivative (8) with m-chloroperbenzoic acid gives a mixture of the (S)-oxide (15) and the racemate of the (R)-oxide (13). The former sulphoxide is stable in boiling dichloromethane, whereas the latter interconverts with the sulphenic acid (24) in dichloromethane at room temperature. This result, which emphasises that a syn-axial arrangement of the sulphinyl group and the tertiary hydrogen atom is a prerequisite for the racemisation, suggests that the sulphenic acid is formed by a concerted intramolecular hydrogen shift.

In the presence of 1,5-diazabicyclo[4.3.0]non-5-ene, the (R)-(13) and the (S)-oxide (15) are equilibrated (as their racemates) to give a mixture containing ca. 18% of the former derivative and 82% of the latter.

The ethoxysulphonium salts (20) and (34), formed from the reaction of the lactone sulphoxides (18) and (33) with triethyloxonium tetrafluoroborate, are transformed into the respective ethoxy-lactones (38) and (36) and hydroxy-lactones (39) and (37) by sodium hydroxide.