Dimethyl Sulfoxide-Acetic Anhydride1


[67-68-5]  · C2H6OS  · Dimethyl Sulfoxide-Acetic Anhydride  · (MW 78.13) (Ac2O)

[108-24-7]  · C4H6O3  · Dimethyl Sulfoxide-Acetic Anhydride  · (MW 102.09)

(oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones, respectively; avoids overoxidation to carboxylic acids; suitable for large-scale oxidation; gives good yields with variable amounts of byproduct methylthiomethyl ethers)

Alternate Name: Albright-Goldman reagent.

Physical Data: DMSO mp 18.4 °C; bp 189 °C; d 1.101 g cm-3. Ac2O: mp -78 °C; bp 138-140 °C; d 1.082 g cm-3.

Solubility: DMSO: sol H2O, alcohol, acetone, THF, CH2Cl2. Ac2O: sol ether, acetone, CH2Cl2.

Form Supplied in: colorless liquids; widely available, including anhydrous grades of DMSO packed under N2.

Preparative Method: the active reagent, presumably Me2+SOAc, forms slowly from a mixture of the coreactants over a period of hours at rt and reacts with the alcohol in situ.

Purification: DMSO: distillation from calcium hydride at 56-57 °C/5 mmHg2a or 83-85 °C/17 mmHg;2b storage over 3Å molecular sieves. Ac2O: distillation from aluminum chloride or calcium carbide.

Handling, Storage, and Precautions: Dimethyl Sulfoxide is readily absorbed through the skin and should always be handled with gloves in a fume hood; its reactions form foul-smelling byproducts and should be carried out with good ventilation, and the waste byproducts and liquids used for washing should be treated with KMnO4 solution to oxidize volatile sulfur compounds; DMSO undergoes appreciable disproportionation to dimethyl sulfide (stench!) and dimethyl sulfone above 90 °C;2c Acetic Anhydride is a corrosive lachrymator.

The title reagent is useful for the oxidation of primary or secondary alcohols to aldehydes and ketones, respectively, at rt without added base. The reagents are inexpensive and the procedure is adaptable to large-scale reactions, such as the oxidation of yohimbine on a 2.5 mol scale.3 The mechanism of this reaction appears to involve formation of activated DMSO by the rather slow reaction of DMSO with Ac2O at rt to form the acyloxysulfonium ion (1); this then reacts with the alcohol to give the alkoxysulfonium ion (2) (eq 1). By analogy to other DMSO-based oxidations, (2) undergoes deprotonation to (3), which forms the oxidation product intramolecularly (eq 2).1a,b A common side reaction of alcohols ROH with activated DMSO is formation of methylthiomethyl ethers ROCH2SMe (4), which probably arise from dissociation of (3) or some other activated form of DMSO to form (5) due to the operational temperature of 25 °C and the long reaction times (12-24 h) (eq 3). Alternatively, (5) could be formed by an intramolecular proton abstraction in (1) via a six-membered transition state. The effect of pressure on the reaction has been examined, and the large negative entropy of activation is consistent with an associative mechanism.4 The reaction is also greatly accelerated by pressure when carried out on a preparative scale.4 Some examples of the procedure are shown in eqs 4-6.5a,b,c

Related Reagents.

N-Chlorosuccinimide-Dimethyl Sulfide; Chromic Acid; Dimethyl Sulfide-Chlorine; Dimethyl Sulfoxide-Dicyclohexylcarbodiimide; Dimethyl Sulfoxide-Methanesulfonic Anhydride; Dimethyl Sulfoxide-Oxalyl Chloride; Dimethyl Sulfoxide-Phosphorus Pentoxide; Dimethyl Sulfoxide-Sulfur Trioxide/Pyridine; Dimethyl Sulfoxide-Trifluoroacetic Anhydride; Dimethyl Sulfoxide-Triphosgene; Manganese Dioxide; Pyridinium Chlorochromate; Pyridinium Dichromate; Ruthenium(VIII) Oxide; Silver(I) Carbonate; 1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one.

1. (a) Tidwell, T. T. OR 1990, 39, 297. (b) Tidwell, T. T. S 1990, 857. (c) Lee, T. V. COS 1991, 7, 291. (d) Haines, A. H. Methods for the Oxidation of Organic Compounds; Academic: London, 1988. (e) Hudlicky, M. Oxidations in Organic Chemistry; ACS: Washington, 1990. (f) Mancuso, A. J.; Swern, D. S 1981, 165. (g) Moffatt, J. G. In Oxidation; Augustine, R. L.; Trecker, D. J., Eds.; Dekker: New York, 1971; Vol. 2, Chapter 1.
2. (a) Iwai, I.; Ide, J. OSC 1988, 6, 531. (b) Insalaco, M. A.; Tarbell, D. S. OSC 1988, 6, 207. (c) Corey, E. J.; Chaykovsky, M. OSC 1973, 5, 755.
3. (a) Albright, J. D.; Goldman, L. JACS 1965, 87, 4214. (b) Albright, J. D.; Goldman, L. JACS 1967, 89, 2416.
4. Isaacs, N. S.; Laila, A. H. JPOC 1991, 4, 639.
5. (a) Rabinsohn, Y.; Fletcher, H. G., Jr. In Methods in Carbohydrate Chemistry, Whistler, R. L.; BeMiller, J. N., Eds.; Academic: New York, 1972; Vol. 6; p 326. (b) Broka, C. A.; Gerlits, J. F. JOC 1988, 53, 2144. (c) Katagiri, N.; Akatsuka, H.; Haneda, T.; Kaneko, C.; Sera, A. JOC 1988, 53, 5464.

Thomas T. Tidwell

University of Toronto, Ontario, Canada

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