IN Nature of March 9, p. 287, we recorded synthetic methods1 which we had worked out for the preparation of dialkyl fluorophosphonates (I) in high yield. These esters are stable liquids of high toxicity, and have powerful miotic action. The physiological action was found to be enhanced when R was a secondary alkyl grouping (for example, ^sopropyl, sec. butyl or q/cfohexyl). In 1942 we handed several of these compounds to Dr. M. Dixon for test with enzymes. He reported2 that esters of fluorophos-phonic acid inhibit the action of the enzyme choline-esterase, and he showed that dwsopropyl fluoro-phosphonate is active in extremely low concentrations (for example, of the order of 10"10 M). On the other hand, sodium fluoride and ammonium fluorophos-phonate require a concentration of 10~2 M to give 50 per cent inhibition of choline esterase activity. No other enzyme was found, the action of which was inhibited by the alkyl fluorophosphonates. In 1942 we reported3 the preparation of a new type of phosphorus-fluorine compound, namely, bis-anilino phosphoryl fluoride (II). This we prepared by the action of phosphorus oxydichlorofluoride on aniline. The condensation was clear-cut, and only the chlorine atoms were replaced.jCI.......+ Hi NHC6H5 OP------;ci + H: NHC6H5 ='*.........................."' F + 2NH2C6H5NHC6H5 OP-NHC6H5 + 2C6H6NH2.HC1 F(II) At a later date, Burg4 in the United States prepared the corresponding bis-(dimethylamino) -phosphoryl fluoride, but used a less direct and less economical process, namely, POF3 in place of POC12F. However, he found the compound to be highly toxic, but without miotic action. We then applied our method5 to the preparation of this compound and found that it worked very satisfactorily. The method was found to be general and was extended to the preparation of amino phosphoryl fluorides from diethylamine, butylamine, methylaniline, benzyl -amine, ci/cZohexylamine, and later from morpholine and piperidine. The method was patented6.About this time we also worked out an alternative but less satisfactory method of preparing amino -phosphoryl fluorides. The principle of the method is given by the equations: Cl/ OP-Cl \ ClNUR OP-NHi? + 2i?NH2,HClNHi? OP-fluorination \NUR OP------NHi? Cl\ We then conceived the idea of 'combining' the toxicities of a fluorophosphonic ester and of an amino-phosphoryl fluoride in a 'hybrid' molecule, and carried out the following synthesis in 19438:Cl OP-Cl F3C6H5NH2 OC2HfiCaH5OH OP-Cl FHC1 OC2H6 OP-NHC6H5F (III)+ 2C8H5NH2,HC1 This new type of compound (III, ethoxy-anilino phosphoryl fluoride) had quite a high toxicity in spite of the presence of the phenyl group, which is known to reduce toxicity3. The L.D. 50 by injection into mice was 12-16 mgm./kgm. At that time we recorded the suggestion8 that a 'hybrid' compound derived from isopropyl alcohol and dimethylamine should be very toxic.In an attempt9 to obtain a substance which might have fluoro-phosphonate-like properties and at the same time be more volatile, we prepared diethyl fluorophosphinate (IV) by the action of phosphorus dichlorofluoride on ethyl alcohol ClP-Cl \ +HOC2H6 + HOC2H5OC2H5 = P-OC2H6 F(IV) 2HC1The compound, unlike the fluorophosphonate, was readily hydrolysed by water, was relatively non-toxic and produced only very feeble miosis. Summary, Bis-amiao phosphoryl fluorides were prepared in this laboratory by the action of phosphorus oxydichlorofluoride on the appropriate amine.A 'hybrid' compound embracing the essential structural features of the amino phosphoryl fluorides and the fluorophosphonates (namely, ethoxy-anilino phosphoryl fluoride) was prepared in 1943. We are indebted to the Director-General of Scientific Research (Defence) for permission to publish the above.The names of members of the team working on these problems have been recorded previously1.