Hexamethylphosphoric Triamide-Thionyl Chloride1

(HMPA)

[680-31-9]  · C6H18N3OP  · Hexamethylphosphoric Triamide-Thionyl Chloride  · (MW 179.24) (SOCl2)

[7719-09-7]  · Cl2OS  · Hexamethylphosphoric Triamide-Thionyl Chloride  · (MW 118.97)

(a chlorinating agent2 for the preparation of alkyl chlorides, acid chlorides, esters, and amides)

Physical Data: see Hexamethylphosphoric Triamide and Thionyl Chloride.

Chlorinating Agent.

The use of thionyl chloride with HMPA is a good procedure for the synthesis of alkyl chlorides from primary, secondary, and tertiary alcohols (eq 2).3 The initial product of the reaction of an alcohol with SOCl2 is thought to be a chlorosulfite (eq 1).4 The further course of the reaction depends on both the structure of the chlorosulfite and the solvent. Highest yields are obtained with primary alcohols (eq 3).

Decomposition of the secondary alkyl chlorosulfite is often greatly influenced by the solvent, forming alkenes and alkyl chlorides in dioxane with retention of configuration (SN1), but forming an alkyl chloride in HMPA with inversion of configuration (SN2). This method is also advantageous for making allylic chlorides and acid chlorides, in particular for a,b-unsaturated acid chlorides, since SOCl2 does not add to the C=C bond (eq 4).3 Esters and amides can be made by treating the carboxylic acid with SOCl2-HMPA at -15 °C followed by addition of an alcohol or amine, respectively (eq 5).2 Esters of tertiary alcohols can be formed in higher yield with HMPA than with pyridine or dimethylaniline.3


1. Pizey, J. S. Synthetic Reagents; Horwood: Chichester, 1974; Vol. 1, p 321.
2. Normant, J. F.; Deshayes, H. BSF 1972, 7, 2854.
3. Normant, J. F.; Foulon, J. P.; Deshayes, H. CR(C) 1969, 269, 1325.
4. Cowdry, W. A.; Hughes, E. D.; Ingold, C. K.; Masterman, S.; Scott, A. D. JCS 1937, 1252.

Weixia Jing

University of Cambridge, UK



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