[463-71-8]  · CCl2S  · Thiophosgene  · (MW 114.98)

(very electrophilic reagent capable of forming isothiocyanates with amines;1 used in forming various heterocycles;12 in combination with phosphorus reagents, capable of forming cis- and trans-alkenes from cyclic thiocarbonates (Corey-Winter alkenation);22 dienophile in Diels-Alder reactions25)

Physical Data: bp 73 °C; d 1.508 g cm-3.

Solubility: sol most organic solvents; decomposes in H2O and alcoholic solvents.

Form Supplied in: red-orange liquid; widely available.

Handling, Storage, and Precautions: wear appropriate safety equipment. Use only in a chemical fume hood; keep container tightly closed; unpleasant odor. Moisture sensitive; store under nitrogen; refrigerate. Highly toxic; may be fatal if inhaled, swallowed, or absorbed through skin; corrosive; lachrymator.

Reactions with Nitrogen Nucleophiles.

Thiophosgene has most commonly been used to convert primary aliphatic and aromatic amines (eq 1) into isothiocyanates2,3 and thioureas (eq 2).4,5 Secondary amines have been converted to aminothiocarbonyl chlorides,6 N,N-disubstituted thiocarbamates,7 and thioureas (eq 3).8 Tertiary amines can be transformed to thiocarbamoyl chlorides9 and isothiocyanato acid chlorides.10

Primary amines react selectively with thiophosgene in the presence of other reactive functional groups (OH, NH, CO2H, CONH, SO3H, or SH), situated far from the reacting amine, to form isothiocyanates (eq 4).11 However, reactive functional groups present in the vicinity of the reactive amino group interact with the thiophosgene or the isothiocyanate generated in situ to afford a wide variety of heterocycles.4,11a,12 Examples include formation of heterocyclic thiones (eq 5)13 and benzoxazines (eq 6).14

The reaction of primary amides with thiophosgene may yield the corresponding isothiocyanate15 or a nitrile and a thione, depending on the reaction conditions.16 Also, subjecting thioureas and thioamides to thiophosgene followed by hydrolysis is a useful way to prepare the corresponding ureas and amides.17 Ketimines which do not have a b-hydrogen atom react with thiophosgene to give a-chloroalkyl isothiocyanates, while those carrying a b-hydrogen give a-alkenyl isothiocyanates.18 A number of fused 2H-1,3-oxazine-2-thiones have been prepared by reacting 1,2-hydroximines with thiophosgene.19 N-Isothiocyanato amines are prepared by reacting hydrazines with thiophosgene.20

Reactions with Oxygen Nucleophiles.

In the presence of thiophosgene, alcohols and phenols have been converted into chlorothioformates21 which can be useful precursors of thiocarbonates, thiocarbamates, and dithiocarbonates.1 Diols have been shown to form cyclic thiocarbonates. Specifically, 1,2-diols have been transformed into cyclic thiocarbonates which can be further transformed stereospecifically to cis- or trans-alkenes (eq 7).22

Reactions with Sulfur Nucleophiles.

Thiols have been converted to chlorodithioformates (eq 8),23 trithiocarbonates,24 and cyclic thiones12 in the presence of thiophosgene, depending on the reaction conditions.

Miscellaneous Reactions.

Thiophosgene has been used as a dienophile in the Diels-Alder reaction.25 Examples include the synthesis of thiopyranones (eq 9)26 and bicyclic systems (eq 10).27 [2 + 2] Cycloaddition reactions have also been achieved with thiophosgene.28 Thiiranes have been prepared from diazo compounds,29 and thioketenylidenetriphenylphosphorane from methylenetriphenylphosphorane,30 when combined with thiophosgene.

