Hofmann Degradation

Definition:

Formation of an olefin and a tertiary amine (Exhaustive Methylation) by pyrolysis of a quaternary ammonium hydroxide:

Frequency of appearance:

        This bar graph represents all of the online articles that were found to contain this specific name reaction in the title of the article. Tetrahedron letters, Tetrahedron, Synthetic letters, Synthesis, Journal of Organic Chemistry and Journal of the American Chemical Society are represented here. This table by no means represents the periodicity of the name reaction found in the literature.

Original References:

1. Hofmann, A.W. Ann., 1851, 78, 253.
2. Hofmann, A.W. Ann., 1851, 79, 2203.
3. Hofmann, A.W. Ber., 1881, 14, 659.

Recent academic references: Click here for more references

4. Synthesis of enantiomerically pure morphine alkaloids: The hydrophenanthrene route

• Trauner, D.; Bats, J. W.; Werner, A.; Mulzer, J.; J. Org. Chem.; 1998; 63(17); 5908-5918.  

• Berkes, D.; Netchitailo, P.;* Morel, J.; Decroix, B. Synth. Commun., 1998, 28, 949-956.

Recent process references:

6. Isoquinoline Alkaloids. 3. Synthesis of the 6-Ethyl and 6-Butyl Analogs of d,l-6-Methyl-5,6,6a,7-tetrahydro-1,2,9,10-tetramethoxy-4H-dibenzo[de,g]- quinoline 1.5 Phosphate (d,l-Glaucine 1.5 Phosphate)

• Goralski, C. T.; Hasha, D. L.; Henton D. R.; Peet, N. P.;
  Org. Process Res. Dev.; 1997; 1(4); 280-286.  

 

Mechanism: http://www.arkat.org/arkat/journal/Named Reactions/Hofmann.htm

Scope and Limitations:

• Primary, secondary and tertiary amines are subject to elimination.
• Reaction often takes place at elevated temperatures (100-200 C) and reduced pressures. ^A+B
• Aqueous or alcoholic solution is often employed. ^A
• Elimination proceeds via an E2 elimination pathway. ^{A+ B}
• Elimination also follows the Hofmann rule: least substituted alkenes will form preferentially. ^{A+ B}
• Side products may include alcohols as the substitution product. ^A

Synonyms:

• Hofmann elimination, exhaustive (methylation) elimination