Organic Letters
Letter
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In cases where compounds were poorly soluble in H2O, we
used a cosolvent to achieve the flow hydrolysis process,
including 1° and 2° alcohols, THF, Me−THF, DME, acetone,
and cyclohexanone. These water-miscible solvents can be used
without affecting the reaction.
In conclusion we have reported a sustainable, mild, and
efficient flow process for the hydration of nitriles, whereby the
solution passed through the heterogeneous catalyst is
concentrated to give the amide product without further workup
or chromatographic purification. Remarkably negligible leach-
ing of the manganese catalyst was detected. The method can be
applied to heteroaromatic, aromatic, and aliphatic nitriles and
tolerated the presence of a wide range of functional groups,
including esters, aldehydes, Michael acceptors, and benzylic
alcohols. Additionally, the protocol is scalable to molar
quantities of material.
ASSOCIATED CONTENT
* Supporting Information
■
S
Characterization of compounds, data related to the catalyst and
the flow setup. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to Pfizer Worldwide Research and Develop-
ment (C.B. and J.M.H.) and the BP endowment (S.V.L.) for
financial support.
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