Written by J.A Dobado | Last Updated on September 15, 2025
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.
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
- Gabriel, S. and Colman, J. (1900), Ueber die Einwirkung von Natriumalkylaten auf Phtalylglycinester und dessen Homologe. [On the effect of sodium alkylates on phthalylglycine esters and its homologs.] Ber. Dtsch. Chem. Ges., 33: 980-995. https://doi.org/10.1002/cber.190003301172
- Gabriel, S. and Colman, J. (1900), Ueber 4-Oxyisocarbostyril. [On 4-oxyisocarbostyril.] Ber. Dtsch. Chem. Ges., 33: 996-1000. https://doi.org/10.1002/cber.190003301173
- Gabriel, S. and Colman, J. (1900), Ueber eine Umlagerung der Phtalimidoketone. [On a rearrangement of phthalimidoketones.] Ber. Dtsch. Chem. Ges., 33: 2630-2634. https://doi.org/10.1002/cber.190003302209
- Gabriel, S. and Colman, J. (1902), Ueber 4-Oxyisocarbostyril. II. [On 4-oxyisocarbostyril. II] Ber. Dtsch. Chem. Ges., 35: 2421-2430. https://doi.org/10.1002/cber.190203502222
Full Professor of Organic Chemistry at the University of Granada, with a long-standing research career in Computational Chemistry and molecular modeling and design.