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Biography Major Discoveries Similar Reactions Reaction Scheme and Mechanism Examples Applications of Hoffmann Rearrangement Reaction
Major Discoveries
Hofmann was the first to introduce molecular models into his public lectures around 1860 Hofmann elimination Hofmanns rule Hofmann rearrangement
Similar Reactions
Citrus Rearrangement
Lossen Rearrangement
Schmidt Rearrangement
Reaction Scheme
In the presence of a strong base, primary amides react with chlorine or bromine to form shortened amines, with the loss of the carbonyl carbon atom. This reaction, called the Hoffmann rearrangement, is used to synthesize primary and aryl amines. The Hofmann rearrangement of 10 amides provides 10 amines exclusively, with no contamination from 20 or 30 amines. This reaction also can be useful for shortening a carbon chain, which explains why it is sometimes referred to as a Hoffmann degradation.
In the Hofmann rearrangement, an unsubstituted amide is treated with sodium hypobromite (or sodium hydroxide and bromine, which is essentially the same thing) to give a primary amine that has one carbon fewer than the starting amide. The actual product is the isocyanate, but this compound is seldom isolated since it is usually hydrolyzed under the reaction conditions. The R group may be alkyl or aryl, but if it is an alkyl group of more than about six or seven carbons, low yields are obtained unless Br2 and NaOMe are used instead of Br2 and NaOH. Another modification uses NBS/NaOMe. Under these conditions the product of addition to the isocyanate is the carbamate RNHCOOMe, which is easily isolated or can be hydrolyzed to the amine. Side reactions when NaOH is the base are formation of ureas RNHCONHR and acylureas RCONHCONHR by addition, respectively, of RNH2 and RCONH2 to RNCO. If acylureas are desired, they can be made the main products by using only one-half of the usual quantities of Br2 and NaOH. Another side product, but only from primary R, is the nitrile derived from oxidation of RNH2.
Source: Smith. M. B., & March . J. (2007). Marchs Advanced Organic Chemistry Reactions, Mechanisms, and Structure. 6th Edition. Chapter 18, 1.2REARRANGEMENTS. p. 1607
Several reagents can substitute for bromine. N-Bromosuccinimide and 1,8-Diazabicyclo[5.4.0]undec-7ene (DBU) can effect a Hofmann rearrangement. In the following example, the intermediate isocyanate is trapped by methanol forming a carbamate. A mild alternative to bromine is also bis(trifluoroacetoxy)iodo)benzene. (Source: http://www.kuwait-md.org/?q=node/1121)