N-Chlorosuccinimide-Dimethyl Sulfide1

(R1 = R2 = Me)

[39095-38-0]  · C6H10ClNO2S  · N-Chlorosuccinimide-Dimethyl Sulfide  · (MW 195.66) (R1 = Me, R2 = Et)

[54959-52-3]  · C7H12ClNO2S  · N-Chlorosuccinimide-Ethyl Methyl Sulfide  · (MW 209.69) (R1 = Me, R2 = n-Pr)

[54959-53-4]  · C8H14ClNO2S  · N-Chlorosuccinimide-Methyl Propyl Sulfide  · (MW 223.72) (R1 = Et, R2 = CH2CH=CH2)

[59321-40-3]  · C9H14ClNO2S  · N-Chlorosuccinimide-Allyl Ethyl Sulfide  · (MW 235.73) (R1 = Me, R2 = CH2CHMe2)

[54959-54-5]  · C9H16ClNO2S  · N-Chlorosuccinimide-Isobutyl Methyl Sulfide  · (MW 237.74) (R1 = R2 = n-Pr)

[59741-19-4]  · C10H18ClNO2S  · N-Chlorosuccinimide-Dipropyl Sulfide  · (MW 251.77) (R1 = Me, R2 = Ph)

[82661-92-5]  · C11H12ClNO2S  · N-Chlorosuccinimide-Methyl Phenyl Sulfide  · (MW 257.73) (R1 = Et, R2 = CH2CH=CMe2)

[59321-43-6]  · C11H18ClNO2S  · N-Chlorosuccinimide-3,3-Dimethylallyl Ethyl Sulfide  · (MW 263.78) (R1 = Me, R2 = CH2Ph)

[65824-49-9]  · C12H14ClNO2S  · N-Chlorosuccinimide-Benzyl Methyl Sulfide  · (MW 271.76) (R1 = Et, R2 = CH2Ph)

[65824-51-3]  · C13H16ClNO2S  · N-Chlorosuccinimide-Benzyl Ethyl Sulfide  · (MW 285.79) (R1 = Et, R2 = CH2C6H4-4-Me)

[65824-52-4]  · C14H18ClNO2S  · N-Chlorosuccinimide-Ethyl p-Tolylmethyl Sulfide  · (MW 299.82) (R1 = Et, R2 = CH2(1-C10H7)

[65824-54-6]  · C17H18ClNO2S  · N-Chlorosuccinimide-Ethyl 1-Naphthylmethyl Sulfide  · (MW 335.85) (R1 = R2 = n-C7H15)

[59741-21-8]  · C20H38ClNO2S  · N-Chlorosuccinimide-Diheptyl Sulfide  · (MW 392.04)

(oxidizing agent for alcohols to aldehydes and ketones,1 catechols and hydroquinones to quinones,2 aromatic amines to sulfilimines,3 hydroxamic acids to acylnitroso compounds;4 chlorination of allylic and benzylic alcohols,5 ortho alkylation and formylation of phenols,6 preparation of chloromethyl thioethers,7 thioalkylation of pyrroles, indoles, and enamines;8 preparation of sulfur ylides of active methylene compounds,9 preparation of sulfonium salts from enamines and cyclopentadienyl anions,10 dehydration to form keto enamines from b-diketones and nitriles from aldoximes11)

Alternate Names: Corey-Kim reagent; dimethyl(succinimido)sulfonuim chloride.

Physical Data: R1 = R2 = Me: mp 70-72 °C.

Solubility: the reagents are slightly more sol in CH2Cl2, toluene, and THF than the NCS from which they are derived.

Form Supplied in: prepared in situ from NCS and dialkyl sulfides.

Handling, Storage, and Precautions: see N-Chlorosuccinimide, Dimethyl Sulfide, and other articles on alkyl sulfides.

N-Chlorosuccinimide-Dialkyl Sulfides.