1. (a) Sharma, S. Sulfur Rep. 1986, 5, 1. (b) Sharma, S. S 1978, 803.
2. Johnson, T. B.; Hemingway, E. H. JACS 1916, 38, 1550.
3. (a) Dzurilla, M.; Kristian, P. CCC 1970, 35, 417. (b) Uher, M.; Floch, L.; Jendrichovsky, J. CCC 1974, 39, 182. (c) Kym, P. R.; Carlson, K. E.; Katzenellenbogen, J. A. JMC 1993, 36, 1111. (d) de Costa, B. R.; Lewin, A. H.; Rice, K. C.; Skolnick, P.; Schoenheimer, J. A. JMC 1991, 34, 1531.
4. Dyson, G. M.; George, H. J.; Hunter, R. F. JCS 1927, 436.
5. Schmidtchen, F. P.; Oswald, H.; Schummer, A. LA 1991, 539.
6. (a) Lieber, E.; Rao, C. N. R.; Lawyer, C. B.; Trivedi, J. P. CJC 1963, 41, 1643. (b) Nakajima, M.; Herget, R. A.; Anselme, J. P. BCJ 1981, 54, 2547.
7. Toth, G.; Szabo, G.; Marso, M.; Nagy, L.; Toth, I.; Montay, T. Hung. Patent 19 949, 1981 (CA 1982, 96, 19 852).
8. Barton, D. H. R.; Elliott, J. D.; Gero, S. D. JCS(P1) 1982, 3, 2085.
9. Skorini, S. J.; Senning, A. T 1980, 36, 539.
10. Kricheldorf, H. R. AG(E) 1975, 14, 502.
11. (a) Dubey, S. K.; Singh, A. K.; Singh, H.; Sharma, S.; Iyer, R. N.; Katiyar, J. C.; Goel, P.; Sen, A. B. JMC 1978, 21, 1178. (b) Abuzar, S.; Sharma, S.; Iyer, R. N. IJC(B) 1980, 19B 599. (c) Kozikowski, A. P.; Fauq, A. H.; Tuckmantel, W.; Casalotti, S. O.; Krueger, K. E. SL 1991, 654.
12. (a) Rousseau, D.; Taurins, A. CJC 1977, 55, 3736. (b) Doleschall, G.; Hornyak, G.; Agai, B.; Simig, G.; Fetter, J.; Lempert, K. T 1976, 32, 57. (c) Morgenstern, O.; Richter, P.; Rouvinen, J.; Malkonen, P. J.; Vainiotalo, P.; Hanninen, K.; Ahlgren, M.; Vepsalainen, J. JHC 1991, 28, 1091.
13. Rastogi, R.; Sharma, S. IJC(B) 1981, 20B, 579.
14. Singh, H.; Sharma, S.; Iyer, R. N. S 1975, 325.
15. Joos, A.; Wirtz, W. Ger. Patent 2 059 872, 1972 (CA 1972, 77, 88 114).
16. Sharma, S.; Bindra, R.; Iyer, R. N. IJC 1973, 11, 1201.
17. Abuzar, S.; Sharma, S.; Iyer, R. N. IJC(B) 1980, 19B 211.
18. Gorbatenko, W. I.; Bondar, W. A.; Samaraj, L. I. AG(E) 1973, 12, 842.
19. Stoss, P. CB 1978, 111, 314.
20. Anthoni, U.; Larsen, C.; Nielsen, P. H. ACS 1967, 21, 2061.
21. Robins, M. J.; Wilson, J. S. JACS 1981, 103, 932.
22. (a) Corey, E. J.; Winter, R. A. E. JACS 1963, 85, 2677. (b) Corey, E. J.; Carey, F. A.; Winter, R. A. E. JACS 1965, 87, 934. (c) Corey, E. J.; Hopkins, P. B. TL 1982, 23, 1979.
23. Nakayama, J.; Dan, S.; Hoshino, M. JCS(P1) 1981, 413.
24. Godt, H. C.; Wann, R. E. JOC 1961, 26, 4047.
25. Middleton, W. J. JOC 1965, 30, 1390.
26. Barluenga, J.; Aznar, F.; Valdes, C. SL 1991, 487.
27. Reich, H. J.; Trend, J. E. JOC 1973, 38, 2637.
28. Pattenden, G.; Shuker, A. J. JCS(P1) 1992, 1215.
29. Chew, W.; Hynes, R. C.; Harpp, D. N. JOC 1993, 58, 4398.
30. Bestmann, H. J.; Schmid, G. AG(E) 1974, 13, 273.

Christopher J. O'Donnell

University of Wisconsin-Madison, WI, USA

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