Hypohalites, amide reaction

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Upon treatment of primary amides with hypohalites, primary amines with one less carbon are obtained via the intermediacy of isocyanate. Also know as the Hofmann degradation reaction. 

A-Haloamides and imides are a most versatile group of halogenating reagents. They are normally prepared in an aqueous solution by reaction of the parent amide/imide with the corresponding hypohalite. An improved method for the synthesis of A-bromo amides/imides has recently been published, in which the parent compounds are oxy-brominated in aqueous solution by a mixture of HBr/NaBr03 or NaBr/NaBr03/H2S04 (equation 95)700. 

Ionica, Filip and Dinulescu50 studied hypohalite halogenation of A-bonded acidic hydrogens, which proceeds considerably faster than corresponding carbon-H halogena-tions. They used Hoffmann degradation of amides as a proof of their mechanism (equation 32). Based on the overall stoichiometry of the reaction they suggested that if their... 

In the Hofmann reaction (Scheme 8.2), an amide is treated with a halogen, usually bromine, in alkali in which the reactive species is the hypohalite ion (XO ). This reaction, which applies to aliphatic as well as aromatic amides, has been thoroughly studied. Evidence supporting... 

The Hofmann reaction involves the conversion of carboxylic primary amides to primary amines or their derivatives. Generally, alkaline hypohalites or a combination of halogens and alkaline hydroxides are used in aqueous solutions. The rearrangement generally occurs by heating. The intermediate isocyanates are easily hydrolyzed to amines under the reaction conditions, as shown in Scheme 3. When sodium methoxide in methanol is used in place of aqueous alkaline hydroxide, the corresponding methylurethanes are formed and may be hydrolyzed to yield amines. 

Hofmann Reaction.72 In contrast to the molecular rearrangements which have been discussed, the Hofmann reaction proceeds in an alkaline medium. In this reaction an amide is treated with a hypohalite solution, and, under the usual conditions of the reaction, an amine with one less carbon atom is obtained ... 

The reaction is generally carried out by warming the amide in aqueous hypohalite solution rapidly to about 70°. Allen and Wolf give the following directions in Organic Syntheses119 for conversion of nicotinamide into 3-pyri-dinamine ... 

The Hofmann reaction generally is carried out by dissolving the amide in a very slight excess of cold aqueous hypohalite solution, followed by rapid warming (with steam distillation if the amine produced is volatile). A valuable modification (p. 282) consists in carrying out the reaction in an alcoholic (usually methanolic) solution, with subsequent hydrolysis of the urethan so obtained. 

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