Toxicity phosphorodiamidic fluorides

Many of these compounds were toxic for example, tetra-methyl phosphorodiamidic fluoride (dimethylaminofluorophos-phine oxide (VII)) had a l.c. 50 of 0-1 mg./l. Unlike the phosphorofluoridate esters, however, they were devoid of myotic action. 

We then decided to combine the toxicities of a phosphoro-fluoridic ester with that of a phosphorodiamidic fluoride in a hybrid molecule, and carried out the following synthesis in 1943 3... 

III) was very much less toxic than (II). This applied to subcutaneous as well as to inhalation experiments. By subcutaneous injection the l.d. 50 of (III) for mice was ca. 160 mg./kg. This close analogy between the two types of compound cannot, however, be pressed too far. The toxicities by subcutaneous injection into mice of other hitherto undescribed substituted phosphorodiamidic fluorides, are given on p. 89. 

In view of the rapid toxic action and myotic effect of the dialkyl phosphorofluoridates and of the high toxicity of some of the phosphorodiamidic fluorides, we prepared2 and examined a hybrid molecule containing the essential features of each type of compound. The first to be examined was ethyl phenyl-phosphoramidofluoridate (VII). One mol. of phosphorus oxy-dichlorofluoride was added to 1 mol. of ethyl alcohol, and the resulting ethyl phosphorofluoridochloridate (which it was not necessary to isolate) was treated with aniline. 

On subcutaneous injection into mice, (VII) had a l.d. 50 of 10 mg./kg., which was unexpectedly high in view of the reduction of toxicity caused by the phenyl group on both the phosphoro-fluoridates (p. 54) and the phosphorodiamidic fluorides (p. 87). 

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