Phosphorus trichloride ammonia reaction with

Salicylamide, prepared by the reaction of methyl salicylate with ammonia, has mild analgesic, antiinflammatory, and antipyretic properties. Salicylanilide, prepared by heating salicylic acid and aniline in the presence of phosphorus trichloride, is used as an intermediate in the production of other chemicals and as a slimicide. fungicide, and medicament. 

This reaction represents the best general method for amide preparation. Cold, concentrated aqueous ammonia is used as in the preparation of iso-butyramide (83%),or the reaction may be carried out by passing dry ammonia into a solution of the acyl halide in anhydrous ether as in the formation of cyclopropanecarboxamide (91%). Separation of the amide from ammonium chloride is usually accomplished by extraction of the amide by organic solvents. Aqueous sodium hydroxide is employed to take up the hydrogen chloride when amine hydrochlorides are used in place of the free amines as in the preparation of N-methylisobutyramide (75%). When phosphorus trichloride is added to a mixture of an amine and a carboxylic acid, phosphazo compounds, RN=PNHR, rather than acyl halides, are believed to be intermediates. These compounds have been shown to react with carboxylic acids to give amides. ... 

Of particular interest in the latter case is the use of N-NMR spectroscopy for the determination of J( P, N) data, of which there are few examples for systems having two coordinate sp -hybridised nitrogen linked to phosphorus. " Various acyclic bis(aminophosphines) have also been reported, including the imino-functional system (96), the bis(phosphino)-hydrazines (97) and -ureas (98), and the l,8-bis[bis(dialkylamino)phosphino]naphthalenes (99). There has also been significant activity in the synthesis of cyclic aminophosphines. An improved route to the four-membered ring system (100) is afforded by the reaction of phosphorus trichloride with t-butylamine in a 1 3 mole ratio in THF. Treatment of this with ammonia in THF/triethylamine at — 78°C gives (101),... 

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