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WANG ET AL.
3 | EXPERIMENTAL
FUNDING INFORMATION
Shandong Province Higher Educational Science and
Technology Program, Grant/Award Number: J16LC13.
Flame-dried 4 Å MS (0.75 g), acid derivative (1 mmol),
amine derivative (1.2 mmol), TiCp2Cl2 (10 mol% of the
acid) and dry THF (10 mL) was placed in an oven-dried
vial equipped with a stirring bar and sealed with a crimp-
on cap. The atmosphere was exchanged for Ar. The
resulting mixture was stirred at 70 ꢀC for 24 hr, after that,
the mixture was cooled to room temperature, filtered, the
filter cake was washed with dichloromethane (3 × 5 mL),
the filtrate was combined and evaporated to dryness, the
residue was purified by flash column to gain the pure
amide.
ORCID
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4 | CONCLUSION
Due to its mild and environmentally friendly features,
catalytic direct amidation using cheap, eco-friendly and
stable catalyst is of great interest in the industry and lab
scale synthesis of amide. The method presented herein is
the first report of TiCp2Cl2-catalyzed protocol for the
direct amidation of non-activated carboxylic acid deriva-
tives with amines. The method afforded amides in mod-
erate to excellent yields depending on the type of
substrate acids and amines, and the enantiomeric purity
of the asymmetric starting materials was retained. The
reaction yield was significantly affected by the steric and
electronic nature of the phenylacetic acid substrates,
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4 Å molecular sieves. The reaction conditions tolerate a
significant number of structurally different acid
substrates including heteroaromatic, aliphatic, α-
halogenerate and α-substituted carboxylic acids, as well
as aminoacids. The possible mechanism of the catalytic
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NOTES
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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We gratefully acknowledge the Shandong Province
Higher Educational Science and Technology Program
(No.J16LC13) for financial support.
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[24] M. E. D. Tharwat, E. William, B. Yohann, R. Jacques,
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SUPPORTING INFORMATION AVAILABLE
Experimental procedures, compound characterization
data and original NMR and HRMS spectrum.