Regioselective and efficient halogenation of 4, 5-unsubstituted alkyl 3-hydroxypyrrole/3-hydroxythiophene-2-yl-carboxylates. Issue 26 (28th June 2017)

• Record Type: Journal Article
• Authors: Castillo-Aguilera, Omar; Depreux, Patrick; Halby, Ludovic; Azaroual, Nathalie; Arimondo, Paola B.; Goossens, Laurence
• Is Part Of: Tetrahedron letters. Volume 58:Issue 26(2017)
• Page Start: 2537
• Page End: 2541
• Publication Date: 2017-06-28
• Subjects: Halogenation -- 3-Hydroxypyrrole -- 3-Hydroxythiophene -- Monobromination -- Monochlorination; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2017.05.025
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Substituted heterocycles, such as pyrrole and thiophene, are commonly found in the field of pharmaceutical and material sciences. Here we studied the reactivity of 4, 5-unsubstituted alkyl 3-hydroxypyrrol-2-yl-carboxylates and 4, 5-unsubstituted alkyl 3-hydroxythiophen-2-yl-carboxylates in different halogenation conditions, due to their interest as building blocks in the synthesis of bioactive compounds and materials. We describe herein the regioselective monohalogenation of 3-hydroxypyrroles and 3-hydroxythiophenes in mild conditions with common halogenation agents. The selectivity of the halogenation was studied. Optimized one-step reaction conditions were found for monobromination and monochlorination. Finally, we observed that bromination with N -bromosuccinimide (NBS) took place at the C4 position of the heterocycle, while chlorination with SO2 Cl2 led to C5-halogenated derivatives. Highlights: Reactivity of 3-hydroxypyrrole/thiophene in different mild halogenation conditions. Regioselective monohalogenation of 3-hydroxypyrroles and 3-hydroxythiophenes. One-step reaction for monobromination/monochlorination of hydroxyheterocycles. Abstract: Substituted heterocycles, such as pyrrole and thiophene, are commonly found in the field of pharmaceutical and material sciences. Here we studied the reactivity of 4, 5-unsubstituted alkyl 3-hydroxypyrrol-2-yl-carboxylates and 4, 5-unsubstituted alkyl 3-hydroxythiophen-2-yl-carboxylates in different halogenation conditions, due to their interest as building blocks in the synthesis of bioactive compounds and materials. We describe herein the regioselective monohalogenation of 3-hydroxypyrroles and 3-hydroxythiophenes in mild conditions with common halogenation agents. The selectivity of the halogenation was studied. Optimized one-step reaction conditions were found for monobromination and monochlorination. Finally, we observed that bromination with N -bromosuccinimide (NBS) took place at the C4 position of the heterocycle, while chlorination with SO2 Cl2 led to C5-halogenated derivatives.