Salicylic amide

Note. A compound may yield more than one product, e.g., salicyl amide, HO C,H,CONH, will give ammonia and phenol. Sulphanilamide will give ammonia and aniline. 

Photolysis of 3-methyl-1,2-benzisoxazole in n-hexane/acetonitrile produced a salicyl-amide. In contrast, photolysis in acetonitrile/methanol (95 5) gave an iminoester which subsequently hydrolyzed to methyl salicylate (Scheme 11) (74HCA376). 

Alam SN, Roberts RJ, Fischer LJ (1977) Age-related differences in salicyl-amide and acetaminophen conjugation in man./ Pediatr 90 130-135. 

To 1 ml of urine add 5 drops of Trinder s reagent A violet colour indicates the presence of salicylate or salicyl-amide. A positive result is obtained after therapeutic doses of aspirin or aminosalicylic acid. 

Povidone K 25 added, jig Lactose Glucose Tartaric acid Acetyl- salicylic acid Thiamine hydro- chloride Brom- isoval Caffeine Ephedrine hydro- chloride Lidocaine Meproba- mate Pheno- barbital Salicyl- amide... 

Figure 7.P29 gives the pH-rate profile for alkaline hydrolysis of two substituted salicylate amides, as compared with benzamide. Consider whether the pH-rate profiles for the salicylamides are more consistent with mechanism (A), intramolecular basic catalysis of water attack, or (B), intramolecular acid catalysis of hydroxide ion attack. 

Also obtained by alkaline hydrolysis of 5-propionyl-salicyl-amide (m.p. 216°) [6939]. 

Finally, attachment of a rather complex side chain to the para position of the benzene ring on the sulfonamide leads to the very potent, long-acting oral antidiabetic agent, glyburide (215). Preparation of this compound starts with the chlorosul-fonation of the acetamide of 3-phenethylamine (209). The resulting sulfonyl chloride (210) is then converted to the sulfonamide (211) and deacylated (212). Reaction with the salicylic acid derivative, 213, in the presence of carbodiimide affords the amide, 214. Condensation of that with cyclohexylisocyanate affords glyburide (215). ... 

Salicylic acid for systemic use has been replaced by acetylsalicylic acid, amides of salicylic acid (salicylamide, ethenzamide, salacetamide), salsalate and diflunisal. 

Many of these salts melt or sublime before or during decomposition and reaction temperatures generally increase with molar mass. Thermal analyses for a selection of ammonium carboxylates have been given by Erdey et al. [915] who conclude that the base strength of the anion increases with temperature until it reaches that of NH3. Decompositions of ammonium acetate (>333 K) and ammonium oxalate (>473 K) proceed through amide formation. Ammonium benzoate and ammonium salicylate sublime (>373 K) without decomposition but ammonium citrate decomposes (>423 K) to yield some residual carbon. 

The salicylimides (4.169) were found to be markedly more resistant to chemical hydrolysis than 4.166. These compounds were hydrolyzed exclusively at the distal amide bond, meaning that hydrolysis produced only sali-cylamide (4.170) and not salicylic acid. This behavior has been ascribed to steric hindrance by the 2-OH group. An intramolecular general base catalysis does not seem to be involved since, as stated, the salicylamides were less reactive than the corresponding benzamides. The rate of plasma-catalyzed hydrolysis of the A-acylsalicylamides was also dependent on the nature of... 

Neighbouring-group participation in the hydrolysis of esters and amides has been reviewed. The effects of urea, Na+ and Li+ on the intramolecular general-base-catalysed glycolysis of phenyl salicylate (217) in glycol-acetonitrile solvent at constant water concentration have been reported. ... 

The a- and /3-cyclodextrins have been found to accelerate the Smiles rearrangement of 4-nitrophenyl salicylate. The reaction of 2,4-dinitrobenzenesulfonamide with acyl chlorides in the presence of excess triethylamine has been found to produce the corresponding nitrile in good yield. Mechanistic studies have indicated that the reaction proceeds via a Smiles rearrangement of the initially formed iV-(2,4-dinitrobenzenesulfonyl)amide to form the nitrile, 2,4-dinitrophenol, and sulfur dioxide (see Scheme 12). l-Chloro-3-fluorophenothiazines have been prepared by Smiles rearrangement of 3-chloro-5-fluoro-2-formamido-2 -nitrophenyl sulfides in alcoholic... 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

An efficient and selective Cu-assisted ortho-hydroxylation procedure for the conversion of benzoate to salicylate has been described, involving trimethylamine N-oxide (TMAO) as the oxidant [191,192]. The reaction was assumed to proceed via oxidation of a Cu carboxylate complex by TMAO to produce the active species (postulated to be a Cu hydroxo complex, but with only circumstantial evidence), followed by oxygen transfer to the benzoate group (Scheme 14). Using a set of different amide derivatives of benzoic acid, Comba and co-workers gained additional mechanistic hints in support of a reactive Cu-oxo or Cu-hydroxo intermediate that is stabilized by a five-membered chelate [193]. A pre-equilibrium involving Cu the ligand, and TMAO was proposed, but details of the reaction are far from clear. 

The formation of amides can be accomplished by dehydration of the ammonium salts of salicylic acid. The more common method for amines is the reaction of the ester, acyl halide, or anhydride with an amine or ammonia. Each step is fast and essentially irreversible. 

This rate equation agrees with the findings that soon after the end of the induction period the rate of oxygen uptake becomes independent of metal concentration with many catalysts (e.g., both cobalt and copper salicylaldimines or diisopropyl salicylates). By contrast cobaltous acetate had a lasting inhibitory effect in the autoxidation of N-butylacetamide and similar N-alkylamides (I). This can, however, be explained by assuming that Reaction 12 predominates over 13 in amide autoxidation since in this case the rate equation becomes ... 

Numerous other aromatic carboxylic acids possess stirne bactericidal, fungicidal, and herhicidal characteristics, as well as growth-regulating properties. Salicylumlide. the amide of salicylic acid, is effective against leaf mold and tomato brown spot. 

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