Phosphoric amide reagents

Diethyl A-alkylphosphonamides, obtained by the Atherton-Todd procedure (see procedure 5.1.13) are (V-alkylated under strongly basic two-phase conditions at reflux temperatures [56], The procedure is obviously limited to alkali-stable reagents and a better route involves the initial formation of the N-sodio salt of the phosphor-amidate, followed by alkylation under essentially neutral conditions (Table 5.28) [57],... 

A mixture of tris(diethylamino)phosphine and startg. thiourea heated to 140° with stirring for 15-20° (evolution of diethylamine), cooled to room temp., and coned. HCl added dropwise to precipitate hydrochloride 2-allyliminothiazolidine. Y 88%. F.e. and phosphorous(III) amide reagents, also 2-iminotetrahydro-l,3-thiazine analogs s. L. Mizrakh et al., Zh. Obshch. Khim. 58, 2246-51 (1988). 

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. 

Another useful reagent for amide formation is compound 1, known as BOP-C1,141 which also proceeds by formation of a mixed carboxylic phosphoric anhydride. 

More recently, the chiral phosphonate 85 has been used as a CDA with chiral amines to form diastereomeric phosphonic amides (86)79 which are analyzed by 31P-NMR spectroscopy for the determination of enantiomeric ratios. The reagent is readily prepared from (5)-2-butanol and phosphorous trichloride, and all a-amino acids and amines thus far examined react quantitatively in a few hours at room temperature in aqueous ethanol79. 

QUINAPHOS ligands are usually synthesized in a one-pot-procedure from readily available 8-substituted quinolines [8] via nucleophilic addition of a lithium reagent [9] to the azomethinic double bond and direct quenching of the resulting 1,2-dihydroquinoline amide 1 with a phosphorochloridite derived from enantio-merically pure binaphthol (1) or from 3,3 -di-t-butyl-5,5 -dimethoxybiphenyl-2,2 -diol (m) [10] (Scheme 2.1.5.1, Method A). Alternatively, the anion 1 can be reacted with an excess (in order to avoid multiple substitution) of phosphorous trichloride to obtain the corresponding phosphorous dichloridite 2, which can be isolated (Scheme 2.1.5.1, Method B). In a second step, 2 is converted into 4 by reaction with the desired diol in the presence of triethylamine. 

Ketoximes may be rearranged directly to amides under a wide variety of conditions. Phosphorus pen-tachloride, phosphorus oxychloride, thionyl chloride, trimediylsilyl iodide (TMS-I), formic acid, poly-phosphoric acid, trimediylsilyl polyphosphate and mineral acids have all been successfully employed. Representative procedures using these and other reagent systems have been documented previously. ... 

Thionyl chloride is frequently the reagent of choice for the dehydration of higher-molecular-weight amides, since the secondary products are gaseous and the nitrile is more readily purified. Oftentimes, the higher fatty acids are converted to the nitriles in a single operation via the intermediate ammonium salts and amides. For this purpose, dry ammonia gas is passed into the molten acids at 290-300° the yields of nitriles are excellent (80-85%). A small amount of 85% phosphoric acid appreciably reduces the reaction time. Another procedure consists in passing the acid vapors mixed with ammonia over silica gel at 500°. This technique... 

Sn[N(TMS)2l2, A, A -carbonyldiimidazole (110, p. 1418), which behaves as in reaction 16-63, POCl3, °" TiCl4, ° molecular sieves,Lawesson s reagent (p. 1278), ° and (MeO)2POCl. ° Certain dicarboxylic acids form amides simply on treatment with primary aromatic amines. In these cases, the cyclic anhydride is an intermediate and is the species actually attacked by the amine. Carboxylic acids can also be converted to amides by heating with amides of carboxylic acids (exchange),sulfonic acids, or phosphoric acids, for example, ... 

Phosphorylation. Chambers et al. found the reagent useful for the preparation of nucleoside diphosphoric acids (3, R —adenine, uracil, etc.). A nucleotide (I) is converted into the 5 -phosphoramidate (2) by reaction with ammonia and dicyclo-hexylcarbodiimide (DCC), and the amidate (2) is treated with dioxane diphosphate in o-chlorophenol (3 hrs..0 ). The diphosphoric acid (3) is precipitated with petroleum ether and purified as the ammonium salt. Yields are around 90%, whereas when 8.5% phosphoric add was used yields were in the order of 50-60%. However, anhydrous... 

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