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Chemical Science
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ARTICLE
Journal Name
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addition of base to complete the product formation. Online
mass spectrometric monitoring enables detection of reaction
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mechanism. Ten examples are shown to illustrate the scope of
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The described mechanism of benzimidazole synthesis has
three elements: (i) the formation of a highly reactive reagent
because of the extraordinary conditions in at the interface
(protonated of the carboxylic acid), (ii) the accelerated
bimolecular reaction because of limited solvation at the
interface and (iii) the thermally assisted elimination of water.
Point (i) is supported by the effect of adding water to the
methanol solvent. Point (ii) is suggested by analogy to other
organic solvent droplet reactions where this mechanism is
supported by experimental and recent computations.53 Point
(iii) is shown directly by the experiments. Note that bimolecular
reaction acceleration is seen in formation of the intermediate
amide and that the thermal elimination of water is a subsequent
and secondary factor. We think that many other droplet-
accelerated reactions will contain some elements in common
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Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
PB thanks IIT Madras and acknowledges a visiting doctoral
fellowship from the Science and Engineering Board of India. RGC
acknowledges support of the US National Science Foundation
(1908057).
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8 | J. Name., 2012, 00, 1-3
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