Fluoroacetyl chloride preparation

Fluoroacetyl chloride, CH2FCOCl, was prepared by the action of phosphorus pentachloride on the free fluoroacetic acid (p. 121).1 It is extremely useful as fluoroacetylating agent in synthetic work. Because of its importance we have recently reinvestigated other methods of preparation.2 These may be summarized as follows (1) direct from fluoroacetamide (p. 125) by the action of phosphorus oxychloride and water (2) the action of phosphorus oxychloride on either sodium fluoroacetate (p. 121) or on barium fluoroacetate (p. 121). Good yields are obtained in both (1) and (2), and in each case the starting materials are more easily available than fluoroacetic acid itself. 

Fluoroacetic anhydride, which was readily prepared by the action of fluoroacetyl chloride on sodium fluoroacetate, is a mobile liquid of b.p. 89°/12 mm. It is a useful fluoroacetylating substance. It was rather more toxic by inhalation than M.F.A. (weight for weight). 

N-2-Chloroethylfluoroacetamide was also prepared by the direct action of 2 mol. of fluoroacetyl chloride on ethanolamine, although we carried out this reaction with the intention of preparing 2-(fluoroacetamide)ethyl fluoroacetate,... 

In view of the fact that fluoroethanol is as toxic as methyl fluoroacetate (or as fluoroacetic acid), it seemed worth while preparing a compound in which the active parts of these molecules were combined, in the hope of obtaining a compound of increased potency. Such a compound is 2-fluoroethyl fluoroacetate, first prepared and described by us in 1943.1 This ester was readily prepared by the action of fluoroacetyl chloride on fluoroethanol. It is a stable, mobile liquid possessing an extremely faint odour. 

Trifluorothreonine is one of the rare fluorinated compounds found in nature (cf. Chapter 4). The best method for the synthesis of fluorothreonines is the acylation of an equivalent of glycinate anion by a fluoroacetic derivative. The four stereoisomers of monofluorothreonine have been prepared. A completely stereoselective chiral approach involves the alkylation of the Seebach imidazolidinone by fluoroacetyl chloride (Figure 5.16). ... 

The method is applied to the greatest extent in making jluoro acyl halides such as fluoroacetyl chloride from sodium fluoroacetate and phosphorus pentachloride. The products are distilled from a mixture of the dry reagents, usually without a solvent. Phosphorus trichloride and phosphorus oxychloride have also been used for the preparation of compounds of this type. 

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