Hoffmann Rearrangement Amber Julius Aroo Aroosa sa Shah Shahid id 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
Biography
of August Wilhelm von Hoffmann Born
8 April 1818 Giessen, 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, 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
Reaction Scheme
Amide reacts with Br 2 and base
Rearranges to lose carbonyl carbon making chain 1 carbon shorter
First published 1881 Hofmann, A. W. Chem. Ber. 1881, 14, 2725.
Gives high yields of arylamines and alkylamines
Hoffmann Rearrangement of Amides
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 H offmann 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 H offmann degradation.
Mechanism of the Hofmann Rearrangement: Steps 1 and 2
Mechanism of the Hofmann Rearrangement: Steps 3 and 4
Summarizing
the Hoffmann rearrangement mechanism
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 Br 2 and NaOMe are used instead of Br 2 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 RNH 2 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 Br 2 and NaOH. Source: Smith.
Another side product, but only from primary R, is the nitrile derived from oxidation of RNH2.
M. B., & March . J. (2007). March¶s Advanced Org anic Chemi stry Reactions, Mechanisms, and Structure. 6th Edition. Chapter 18, 1.2REARRANGEMENTS. p. 1607
Examples of reactions involving Hoffmann rearrangement
Examples of reactions involving Hoffmann rearrangement (Contd.)
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 )
Applications of Hoffmann rearrangement reactions
Aliphatic & aromatic amides are converted into aliphatic and aromatic amines, 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. ( Dirk Landberg, Markus K al esse)
