Model studies related to the cofactor of oxomolybdoenzymes. Part 3

Abstract

2-(D-arabino-Tetrahydroxybutyl)quinoxaline (2) reacted selectively to give the diol acetal (3a) which was converted into mono- and di-mesylates and-tosylates, and, via the ethyl ortho ester (4) into the alkene acetal (5a). Both thiocyanogen and bromine added to the alkene; all attempted conversions of the former adduct into a 1,2-dithiol failed; attempts to displace halogen from the latter with sulphur nucleophiles led in most cases simply to elimination of halogen. However, dimethyldithiocarbamate effected hydrogen bromide elimination and thus formation of the bromoalkene acetal (5c). On further reaction of this with bromine, a tribromo adduct (6d) was obtained, methoxide treatment of which gave the dibromoalkene acetal (5d). The epoxide acetals (9a) and (9b) were formed by base treatment of monomesylates (3d) and (3e), but attempted use of the epoxides for the introduction of sulphur functionality at best caused elimination thence reversion to the alkene acetal (5a), and more often resulted in complex product mixtures. Exposure of the di-mesylate (3f) and di-tosylate (3b) to sodium N,N-dimethyldithiocarbamate led to the enol mesylate (5e) and tosylate (5f). Exposure of the mono-mesylates (3d) and (3e) to sodium N,N-dimethyldithiocarbamate, then acid, then hydrogen sulphide gave, according to exact conditions, the thiole (13) or thiolane (12a), together with the alcohol (6f). The α-bromo ketone (14b) was prepared by bromination of the ketone (14a), itself available from reaction of the diol acetal (3a) with phosphorus pentasulphide, or better from the enol mesylate (5e)via addition of bromine then hydrolysis. Displacements of bromine in the bromo ketone with sulphur nucleophiles were successful, but the products could not then be converted into thioketones. The pyrazine ring in (4) could be selectively reduced with lithium aluminium hydride. Treatment of the dibromoalkene (5d) with dipotassium trithiocarbonate gave some thiole (13), but mainly the thieno[2,3-b]quinoxaline (16); similarly, reaction of the thiole (13) with base followed by iodomethane and then acetic anhydride gave the thieno[2,3-b]quinoxaline (24).