With cyanogen bromide

Treatment of quinoline with cyanogen bromide, the von Braun reaction (17), in methanol with sodium bicarbonate produces a high yield of l-cyano-2-methoxy-l,2-dihydroquinoline [880-95-5] (5) (18). Compound (5) is quantitatively converted to 3-bromoquinoline [5332-24-1], through the intermediate (6) [66438-70-8]. These conversions are accompHshed by sequential treatment with bromine in methanol, sodium carbonate, or concentrated hydrochloric acid in methanol. Similar conditions provide high yields of 3-bromomethylquinoHnes. 

The N-oxides of isoquinolines have proved to be excellent intermediates for the preparation of many compounds. Trialkylboranes give 1-alkyl derivatives (147). With cyanogen bromide in ethanol, ethyl N-(l- and 4-isoquinolyl)carbamates are formed (148). A compHcated but potentially important reaction is the formation of 1-acetonyLisoquinoline and 1-cyanoisoquinoline [1198-30-7] when isoquinoline N-oxide reacts with metbacrylonitrile in the presence of hydroquinone (149). Isoquinoline N-oxide undergoes direct acylamination with /V-benzoylanilinoisoquinoline salts to form 1-/V-benzoylanilinoisoquinoline [53112-20-4] in 55% yield (150). A similar reaction of AJ-sulfinyl- -toluenesulfonamide leads to l-(tos5larriino)isoquinoline [25770-51-8] which is readily hydrolyzed to 1-aminoisoquinoline (151). 

Azoles can form stable compounds in which metallic and metalloid atoms are linked to nitrogen. For example, pyrazoles and imidazoles Af-substituted by B, Si, P and Hg groups are made in this way. Imidazoles with a free NH group can be Af-trimethylsilylated and Af-cyanated (with cyanogen bromide). Imidazoles of low basicity can be Af-nitrated. 

Dendrobine methiodide is convertible into the methohydroxide, m.p. 251° dec.). With cyanogen bromide cyanonordendrobine, m.p. 188°, was obtained, from which nordendrobine, m.p. 117-8°, — 21-6°... 

The pyrrolidine enamine of 2-tetralone (177) was converted to l-cyano-2-tetralone, which exists almost entirely in the enolic form (178), by reaction with cyanogen chloride (J23). Reaction of 177 with cyanogen bromide gave N-naphthylpyrrolidine (179), presumably via the unstable bromoenamine (180). The latter observation is in accord with the mode of reaction of the heterocyclic enamine (126) with cyanogen bromide, which resulted in the... 

Diaminopyrimidines (22) were also cyclized with cyanogen bromide (90JHC851) or phenyl isothiocyanate (97PHA753) to give the corresponding 2-amino- or 2-anilino-l,2,4-triazolo[l,5-c]pyrimidines 30 and 31 respectively (Scheme 15). 

A particularly interesting example of this method of synthesis is the cy-clrzation of the 4-amino-3-(2-aminophyenyl)-l,2,4-triazoloes 73 with cyanogen bromide. Primarily, this reaction was applied to synthesize the 6-amino-l,2,4-triazolo[4,3-d]benzodiazepine hydrobromides 74 the obtained products, however, were found to be the l,5-diamino-l,2,4-triazolo-[l,5-c]quinazolin-ium bromides 77. Structure elucidation of 77 was accomplished by direct... 

The hydroxy group of furazan 263 reacted with cyanogen bromide in glyme in the presence of Li2C03 to give cyanate 264 in 70-85% yield (97MI8). Upon treatment with Mc4NN3 and subsequently with a basic solution of hydroxylamine-0-sulfonic acid, /V-aminotetrazole 265 was obtained in 35% yield (Scheme 171). 

The proposed structure of 97 isolated from broiled sardines was confirmed by straightforward synthesis starting from5,6-diaminoquinolines. After reaction with cyanogen bromide it afforded the 2-amino-imidazo[4,5-/]quinolines 99 (R = H, Me), which was then converted into its 3-A-methyl derivative 100 by... 

Independent synthesis of IQ, eliminating the alkylating reaction step, involved the cyclizations of 7-R-5-amino-6-methylaminoquinolines with cyanogen bromide. When " C-labeled BrCN was used, the corresponding 2- " C-labeled analogues of IQ and MelQ were synthesized (83ACSI57). The diamines are available from 5-nitroderivatives, which in turn have been prepared by nitration of methylami-noderivatives (82CPB1857). 

