Salicylamide, reactions

Aqueous solutions (when obtainable) give no reaction with ferric chloride. This is an important distinction from ammonium salts (sec above). Salicylamide, being also a phenol, is however an exception (p. 344). 

The 3-phenyl derivative 3a was similarly obtained by cyclodehydration of O-phenacylsalicylam-ide.33 An analogous reaction of O-acetonylsalicylamide gives 3-methyl-l,4-benzoxazepin-5(4//)-one (3b).34 The 2-phenyl compound can also be obtained from the corresponding salicylamide derivative in 56% yield.420... 

Irreversible reaction of [18] iodine with acetylsalicylic acid, aethaverine, amidopyrine, ascorbic acid, benzo-caine, quinine, dihydrocodeine, fluorescein, glycine, hydrocortisone acetate, isoni-azid, metamizole, papaverine, paracetamol, phenacetin, phenol-phthalein, piperazine, resorcinol, salicylic acid, salicylamide, sulfaguanidine, thymol, triethanolamine, tris buffer detection by reaction chromatography... 

Reaction of salicylamide 185 (obtainable from a suitable activated derivative of salicylic acid and N,N-diethylethylenediamine) with ethyl chloroformate... 

A series of /> ra-substituted ort o-nitroanilines 1274 is converted in this way to benzotriazolyl derivatives 1277, which are of interest as potassium channel activators. In the first step, nitroanilines 1274 are treated with salicylyl chloride to provide salicylamides 1275 in 70-95% yield. The nitro group is catalytically reduced, and the obtained intermediates 1276 are subjected to a reaction with nitrous acid, generated in situ from NaN02, to afford 5-substituted T(2-hydroxybenzoyl)-17/-benzotriazoles 1277 in 52-96% yield (Scheme 213) <2001FA827>. 

Lactam-forming activity in rat liver microsomes has been demonstrated with the cyclization of 2-(carbamoyloxy)benzoates (11.139) and 2-(sulfamoyl-oxy)benzoates (11.141) (R = alkyl or aryl R = H, Cl, Br, Me) [158], Good yields (60 - 80%) of the products 11.140 and 11.142, respectively, were obtained following incubation for 20 h at 20 - 25°. Incubation at 35 - 37° yielded mostly salicylamides 11.143, i.e., the common products of ring hydrolysis. No reaction was seen with heat-inactivated microsomes, seemingly ruling out nonenzymatic cyclization. Again, similarity with Sect. 8.5.7 is clear. 

When the preceding reactions were carried out with salicylamide, the N-hydroxymethylbenzoxazinone was formed, which, after thermal decomposition, gave the previously unknown parent benzoxazinone 139 (92T4963). 

Hypersensitivity to salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs). Use extreme caution in patients with history of adverse reactions to salicylates. Cross-sensitivity may exist between aspirin and other NSAIDs that inhibit prostaglandin synthesis, and aspirin, and tartrazine. Aspirin cross-sensitivity does not appear to occur with sodium salicylate, salicylamide, or choline salicylate. Aspirin hypersensitivity is more prevalent in those with asthma, nasal polyposis, chronic urticaria. 

Salicylamide [65-45-2] is prepared by the reaction of methyl salicylate with ammonia. Salicylamide has mild analgesic, antiinflammatory, and antipyretic properties. Salicylamide is unlike other salicylates in that it causes sedation and central nervous system depression. Salicylamide is not hydrolyzed to salicylate and its action depends on the entire molecule. Salicylamide has been useful for protection against mildew and fungus in a variety of soaps, salves, lotions, and oils. The May 1996 price was 8.00/kg (18). 

Via (N—C—C—C—O—C—C) intermediates (type c). Salicylamide (351 R = H) can be converted to 1,4-benzoxazepine derivatives, e.g. its reaction with 2-chloropheny-lacetic acid gives (351 R = CH(Ph)C02H) which on treatment with acetyl chloride cyclizes to the 3,5-dione (352). Similarly reaction of (351 R = H) with phenacyl bromide gives (351 R = CH2COPh) which undergoes acid-catalyzed cyclization to give (353). 

