Amines reaction with hypobromites

It seems that treatment of the parent compound with NBS or NCS in DMF, or reaction with aqueous sodium hypobromite, results in halogena-tion at the 3-position. The ring system has been described as being as inert to electrophilic substitution as indazole but more reactive than quinoxaline. Nitration under imspecified conditions of the heterocycle results in a mixture of mononitro compounds, the major product being either the 6- or 7-nitro derivative and the minor product having a nitro group in either the 5- or the 8-position. Both nitro compounds were reduced to the corresponding primary amines with stannous chloride. 

The reactions of the amides with hypobromites are analogous to those of the primary and secondary amines with this reagent one or two atoms of hydrogen are replaced by bromine ... 

It has already been known that the reaction of primary amines with alkaline hypobromite gives nitriles, and the reaction of hydrazo compounds with bromine affords azo compounds. Recently, we also found that the reaction of primary amines and hydrazo compounds with BTMA Br3 in aq. sodium hydroxide or in water gave corresponding nitriles and azo compounds in satisfactory yields, respectively (Fig. 27) (ref. 35). 

Treatment with sodium hypochlorite or hypobromite converts primary amines into N-halo- or N,N-dihaloamines. Secondary amines can be converted to N-halo secondary amines. Similar reactions can be carried out on unsubstituted and N-substituted amides and on sulfonamides. With unsubstituted amides the N-halo-gen product is seldom isolated but usually rearranges (see 18-13) however, N-halo-N-alkyl amides and N-halo imides are quite stable. The important reagent NBS is made in this manner. N-Halogenation has also been accomplished with other reagents, (e.g., sodium bromite NaBr02) benzyltrimethylammonium tribromide (PhCH2NMe3 Br3"), and NCS. The mechanisms of these reactions involve attack by a positive halogen and are probably similar to those of 12-47 and 12-49.N-Fluorination can be accomplished by direct treatment of amines °° or... 

Another reaction that can be used for conversion of carboxylic acids to the corresponding amines with loss of carbon dioxide is the Hofmann rearrangement. The classic reagent is hypobromite ion, which reacts to form an A-bromoamide intermediate. Like the Curtius reaction, this rearrangement is believed to be a concerted process and proceeds through an isocyanate intermediate. 

By treatment of an amide with sodium hypobromite or sodium hypochlorite solution (or with halogen admixed with aqueous alkali), a primary amine having one less carbon atom is produced. Good yields are obtained when the reaction is applied to most aliphatic and aromatic amides. Examples are provided by the preparation of anthranilic acid and 3-aminopyridine (Expt 6.53). 

The synthesis of BENZYL ISOCYANIDE from benzaldehyde via reductive amination with 5-aminotetrazole followed by oxidation of the resultant amine with sodium hypobromite provides a general method for the synthesis of isocyanides. The preparation of BIS(2,2,2-TRICHLOROETHYL) AZODICARBOXYLATE makes available an alternative to dimethyl azodicarboxylate that is not only more reactive in Diels-Alder reactions but whose ester groups can be removed under neutral conditions. 

Amides react with alkaline hypochlorite or hypobromite solutions to form primary amines having one less carbon atom. The reaction involves the hydrolysis of an isocyanate, which is seldom isolated. Isocyanates are also intermediates in the Curtius and Lossen rearrangements (methods 447 and 448). Although diese methods have a common mechanism and intermediate, they involve three separate and distinct types of starting materials and are, therefore, treated individually. A comparison of these reactions has been made. A detailed discussion of the Hofmann reaction, which includes conditions, typical procedures, and compounds prepared thereby, has been presented. ... 

Hofmann established a route to higher homologues of aromatic amines by intramolecular rearrangement of /V-alkylated anilines, a reaction that was of great theoretical and technical importance. In 1870, he reported the conversion of an acid amide into an amine, with loss of one carbon. In 1881, he discovered that when the degradation was carried out with sodium hypochlorite or hypobromite, the yields of primary amines were excellent. This is the Hofmann degradation, or reaction, that takes place via formation of isocyanate60. 

Isocyanates derived from the higher aliphatic amides react more rapidly with the haloamide salts than with water and alkali, so that, when these amides are subjected to the Hofmann reaction in aqueous mediiun, only small amounts of the expected amines are formed. Although amines arise from the hydrolysis of the alkyl acyl ureas, they are largely oxidized to nitriles by the excess of hypobromite present. 

An excess of bromine amounting to 10-20% is advisable, since even with the most carefully prepared hypobromite solutions only 80 to 90% of the expected activity is realized. A larger excess is usually to be avoided, however otherwise the yield of amine may be seriously reduced by the side reactions discussed earher. Occasionally, if the resulting amine is relatively unreactive toward the reagent, a considerable excess of both alkali and bromine may be employed without adverse consequences, sometimes, indeed, to considerable advantage when the amide is also unreactive. Thus 3,5-dinitro-2-a-naphthylbenzamide is converted most smoothly to 3,5-dinitro-2-a-naphthylaniline when the amide (0.01 mole) is treated with a hypobromite solution prepared from 0.16 mole (8 cc.) of bromine and 1.5 mole (60 g.) of sodium hydroxide in 100 cc. of water In addition, it must be emphasized that only hypobromite solutions which have been freshly prepared are satisfactory. Serious loss of activity always occurs on standing, even in the dark. ... 

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