Hofmanns reaction

It is prepared by the action of sodium hydroxide and sodium hypochlorite on phthalimide (Hofmann reaction). When heated with soda lime it gives aniline. 

The conversion of an amide into an amine in this way is termed the Hofmann reaction or the Hofmann rearrangement. 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

Diamides and triamides have been obtained from the action of an aqueous saturated solution of ammonia on the corresponding ester (Scheme 18) (88). Amides can also be obtained by the Curtius (16) or Hofmann reactions (80). Thus the Curtius reaction with 2-substituted 4-thiazolecarboxylic acids gives the 4-acetamido compounds (16). 

Amides. Because amides are less basic, they chlorinate less rapidly than amines. A/-Halamides are converted to amines in basic solution via intermediate formation of an isocyanate (Hofmann reaction) (91). 

Ureas. Chlorination of aqueous urea yields unstable A/-chloro compounds. With excess C10 decomposition yields CO2, N2O, and NCl the latter decomposes further to NO (96). Only two soHd derivatives have been isolated A/-chlorourea [3135-74-8] mp 74—76°C, and N,lSf-dichlorourea [2959-01-5] which decomposes at its mp of 83°C with evolution of NCl. As an amide, urea also undergoes the Hofmann reaction yielding hydrazine. This route to hydrazine was once employed commercially. 

Methyl chloride reacts with ammonia alcohoHc solution or ia the vapor phase by the Hofmann reaction to form a mixture of the hydrochlorides of methylamine, dimethylamine, trimethyl amine, and tetramethyl ammonium chloride. With tertiary amines, methyl chloride forms quaternary derivatives. 

Numerous other methods are available for the preparation of amino derivatives, and these include direct synthesis (see Section 2.14.3.2) and more traditional transformations such as the Hofmann reaction. Aminopyrazine has been prepared from pyrazinamide (60G1807) and 2-aminoquinoxaline from the corresponding carboxamide (71JOC1158). The... 

Imidazole-4-catbonitrile, 5-amino-synthesis, 5, 463 Imidazolecarboxamide, cyano-reactions, 5, 436 Imidazole-4-carboxamide Hofmann reaction, 5, 435 Imidazole-4-carboxamide, 5-amino-in histidine biosynthesis, 1, 90 reactions... 

In 1878, Hofmann reported that treatment of D-l-bromo-2-propylpiperidine (3) with hot sulfuric acid gave rise to a tertiary amine 4, D-octahydroindolizine. In the ensuing decade, Loffler and Freytag extended the reaction to simple secondary amines and found it to be a general way to synthesize pyrrolidines as exemplified by transformation of N-bromo-A-methyl-2-butylaminylpyridine 5 to nicotine (6). The Hofmann-Loffler-Freytag reaction is sometimes referred to as Loffler s method, Hofmann-Loffler reaction, Loffler-Hofmann reaction, as well as Loffler-Freytag reaction. 

Haworth reaction Hell-Volhard-Zelinsky reaction Hoesch reaction Hofmann reaction. ... 

Among the recent applications of the Hofmann reaction has been the preparation of relatively unstable geminal diamides and carbinolamides. For example, 1,1-diacetamidocyclohexane can be prepared in this way.277... 

Among the most concrete evidence obtainable about the mechanism of a reaction is that provided by the actual isolation of one or more intermediates from the reaction mixture. Thus in the Hofmann reaction (p. 122), by which amides are converted into amines,... 

A typical example is the conversion of an amide (57) to an amine (58), containing one carbon less, by the action of alkaline hypobromite, the Hofmann reaction ... 

The Hofmann reaction of an amide with bromine and alkali apparently goes by way of the iV-bromoamide and unicovalent electron-deficient nitrogen. 

The Lossen rearrangement of an hydroxamic acid under basic conditions is a variant of the Hofmann reaction in which the aroyloxy group fills the role of the bromine.314... 

In addition to the present method,2 1-amino-1-methylcyclo-hexane has been synthesized by the following procedures Ritter reaction, e.g., with 1-methylcyclohexanol (76%, 67%)3i 4 or 1-methylcyclohexene (35%,) 4 5 Hofmann reaction with 1-methyl-cyclohexanecarboxamide (80% as hydrochloride) 6 reduction of 1-methyl-l-nitrocyclohexane (63%) 6 Schmidt reaction with 1-methylcyclohexanecarboxylic acid (42%).6... 

Hofmann reaction, 76 320. See also Hoffman reaction Hofmann rearrangement, 77 741 Hofmann-type inclusion compounds, 74 171-172... 

Further Experiments.—A solution of urea is made alkaline with sodium hydroxide solution and is then shaken with a few drops of bromine. Nitrogen is evolved. Compare, in this connexion, the Hofmann reaction (p. 155). 

By the action of hypobromite on the —CONH2-group one hydrogen atom of the NH2-group is replaced by bromine. The first product of the Hofmann reaction, the N-bromoamide, can be isolated in certain cases. 

The reaction of Curtius, which is especially to be preferred in the case of the higher members on account of the favourable solubilities of the intermediate products, involves as its first stage the preparation of the hydrazide from an ester (or acid chloride). The hydrazide is then converted, usually very readily, by the action of nitrous acid into the azide. In many cases it is more convenient to prepare the azide by treating an acid chloride with sodium azide previously activated with hydrazine hydrate.1 Azides easily undergo thermal decomposition, the two azo nitrogen atoms being eliminated as elementary nitrogen. In this way, however, the same radicle is formed as was invoked above to explain the Hofmann reaction ... 

An important application of the Hofmann reaction occurs in the first technical synthesis of indigo and consists in the degradation of phthalimide to anthranilic add. See p. 372. 

The stability of the base resins produced by the Hofmann reaction was tested by shaking 2.0g lots of H16 in 50 ml of 2% NaOH, 10% NaCl solution. The amine capacity decreased with time as shown in Table III. Because of this instability and the relatively low amine capacities attained, the products were not suitable for the intended applications. 

Origin of Catalyst Decomposition. The dependence of crosslink density reduction on catalyst concentration suggests that the catalyst decomposes during devulcanization. The Hofmann reaction (Equation 1) is a prime suspect under these conditions. 

Hofmann reaction org chem A reaction in which amides are degraded by treatment with bromine and alkali (caustic soda) to amines containing one less carbon used commercially in the production of nylon. haf-mon re,ak-sh3n )... 

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