In contrast, much more effective asymmetric reactions have been obtained by using chiral copper catalysts. Since the pioneering work of Nozaki and coworkers61 with a chiral salicylamide catalyst (30), a wide variety of other chiral complexes has been developed, the most significant of which are (31M34). Another useful catalyst is the cobalt complex (35). 

The reaction of methyl salicylate with DMAD in presence of triethylamine yields a mixture of o-carbomethoxyphenoxymaleate (315) and fumarate (316) [Eq. (45)].134 Similarly, salicylamide (317a) and... 

Some amides do not dissolve in glacial acetic acid in such cases a mixture of 2 ml of glacial acetic acid and 3 ml of water may be used as a solvent for the reaction. Urea may be characterised as the di-xanthyl derivative (m.p. 274 °C) prepared in acetic acid. Di- and tri-chloroacetamide, oxamide, and salicylamide do not give satisfactory results. 

Salicylamide gives a blue violet color with ferric chloride solution, a color reaction indicative to salicylate derivatives. 

A full report for the identification of salicylamide through melting point, reactions of the amide group, the phenolic group, the benzene ring, and the formation of chelate compounds has been published (9). 

Other method was described by Wagner (1+6) for the analysis and detection of salicylic acid and derivatives including salicylamide. Development was effected by using color reactions, with ferric ammonium sulphate, ammoniacal silver nitrate solution, potassium nitrate, HC1 and 5% KOH through diazotization and coupling with, 2-naphthol and coupling with diazotized sulphanilic acid. 

Dialonzo and Siggia reported a method for determining several compounds including salicylamide based on the use of Hofmann reaction for the synthesis of amines... 

Ferrini and Marxer65 have recently shown that vinylene carbonate reacts with primary amides, in the presence of polyphosphoric acid, to yield 2-substituted oxazole derivatives. Yields are low (2-34%), and phenoxy- and phenyl-acetamide, p-methylbenzamide, and salicylamide do not give oxazole derivatives. Although the reaction has been interpreted according to Scheme 3, the nucleophilic attack of a nitrile molecule (from the amide dehydration), with a nitrilium salt as intermediate (Scheme 4), cannot be excluded.06... 

DAIB-induced conversions of the anthranilamides 195 and salicylamides 196 to the benzimidazolones 197 and benzoxazolones 198, respectively, and similar rearrangements of two representative pyridinecarboxamides, are recent examples of direct heterocyclic ring-construction by the iodine(III)-Hofmann pathway (Scheme 57) (01S541). These reactions may be contrasted with BTIB-oxidations of the 2-aminonicotinamides 67 and amidopyridones 69 in aqueous DMF (Section II.A.2) which lead, without rearrangement, to N-N and N-O bond formation (97SC2217). 

H)-Oxazolones are formed by the spontaneous cyclization of /3-oxo isocyanates (equation 134). Similarly, o-hydroxyphenyl isocyanate, produced by the Curtius rearrangement of the azide of salicylic acid or by the action of sodium hypochlorite on salicylamide, forms benzoxazolone (equation 135). An analogous reaction is the formation of IV-phenyl-benzoxazolone by the action of thionyl chloride on the hydroxamic acid shown in equation (136) (78TL2325). Pyrolysis of aryl azidoformates affords benzoxazolones by nitrene insertion (equation 137) (81CC241). 

In orthoesters (458 Scheme 84) one alkoxy group can be replaced by aminoacyl groups, by aminosul-fonyl groups or by the 1-imidazolyl group on reaction with ureas,imides, salicylamide, N-alkylsulfonamides in the presence of Lewis acids or with imidazoles under acid cat ysis. Excess aryl isocyanates convert orthoformates to acetals of parabanic acid. ... 

Salicylamide reportedly exerts a moderately quicker and deeper analgesic effect than aspirin. Long-term studies on rats revealed no untoward symptomatic or physiological reactions. Its metabolism differs from that of other salicylic compounds, and it is not hydrolyzed to salicylic acid." Its analge.sic and antipyretic activity is probably no greater than that of aspirin, and possibly less. It can be used in place of salicylates, however, and is particularly useful for patients with a demonstrated sensitivity to salicylates. It is excreted much more rapidly than other salicylates, which probably accounts for its lower toxicity and. thus, does not permit high blixHl levels. 

---