Phosphorodiamidates

Alkyl halides, reaction of sugar phosphorodiamide and phosphonamide derivatives with 178... 

Well known carbanionic sigmatropic rearrangements, applied to mixed P and S compounds, regio- and/or stereoselectively lead to new (a-sulfanylalkyl) or P-sulfanylaryl) phosphonates, phosphine oxides, or phosphorodiamidates. In these difunctional compounds, chirality can be either introduced on the phosphorus, on the a-carbon, or on the sulfur atom. 

General preparative procedures for the preparation of A -alkyl phos-phoramidic dichlorides (10) and A TV -dialkyl phosphorodiamidic chlorides (11) from the appropriate amine and phosphoryl chloride have been described. With weakly basic amines, pyrophosphoryl chloride was... 

Evidence for an intermediate metaphosphorimidate is also provided by a three-phase experiment110b,139) treatment of a suspension of the two functionalized polymers 203 and 205 in dioxane with proton sponge leads to formal transfer of a phosphorodiamidate moiety from 203 to 205 with formation of 206. It appears... 

The reaction was found to be general and was extended to the preparation of a large range of phosphorodiamidic fluorides, e.g-from diethylamine, butylamine, methylaniline, benzylamine, cycfohexylamine, morpholine and piperidine. The method was patented. 

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. 

About this time2 we also worked out the conditions for an alternative method for preparing phosphorodiamidic fluorides from phosphorus oxychloride. The principle of the method is given by the following equations ... 

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. 

The phosphorodiamidic chloride thus obtained was then fluorinated. For example, diphenylphosphorodiamidic chloride was readily fluorinated by heating it with potassium fluoride in benzene, POCl(NHPh)2 + KF - POF(NHPh), + KCl. 

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). 

Two mechanisms have been proposed for the ATP-dependent enzymic formylation of tetrahydrofolate at N-10. In the first, ATP and formate react initially to generate formylphosphate, which is the active formylating species. In the second mechanism, a cyclic phosphorodiamidate (37) is formed in the initial reaction between ATP and... 

Amitrole (i. e., a weakly basic pesticide) and the insecticide Dimefox (tetra-methyl phosphorodiamidic fluoride) have been shown to be adsorbed by HA through ionic bonding [17, 151-153]. The interaction between the cationic pesticide Chlorodimeform and SPHA was studied and, based on IR data, Maqueda et al. [154] indicated that an ion exchange bonding mechanism occurred. 

Furyl N,N,N, N -tetramethyld1amidophosphate Phosphorodiamidic acid, tetramethyl-, 2-furanyl ester (12) (105262-58-6)... 

The present preparation illustrates a general and convenient method for a two-step deoxygenation of carbonyl compounds to olefins. Related procedures comprise the basic decomposition of p-toluenesulfonylhydrazones, the hydride reduction of enol ethers, enol acetates, enamines, the reduction of enol phosphates (and/or enol phosphorodiamidates) by lithium metal in ethylamine (or liquid ammonia),the reduction of enol phosphates by titanium metal... 

Previous investigations by Traylor and Westheimer26 and Crunden and Hudson27 had strongly supported the suggestion that the rapid alkaline reaction of phosphorodiamidic fluorides or chlorides and pyrophosphoramides which contain at least one amide hydrogen was by way of an anion derived from the amidate, viz. 

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