Synthesis and Rearrangements of Alkyl Phosphorothioates

Thomas J. Meade, Radha Iyengar, Perry A. Frey

Research output: Contribution to journalArticlepeer-review


Reaction of PSCl3 with benzyl alcohol in triethyl phosphate followed by aqueous workup produces S-benzyl phosphorothioate, 2, while similar reaction of cyclohexanol produces O-cyclohexyl phosphorothioate. The S-benzyl ester is postulated to arise from rearrangement of either O-benzyl phosphorodichloridate, 5, or a hydrolysis product. Reaction of P1-O-cyclohexyl P2-n-propyl 1-thiodiphosphate, 3, with BrCN in aqueous solutions buffered at pH 7.2 with lutidine or at pH 10.3 with triethylamine produces P1-cyclohexyl P2-n-propyl diphosphate, 4, in essentially quantitative yield within 10 min. Similar reaction in H2 180 produces exclusively [P1-18O\4 with no indication of the presence of 18O at P2. The reaction is postulated to involve the intermediate formation of P1-O-cyclohexyl P2-n-propyl 1-thiocyanatodiphosphate, 9, by reaction of 3 with BrCN. 9 undergoes hydrolysis with displacement of SCN-by H2O, producing 4. Similar reaction of P1~O-cyclohexyl 1-thiodiphosphate in H2 18O produces cyclohexyl [l-18O,2-18O\diphosphate in high yield, with approximately 50% 18O-enrichment at each position. This labeling pattern is postulated to arise from neighboring group participation by the terminal phosphoryl group. Initial reaction of P1-O-cyclohexyl 1-thiodiphosphate produces the intermediate P1-O-cyclohexyl 1-thiocyanatodiphosphate, 10. The latter is partitioned between two pathways, direct displacement of SCN-by water to form cyclohexyl diphosphate and internal displacement of SCN-by the neighboring phosphoryl group to form cyclohexyl cyclodiphosphate, 11, a highly reactive species which undergoes immediate hydrolysis to cyclohexyl diphosphate.

Original languageEnglish (US)
Pages (from-to)936-940
Number of pages5
JournalJournal of Organic Chemistry
Issue number7
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Organic Chemistry


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