Comforth rearrangement

What is Comforth rearrangement?

The Cornforth rearrangement is a process where 4-carbonyl substituted oxazoles undergo thermal interconversion with exchange between the C-C-O side-chain and the C-C-O fragment of the oxazole ring, typically involving compounds where a heteroatom (-OR, -SR, -Cl) is attached to the 5-position (R2) of the initial oxazole.

Comforth rearrangement - general reaction scheme
Comforth rearrangement (general reaction scheme)

In 1949, Cornforth observed that upon heating, 2-phenyl-5-ethoxyoxazole-4-carboxamide (1) underwent rearrangement to form ethyl 2-phenyl-5-aminooxazole-4-carboxylate (2).

Comforth rearrangement - 2-phenyl-5-ethoxyoxazole-4-carboxamide - ethyl 2-phenyl-5-aminooxazole-4-carboxylate - original reaction
Comforth rearrangement (original reaction)

References

Cornforth, J. W. In The Chemistry of Penicillin, Princeton University Press: Princeton, N.J. 1949, p 700.

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