Aniline Salicylanilide

Salicyl-u-toluide has been prepared only by the action of phosphorus oxychloride upon a mixture of salicylic acid and o-toluidine. The useful methods of preparation of salicylanilide are by the interaction of salicylic acid and aniline in the presence of phosphorus trichloride, by heating phenyl salicylate and aniline, and from o-hydroxybenzamide and bromobenzene in the presence of small amounts of sodium acetate and metallic copper. A number of these and other anilides have been described. ... 

Salicylanilide is ordinarily made by reacting salicylic acid with aniline in the presence of phosphorus trichloride at an elevated temperature. The theoretical proportions of reactants are usually employed for best results, that is, one mol each of aniline and salicylic acid to a third of a mol of phosphorus trichloride. An improved process employs an inert organic solvent as a reaction diluent. 

Methenolone acetate A ndro tardy 1-0 estradiol Estradiol valerate Aniline Fentanyl Salicylanilide Anisoyl chloride Benzobromarone... 

Toma and coworkers have described the solvent-free synthesis of salicylanilides from phenyl salicylate or phenyl 4-methoxysalicylate and substituted anilines (Scheme 6.155) [302]. By exposing an equimolar mixture of the ester and the amine to microwave irradiation at 150-220 °C for 4—8 min under open-vessel conditions, good yields of the corresponding salicylanilides were obtained. This synthesis was carried out on a multigram scale (0.1 mol). 

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. 

Introduction of a bromo group in either the acid part or aniline part of the niclosamide molecule is known to evoke a better anthelmintic response. This observation has led to the synthesis of a large variety of bromosalicylanilides [3,11,17-19]. The effective salicylanilides, thus emerged, are brotianide (Bayer 4059, Dirian, 8), hi-lomid, an equimolar mixture of 3,4, 5-tribromosalicylanilide (tribromsalan, 9a) and... 

Introduction of an isothiocyanate moiety in the benzene ring of the aniline part of salicylanilide has been found to evoke high order of cestodicidal activit. This effect was more pronounced when the isothiocyanate group was located at 3 -or 4 -positions. Thus, 2, 5-dichloro-4 -isothiocyanatosalicylanilide (18) and 3,5-di-bromo-2 -substituted-4 -isothiocyanatosalicylanilides (19) removed 100% of the H. nana infection from rats at a dose of 10-30 mg/kg [17,18,28,29,31]. 

The most widely used method to prepare salicylanilides (35) involves condensation of an appropriate salicylic acid (33) with an aniline (34) in the presence of phosphorus trichloride [7,50-54] or phosphorus oxychloride [55] in boiling chlorobenzene, toluene or xylene. In these reactions salicyloyl chloride (36) is generated in situ, which then reacts with aniline to form 35. Alternatively salicyloyl chloride... 

The salicylanilides may also be conveniently synthesized by reaction of salicylic acid with aniline in the presence of P2O5 [58], tetraalkylpyrophosphite [59,60], Me2As(0)0H [61], H3PO4 or H4P2O7 [62] or DCC [45]. In another approach salicylic acid is converted into the phenyl ester (37), which is heated witli appropriate aniline at high temperatures to yield the corresponding salicylanilides [63-65]. 

Salicylanilide is ordinarily made by reacting salicylic acid with aniline in the presence of phosphorus trichloride at an elevated temperature. The theoretical proportions of reactants... 

Fasciolicidal action was also reported for another series of salicylanilides in which an electronegative substituent was introduced in the 3-position. The choice of substituents in the aniline ring was restricted to halogens, methyl groups and tri-halogenated methyls (which improve lipid solubility). The most effective compounds were 3-nitro-2,6-dihydroxybenzoic acid anilides. 

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