These reagents are generally prepared in situ in solvents such as toluene, CH2Cl2, or THF. The reagents themselves are generally more soluble than the NCS from which they are derived and are often prepared at a temperature of about 0 °C to facilitate reaction with the limitedly soluble NCS, but because of their thermal instability are not prepared at higher temperature. They are often used at temperatures as low as -78 °C.

Oxidations.

N-Chlorosuccinimide-dimethyl sulfide (NCS-DMS) is one of several reagents for converting alcohols to alkoxydimethylsulfonium salts, which in the presence of base convert to the corresponding carbonyl compounds via intramolecular proton transfer and loss of dimethyl sulfoxide.1,12 These oxidations are among the mildest and most selective for conversions of alcohols to aldehydes and ketones. This reaction does not suffer the overoxidation to acids or the carbon-carbon bond cleavages which are often encountered in chromium(VI) or manganese(VII) oxidations (eq 1).1,13

Several higher members of this class, including the NCS-diisopropyl sulfide reagent, are reported to show unusual selectivity for primary and secondary alcohols. Thus at 0 °C the reagent selectively oxidizes primary alcohols rather than secondary, whereas at -78 °C it selectively oxidizes secondary alcohols rather than primary (eq 2).14

These reagents are also effective in the oxidation of s,t-1,2-diols to a-ketols (eq 3).13 Metal-based reagents give carbon-carbon bond cleavage with such diols.

Oxidation of 1,3-keto alcohols or 1,3-diketones gives 1,3-diketo sulfonium ylides, which may be reduced to the 1,3-diketones (eq 4).9

Catechols and hydroquinones are oxidized to quinones (eq 5),3 and N-hydroxyureas are oxidized to nitroso compounds (eq 6).4

Halogenations.

Allylic, benzylic, and cyclopropyl carbinyl alcohols are reported to undergo chlorination with or without allyl rearrangement, depending upon structure.15 Thus primary and secondary allylic carbinols generally give the chlorides without rearrangement (eqs 7 and 8), whereas 2-formyl secondary allylic alcohols give the rearranged product (eq 9).5

The NCS-dialkyl sulfide reagents are thermally labile, and depending on structure undergo a variety of transformations leading ultimately to a-chlorination of the sulfide (eq 10).7

O-Alkylation of Anilines and Phenols.

Treatment of anilines with NCS-DMS leads to sulfilimines, which may be converted to 2-alkylanilines (eq 11).3 Similarly, phenols give directly the 2-substituted product (eq 12).6

Other Alkylations.

NCS and allylic sulfides react with 3-unsubstituted indoles at -20 °C to give initially 3-sulfonium salts which on warming to 20 °C rearrange to 2-allyl-3-thiomethylindoles (eq 13). These are readily desulfurized, either with or without concomitant reduction of the allylic double bond, to give 3-allyl or 3-alkyl substituted indoles.8b,8c

On the other hand, 3-alkyl-1H-indoles react with NCS-dialkyl sulfides in the presence of base to give 3-alkyl-3-alkylthioalkyl-3H-indoles (indolinenes, eq 14).16

NCS-DMS reacts with cyanoacetate anions nearly exclusively at nitrogen to give N-alkylthiomethylketenimines (eq 15).17

Thioalkylation.

Treatment of pyrroles with NCS-DMS leads to 2-thiomethylpyrroles (eq 16). Indoles give 3-thioalkylindoles (eq 17).8a-c

NCS-DMS reacts with enamines to give sulfonium salts (eq 18),10a,10b and with cyclopentadienyl anions to give bis- and tris-substituted sulfonium salts (eq 19).10c

Dehydrations.

While certain 1,3-diketones produce the sulfonium ylide, the treatment of N-acetylpiperidine-3,5-dione first with NCS-DMS and then with an amine in the presence of TFA resulted in the formation of the enaminone. The yields for this conversion were report to be significantly better than in the traditional method of azeotropic water removal (eq 20).11a

It was found during an attempt to produce N-methylthiomethyl nitrones that treatment of aldoximes with NCS-DMS resulted in high yields of nitriles (eq 21).11b

Related Reagents.

