3-Benzoyl[b]benzofurans are structural cores to a host of bioactive molecules in pharmaceutical use or development. Representative examples include amiodarone, a clinically used drug for controlling intractable cardiac arrhythmias, LY 320135, a potent cannabinoid CB1 receptor antagonist, and benzbromarone, an uricosuric agent. Numerous approaches to the benzofurane scaffold have been disclosed in the literature. Most synthetic approaches to 2,3-disubstituted benzofurans introduce the C3-substituent on the preformed benzo[b]furan ring at the end of the synthesis. Traditionally, the simple and straightforward method for the C3 acylation of benzofurans appeared to be the Friedel-Craft reaction using acylchlorides. However this method suffer from some limitations e.g. the poor regioselectivity, especially when strongly deactivated acylchloride are used. In the course of our program directed at the synthesis of novel MAO inhibitors, we planned to synthesize 2-phenylbenzofuranes using the intramolecular Wittig procedure due to its ease and simplicity. Using this procedure, we found that the GC/MS analysis of the crude reaction mixture revealed, together with the desired product of cyclization (2-phenylbenzofuran), one unexpected side product, which, after extensive analysis by NMR and mass spectrometry, turned out to be the 2-phenyl-3-benzoyl benzofurane. In this scenario, our findings could be extended to design and develop new potentially therapeutic molecules, especially useful in neurodegenerative diseases.

Synthesis of 2-Phenyl-3-benzoylbenzofurans under Wittig Conditions

DELOGU, GIOVANNA LUCIA;BEGALA, MICHELA
2016

Abstract

3-Benzoyl[b]benzofurans are structural cores to a host of bioactive molecules in pharmaceutical use or development. Representative examples include amiodarone, a clinically used drug for controlling intractable cardiac arrhythmias, LY 320135, a potent cannabinoid CB1 receptor antagonist, and benzbromarone, an uricosuric agent. Numerous approaches to the benzofurane scaffold have been disclosed in the literature. Most synthetic approaches to 2,3-disubstituted benzofurans introduce the C3-substituent on the preformed benzo[b]furan ring at the end of the synthesis. Traditionally, the simple and straightforward method for the C3 acylation of benzofurans appeared to be the Friedel-Craft reaction using acylchlorides. However this method suffer from some limitations e.g. the poor regioselectivity, especially when strongly deactivated acylchloride are used. In the course of our program directed at the synthesis of novel MAO inhibitors, we planned to synthesize 2-phenylbenzofuranes using the intramolecular Wittig procedure due to its ease and simplicity. Using this procedure, we found that the GC/MS analysis of the crude reaction mixture revealed, together with the desired product of cyclization (2-phenylbenzofuran), one unexpected side product, which, after extensive analysis by NMR and mass spectrometry, turned out to be the 2-phenyl-3-benzoyl benzofurane. In this scenario, our findings could be extended to design and develop new potentially therapeutic molecules, especially useful in neurodegenerative diseases.
Synthetic method; 3-Aroylbenzofuranes; Intramolecular Wittig reaction
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/184342
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