Phosphorofluoridates general

At the beginning of the war we synthesized, by methods described below and also in Chapter iv, a series of dialkyl phosphorofluoridates (I). In general, these compounds were colourless, stable and almost odourless liquids. With them we carried out tests (a) on ourselves, (6) on animals, (c) on enzyme systems. The very close collaboration of the Departments of Chemistry, Physiology, Biochemistry and Pathology at Cambridge permitted of the initial screening of a compound often within a few... 

It was quite obvious that the fusion of phosphoric anhydride and ammonium bifluoride would not form the basis of a practicable method. We accordingly paid attention to entirely different methods of preparation. Brief reference has already been made to two new general methods (pp. 5, 7). The first and more important of these new methods depended upon the conversion of a dialkyl phosphorochloridate into the corresponding dialkyl phosphorofluoridate by means of an inorganic fluoride. Con-lideration therefore had to be given to the most convenient method for preparation of the intermediate phosphoro-chloridate.1 In the first instance three methods for the preparation of chloro compounds (I) were considered ... 

The reaction depended upon the marked difference in reactivity between the chlorine atoms and the fluorine atom in phosphorus oxydichlorofluoride. In general, the reaction with alcohols waa clear-cut, and most of the phosphorofluoridic esters were obtained in excellent yield and uncontaminated with the phosphoric triester. For example, when ethyl alcohol and phosphorus oxydichlorofluoride were allowed to react in the odd, diethyl phosphorofluoridate (VII, R = Et) was obtained in 93 per cent yield. No tertiary base was necessary to remove the hydrogen chloride produced in the reaction. The general process was patented during the war.1... 

Esters of phosphorofluoridic acid. Two procedures for the preparation of the esters of phosphorofluoridic acid were developed, a general one applicable to most alcohols and a special one for cyclohexanol. 

Combination of fluoroacetate activity and certain other recognizable physiological effects have been successfully combined in fluoroaspirin (drugged sleep), triethyl-lead fluoroacetate (sternutation), difluoroethyl phosphorofluoridate (myosis, but not powerful). In general, quaternary ammonium... 

Although this hydrolysis is usually fairly rapid it is desirable to obtain conditions of a general nature that would be likely (a) to effect the complete hydrolysis of the more resistant phosphorofluoridates, (6) to ensure homogeneity of the reaction mixture so as to avoid possible mechanical losses of oily material, and (c) to ensure that the hydrolysis does not proceed so far as to cause an accumulation of phosphate ions, which might interfere with the subsequent determination. 

Murachi T (1963). A general reaction of diisopropyl phosphorofluoridate with proteins without direct effect on enzymic activities. Biochim BiophysActa, 71, 239-241. 

In general, with a phosphorofluoridate of unknown composition, 45 min. should be allowed. 

At an early date it was noticed that di-isopropyl phosphorofluoridate (DFP) (Section 12.13) and other nerve gas compounds were very effective against flies and other pests. Pioneering work in this field carried out in Germany by Schrader over 60 years ago led to his proposing the general insecticide formula (12.95a), where R = alkyl, alkoxy, amino, X=0 or S, and acyl = any acid anion such as F, CN, SH and so on. 

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