Hofmann degradation of amides

Subsequent chlorination of the amide takes place ia a two-phase reaction mixture (a dispersion of diamide ia hydrochloric acid) through which a chlorine stream is passed. The temperature of this step must be maintained below 10°C to retard the formation of the product resulting from the Hofmann degradation of amides. Reaction of the A/,A/-dichloroamide with diethylamine [109-89-7] ia the presence of base yields /n j -l,4-cyclohexane-bis-l,3-diethylurea (35), which is transformed to the urea hydrochloride and pyroly2ed to yield the diisocyanate (36). 

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. 

Fig. 31. N-Bromination of amides with BTMA Br3 Hofmann degradation of amides...

Fig. 32. Reaction scheme of the Hofmann degradation of amides with BTMA Br3 BTMA Bfj, rt or 70 C...

Amines have been prepared on insoluble supports by Hofmann degradation of amides [222] followed by hydrolysis of the intermediate isocyanates (Figure 10.5). One reagent suitable for this purpose is [bis(trifluoroacetoxy)iodo]benzene, which can be used both on cross-linked polystyrene [223] and on more hydrophilic supports such as polyacrylamides (Figure 10.6). Support-bound carboxylic acids can also be degraded via the acyl azides (Curtius degradation [224,225]) to yield isocyanates. 

Hoesch-Houben reaction, 321 Hofmann degradation of amides, 103, 296, 674... 

A number of methods involve the rearrangement of carboxylic acid derivatives via nitrenes. The best known of these is the Hofmann degradation of amides. This involves treating an amide with bromine and alkali. The A-bromo compound undergoes an a-elimination in the presence... 

As a method of synthesis of amines, the Hofmann degradation of amides has the special feature of yielding a product containing one less carbon than the starting material. As we can see, reaction involves migration of a group from carbonyl... 

Let us begin with a reaction that we encountered earlier as a method of synthesis of amines the Hofmann degradation of amides. Whatever the mechanism... 

Kajigaeshi, S., Asano, K., Fujisaki, S., Kakinami, T., Okamoto, T. Oxidation using quaternary ammonium poiyhaiides. i. An efficient method for the Hofmann degradation of amides by use of benzyitrimethyiammonium tribromide. Chem. Lett. 1989, 463-464. 

This process chemistry is analogous to the Hofmann degradation of amides to primary amines. However, due to several drawbacks including those of the Raschig process, the urea-based Schestakov process has not been employed commercially. 

A mixture of Br2 and NaOH produces Na -OBr, which is the reagent used in the Hofmann degradation of amides to primary amines. Hofmann degradation can be illustrated as ... 

This means the synthesis must employ a reaction that generates an amine of 1 less carbon from succinic anhydride. Such a reaction is the Hofmann degradation of amides. As seen below, the reaction involves the migration of a group from carbonyl carbon to the adjacent nitrogen atom. It is therefore an example of a molecular rearrangement. ... 

Azide ion, hexamethyienetetramine, or phthaiimide can be used as synthons for ammonia in amine synthesis by nucieophiiic substitution. The cyanide ion is a synthon for [HjNCHj] . Amines may be synthesized by reduction or Hofmann degradation of amides. 

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