Phosphorylation of amines

Atherton, F.R., Openshaw, H.T., and Todd, A.R., Phosphorylation. II. Reaction of dialkyl phosphites with polyhalogen compounds in the presence of bases — method for the phosphorylation of amines, /. Chem. Soc., 660, 1945. 

Use.1 This is said to be a highly selective reagent for phosphorylation of amines even in dilute aqueous solution. 

Acylation of Amines. Acylation of amines is also faster in the presence of DMAP, as is acylation of indoles, phosphorylation of amines or hydrazines, and conversion of carboxylic acids into anilides by means of Phenyl Isocyanate /3-Lactam formation from /3-amino acids has been carried out with DCC-DMAP, but epimerization occurs. ... 

It was shown that the phosphorylation of amines by the Atherton-Todd reaction could be carried out conveniently and easily under phase-transfer conditions in the presence of catalytic amounts (about 5 mol %) of triethylbenzylammonium chloride (TEBA) [91]. 

Other PT processes reported recently include the phosphorylation of amines " or alcohols, and the conversion of aromatic amines to azides by diazo transfer (Equation 8) to the amine anion. An interesting recent development is the use of PTC in organometallic chemistry, notably the conversion of aryl halides to carboxylic acids mediated by a Pd complex (Equation 9). 

A simpler nonphosgene process for the manufacture of isocyanates consists of the reaction of amines with carbon dioxide in the presence of an aprotic organic solvent and a nitrogeneous base. The corresponding ammonium carbamate is treated with a dehydrating agent. This concept has been apphed to the synthesis of aromatic and aUphatic isocyanates. The process rehes on the facile formation of amine—carbon dioxide salts using acid haUdes such as phosphoryl chloride [10025-87-3] and thionyl chloride [7719-09-7] (30). 

The decomposition of (536) with hydrogen sulfide yields pyrazole (76T1909). The 1-phosphorylpyrazoles (537) are suitable reagents for the phosphorylation of alcohols, amines, hydrazines and azides (76AG(E)378). 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Phosphatidylethanolamine synthesis begins with phosphorylation of ethanol-amine to form phosphoethanolamine (Figure 25.19). The next reaction involves transfer of a cytidylyl group from CTP to form CDP-ethanolamine and pyrophosphate. As always, PP, hydrolysis drives this reaction forward. A specific phosphoethanolamine transferase then links phosphoethanolamine to the diacylglycerol backbone. Biosynthesis of phosphatidylcholine is entirely analogous because animals synthesize it directly. All of the choline utilized in this pathway must be acquired from the diet. Yeast, certain bacteria, and animal livers, however, can convert phosphatidylethanolamine to phosphatidylcholine by methylation reactions involving S-adenosylmethionine (see Chapter 26). 

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. 

Full details on the phosphorylation of water and alcohols by 4-nitrophenyl dihydrogen phosphate and the NfC H ) - and N(CH3) -salts of its mono- and dianion have been published 146>. Phosphoryl group transfer from the monoanion and dianion is thought to proceed via the monomeric POf ion. Addition of the sterically unhindered amine quinuclidine to an acetonitrile solution containing the phosphate monoanion and tert-butanol produces t-butyl phosphate at a faster rate than does the addition of the more hindered diisopropylethylamine. This nucleophilic catalysis of the phosphorylation reaction is also explained by the intermediacy of the POf ion. 

On pp. 45 and 57 we referred to the action of chlorine1 and of N-chlorosuccinimide2 on dialkyl phosphites producing dialkyl phosphorochloridates. We have made use of the latter in producing a variety of esters of orthophosphoric acid and of phos-phoramidates, and reference has already been made to many such reactions (p. 82). These processes are, in a sense, phosphorylations of the alcohols or of the amines respectively. 

Addition of amines to allenephosphonates yields C-phosphorylated enamines, the stereochemistry of which partly depends on the nature of R2 and R3 (147). When Ra is hydrogen, intramolecular hydrogen bonding with the phosphoryl group is possible in the Z-isomer, and indeed this is the isomer which is then produced in greater yield. The carbon-carbon double bond can be reduced with KBH4.116... 

The ease with which the phosphorylation can be carried out and the simple reversion to the amine upon treatment with gaseous hydrogen chloride in tetrahydrofuran at room temperature provides a convenient procedure for the protection of amines. 

A lot of biologic membrane systems and cellular organelles contain kinases, which transfer phosphate groups to proteins, especially to serine, threonine, and tyrosine residues. Self-phosphorylation of enzymes leading to acylphosphates or phosphoamides can be observed, too. With respect to their chemical stability, these phos-phoproteins are classified into acid-stable (alkali labile), hydroxyl-amine-sensitive, and acid labile. 

No nucleophilic substitutions are reported for compound 1 or its derivatives. The only nucleophilic substitution of a derivative of compound 2 is the haloalkoxylation of the 8-nitro derivative to give compound 237.66 Nucleophilic replacement of halogen in position 3 of the 7-phenyl derivative of compound 3 by a number of amines gives the amines 238,232,243 and the triazolopyridin-3-one 214 reacts with phosphoryl chloride to give the... 

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