Amides, Hofmann reaction

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

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. 

Our recent studies on effective bromination and oxidation using benzyltrimethylammonium tribromide (BTMA Br3), stable solid, are described. Those involve electrophilic bromination of aromatic compounds such as phenols, aromatic amines, aromatic ethers, acetanilides, arenes, and thiophene, a-bromination of arenes and acetophenones, and also bromo-addition to alkenes by the use of BTMA Br3. Furthermore, oxidation of alcohols, ethers, 1,4-benzenediols, hindered phenols, primary amines, hydrazo compounds, sulfides, and thiols, haloform reaction of methylketones, N-bromination of amides, Hofmann degradation of amides, and preparation of acylureas and carbamates by the use of BTMA Br3 are also presented. 

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. 

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 )... 

Amino-l-phenylpropane (8.1.2.2) is also synthesized in a Hofmann reaction from a-benzylpropionic acid amide [4,5]. 

The above procedure is essentially that of Ullmann and Bleier.2 2-Aminobenzophenone has also been prepared by reduction of 2-nitrobenzophenone,3 by the Hofmann reaction of the amide of o-benzoylbenzoic acid with sodium hypobromite,4 by the action of an excess of benzoyl chloride on aniline at 220°,6 and by hydrolysis of the acetyl derivative which is obtained by the action of phenylmagnesium bromide on 2-methyl-3,l,4-benzoxaz-4-one (from anthranilic acid and acetic anhydride).6 Various methods for the preparation of 2-aminobenzophenones have been summarized critically by Simpson, Atkinson, Schofield, and Stephenson.7... 

From the chloride of the monobasic acid the amide can be eaeily obtained ana fiom this oy the usual Hofmann reaction the cycloprop. ns amine, ... 

The conversion of an amide in this way is termed the Hofmann reaction or the Hofmann rearrangement. The mechanism of the reaction involves an intramolecular 1,2-carbon-to-nitrogen nucleophilic shift of the alkyl (or aryl) group... 

For the preparation of anthranilic acid the starting material is phthalimide, the cyclic imide ring of which is opened by alkaline hydrolysis in the first step of the reaction to give the sodium salt of phthalimidic acid (the half amide of phthalic acid). The intermediate undergoes the Hofmann reaction in the manner outlined on p. 783 yielding o-aminobenzoic acid (anthranilic acid). 

Another example is the Hofmann reaction in which an amide is converted to an amine having one fewer carbon atoms (Equation 2.6 and Scheme 2.11). The reaction is usually initiated by adding the amide to cold alkaline sodium hypobromite solution (bromine and aqueous NaOH), followed by rapid warming [22] ... 

Answer Procedures XI-3, which requires an amide and Hint (lie desired amine contains the grouping N-CHa-, and procedure XI-4, which is the Hofmann reaction. Let us use procedure XI-3. The student may prepare Xl b via procedure XI-4 as an exercise. 

The amides of pyrazine-2-carboxylic acids and -2,3-dicarboxylic acids undergo the Hofmann reaction. In the case of the conversion of pyrazinamide to aminopyrazine (Scheme 20), the intermediate sodium carbamate can be isolated.219 Pyrazinamides react with phosphoryl chloride to give the corresponding cyanopyra-... 

The Hofmann and Curtius reactions as applied to both the mono-and diamides and hydrazides have been reported. Marquardt found that a low yield of the amine can be obtained in the Hofmann reaction of l,2,5-thiadiazole-3-carboxamide. The main side reaction was hydrolysis of the electron-deficient amide to the carboxylic acid. Under the same conditions the dicarboxamide (78) formed the amino acid (16b). Attempts to prepare diaminothiadiazole via the Hofmann reaction of the amino amide (16a) resulted only in amide hydrolysis and the formation of the same amino acid. 

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... 

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. ... 

Imidazole-4-carboxamides do not take part in the Hofmann reaction. 5-Aminoimidazole-4-carboxamide forms a fairly stable diazocarboxamide when treated with nitrous acid under acid, basic or neutral aqueous conditions this product cyclizes to a triazine. Amide functions can be converted into thioamide which is then susceptible to methylation on the sulfur atom. 

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