Diethyl phosphorofluoridate

We carried out a great deal of work on the relationship between the above physiological effects and chemical constitution, and it was shown conclusively that the more potent compounds were those derived from secondary alcohols.3 Thus, for example, di-isopropyl phosphorofluoridate is very much more potent than diethyl phosphorofluoridate or di-ra-propyl phosphorofluoridate and the toxicity of the dicycZohexyl ester is of a high order (L.C. 50 for mice, rats and rabbits was 0-11 mg./l.). Din-butyl phosphorofluoridate had low toxicity and produced only feeble... 

Until this work began in Cambridge at the beginning of the war, the alkyl phosphorofluoridates had received practically no attention. Lange1 had given a tedious and laborious method for preparing dimethyl and diethyl phosphorofluoridates in very poor yield as follows. 

Dimethyl and diethyl phosphorofluoridate were hydrolysed much more quickly, the order being Me>Et>Pr complete hydrolysis of the ethyl ester took about 4 hr. Small quantities of the di-isopropyl, but not the diethyl ester, could be steam-distilled. Bi-isopropyl phosphorochloridate can be readily identified by allowing it to react with aniline to give the crystalline phenylphosphoramidate ... 

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... 

Whereas diethyl phosphorofluoridate was hydrolysed in aqueous solution in about 4 hr., the di-isopropyl ester required 72 hr. for complete hydrolysis, and small quantities could be steam-distilled. DicycZohexyl phosphorofluoridate was very stable, and vigorous shaking with water did not produce any appreciable hydrolysis. It was hydrolysed by boiling water only after several hours. When stirred vigorously with 2 per cent sodium hydroxide solution at 28-5°, the time taken to bring about hydrolysis according to the equation... 

Turning again to primary phosphorofluoridates (R = H), if R is substituted, e.g. in di-(2-chloroethyl) phosphorofluoridates, the toxicity and myotic effect are greatly inferior to those shown by the unsubstituted diethyl phosphorofluoridates. Toxicity is also very low in the aromatic series for example, diphenyl phos-phorofluoridate is non-toxic and devoid of myotic properties. Similar remarks apply to certain sulphur analogues, e.g. diethyl phosphorofluoridodithiolate, POF(SEt)2 (preparation, p. 54). 

Ethyl phosphorodifluoridate (XXI) was obtained by the action of sodium fluoride on the corresponding phosphoro-dichloridate unlike diethyl phosphorofluoridate, it was rapidly attacked by cold water. Alcohol converted (XXI) into the phosphorofluoridate ... 

The same method is used for the preparation of diethyl phosphorofluoridate, fluorotriphenylmethane, andN-fluorodimethylamine. The reaction vessel is a 50-mL Pyrex glass, round-bottomed flask that is equipped with a magnetic stirring bar and an inner 14/20 standard taper joint. The flask is fitted with a 2-mm Kontes Teflon stopcock to which are attached outer 14/20 and inner 10/30 standard taper joints. The reactions are carried out at less than 1 atm pressure. 

Diethyl phosphorofluoridate is a colorless liquid that can be readily distilled under reduced pressure. It is very soluble in benzene, hexane, and diethyl ether. It is stable for long periods under anhydrous conditions. The mass spectrum gives a molecular ion at mie 155. P NMR (H3PO4) 8 -9.52 (d, 7p F = 964 Hz) F NMR (CCI3F) < ) -81.46 (d). 

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