Amines reactions with cyanogen bromide

Halides derived from hydrogen cyanide also react smoothly with primary amines. Reaction with cyanogen bromide is to be recommended as a method of preparing cyanamides, but it is advisable to arrange for good cooling so as to avoid formation of guanidines. 

In this series, too, replacement of the N-methyl by a group such as cyclopropylmethyl leads to a compound with reduced abuse potential by virtue of mixed agonist-antagonist action. To accomplish this, reduction of 24 followed by reaction with tertiary butylmagnesium chloride gives the tertiary carbinol 27. The N-methyl group is then removed by the classic von Braun procedure. Thus, reaction with cyanogen bromide leads to the N-cyano derivative (28) hydrolysis affords the secondary amine 29. (One of the more efficient demethylation procedures, such as reaction with ethyl chloroformate would presumably be used today.) Acylation with cyclopropylcarbonyl chloride then leads to the amide 30. Reduction with lithium aluminum hydride (31) followed by demethylation of the phenolic ether affords buprenorphine (32).9... 

Generation of benzomorphan secondary amines, for conversion to appropriate N-substituted derivatives, usually requires N-demethylation of the corresponding tertiary amine. This may be effected by the von Braun reaction with cyanogen bromide or by the use of alkyl-, halogenated alkyl-, and arylchloroformates or diethylazodicarboxylate. Methods for N-demethylation in the series have been summarized by Rice.(62) Removal of an N-benzyl substituent affords an alternative path to norbenzomorphans and is exemplified by Michne and co-workers(63) and Kametani and Aoyama.(s4)... 

Nicotinic acid can be measured as an indication of nicotinamide deficiency. It can be estimated by its colorimetric reaction with cyanogen bromide and an aromatic amine. Nicotinic acid can also be measured as its urinary metabolite, -methylnico-tinamide, which reacts with ketones to give a fluorescent compound. 

Hydrobromides 13 of 3//-1,3,4-benzotriazepin-2-amines are formed in the reaction of 2-aminobenzophenone hydrazones 12 with cyanogen bromide. Selected examples are given.356... 

A procedure for application of the reaction to N.N-dimelhyl-( -naphthylamine5 calls for refluxing the amine with cyanogen bromide for 16 hrs. The cooled mixture is treated with ether and the. solution filtered from u little insoluble n-nuphthyl-trimethylammonium bromide. The solution is extracted with dilute hydrochloric... 

VOll Braun reaction. Reaction of tertiary amines with cyanogen bromide to form disubsti-tuted cyanamides and an alkyl halide. 

The first synthesis of a 1 HA, 2,4-benzothiadiazine 1-oxide and simultaneously of the first cyclic sulfoximine were reported in 1964. 22 1 //-1,2,4-Benzothiadiazines were later prepared123 by reaction of S-(2-aminophenyl)sulfoximine 1 with cyanogen bromide to give 1//-1,2,4-thiadi-azin-3-amine 1-oxide 2a. Compounds 1 also react with phosgene to yield 1//-1,2,4-benzo-thiadiazin-3-amine 1-oxides 2b and c.123 An alternative route to 1 H-, 2,4-benzothiadiazine 1-oxides from sulfoximines and C-synthons has also been reported. 24 128... 

The synthesis of buprenorphine has a certain similarity to that of etorphine. After the Diels-Alder reaction of thebaine with methyl vinyl ketone, the double bond is hydrogenated. Then follows a Grignard reaction with t-butyhnagnesium chloride. For modification of the tertiary amine, this is demethylated with cyanogen bromide (von Braun reaction) and treated with cyclopropanecarbonyl chloride. Following reduction with lithium aluminium hydride, the aromatic methoxy-group is finally replaced by nucleophihc substitution under forcing conditions. 

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. 

The characteristic color reaction of nicotinic acid with cyanogen bromide and /3-naphthylamine has been studied. The product is believed to be X-201. Argentic picolinate is a powerful oxidizing agent Thus, toluene is oxidized to benzyl alcohol, benzaldehyde, and benzoic acid in a stepwise, controllable manner. Primary alcohols were converted to aldehydes, secondary alcohols to ketones. Amines were oxidized to aldehydes or ketones in dimethylsulfoxide. 

The most serious problem encoimtered with agarose is the formation of an unstable isourea function from the reaction of cyanogen bromide-activated agarose with primary amines. This isomea forms a positively charged derivative ... 

This is based on the reaction of derivatives of pyridine with cyanogen bromide in the presence of an aromatic amine giving specific colors. Amines commonly used are 2-naphthylamine-i-sulfonic acid, />-aminoacetophenone, iV-methyl-aminophenol sulphate, aniline and />-naphthylamine. The reaction gives a yellowish-green color which is measured photometrically. The color is soluble in amyl alcohol which can be used to extract it from water solutions, but is not stable unless a phosphate buffer of pH 6.i is used. This method is not specific for nicotinic acid since other pyridine derivatives and derivatives of nicotinic acid such as trigonelline, nicotinuric acid and nicotine give a similar color. 

Carbonates are also formed when carbohydrates are reacted with cyanogen bromide, followed by reaction with a second molecule containing a reactive amine or alcohol group. These reactions are used to couple various ligands such as enzymes, antibodies, affinity ligands, and so forth to an insoluble carbohydrate carrier for use in affinity chromatography or for the immobilization of enzymes (see section 7.8 in Chapter 7). 

When cyanogen bromide was used instead of CS2, the corresponding guanidines 169 were obtained under analogous conditions [108]. Moreover, differently substituted guanidines 171 could be obtained in very good yields when the isothiourea 168 was alkylated with Mel under microwave irradiation and the product treated with a primary amine. An intramolecular version of this reaction was also described for the preparation of structure 172 present in several important natural products (Scheme 61). 

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