Twice as Nice: The Duff Formylation of Umbelliferone Revised.

Vladislav V Skarga,Vadim V Negrebetsky,Yuri I Baukov,Mikhail V Malakhov

doi:10.3390/molecules26247482

Vladislav V Skarga, Vadim V Negrebetsky + Show 2 more

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https://doi.org/10.3390/molecules26247482

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Abstract

More efficient and preferably more convenient and greener synthetic solutions in coumarin scaffold functionalization are in steady demand. The Duff ortho-formylation of unsubstituted umbelliferone was revised in this study. The reaction conditions were optimized based upon data from the literature analysis and resulted in unexpectedly rapid ortho-formylation of umbelliferone, yielding a mixture of ortho-formyl position isomers. Thorough studies on the separation of ortho-formylated umbelliferones using chromatographic and recrystallization methods as well as the evaluation of their solubility in common organic solvents led to complete resolution of 8-formyl- and 6-formylumbelliferones. The precise protocol for simultaneous preparation, extraction, and purification of 8-formyl- and 6-formylumbelliferones is provided, and the prospective studies of biological and pharmacological activities of these compounds are synopsized.

Highlights

Coumarins are a large family of natural and synthetic compounds with a variety of biological activities and bioanalytical applications [1,2,3,4,5]
(8-FUmb) as a reference compound for the above-mentioned studies, we found it important to revise the Duff ortho-formylation of unsubstituted umbelliferone (Umb) and re-evaluate the 8-FUmb and 6-FUmb yields in this convenient and cost-effective reaction
Based upon of data the literature analysis concerning the methodology of the Duff ortho-formylation of umbelliferones

Summary

Introduction

Coumarins are a large family of natural and synthetic compounds with a variety of biological activities and bioanalytical applications [1,2,3,4,5]. The Duff reaction is an example of regioselective derivatization routinely used for ortho-formylation of aromatic phenols [8]. The Duff ortho-formylation of umbelliferones was numerously reported earlier [9,10,11,12,13,14,15,16,17,18,19], while the vast majority of reports were notably focused on the preparation of 8-formylumbelliferones, which are well-described and routinely used dyes. The data on the production of the 6-formylumbelliferones during the Duff reaction was nearly absent in literature [16,18]

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