3
aldehydes with electron-withdrawing groups, such as chloro,
fluoro, bromo, nitro, cyano, and trifluoromethyl groups gave
good to excellent yields (2d-2i, 2l, and 2m). Aryl aldehydes with
electron-donating groups, such as methyl (2j), methoxy (2k) and
dimethylamino (2n) also gave good yields. The low yield of
anthraldehyde (2q) could be attributed to steric hindrance. It is
noteworthy that dialdehyde-containing substrates, such as o-
phthalaldehyde (2p), also gave good yields. To our delight,
heterocyclic substrates, such as 4-pyridinecarboxaldehyde, 2-
thiophenecarboxaldehyde and 2-furaldehyde were converted into
the corresponding nitriles (2s-u). Alkyl aldehydes and α,β-
unsaturated aldehydes also underwent the transformation (2v and
2w).
is reduced to I- which participates in the oxidation of I- to I2
allowing the catalytic oxidation reaction to continue.
Scheme 1. Plausible reaction mechanism.
In conclusion, a novel method for the synthesis of nitriles
from aldehydes has been developed. Using NH3·H2O
/FeCl2/NaI/Na2S2O8, various nitriles bearing either electron-
withdrawing or electron-donating groups, such as fluoro, chloro,
bromo, alkyl, and alkoxy, were obtained in good to excellent
yields. Notably, the method was efficient for the preparation of
febuxostat and its intermediate, ethyl 2-[3-cyano-4-(2-
methylpropoxy) phenyl]-4-methyl-5-thiazolecarboxylate.
Table 4. Preparation of nitrile derivatives.a
Acknowledgments
The authors gratefully acknowledge the financial support of
the National Natural Science Foundation of China (No.
21576041). We also thank Prof. Baomin Wang and Dr. Yuming
Song for valuable discussions.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://
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