Hofmann rearrangement
The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one fewer carbon atom.[1][2][3]
The reaction is named after its discoverer: August Wilhelm von Hofmann. This reaction is also sometimes called the Hofmann degradation, and should not be confused with the Hofmann elimination.
Contents |
[edit] Mechanism
The reaction of bromine with sodium hydroxide forms sodium hypobromite in situ, which transforms the primary amide into an intermediate isocyanate. The intermediate isocyanate is hydrolyzed to a primary amine, giving off carbon dioxide.
[edit] Variations
Several reagents can substitute for bromine. N-Bromosuccinimide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) can effect a Hofmann rearrangement. In the following example, the intermediate isocyanate is trapped by methanol, forming a carbamate.[4]
In a similar fashion, the intermediate isocyanate can be trapped by tert-butanol, yielding the t-butoxycarbonyl (Boc)-protected amine.
A mild alternative to bromine is also (bis(trifluoroacetoxy)iodo)benzene.[5]
[edit] Applications
- 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
- The Symmetrical structure of α-phenyl propanamide does not change after hofmann reaction.
[edit] See also
- Beckmann rearrangement
- Curtius rearrangement
- Iodoform reaction
- Lossen rearrangement
- Schmidt reaction
- Weerman degradation
[edit] References
- ^ Hofmann, A. W. v. (1881). Ber. 14: 2725.
- ^ Wallis, E. S.; Lane, J. F. (1949). Org. React. 3: 267–306.
- ^ Shioiri, T. (1991). Comp. Org. Syn. 6: 800–806.
- ^ Keillor, J. W.; Huang, X. (2004), "Methyl Carbamate Formation via Modified Hofmann Rearrangement Reactions: Methyl N-(p-Methoxyphenyl)carbamate", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v78p0234; Coll. Vol. 10: 549
- ^ Almond, M. R.; Stimmel, J. B.; Thompson, E. A.; Loudon, G.M. (1993), "Hofmann Rearrangement under Mildly Acidic Conditions using [I,I-Bis(Trifluoroacetoxy)]iodobenzene: Cyclobutylamine Hydrochloride from Cyclobutanecarboxamide", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv8p0132; Coll. Vol. 8: 132
[edit] External links
[edit] Bibliography
- Clayden, Jonnathan (2007). Organic Chemistry. Oxfort University Press Inc.. pp. 1073. ISBN 978-0-19-850346-0.
- Fieser, Louis F. (1962). Advanced Organic Chemistry. Reinhold Publishing Corporation, Chapman & Hall, Ltd.. pp. 499–501.
