Dimethylthiocarbamoyl Chloride1

[16420-13-6]  · C3H6ClNS  · Dimethylthiocarbamoyl Chloride  · (MW 123.62)

(conversion of phenols to thiophenols;2 and, through subsequent desulfurization, for deoxygenation of phenols;2 conversion of allylic alcohols to 1,3-rearranged S-allyl dimethylthiocarbamates3 which can be hydrolyzed to the thiols or further oxidized to a,b-unsaturated carbonyl compounds;4 conversion of a-hydroxy-a,b-unsaturated ketones (diosphenols) to a-chloro- and a-bromo-a,b-unsaturated ketones;5a,b deoxygenation of diosphenols to a,b-unsaturated ketones;5c deoxygenation of pyridine N-oxides;6 dehydration of primary and secondary alcohols7)

Physical Data: mp 42-44 °C; bp 90-95 °C/0.5 mmHg; 62-65 °C/0.2 mmHg.

Solubility: very sol chloroform, THF; reacts (slowly) with protic solvents.

Form Supplied in: large lumps; commercially available.

Preparative Methods: treatment of tetramethylthiuram disulfide with Chlorine7 or Sulfuryl Chloride.8

Purification: vacuum distillation.

Handling, Storage, and Precautions: stable for years at 0 °C.

Conversion of Phenols to Thiophenols.

O-Aryl dimethylthiocarbamates (1), prepared by sequential treatment of phenols with base (usually Sodium Hydride in DMF) and dimethylthiocarbamoyl chloride, rearrange to S-aryl dimethylthiocarbamates (2) when heated at typically 200-300 °C (the Newman-Kwart rearrangement) (eq 1).2 For the purpose of preparing aryl-sulfur compounds, this process is a significant improvement over the pyrolysis of di-O-aryl thiocarbonates (the Schönberg rearrangement),9 where only one of the two aryl groups becomes connected to sulfur.

The product (2) may be transformed to the corresponding thiophenol by hydrolysis, or by reduction with Lithium Aluminum Hydride10a or Sodium-Ammonia.10b Alternatively, (2) may be oxidized with Hydrogen Peroxide/Formic Acid to the arenesulfonic acid,11a oxidized with Chlorine/Acetic Acid to the arenesulfonyl chloride,11b,c or desulfurized with Raney Nickel.12 Derivatization of phenols with the analog diethylthiocarbamoyl chloride sets the stage for ortho-deprotonation and alkylation with various electrophiles prior to effecting O-aryl -> S-aryl rearrangement.13 A wide variety of phenols has been successfully utilized in these processes; consequently the Newman-Kwart reaction is one of the most important methods for preparing aryl-sulfur compounds. Applications of the rearrangement can be found in medicinal chemistry,14 molecular recognition and supramolecular chemistry,15 and inorganic chemistry.16

Phenols bearing an electron-withdrawing group at the ortho or para position rearrange most readily (2-nitrophenol requires 20 min at 170 °C), consistent with the intermediacy of (4) (eq 2);2,9b this mechanism is supported by the correlation of rearrangement rates with s-values.17

If two o,p-electron-withdrawing groups are present, as in (6) (eq 3),18 or if an aza-aromatic system can be activated through protonation, as in (8) (eq 4),2a rearrangements occur much more readily. Conversely, electron-donating groups retard the reaction (e.g. 4-dimethylaminophenol requires 20 min at 295 °C).

Large alkyl or aryl groups at ortho positions slow the reaction2a,19a and, in general, cause lower yields.2a,14a,16b,c In some cases the preparation of dimethylthiocarbamates from hindered phenols is attended by thioacylation of the aromatic ring.19b Reactive functional groups at ortho positions can divert the course of the reaction (e.g. eq 5);19c in some cases these difficulties can be minimized by careful selection of reaction conditions.20

Whereas rearrangement fails in the case of 1-naphthol,21a exemplary results are obtained with 2-naphthol,2a,21b 6-nitro-2-naphthol,21c and 3-phenanthrol.2a The enantiomerically pure bis(dimethylthiocarbamate) (13) undergoes rearrangement without racemization (eq 6).15e O-Thioacylation of 2-azulenol and 6-azulenol is complicated by concurrent C-thioacylation; use of the 1,3-bis(methoxycarbonyl) analogs, followed by hydrolysis/decarboxylation, circumvents this problem.22a There is only one hydroxythiophene example in the literature,22b and no examples involving hydroxyfurans or hydroxypyrroles.

A nice application of the Newman-Kwart rearrangement is seen in the preparation of the otherwise difficult to access 5-hydroxyisoflavone (19) from the easily accessible 5,7-dihydroxyisoflavone (16) (eq 7).12

Conversion of Allylic Alcohols to 1,3-Rearranged S-Allyl Dimethylthiocarbamates.

