Thiophosphoryl Chloride

[3982-91-0]  · Cl3PS  · Thiophosphoryl Chloride  · (MW 169.39)

(thionation of amides; thiophosphorylating agent for alcohols, amines, diols, amino alcohols, diamines, etc.)

Physical Data: mp -35 °C; bp 125 °C; nD 1.550; d 1.668 g cm-3.

Solubility: sol benzene; CCl4, CHCl3, CS2; reacts with alcohols and amines.

Form Supplied in: liquid; widely available.

Analysis of Reagent Purity: 31P NMR.

Purification: distillation.1

Handling, Storage, and Precautions: highly toxic; corrosive, undergoes slow hydrolysis when exposed to moisture. Must handled in a fume hood and reactions performed under a dry, inert atmosphere.

Thionation of Tertiary Amides.2

Thiophosphoryl chloride and its N,N-dimethylamide derivatives (eq 1)3 react with amides at elevated temperature to give thioamides in good yield. The reaction is run in an excess of the thiophosphorus compounds. The most efficient of the thionating agents examined is N,N,N,N-tetramethylamidophosphonothioic chloride.


Thiophosphoryl chloride will thiophosphorylate amines,3 alcohols,4 amino alcohols,5 diols,6 and diamines.7 The rate of reaction decreases as each chlorine atom in replaced; thus it is possible to replace each chlorine atom with a different substituent under controlled reaction conditions. Thiophosphoryl derivatives of chiral amino alcohols have been studied extensively as stereochemical probes for the stepwise hydrolyses and alcoholysis of thiophosphates (eq 2), which can lead to the formation of nonracemic chiral thiophosphates.8 They have also been used as chiral derivatizing agents for the NMR analysis of chiral alcohols and amines.9

1. Moeller, T.; Birch, H. J.; Nielsen, N. C. Inorg. Synth. 1935, 4, 71.
2. Pedersen, B. S.; Lawesson, S. O. BSB 1977, 86, 693.
3. Keat, R.; Shaw, R. A. JCS 1965, 4802.
4. Cremlyn, R. J. W.; Ellam, R. M.; Akhtar, N. PS 1978, 5, 1.
5. Bentrude, W. G.; Setzer, W. N.; Sopchik, A. E.; Bajwa, G. S.; Burright, D. D.; Hutchinson, J. P. JACS 1986, 108, 6669.
6. Schultz, C.; Metschies, T.; Jastorff, B. TL 1988, 29, 3919; Mikolajczyk, M.; Witczak, M.; Wieczorek, M.; Bokij, N. G.; Struchkov, Y. T. JCS(P1) 1976, 371.
7. Barluenga, J.; Jardon, J.; Palacios, F.; Gotor, V. S 1985, 309; Cremlyn, R. J. W.; Frearson, J.; Milnes, D. PS 1975, 6, 29.
8. Cooper, D. B.; Hall, C. R.; Harrison, J. M.; Inch, T. D. JCS(P1) 1977, 1969; Harrison, J. M.; Inch, T. D.; Lewis, G. J. JCS(P1) 1975, 1892; Harrison, J. M.; Inch, T. D.; Lewis, G. J.; Chittenden, R. A. CC 1975, 720; Cooper, D. B.; Hall, C. R.; Inch, T. D. CC 1975, 721.
9. Johnson, C. R.; Elliot, R. C.; Penning, T. D. JACS 1984, 106, 5019.

Christopher D. Spilling

University of Missouri-St. Louis, MO, USA

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