Dimethyl Sulfoxide-Oxalyl Chloride; Dimethyl Sulfoxide-Phosgene; Dimethyl Sulfoxide-Triphosgene.


1. (a) Tidwell, T. T. OR 1990, 39, 297. (b) Tidwell, T. T. S 1990, 857. (c) Fisher, L. E.; Muchowski, J. M. OPP 1990, 22, 399.
2. Marino, J. P.; Schwartz, A. CC 1974, 812.
3. (a) Claus, P. K.; Rieder, W.; Hofbauer, P.; Vilsmaier, E. T 1975, 31, 505. (b) Claus, P. K.; Vycudilik, W.; Rieder, W. M 1971, 102, 1571. (c) Gassman, P. G.; Gruetzmacher, G. D. JACS 1974, 96, 5487. (d) Gassman, P. G.; Parton, R. L. TL 1977, 2055.
4. Gouverneur, V.; Ghosez, L. TL 1991, 32, 5349.
5. (a) Corey, E. J.; Kim, C. U.; Takeda, M. TL 1972, 4339. (b) Depezay, J. C.; Le Merrer, Y. TL 1974, 2751. (c) Depezay, J. C.; Le Merrer, Y. TL 1974, 2755.
6. (a) Gassman, P. G.; Amick, D. R. TL 1974, 889. (b) Gassman, P. G.; Amick, D. R. TL 1974, 3463. (c) Gassman, P. G.; Amick, D. R. JACS 1978, 100, 7611.
7. (a) Vilsmaier, E.; Sprugel, W. LA 1971, 747, 151. (b) Vilsmaier, E.; Dittrich, K. H.; Sprugel, W. TL 1974, 3601.
8. (a) Franco, F.; Greenhouse, R.; Muchowski, J. M. JOC 1982, 47, 1682. (b) Tomita, K.; Terada, A.; Tachikawa, R. H 1976, 4, 729. (c) Tomita, K.; Terada, A.; Tachikawa, R. H 1976, 4, 733. (c) Vilsmaier, E.; Sprugel, W.; Gagel, K. TL 1974, 2475. (d) Vilsmaier, E.; Troger, W.; Sprugel, W.; Gagel, K. CB 1979, 112, 2997.
9. (a) Katayama, S.; Fukuda, K.; Watanabe, T.; Yamauchi, M. S 1988, 178. (b) Katayama, S.; Watanabe, T.; Yamauchi, M. CL 1989, 973. (c) Katayama, S.; Watanabe, T.; Yamauchi, M. CPB 1990, 38, 3314.
10. (a) Vilsmaier, E.; Sprugel, W.; Gagel, K. TL 1974, 2475. (b) Vilsmaier, E.; Troger, W.; Sprugel, W.; Gagel, K. CB 1979, 112, 2997. (c) Schlingensief, K. H.; Hartke, K. TL 1977, 1269.
11. (a) Tamura, Y.; Chen, L. C.; Fujita, M.; Kiyokawa, H.; Kita, Y. CI(L) 1979, 668. (b) Dalgard, N. K. A.; Larsen, K. E.; Torssell, K. B. G. ACS,B 1984, 38, 423.
12. McCormick, J. P. TL 1974, 1701.
13. Corey, E. J.; Kim, C. U.; Misco, P. F. OSC 1988, 6, 220.
14. Kim, K. S.; Cho, I. H.; Yoo, B. K.; Song, Y. H.; Hahn, C. S. CC 1984, 762.
15. Murray, R. K.; Jr.; Babiak, K. A. TL 1974, 311.
16. Katayama, S.; Watanabe, T.; Yamauchi, M. CPB 1992, 40, 2836.
17. Morel, G.; LeMoing-Orliac, M. A.; Khamsitthideth, S.; Foucaud, A. T 1992, 38, 527.

Robert C. Kelly

The Upjohn Company, Kalamazoo, MI, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.