Allylic dimethylthiocarbamates (from reaction of allylic alcoholates with dimethylthiocarbamoyl chloride) undergo [3,3]-sigmatropic rearrangement when heated at 100-130 °C.3 The products may be hydrolyzed with base or (better) reduced with lithium aluminum hydride to the allylic thiols (note: tertiary allylic thiols undergo allylic equilibration during aqueous hydrolysis). Although the rearrangement is somewhat slower3b than the more familiar rearrangement of allylic xanthates,23 the products lend themselves to deprotonation and alkylation with electrophiles. This sequence has been used by Nakai, et al. for the synthesis of several acyclic terpenes such as the ant pheromone manicone (24) (eq 8).4

Conversion of a-Hydroxy-a,b-Unsaturated Ketones (Diosphenols) to a-X-a,b-Unsaturated Ketones (X = H, Cl or Br).

The hydroxy group of diosphenols may be activated towards substitution by conversion to the dimethylthiocarbamate. These derivatives, irrespective of substitution pattern in the diosphenol, are deoxygenated in near-quantitative yield to a,b-unsaturated ketones by Lithium Iodide in hot acetic acid.5c Dimethylthiocarbamates of diosphenols whose b-carbon atom is unhindered react with Lithium Chloride or Lithium Bromide in acetic acid to furnish the corresponding halo compounds;5a if the b-carbon atom is substituted, a variety of products is obtained.5b Evidence is provided for the intermediacy of cyclized compounds like (27) in these reactions (eq 9).5

Deoxygenation of Pyridine N-Oxides and Related Compounds.

Treatment of pyridine N-oxides with dimethylthiocarbamoyl chloride and lithium iodide in acetonitrile at rt or below gives chemoselective deoxygenation (eq 10).6 Neither oxalyl chloride nor tosyl chloride can be used as activating agents, and it is speculated that the reaction proceeds through an intermediate like (30), analogous to (27).

Dehydration of Primary and Secondary Alcohols.

Dimethylthiocarbamates of primary and secondary alcohols bearing a b-hydrogen give alkenes when heated at 180-200 °C.7 This procedure has some advantages over xanthate pyrolysis:24 (a) one-step preparation of derivatives; (b) yields of elimination products are often better; and (c) no thiol is produced upon pyrolysis. This latter consideration is important in the dehydration-aromatization of (33) (eq 11).25


