Accelerated microdroplet synthesis of benzimidazoles by nucleophilic addition to protonated carboxylic acids.

Chemical Science
Pallab BasuriR Graham Cooks

Abstract

We report a metal-free novel route for the accelerated synthesis of benzimidazole and its derivatives in the ambient atmosphere. The synthetic procedure involves 1,2-aromatic diamines and alkyl or aryl carboxylic acids reacting in electrostatically charged microdroplets generated using a nano-electrospray (nESI) ion source. The reactions are accelerated by orders of magnitude in comparison to the bulk. No other acid, base or catalyst is used. Online analysis of the microdroplet accelerated reaction products is performed by mass spectrometry. We provide evidence for an acid catalyzed reaction mechanism based on identification of the intermediate arylamides. Their dehydration to give benzimidazoles occurs in a subsequent thermally enhanced step. It is suggested that the extraordinary acidity at the droplet surface allows the carboxylic acid to function as a C-centered electrophile. Comparisons of this methodology with data from thin film and bulk synthesis lead to the proposal of three key steps in the reaction: (i) formation of an unusual reagent (protonated carboxylic acid) because of the extraordinary conditions at the droplet interface, (ii) accelerated bimolecular reaction because of limited solvation at the interface and (i...Continue Reading

References

Nov 1, 1985·Digestive Diseases and Sciences·A Bettarello
Mar 29, 2006·Proceedings of the National Academy of Sciences of the United States of America·Martin J Warren
Apr 3, 2010·Bioorganic & Medicinal Chemistry·Michele TonelliPaolo La Colla
Mar 20, 2012·Journal of the American Society for Mass Spectrometry·Abraham K Badu-TawiahR Graham Cooks
Oct 4, 2012·The Journal of Organic Chemistry·Jessie E R SadigMichael C Willis
Feb 20, 2013·Journal of Agricultural and Food Chemistry·Yu-Bin BaiJin-Ming Gao
Apr 4, 2014·Chemical Society Reviews·Chuan-Ling Zhang, Shu-Hong Yu
Jan 15, 2015·The Journal of Organic Chemistry·Devulapally MaheshTharmalingam Punniyamurthy
Oct 10, 2015·Angewandte Chemie·Shibdas Banerjee, Richard N Zare
Oct 29, 2015·Chemical Society Reviews·Tim CernakShane W Krska
Dec 23, 2015·ACS Applied Materials & Interfaces·Rounak NaphadeSatishchandra B Ogale
Jan 21, 2016·Advanced Materials·Depanjan SarkarThalappil Pradeep
Jul 29, 2016·Angewandte Chemie·Ryan M BainR Graham Cooks
Oct 1, 2016·Chemical Reviews·Paula Ruiz-Castillo, Stephen L Buchwald
Jan 25, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Alessia BinoSilvia Vertuani
Feb 15, 2017·Journal of the American Society for Mass Spectrometry·Ryan M BainR Graham Cooks
Oct 11, 2017·Angewandte Chemie·Ryan M BainRichard N Zare
Nov 28, 2017·BMC Veterinary Research·Lauren Hubert Jaeger, Filipe Anibal Carvalho-Costa
Jun 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Haoran WeiPeter J Vikesland
Apr 25, 2019·Nature Communications·Alain ReiserRalph Spolenak
Jun 28, 2019·Journal of the American Chemical Society·Jae Kyoo LeeRichard N Zare
Aug 9, 2019·Journal of the American Society for Mass Spectrometry·Patrick W FedickR Graham Cooks
Aug 23, 2019·The Journal of Physical Chemistry. a·Shibdas Banerjee, Richard N Zare
Dec 15, 2019·Angewandte Chemie·Elumalai GnanamaniRichard N Zare
Feb 12, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Yong YangMichael R Zachariah
Feb 29, 2020·Chemical Science·Chengyuan LiuRichard N Zare
May 27, 2020·The Journal of Physical Chemistry. a·Namita NarendraTillmann Kubis

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Citations

Feb 17, 2021·Analytical Chemistry·Pengyi ZhaoHao Chen
Mar 27, 2021·The Journal of Physical Chemistry. a·Martin Mayer, Knut R Asmis
Jun 15, 2021·Chemical Science·Jaya Mehara, Jana Roithová

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Methods Mentioned

BETA
NMR
column chromatography

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