Gabriel-Colman rearrangement

What is Gabriel-Colman rearrangement?

The Gabriel-Colman rearrangement, also known as the Gabriel isoquinoline synthesis,  or phthalimidoacetic ester → isoquinoline rearrangement, is a reaction first reported in 1900 by Gabriel and Colman. This reaction involves the rearrangement of alkyl phthalimidoacetate to form isoquinoline derivatives (or substituted benzothiazines) using alkoxide treatment. However, it is limited to phthalimido derivatives that have an enolizable carbon attached to nitrogen.

Gabriel-Coleman rearrangement - phthalimidoacetic ester → isoquinoline rearrangement - Gabriel isoquinoline synthesis
Gabriel-Colman rearrangement
Gabriel-Coleman rearrangement - phthalimidoacetic ester → isoquinoline rearrangement - Gabriel isoquinoline synthesis
Gabriel-Colman rearrangement

R = alkyl, aryl, OH, etc. (see list of acronyms)

The Gabriel-Colman rearrangement is triggered by the action of alkoxides on phthalimidoacetic or saccharin esters or ketones.

During the reaction, the phthalimido ring is cleaved and closed at the methylene carbon to produce 3-carboethoxy-4-hydroxyisocarbostyril as the ultimate product. For phthalyl derivatives of amino acids other than glycine, the corresponding products are 3-alkyl (or aryl)-4-hydroxyisocarbostyrils. The product formed depends on the reaction conditions; under acidic conditions, 3-carboethoxyl-4-hydroxyisocarbostyril is predominant, while under neutral conditions, the tetrahydroisoquinolinedione dominates.

References

Shares