Cyanides from carboxamides

The use of oxalyl chloride as a dehydrating agent has been developed into a general procedure for preparing cyanides from carboxamides under Swem oxidation conditions, affording a great variety of structures such as 1392-1396 in mostly excellent yields [1059]. The proposed mechanism is outlined. 

Nitriles, which are important intermediates in the manufacture of a wide variety of organic compounds such as amines, aldehydes, amidines, and heterocycles, are manufactured either from alkali cyanides or from carboxamides. The cyanides route is obviously highly toxic, whereas the carboxamide consumes the reagent in stoichiometric quantities. Solid superacids offer a clear alternative to the traditional catalysts. Thus the use of sulfated zirconia enables the dehydration to be accomplished under much milder conditions in the liquid state (Joshi and Rajadhyaksha, 1986 Rajadhyaksha and Joshi, 1991). 

The preparation of cyanides by dehydration is best accomplished from aldoximes (standard method) rather than from carboxamides, because the former require milder reaction conditions. However, carboxamides, as carboxylic acid derivatives, are more easily accessible. Phosgene has been applied in the dehydration of carboxamides rather than of aldoximes. 

Some reviews on the preparation of cyanides from aldoximes [1045, 1046] and from carboxamides [1047,1048] are available. Often used dehydration reagents are acetic anhydride for aldoximes and phosphorus pentoxide for carboxamides. In the following sections, dehydration reactions affording cyanides are described with various dehydration reagents, classified into acidic and basic reagents. 

General procedure. Cyanides 1379 from carboxamides 1377 [1056] To a stirred solution of an amide (4 mmol) and triphosgene (0.6 g, 2 mmol) in absolute chloroform (40 mL), a solution of triethylamine (1.7 mL, 12 mmol) in absolute chloroform... 

General procedure. Cyanides 1379 from carboxamides 1377 [1057] Phenyl chloroformate (5.5 mmol) was added dropwise to a stirred, iceamide/thioamide (5.0 mmol) in dry dichloromethane (25 mL) and anhydrous pyridine (10.0 mmol) at such a rate that the temperature remained below 5 °C. The reaction mixture was allowed to warm to room temperature and was stirred for 8-10 h (completion of the reaction was verified by TLC). It was then quenched with water (8 mL) and extracted with dichloromethane (2 x 25 mL). The combined organic phases were washed with brine, dried (Na2S04), and the solvent was removed in vacuo to afford the crude product, which was purified by column chromatography on silica gel. Pure cyanides 1379 were obtained in yields of 80-95%. 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

The hydrochlorides of 64, 65, and 66 were obtained by reaction of iV-phenylbenzimidyl chloride and hydrogen cyanide with the appropriate heterocyclic base. As is typical of the Reissert compounds, these three compounds lack absorption peaks in the region 2200-2400 cm h To further the analogy to Reissert compounds, acid-catalyzed hydrolysis of 64, 65, and 66 gave benzaldehyde. Picolinio acid, quinaldic acid, and isoquinaldic acid, respectively, as well as aniline, are also obtained from the hydrolysis. Nitrobenzene oxidation of the three compounds gave pyridine-2-carboxamide, quinaldonitrile, and isoquinaldonitrile, respectively. ... 

Hydrolysis of acid chlorides, acid anhydrides, esters and carboxamides leads to the carboxylic acid, although these compounds are often derived from a carboxylic acid group in the first place (Scheme 5.5). Nitriles are usually derived from amines via diazotization and reaction with copper(I) cyanide (see Chapter 8) and so the hydrolysis of a nitrile group is of more value. In all cases, alkaline hydrolysis gives the salt of the acid, from which the free acid is obtained by addition of mineral acid. 

Aminotriazole, and some of its 5-substituted derivatives, when fused with 1,2,3,5-tetra-O-acetyl- or -benzoyl-/ -D-ribofuranose, gave a 1 1-mixture of 2- and 3-ribofuranosyltriazoles (76USP3968103). 4-Acetamidotriazole-5-carboxamide, mercuric cyanide, and tri-0-benzoyl-/ -D-ribofuranosyl chloride, when refluxed in nitromethane, furnished 4-acetamido-l- 2, 3, 5-tri-O-benzoyl-/S-D-ribofuranosyl)triazole-5-carboxamide (3 hr, 48%), from which the benzoyl groups were removed in methanolic ammonia (0°C, 3 days, 54%) (72BCJ2577). Occupation of the 1 position in this and other ribosylations was unexpected but was carefully verified. 

Methods derived from this fundamental process involve the condensation of one-, two- and three-carbon units such as amidines, amino-nitriles and carboxamides, which represent intermediate stages of the ammonia/hydrogen cyanide reaction. Pyrimidines or imidazoles are usually intermediates. ... 

Aldehydes can be used to catalyze water transfer from a primary carboxamide 1377 to acetonitrile to furnish the corresponding cyanide 1379 and acetamide as byproduct [1140]. The reactions are performed in refluxing acetonitrile, the reaction time is 12 h, and yields of 64—92% have been reported for several aromatic and aliphatic nitriles. 

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