Chloromethyl chlorosulfate: a new, catalytic method of preparation and reactions with some nucleophiles

Abstract

The reaction of liquid (γ-) SO₃ with CH₂Cl₂ at room temperature leads to SO₃ insertion into the C–Cl bonds, giving the useful chloromethylating agent chloromethyl chlorosulfate (CMCS). The process is very slow but becomes rapid on addition of catalytic quantities of trimethyl borate. The product mixture consists almost entirely of CMCS and the product of further sulfation, methylene bis(chlorosulfate) (MBCS), in a ratio of ca. 2 : 1, but typical yields of CMCS, isolated by distillation, are only 30–35%. The catalysed reaction in the homogeneous liquid phase at −45 °C has been followed as a function of time and of reactant concentration by ¹H nmr spectroscopy. It is observed that, besides CMCS and MBCS, three additional, transient products (designated A, B and C) are formed. Products A, B and C decompose slowly at −45 °C but much more rapidly if the reaction mixture is raised to room temperature, giving additional CMCS and MBCS. From an analysis of the SO₃ balance, it is inferred that products A, B and C arise from the reaction of one molecule of CH₂Cl₂ with respectively two, three and four molecules of SO₃; they are suggested to be chloromethyl chloropolysulfates. By measuring initial rates of CMCS formation or total CH₂Cl₂ consumption, it is shown that the reaction is first order in the catalyst and roughly third order in SO₃. A mechanistic scheme is proposed in which SO₃ forms equilibrating zwitterionic molecular complexes with CH₂Cl₂. of 1 : 1, 2 : 1 and higher stoichiometries. The boron-containing catalyst can activate these complexes towards nucleophilic attack at carbon by the negatively charged oxygen of another zwitterion. An analogous mechanism can be written for the conversion of CMCS into MBCS by SO₃ in the presence of trimethyl borate. CMCS reacts rapidly with anionic nucleophiles, such as halide or acetate ions (X⁻), in homogeneous solution of their tetrabutylammonium salts in CD₃CN, or in a two-phase system (CDCl₃/H₂O) using alkali-metal salts in conjunction with a phase-transfer catalyst. In both situations the products (ClCH₂X) arise by rapid nucleophilic displacement of the chlorosulfate moiety; this then more slowly liberates chloride ion, which converts further CMCS into CH₂Cl₂. The reactivity of CMCS has been compared with that of MBCS and methyl chlorosulfate (MCS) in competitive experiments; the reactivity order is MCS > MBCS > CMCS >> CH₂Cl₂. Evidence is also presented suggesting that, in contrast to the halide nucleophiles, reaction of CMCS with sodium phenoxide in tetrahydrofuran solution leads to nucleophilic displacement of the sulfur-bound chloride.