Hofmann degradation nitriles

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

Ronsch (129,130) described the synthesis of ene lactam 152, formally belonging to cordrastine series, from the rhoeadine alkaloid, alpinigenine (150), by Hofmann degradation of its derivative 151 (Scheme 26). Treatment of the nitrile 151 with methyl iodide and then with potassium hydroxide gave ene lactam 152, for which the Z configuration could be deduced on the grounds of UV (365 nm) and H-NMR (57.09 and 7.39, J = 8 Hz) spectral data. 

Problem 18.8 Prepare ethylamine by (a) Gabriel synthesis, (6) alkyl halide amination, (c) nitrile reduction, (d) reductive amination, (e) Hofmann degradation. ... 

The amine group in primary amines can be replaced by halogen by warming the benzoyl derivative with phosphorus pentachloride or phosphorus pentabromide. Oftentimes, the separation of the halide from the benzonitrile, which is also formed, is troublesome. The process has been applied mostly to high-moIecuIar-weight amines obtained by the Hofmann degradation of acid amides or by reduction of nitriles." Diamines lead to dihalogen derivatives." If N-benzoyl piperidines are treated, substituted pentamethylene halides are formed. An example is the synthesis of pentamethylene bromide by the action of phosphorus pentabromide on N-benzoyl piperidine (72%). ... 

A Hofmann degradation is used to synthesize pyrido[3,4-t/]pyrimidines starting from 3-cyano-6-methylpyridine-4-carboxamidc.478 By heating the amide in aqueous potassium hydroxide/ sodium hypochlorite at 80 JC, a 70% yield of 6-methylpyrido[3,4-tf]pyrimidine-2,4(1 7/,3/f)-dione (17) is obtained, together with a minor amount of 2-methylpyridine-4,5-diamine. It is concluded that, under alkaline conditions, hydration of the nitrile to the amide apparently proceeds even faster than hydrolysis of the amide in the 4-position. 

Sandmeyer s synthesis of aromatic nitriles is far more elegant than the removal of water from the ammonium salts of carboxylic acids, which latter reaction is also applicable to benzene derivatives. In particular, the former synthesis permits of the preparation of carboxylic acids via the nitriles, and so provides a complete substitute for Kolbe s synthesis (alkyl halide and potassium cyanide), which is inapplicable to aromatic compounds. The simplest example is the conversion of aniline into benzoic add. The converse transformation is Hofmann s degradation (benzamide aniline, see p. 152). 

Amide degradation. In a liquid triphasic system made up of NaOCl, NaBr, a phase-tranfer agent, Na3P04, benzene, and water, primary amides are degraded to nitriles of one fewer carbon atom. After Hofmann rearrangement the amine products undergo bromination and eventually elimination. 

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