1. (a) Fieser, L. F.; Fieser, M. FF 1969, 2, 173. (b) Fieser, L. F.; Fieser, M. FF 1972, 3, 127. (c) Fieser, L. F.; Fieser, M. FF 1974, 4, 202. (d) Fieser, L. F.; Fieser, M. FF 1980, 8, 200.
2. (a) Newman, M. S.; Karnes, H. A. JOC 1966, 31, 3980. (b) Kwart, H.; Evans, E. R. JOC 1966, 31, 410.
3. (a) Hackler, R. E.; Balko, T. W. JOC 1973, 38, 2106. (b) Nakai, T.; Ari-izumi, A. TL 1976, 2335.
4. (a) Nakai, T.; Mimura, T.; Ari-izumi, A. TL 1977, 2425. (b) Nakai, T.; Mimura, T.; Kurokawa, T. TL 1978, 2895. (c) Mimura, T.; Kimura, Y.; Nakai, T. CL 1979, 1361.
5. (a) Ponaras, A. A.; Zaim, &OOuml;. JOC 1986, 51, 4741. (b) Ponaras, A. A.; Zaim, &OOuml;. JOC 1987, 52, 5630. (c) Ponaras, A. A.; Zaim, &OOuml;.; Pazo, Y.; Ohannesian, L. JOC 1988, 53, 1110.
6. Ponaras, A. A., unpublished results.
7. Newman, M. S.; Hetzel, F. W. JOC 1969, 34, 3604.
8. Vilkas, M.; Qasmi, D. SC 1990, 20, 2769.
9. (a) Schönberg, A.; Vargha, L. V. CB 1930, 63, 178. (b) Powers, D. H.; Tarbell, D. S. JACS 1956, 78, 70.
10. (a) Hori, M.; Ban, M.; Imai, E.; Iwata, N.; Baba, Y.; Fujimura, H.; Nozaki, M.; Niwa, M. H 1983, 20, 2359. (b) Besserer, K.; Köhler, H.; Rundel, W. CB 1982, 115, 3678.
11. (a) Cooper, J. E.; Paul, J. M. JOC 1970, 35, 2046. (b) Wagenaar, A.; Engberts, J. B. F. N. RTC 1982, 101, 91. (c) Similarly, (2) has been converted to the the arenesulfonyl chloride by treatment with conc. H2SO4 (giving the disulfide) followed by treatment with chlorine: Miller, M. W.; Mylari B. L.; Howes, H. L., Jr.; Figdor, S. K.; Lynch, M. J.; Lynch, J. E.; Koch, R. C. JMC 1980, 23, 1083.
12. Lévai, A.; Sebõk, P. SC 1992, 22, 1735.
13. Beaulieu, F.; Snieckus, V. S 1992, 112.
14. Selected examples: (a) Matsumoto, K.; Stark, P.; Meister, R. G. JMC 1977, 20, 17. (b) Holt, D. A.; Oh, H.-J.; Levy, M. A.; Metcalf, B. W. Steroids 1991, 56, 4. (c) Taraporewala, I. B.; Kauffman, J. M. JPS 1990, 79, 173. (d) Debono, M.; Abbott, B. J.; Fukuda, D. S.; Barnhart, M.; Willard, K. E.; Molloy, R. M.; Michel, K. H.; Turner, J. R. Butler, T. F.; Hunt, A. H. J. Antibiot. 1989, 432, 389. (e) Montéro, J.-L.; Bello-Roufai, N.; Leydet, A.; Dewynter, G.; N'Guessan, T. Y.; Winternitz, F. BSF(2) 1987, 302. (f) Kirchlechner, R.; Seubert, J. AP 1982, 315, 519.
15. (a) Cram, D. J.; Helgeson, R. C.; Koga, K.; Kyba, E. P.; Madan, K.; Sousa, L. R.; Siegel, M. G.; Morean, P.; Gogel, G. W.; Timko, J. M.; Sogah, G. D. Y. JOC 1978, 43, 2758. (b) Hardy, A. D. U.; MacNicol, D. D.; Wilson, D. R. JCS(P2) 1979, 1011. (c) Di Furia, F.; Licini, G.; Modena, G.; Valle, G. BSF(2) 1990, 734. (d) Garcia, C.; Andraud, C.; Collet, A. Supramol. Chem. 1992, 1, 31. (e) Fabbri, D.; Delogu, G.; De Lucchi, O. JOC 1993, 58, 1748.
16. (a) Evans, D. J.; Garcia, G.; Leigh, G. J.; Newton, M. S.; Santana, M. D. JCS(D) 1992, 3229. (b) Bishop, P. T.; Dilworth, J. R.; Nicholson, T,; Zubieta, J. A. JCS(D) 1991, 385. (c) Blower, P. J.; Dilworth, J. R.; Hutchinson, J. P.; Zubieta, J. A. JCS(D) 1985, 1533.
17. Kaji, A.; Araki, Y.; Miyazaki, K. BCJ 1971, 44, 1393.
18. Hirano, M.; Miyashita, A.; Nohira, H. CL 1991, 209.
19. (a) Relles, H. M.; Pizzolato, G. JOC 1968, 33, 2249. (b) Rundel, W.; Köhler, H. CB 1972, 105, 1087. (c) Reineke, C. E.; Goralski, C. T. JOC 1977, 42, 1139.
20. (a) Hori, M.; Kataoka, T.; Shimizu, H.; Imai, E.; Iwamura, T.; Nozaki, M.; Niwa, M.; Fujimura, H. CPB 1984, 32, 1268. (b) Rahman, L. K. A.; Scrowston, R. M. JCS(P1) 1983, 2973. (c) Lau, C. K.; Bélanger, P. C.; Dufresne, C.; Scheigetz, J. JOC 1987, 52, 1670. (d) Traxler, J. T. JOC 1979, 44, 4971.
21. (a) Daub, G. H.; Whaley, T. W. JOC 1978, 43, 4659. (b) Newman, M. S.; Hetzel, F. W. OS 1971, 51, 139. (c) Aslam, M.; Davenport, K. G. SC 1987, 17, 1761.
22. (a) Asao, T.; Ito, S.; Morita, N. TL 1989, 30, 6345. (b) Corral, C.; Lissavetzky, J.; Valdeolmillos, A. M. S 1984, 172.
23. (a) Barrett, A. G. M.; Sakadarat, S. JOC 1990, 55, 5110. (b) Ueno, Y.; Sano, H.; Okawara, M. TL 1980, 21, 1767.
24. Nace, H. R. OR 1962, 12, 57.
25. Klein, R. F. X.; Horak, V. JOC 1986, 51, 4644.

Anthony A. Ponaras

The Catholic University of America, Washington, DC, USA

&OOuml;mer Zaim

Trakya University, Edirne, Turkey



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