The 6-methylacetylamino-l,2,3,4-tetrahydroquinoline, after nitration and separation of isomers, following reduction and deprotection, gave the 7-amino-6-methylamino derivative, which cyclized with cyanogen bromide. Alkylation of the cyclization products afforded inhibitors of thymidylate synthase, 5-substituted 2-amino-l//-l-methyl-5,6,7,8-tetrahydroimidazo[4,5-g]quinolines 136, designed for use in iterative protein crystal analysis (Scheme 42) (92JMC847). 

The prototype of this series is synthesized by first reacting morphine with cyanogen bromide. This reagent in effect serves to replace the methyl group by cyano. Hydrolysis of the intermediate (11) affords desmethylmorphine (12). Alkylation of the last with allyl bromide affords nalorphine (13). ... 

The key to clinical agents in this series, the secondary amine, 65, is obtained by a sequence analogous to that used to obtain desmethymorphine. Thus, the phenol (63) is first acetyl-ated (64), and then demethylated by treatment with cyanogen bromide hydrolysis gives the desired aminophenol (65). Alkylation... 

Reaction with cyanogen bromide possibly gives cyanamide 131... 

Demethylation of the tricyclic antihistamine 9, with cyanogen bromide gives the secondary amine 10 acylation of that intermediate with ethyl chloroformate affords the nonsedating H-1 antihistaminic agent loratidine (11) [3], It is of interest that this compound does not contain the zwitterionic funcrion which is thought to prevent passage through the blood-brain barrier, characteristic of this class of compounds. 

Proteins can be cleaved specifically at the amide bond on the carboxyl side of methionine residues by reaction with cyanogen bromide. BrC=N. 

Photolysis of ethyl l-azido-A-cyanoformimidate (21) (readily prepared by the treatment of 5-ethoxytetrazole with cyanogen bromide) in benzene produces a 1.17 1 mixture (not separated) of l-(jV-cyanoethoxycarbonimidoyl)-l//-azepine(22) and 2-ethoxy-l-phenylisourea-3-carboni-trile (23).166 More recently, a similar reaction has been reported under thermal conditions.293... 

Chloro-7-(2-fluorophenyl)-5/f-dibenz[c,e]azepine (54) has been prepared in a similar manner from 2-[2-(bromomethyl)phenyl)-5-chloro-2 -fluorodiphenyl ketone (53, X = Br),93 but can be obtained in a superior yield (85%) as the methanesulfonate salt by cleavage of the [(dimethylamino)methyl] derivative 53 (X = NMe2) with cyanogen bromide followed by treatment with ethanolic ammonia.94... 

Dibenz[b,/]azepinc-5-carbonitrile (14), an alternative intermediate for the synthesis of Car-bamazepine, is obtained (47%, as the hydrobromide) by stirring 5//-dibenz[b,/]azepine (5) with cyanogen bromide in chloroform solution at room temperature,203 or with cyanogen chloride in dimethylacetamide.204... 

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... 

The hydrazone 12 (10 mmol) was dissolved in EtOH (80 mL) with warming and the stirred cooled solution was treated with cyanogen bromide (1.06 g, 10 mmol) and kept for 3 d. The solvent was removed and the residue was triturated with acetone. The resultant solid was collected, dissolved in warm MeOH and the solution was treated with coned IIBr. Et20 was added to incipient turbidity, whereupon the product crystallized. 

Treatment of methylhydrazides of 2-aminobenzoic acids with cyanogen bromide provides 2-amino-l,3,4-bcnzotriazepin-5-one hydrobromides 16. Selected examples are given.358... 

Cyclization of 3-hydrazinotriazines 712 with cyanogen bromide afforded [76JCS(P1)1492] the hydrobromide of a weakly basic amine 721 via intermediate 720. Deamination of 721 with pentyl nitrite gave triazolo [4,3-6][l,2,4]triazine 722. Similarly, 7-oxo analogues were obtained (81JHC1353). 

Novolac hydroxyl groups reacted with cyanogen bromide under basic conditions to produce cyanate ester resins (Fig. 7.41).105,106 Cyanate esters can thermally crosslink to form void-free networks, wherein at least some triazine rings form. The resultant networks possess high s, high char yields at 900°C, and high decomposition temperatures.105... 

Cleavage of tertiary amines with cyanogen bromide (von Braun) Dehydration of disubstituted ureas... 

---