Cyanogen bromide reaction

H. A. Hageman, "The Von Braun Cyanogen Bromide Reaction," in R. Adams and co-workers, eds.. Organic Reactions, Vol. 7, John Wiley Sons,... 

Nicotinic acid and related compounds react with l-chloro-2,4-dinitrobenzene in the manner of the cyanogen bromide reaction to yield derivative I, which possibly also decarboxylates at elevated temperature. In alkaline medium this derivative first adds an hydroxyl ion and then undergoes ring opening to yield the colored derivative II. 

Cyanoethylation, 5, 2 Cyanogen bromide, reactions with tertiary amines, 7, 4... 

The cyanogen bromide reaction with the nucleoside adenosine 1-oxide (604) gives the 2-imino-7-/3-D-ribofuranosyl[l,2,4]oxadiazolo[2,3-/]purine (605) as the HBr salt. The latter on neutralization tautomerizes to iV6-cyanoadenosine 1-oxide (78CPB2122). 

K. H. Pausacker, Current Trends Heterocyclic Chem., Proc. Symp., Canberra, 1957 p. 8. Academic Press, New York, 1958. von Braun reaction (cyanogen bromide reaction of amines, including heterocycles) ... 

Gross E. The cyanogen bromide reaction. Methods Enzymol. 1967 11 238-255. 

One additional point to be borne in mind when using the cyanogen bromide reaction is the short half-life of the intermediate, approximately 20 min at 40°C. Washing of the activated intermediate to remove excess cyanogen bromide prior to coupling has to be performed quickly to avoid excessive loss of coupling efficiency. Affinity media prepared in this manner are stable for considerable periods of time and many commercial preparations are available based on cyanogen bromide-insolubilized biopolymers. 

FIGURE 3.13 Schematic representation of (a) cyanogen bromide reaction, (b) cyclic rranr-2,3-carbonate activation method, (c) triazine activation method, and (d) carbonylation reaction. 

Polysaccharides. Polysaccharides possess readily accessible hydroxyl groups that may be derivatized for selective protein immobilization. We will consider the two most commonly used immobilization reactions, the triazine and the cyanogen bromide reactions. 

The intermediate jV-cyanoammonium salts derived from cyanogen bromide reaction with (264) may be attacked by a hydroxylic solvent to give (265) <79C1(L)3I9, 81CC1209, 84AJC367>. An intramolecular version of this reaction has been described by Bremner et al. The treatment of (266) with cyanogen bromide resulted in the formation of the thieno-fused oxazonine (267) in moderate yield (Scheme 30) <84AJC1043>. 

The reaction has found use in the degradation of alkaloids . Unlike the Hofinann exhaustive methylation procedure which may be repeated until the nitrogen of the natural product is freed as tertiary amine, the cyanogen bromide reaction is only practicable with tertiary amines. With secondary amines, cyanogen bromide yields disubstituted cyanamides direcdy and these react further with the amine hydrobromide formed at the same time to give guanidines (equation 53) . 

Reaction with alumina, porous glass, or titania treated with cyanogen bromide Reaction with 4-diazobenzylcellulose... 

Polysaccharides and cross-linked polysaccharides can be activated by reaction with alkaline cyanogen bromide (reaction 7.19). Polysaccharides such as cross-linked dextran, agaran, and cellulose have been activated by this reaction [37,38]. The activated polysaccharides can then react with amino groups of various ligands that can be used in affinity chromatography [39], or they can react with amino groups on the surface of enzymes to give immobilized enzymes [40] (reaction 7.20). 

Neostrychnine. Neither the Hofmann, Emde, or cyanogen bromide reactions have been particularly useful as starting points for systematic degradations of strychnine because of the stereochemistry which is not suitable for eliminations and instead a multiplicity of Sn2 products were usually formed. It was a study of the Hofmann degradation that first led to neostrychnine (Chart 6.4), a double bond isomer (J20,2i Qf strychnine, a compound more readily made by heating strychnine with selenium or Raney... 

The results of one of the first multistep enzyme systems to be immobilized were presented in 1970 by Mosbach and Mattiasson (3). They covalently bonded hexokinase (HK) and glucose-6-phosphate dehydrogenase (G-6-PDH) to individual polymer particles via the cyanogen bromide reaction. Using a solution containing glucose, ATP and NADP" ", they demonstrated that the coimmobilized enzymes formed product... 

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