Hoffmann Rearrangement

Amber Julius Aroosa Shahid Faisal Jamil
CHEM 443, January 16, 2012 Forman Christian College

Presentation Outline ‡ ‡ ‡ ‡ ‡ ‡ Biography Major Discoveries Similar Reactions Reaction Scheme and Mechanism Examples Applications of Hoffmann Rearrangement Reaction .

Germany Alma mater University of Gottingen Doctoral advisor Justus von Liebig Doctoral students Richard Abegg Adolf Pinner Fritz Haber Karl Friedrich von Auwers Rudolf Hugo Nietzki Ferdinand Tiemann Eugen Bamberger Died 5 May 1892 (aged 74) Berlin.Biography of August Wilhelm von Hoffmann Born 8 April 1818 Giessen. Germany .

Major Discoveries ‡ Hofmann was the first to introduce molecular models into his public lectures around 1860 ‡ Hofmann elimination ‡ Hofmann¶s rule ‡ Hofmann rearrangement .

Similar Reactions .

Citrus Rearrangement .

Lossen Rearrangement .

Schmidt Rearrangement .

Ber. 2725. . 14. 1881. A.Reaction Scheme Amide reacts with Br2 and base Rearranges to lose carbonyl carbon making chain 1 carbon shorter Gives high yields of arylamines and alkylamines ‡ First published 1881 Hofmann. Chem. W.

Hoffmann Rearrangement of Amides ‡ In the presence of a strong base. The Hofmann rearrangement of 10 amides provides 10 amines exclusively. This reaction. with the loss of the carbonyl carbon atom. called the Hoffmann rearrangement. primary amides react with chlorine or bromine to form shortened amines. which explains why it is sometimes referred to as a Hoffmann degradation. This reaction also can be useful for shortening a carbon chain. is used to synthesize primary and aryl amines. ‡ ‡ . with no contamination from 20 or 30 amines.

Mechanism of the Hofmann Rearrangement: Steps 1 and 2 .

Mechanism of the Hofmann Rearrangement: Steps 3 and 4 .

Summarizing the Hoffmann rearrangement mechanism .

respectively. Chapter 18. low yields are obtained unless Br2 and NaOMe are used instead of Br2 and NaOH. but only from primary R. 6th Edition. which is essentially the same thing) to give a primary amine that has one carbon fewer than the starting amide. M. 1607 . p. If acylureas are desired. but if it is an alkyl group of more than about six or seven carbons. Another side product. The actual product is the isocyanate. which is easily isolated or can be hydrolyzed to the amine. but this compound is seldom isolated since it is usually hydrolyzed under the reaction conditions. Side reactions when NaOH is the base are formation of ureas RNHCONHR and acylureas RCONHCONHR by addition..In the Hofmann rearrangement. they can be made the main products by using only one-half of the usual quantities of Br2 and NaOH. Source: Smith. of RNH2 and RCONH2 to RNCO. J. Mechanisms. Under these conditions the product of addition to the isocyanate is the carbamate RNHCOOMe. 1.2REARRANGEMENTS. & March . an unsubstituted amide is treated with sodium hypobromite (or sodium hydroxide and bromine. is the nitrile derived from oxidation of RNH2. and Structure. B. March¶s Advanced Organic Chemistry Reactions. Another modification uses NBS/NaOMe. (2007). The R group may be alkyl or aryl.

Examples of reactions involving Hoffmann rearrangement .

8-Diazabicyclo[5.0]undec-7ene (DBU) can effect a Hofmann rearrangement. In the following example. N-Bromosuccinimide and 1. (Source: http://www. the intermediate isocyanate is trapped by methanol forming a carbamate.4.) Several reagents can substitute for bromine.kuwait-md.org/?q=node/1121) .Examples of reactions involving Hoffmann rearrangement (Contd. A mild alternative to bromine is also bis(trifluoroacetoxy)iodo)benzene.

(Dirk Landberg.Applications of Hoffmann rearrangement reactions ‡ Aliphatic & aromatic amides are converted into aliphatic and aromatic amines. Markus Kalesse) . respectively ‡ In the preparations of Anthranilic Acid from Phthalimide ‡ Nicotinic acid is converted into 3-Amino pyridine ‡ Synthesis of Symmetrical Ureas by (Diacetoyxiodo)benzeneInduced Hoffmann Rearrangement.

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