Dimethyl Sulfoxide-Dicyclohexylcarbodiimide1

(DMSO)

[67-68-5]  · C2H6OS  · Dimethyl Sulfoxide-Dicyclohexylcarbodiimide  · (MW 78.13) (DCC)

[538-75-0]  · C13H22N2  · Dimethyl Sulfoxide-Dicyclohexylcarbodiimide  · (MW 206.33)

(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: DMSO-DCC; Pfitzner-Moffatt reagent.

Physical Data: DMSO: mp 18.4 °C; bp 189 °C; d 1.101 g cm-3. DCC: mp 34-35 °C; bp 122-124 °C/6 mmHg.

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

Form Supplied in: DMSO is a colorless liquid that is widely available, including anhydrous grades of 99%+ purity and <0.005% H2O under N2; DCC is a low-melting but crystalline solid that is widely available.

Preparative Method: the active oxidant, CyNHC(O+SMe2)NCy, is generated in the presence of the alcohol substrate by the reaction of DCC, an acid, and pyridine, and reacts with the alcohol in situ.

Purification: DMSO: distillation from CaH2 at 56-57 °C/5 mmHg2a or 83-85 °C/17 mmHg;2b storage over 3&AAring; molecular sieves. DCC: distillation at reduced pressure.

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 1,3-Dicyclohexylcarbodiimide is moisture sensitive and should be dry, crystalline material, otherwise it can be distilled at 140 °C/5 mmHg;4a it is toxic and corrosive and should be handled with gloves in a fume hood.

The title reagent was the first of the activated DMSO reagents to be developed,3 and offers the advantage not shared by many oxidizing methods of giving rapid oxidation at rt, without problems of overoxidation to give carboxylic acids. The disadvantages of the reagent are that the yields, though good, are not excellent, methylthiomethyl ethers occur as byproducts, and removal of the byproduct dicyclohexylurea can be a problem. The reaction mechanism has subtle differences from those of other DMSO-based oxidations and has been thoroughly documented by isotopic studies.1a,g The first step involves catalysis by acids such as Phosphoric Acid or Trifluoroacetic Acid in the presence of Pyridine (eq 1). Intramolecular proton abstraction via (2) is unique to this process, providing the ylide (3) (eq 2) common to all DMSO-based alcohol oxidations, which gives the carbonyl product by an intramolecular process (eq 3). In addition to previously summarized mechanistic studies, the effect of pressure on this reaction has also been examined, and the negative activation volume is consistent with an associative process.2d

Some typical examples of this process are shown in eqs 4 and 5.4 Water-soluble4c and polymeric4d carbodiimides have also been utilized to assist in the separation of the product from the product urea. Other recent examples shown include oxidation of a nucleoside (eq 6),4e formation of an a-hydroxy ketone (eq 7),4f and formation of a diketone (eq 8).4g Elimination occurs in substrates sensitive to the acidic conditions (eq 9).4h

In the procedure of eq 10 the crude aldehyde from the first step was subjected directly to allylboration with (E)-crotyldiisopinocampheylborane (see B-Crotyldiisopinocampheylborane) to give the product in 70% yield for the two steps.5a The product aldehydes have also been used in Wittig homologations; prior isolation of the aldehydes is required.5b,c

Related Reagents.

N-Chlorosuccinimide-Dimethyl Sulfide; Chromic Acid; Dimethyl Sulfide-Chlorine; Dimethyl Sulfoxide-Acetic Anhydride; 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. (d) Isaacs, N. S.; Laila, A. H. JPOC 1991, 4, 639.
3. (a) Pfitzner, K. E.; Moffatt, J. G. JACS 1963, 85, 3027. (b) Pfitzner, K. E.; Moffatt, J. G. JACS 1965, 87, 5661.
4. (a) Moffatt, J. G. OSC 1973, 5, 242. (b) Jones, G. H.; Moffatt, J. G. In Methods in Carbohydrate Chemistry; Whistler, R. L.; BeMiller, J. N., Eds; Academic: New York, 1972; Vol. 6, p 315. (c) Hanessian, S.; Lavallee, P. CJC 1981, 59, 870. (d) Weinshenker, N. M.; Shen, C. M.; Wong, J.-Y. OSC 1988, 6, 218. (e) Danishefsky, S. J.; DeNinno, S. L.; Chen, S.; Boisvert, L.; Barbachyn, M. JACS 1989, 111, 5810. (f) Bowden, M. C.; Pattenden, G. TL 1988, 29, 711. (g) Schobert, R. S 1987, 741. (h) Johnson, C. R.; Penning, T. D. JACS 1988, 110, 4726.
5. (a) Sunazuka, T.; Nagamitsu, T.; Matsuzaki, K.; Tanaka, H.; &OOmacr;mura, S.; Smith, A. B., III. JACS 1993, 115, 5302. (b) Jones, R. J.; Swaminathan, S.; Milligan, J. F.; Wadwani, S.; Froehler, B. C.; Matteucci, M. D. JACS 1993, 115, 9816. (c) Montgomery, J. A.; Thomas, H. J. JOC 1981, 46, 594.

Thomas T. Tidwell

University of Toronto, Ontario, Canada



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