Sulfuric acid, reaction with nitriles

The isolation of oxazole derivatives from Ritter-type reactions dates back to 1893, when Japp and Murray reported that benzoin and sulfuric acid reacted with nitriles (equation 33). Better yields of such products are obtained from reaction of chloro ketones (54) with nitrile-SnCU complexes (equation 34). Likely mechanisms for these processes have been discussed by Meyers and Sircar. ... 

Antispasmodic activity, interestingly, is maintained even in the face of the deletion of the ethanolamine ester side chain. Reaction of anisaldehyde with potassium cyanide and dibutylamine hydrochloride affords the corresponding a-aminonitrile (72) (a functionality analogous to a cyanohydrin). Treatment with sulfuric acid hydrolyzes the nitrile to the amide to yield ambucet-amide (73). ... 

This is a new reaction for the preparation of N-alkyl amides. Nitriles and various substituted cyano compounds are treated with active olefins in the presence of sulfuric acid. Reaction occurs at room temperature in glacial acetic acid or dibutyl ether solution. The use of hydrogen cyanide in the reaction leads to the formation of N-alkylformamides. /-Butyl alcohol and sodium cyanide are used in place of the olefin and hydrogen cyanide in the preparation of N-/-butylfotmamide (50%). The reaction has been extended to the synthesis of N-alkyl diamides from dinitriles and olefins or alcohols. ... 

The scope of conditions of the ketone-nitrile reaction is very broad. For instance, the polyfluorinated ketones 156 and 158 react with nitriles in the presence of concentrated sulfuric acid and with cyanoamides 159 by reaction mixtures at room temperature in the absence of acid catalyst ° ° (equations 52 and 53). 

Powdered potassium permanganate (94 mg) is added to an ice-cold, stirred solution of 0.1 g of the unsaturated nitrile in 3.5 ml of acetone containing 0.11 ml of piperidine. The reaction mixture is stirred at 0° for 1.5 hr, allowed to warm to room temperature (30 min) and then treated with 0.02 ml of acetic acid in 0.2 ml of acetone. After stirring at room temperature for an additional 1.5 hr the mixture is treated with chloroform, aqueous sodium bisulfite and sufficient 1 N sulfuric acid to reduce all of the manganese dioxide. 

A multitude of 1,4-dicarbonyls (1) undergo the Paal-Knorr reaction with and ranging from H to alkyl, aryl, carbonyl, nitrile, and phosphonate, while R and R vary between H, alkyl, aryl, trialkylsilyl, and O-alkyl. Protic acid catalysts are typically used with sulfuric, hydrochloric, and p-toluenesulfonic acids the most popular. Conversion to the furan takes place either at room temperature or upon heating with reaction times varying from five minutes to 24 hours and yields ranging from 17-100%. 

Scheme 21 presents the successful sequence of reactions that solved the remaining two problems and led to the completion of the synthesis of cobyric acid. Exposure of 96 to concentrated sulfuric acid for one hour brings about a clean conversion of the nitrile grouping to the corresponding primary amide grouping. The stability of die corrin nucleus under these rather severe conditions is noteworthy. This new substance, intermediate 97, is identified as cobyrinic acid abcdeg hexamethylester f amide and it is produced along with a very similar substance which is epimeric to 97 at C-13. The action of sulfuric acid on 96 produces a diastereomeric... 

Reaction of azines 86 with nitriles in the presence of alkyllithium and subsequent treatment of the formed product with sulfuric acid gave the pyrazolo[l,5-u]pyrimidine 87 (82CC454). 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

The sulfuric acid-catalyzed condensation of oxetanes with nitriles gives dihydro-1,3-oxazines (45). This reaction has been reported for a wide variety of 2,2-disubstituted oxetanes and nitriles, generally giving fair yields (74ZOR95, 82ZOR181). The nitrogen atom of the nitrile always bonds to the more substituted a-carbon of the oxetane. 

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