Dimethyl Sulfide-Chlorine1


[75-18-3]  · C2H6S  · Dimethyl Sulfide-Chlorine  · (MW 62.15) (Cl2)

[7782-50-5]  · Cl2  · Dimethyl Sulfide-Chlorine  · (MW 70.90)

(mild oxidizing agent for primary and secondary alcohols2 and vicinal diols;3 chlorinating agent for phenols, phenol ethers, and anilines;4 reagent for synthesis of methylthiomethyl esters,5 for dehydration of aldoximes to nitriles,6 and for synthesis of a-chloro ketones7)

Alternate Name: chlorodimethylsulfonium chloride

Solubility: sol CH2Cl2, CCl4, toluene, acetonitrile.

Preparative Method: prepared in situ by slow addition of a solution of Dimethyl Sulfide (1.25 equiv) in CH2Cl2 to a solution of Chlorine (1 equiv) in CH2Cl2 at -25 °C under an inert atmosphere;4 typical scale is 3 mmol in 10 mL CH2Cl2.

Handling, Storage, and Precautions: chlorine gas is toxic and corrosive; when introducing the gas to CH2Cl2, ensure that the apparatus is properly trapped and vented in a fume hood to avoid escape of chlorine and overpressurization of the reaction vessel.

Oxidation of Alcohols to Aldehydes or Ketones.

Dimethyl sulfide-chlorine (DMS-Cl2) and its derivatives (e.g. chlorine-methyl phenyl sulfide) have shown excellent utility as oxidizing agents for primary and secondary alcohols.2 This reagent system is part of a family of halosulfonium salt reagents (see Dimethyl Sulfoxide-Oxalyl Chloride, Dimethyl Sulfoxide-Dicyclohexylcarbodiimide, Dimethyl Sulfoxide-Trifluoroacetic Anhydride, Dimethyl Sulfoxide-Phosphorus Pentoxide)1b and is closely related in its oxidizing properties to N-Chlorosuccinimide-Dimethyl Sulfide (DMS-NCS). The oxidation proceeds through a sulfoxonium ion complex (2), which is converted to the carbonyl by addition of Triethylamine (eq 1).2

The oxidation of vicinal diols has been problematic with some oxidizing agents.3 Carbon-carbon bond cleavage occurs with certain of these reagents (Chromic Acid, Pyridinium Chlorochromate, Pyridinium Dichromate, Silver(I) Carbonate). DMS-Cl2 oxidizes s,t-1,2-diols to a-hydroxy ketones as illustrated in eq 23 and eq 3.6 The yields are moderate; in eq 2 they can be improved to 85% by substituting methyl phenyl sulfide for dimethyl sulfide. In some instances methyl phenyl sulfide has been found to be superior to dimethyl sulfide.3,9,10 Two good alternative reagents to DMS-Cl2 are Dimethyl Sulfoxide-Chlorine3 and DMS-NCS, which also give good to excellent yields of keto alcohols without C-C cleavage. The oxidation shown in eq 3 was attempted with silver carbonate but gave only a 12% yield of hydroxy ketone.8

Another advantage of DMS-Cl2 is its potential use in large-scale processes. The reagent is very inexpensive and the reaction byproducts are dimethyl sulfide (which can be recycled) and HCl.

Chlorination of Activated Aromatic Compounds.

DMS-Cl2 regioselectively p-chlorinates activated aromatic compounds such as phenol, anisole, and N,N-dimethylaniline in good to excellent yields.4 Eq 4 shows three general examples of this reaction. The reaction is complete in 5 min at -25 °C.

Synthesis of Methylthiomethyl Esters.

Methythiomethyl esters can be synthesized by reaction of the triethylamine salt of a carboxylic acid with freshly prepared DMS-Cl2 at -70 °C to rt (e.g. eq 5).5 Yields for simple alkyl and aryl carboxylates range from 80 to 85%.

Dehydration of Aldoximes to Nitriles.

DMS-Cl2 rapidly dehydrates aldoximes at low temperature.6 Excess DMS-Cl2 is formed at -78 °C in acetonitrile and treated with an aldoxime. Warming to -25 °C and addition of triethylamine affords the nitrile in excellent yield (eq 6).

Synthesis of a-Chloro Ketones.

a-Chloro ketones can be synthesized by treatment of an epoxide with DMS-Cl2 in CH2Cl2 at low temperature.7 Triethylamine is required to decompose the intermediate sulfonium salt to the a-chloro ketone (eq 7). Yields are greater than 80% but in some cases there is no control of regiochemistry.

1. (a) Wilson, G. E. T 1982, 38, 2597. (b) Tidwell, T. T. S 1990, 857. (c) Haines, A. H. CL(L) 1976, 883.
2. Corey, E. J.; Kim, C. U. JACS 1972, 94, 7586.
3. Corey, E. J.; Kim, C. U. TL 1974, 287.
4. Olah, G. A.; Ohannesian, L.; Arvanaghi, M. S 1986, 868.
5. Ho, T.-L. SC 1979, 9, 267.
6. Ho, T.-L.; Wong, C. M. SC 1975, 5, 423.
7. Olah, G. A.; Vankar, Y. D.; Arvanaghi, M. TL 1979, 3653.
8. Takeuchi, K.; Ikai, K.; Yoshida, M.; Tsugeno, A. T 1988, 44, 5681.
9. Nakai, H.; Kurono, M. CL 1977, 995.
10. Maturana, H; Sierra, J.; López, J.; Cortés, M. SC 1984, 14, 661.

William V. Murray

The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA

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