Subject phosphoramide

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

Tertiary amines may be used as the base in the Michaelis-Becker reaction with highly reactive substrates. This approach has the advantage of overcoming the common problem of the low solubility of the metal dialkylphosphonate salts 22. However, amines are used as the base in the Atherton-Todd syntheses of phos-phorochloridates 27 and phosphoramidates 28 (Scheme 16), pathways which may thus compete with the Michaelis-Becker reaction of highly chlorinated substrates under such conditions the precise mechanism of the Atherton-Todd reaction is a subject of debate.61... 

Much greater differences are observed when bulk tolerances are considered in the binding step prior to Irreversible inhibition. Though not the subject of this paper, differences in bulk tolerance at the esteratic site between OC s and OP s are simply Immense in molecular terms. The carbamate N-alkyl group is limited in size to methyl for commercial activity while phosphates, phosphoramidates, and phosphonates typically accommodate Isopropyl and phenyl groups. The variation is extensive, however, with some esteratic sites (OP resistant mites) (18), unable to accept an 0,0-dimethylphosphoryl group while others (electric eel AChE) are able to bind a dlphenyl-phosphinyl group (19). 

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