Von Braun amide degradation

The tertiary amines 303 and the acid chlorides 304 (X = Cl) initially formed acylammonium salts 305, which underwent a von Braun type degradation by an attack of the nucleophilic chloride ion at the allyl system to give allyl chlorides 306/307 and carboxylic acid amide functions. 

The von Braun degradation (85, 67) was reinvestigated and fully worked out by Boit (86). The reaction of strychnine with cyanogen bromide in hot benzene leads to the formation of two products, the amorphous bromocyanamide-I (LXXX) and the crystalline bromo-cyanamide-II (LXXXI). Dihydrostrychnine, on the other hand, gives only one product (LXXXII), which is identical with the product of catalytic hydrogenation (platinum in ethyl acetate) of bromocyan-amide-II. The corresponding brucine compounds behave analogously. 

Some ideas exist on circumventing the problem. Amine hydrochlorides at higher temperatures are in equilibrium with HCl and the amine. Provided the amide chloride is thermally stable (no von Braun degradation, no selfcondensation), which is true for a lot of aromatic amide chlorides or formamide chlorides, the amine hydrochloride can be reacted at elevated temperatures (150-170 C) for strongly basic aliphatic amines, whereas weakly basic aromatic amides react under more gentle conditions. In another approach, instead of the amine the A(,A(-dialkylsilylamine is used, hence trimethylsilyl chloride is formed as a byproduct, which can be removed by distillation. 

Different from the von Braun degradation reaction (amide to nitrile), the von Braun reaction refers to the treatment of tertiary amines with cyanogen bromide, resulting in a substituted cyanamide. 

Reactions with Secondary Amides. Treatment of AT-alkyl or A -aryl secondary amides with thionyl chloride in an inert solvent such as methylene chloride results in the formation of imidoyl chlorides (eq Q)." Upon heating, the imidoyl chlorides from N-alkylamides undergo scission to generate nitriles and alkyl chlorides via the von Braun degradation (eq 10). ... 

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