Phosphorodiamidates phenyl phosphorodiamidate

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). 

Phenylquinazolin-2-amines 13 are prepared in one step from 4-phenylquinazolin-2(l H)-ones 8 employing phenyl phosphorodiamidate. ... 

A. Williams and K.T. Douglas, El b Mechanism Part II. Base Hydrolysis of Substituted Phenyl Phosphorodiamidates, J. Chem. Soc. Perkin Trans. 2, 1972, 1454. 

NTE is an integral membrane protein in neurons and some non-neural cell types of vertebrates [3,27,32] and its activity depends on lipid contents. It is present in all neurons, but is absent from glia [32], NTE can hydrolyze many esters of carboxylic acids. NTE is conveniently detected in vitro by its ability to catalyse OP-sensitive hydrolysis of an artificial substrate, phenyl valerate. Its activity is operationally defined as phenyl valerate hydrolysis resistant to inhibition by 0,0-diethyl-4-nitrophenyl phosphate (paraoxon, non-neuropathic) and sensitive to inhibition by NJ T-diisopropyl phosphorodiamidic fluoride (mipafox, neuropathic), determined under specified conditions [3]. Differential centrifugation of brain homogenates resulted in an enrichment of NTE in microsomal fractions containing elements of endoplasmic reticulum (ER), Goldgi, and plasma membrane [39],... 

Phosphorodiamidic acid, A/,A/ -dimethyI-, phenyl ester Diamidafos ... 

Phosphoramidates and phosphorodiamidates can be conveniently prepared by reacting ammonia with the corresponding phenyl phosphorochloridates (7.53) and (7.54). The latter are made from phenol and POCI3 (5.294) and (5.295). 

A distinct order of reactivity is observed in these reactions with (1) carboxylate anion aliphatic amines 3> aromatic amines. This has led to slight variations in the practical procedures for preparing the amides but these are well documented in the literature. The first route involves a one-step procedure the second involves reaction of (1) with the carboxylate anion and subsequent treatment with the amine and is the preferred method for converting alkanamines to the amides since the first one-step method produces large amounts of phenyl phosphorodiamidates as well as the amide, by nucleophilic attack of (1) by the amine. The final method prevents the formation of phenyl phosphorodiamidates as the carboxylic acid first reacts with 0.5 equiv of (1) to... 

Generally, phenyl iV-phenylphosphoramidochloridate and other very similar related organophosphorus reagents e.g. phosphorus oxychloride, phenyl dichlorophosphate, diphenylchlorophos-phate and iV,W -bis(2-oxo-3-oxazolinyl)phosphorodiamidic chloride have been utilised in recent years not only to form symmetrical carboxylic acid anhydrides but also in esterification and thiol esterification reactions although phenyl N-phenylphosphoramidochloridate is not so efficient for the latter two reactions compared to its analogs but is probably the best choice for forming the anhydride. ... 

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