Phosphoric amides, reactivity

This conclusion has been drawn by Moffatt and Khorana,2 based on limited data. A subsequent, more detailed study [R. K. Ledneva, N. N. Preobrazhenskaya, Z. A. Shabarova, and M. A. Prokof ev, Molek. Biologiya, 5, 264 (1971)] clearly shows an unexpected decrease in the rate of the acid hydrolysis of the phosphor-amidates derived from strong amines. If a similar order of reactivities exists for the pyrophosphate synthesis, the phosphomorpholidate derivative seems close to being the most active. 

Milatovic, D., Johnson, M.K. (1993). Reactivation of phosphor-amidated acetylcholinesterase and neuropathy target esterase hy treatment of inhibited enzyme with potassium fluoride. Chem. Biol. Interact. 87 425-30. 

A one-pot process has been devised for the synthesis of dialkyl [(a-phenylamino)ben-zyljphosphonates from dialkyl hydrogenphosphonate, benzaldehyde and aniline, presumably adaptable for other aromatic amines or aldehydes To avoid multiple reactions of the Mannich type when using a primary amine and a particularly reactive carbonyl component such as formaldehyde, initial silylation of the amine, or the use of diethyl trimethylsilyl phosphite, are valuable moderating variations The amine can be replaced by a carboxamide" or carbamate ester, conveniently the benzyl ester , and the product can then be selectively deacylated with HBr in acetic acid at room temperature or by hydrogenolysis. Alternatively, even a phosphoric amide may be used to afford an A-phos-phorylated product (221)" ... 

The neutral and acid-catalyzed hydrolyses of a series of phosphoric carboxylic imides X2P(0)NRC(0)R (28) (X = EtO, MeO, Et R = H, Me R = Me, Ph) have been compared with the behavior of related carboxylic acid and phosphoric amides, particularly in acidic conditions where the latter two systems differ greatly. In acid the carboxylic amides react slowly by attack of solvent on the oxygen-protonated form of the substrate and the phosphoric amide reacts rapidly by direct Sjv2(P) displacement via an N-protonated substrate. The acid hydrolysis of (28) lies between these two extremes with the protonation of carbonyl oxygen stabilizing the resonance structure which renders the phosphorus atom more electrophilic and the P-N bond less labile with the consequence that the reactivity of the P-N and C-N linkages become comparable. ... 

Carboxylic acids can also be activated by the formation of mixed anhydrides with various phosphoric acid derivatives. Diphenyl phosphoryl azide, for example, is an effective reagent for conversion of amines to amides.140 The proposed mechanism involves formation of the acyl azide as a reactive intermediate. 

The N-phosphonium salts of pyridines given by the oxidation of phosphorous acid and its esters are very reactive to nucleophiles, activating carboxy, amino, or hydroxy compounds to yield the corresponding carboxylic amides and esters in high yields on further aminolysis, alcoholysis, and acidolysis2 ... 

Double amidation of phosgene, to give symmetrical ureas, is considerably easier to perform. Considerable interest is attached to the recent reaction of imidazole with phosgene, which led to l,T-carbonyldiimidazole, an extremely reactive compound on account of the lability of its amide bonds 597 The ease with which the imidazole group can be replaced by other groups offers the widest possibilities for synthesis of other carbonic acid derivatives, carboxylic esters, amides, and hydrazides, peptides, phosphoric esters, etc., all under the mildest conditions.598 Since l,T-carbonyldiimidazole is hydrolysed even by atmospheric moisture, it must be prepared under the most strictly anhydrous conditions. 

A new peptide synthesis with adducts of phosphorous compounds and tetrahalomethanes has been reported N-(Chlorophosphoryl)pyri-dinium betaines are remarkably reactive acylating agents for the preparation of esters, amides, and peptides. They can easily be prepared from phosphorous acid or its esters, pyridine, and mercuric chloride Peptides have also been prepared through polymeric N-acoxydicar-boxylic acid imides with markedly reduced coupling times at elevated temperature (70°). The solid-phase method, first used in the synthesis of peptides, gains wider application. Recently a solid-phase Wit-tig synthesis of olefins has been published . 

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