Categories: C=N Bond Formation >
Synthesis of amidines
The condensation of primary amine with N,N-dimethylacetamide dimethyl acetal yields a mixture of acetamidine and imidate ester depending on the temperature, solvent, and structure of the primary amine. It is possible to suppress the formation of imidate ester by performing the reaction in the presence of excess dimethyl amine, yielding acetamidine as the exclusive product.
J. R. Harjani, C. Liang, P. G. Jessop, J. Org. Chem., 2011, 76, 1683-1691.
The reaction of enamines with azides proceeds under catalyst-free conditions and results in the formation of either sulfonyl amidine or β-amino sulfonyl enamine derivative in good yields.
T. Gao, M. Zhao, X. Meng, C. Li, B. Chen, Synlett, 2011, 1281-1284.
The addition of amines to nitriles catalyzed by ytterbium amides gives monosubstituted N-arylamidinates in good to excellent yields at 100°C under solvent-free conditions.
J. Wang, F. Xu, Q. Shen, Org. Lett., 2008, 10, 445-448.
A mild, metal-free, multicomponent reaction provides N-acyl amidines from nitroalkene derivatives, dibromo amides, and amines via formation of an initial α,α-dibromonitroalkane intermediate that can undergo C-C bond cleavage. This alternative approach toward N-acyl amidines enables rapid construction of amidine frameworks with high diversity and complexity.
M. Zhou, J. Li, C. Tian, X. Sun, X. Zhu, Y. Cheng, G. An, G. Li, J. Org. Chem., 2019, 84, 1015-1024.
NaI-catalyzed direct condensation of sulfonamides and formamides enables N-sulfonyl formamidine synthesis without hazardous reagents or transition-metal catalysts. The green methodology features high atom economy, operational simplicity, and good tolerance with diverse functional groups.
S. Chen, Y. Xu, X. Wan, Org. Lett., 2011, 13, 6152-6155.
A silver-catalyzed, one-pot, four-component reaction of terminal alkynes, TMSN3, sodium sulfinate, and sulfonyl azide provides amidines. A possible cascade reaction mechanism consists of alkyne hydroazidation, sulfonyl radical addition, 1,3-dipolar cycloaddition of TMSN3, and retro-1,3-dipolar cycloaddition.
B. Liu, Y. Ning, M. Virelli, G. Zanoni, E. A. Anderson, X. Bi, J. Am. Chem. Soc., 2019, 141, 1593-1598.
Cu-catalyzed aerobic oxidative three-component coupling of a terminal alkyne, secondary amine, and sulfonamide enables an efficient synthesis of amidines. The use of Cu(OTf)2 as catalyst produces amidines selectively via an initial oxidative coupling of the terminal alkyne with the secondary amine, followed by hydroamidation of the ynamine intermediate with the sulfonamide. Glaser-Hay alkyne homocoupling products are not observed.
J. Kim, S. S. Stahl, J. Org. Chem., 2015, 80, 2448-2454.
A highly efficient, mild, copper-catalyzed multicomponent reaction for the synthesis of N-sulfonylamidines has been developed. This reaction has an extremely wide scope with regard to all three coupling components of alkyne, sulfonyl azide, and amine. Two plausible mechanistic pathways are discussed.
I. Bae, H. Han, S. Chang, J. Am. Chem. Soc., 2005, 127, 2038-2039.
Yb(OTf)3 catalyzes a regioselective hydroamination of ynamides with anilines and p-toluenesulfonamide to provide a diverse range of amidines with good functional group tolerance in good yields.
X. Zeng, Q. Gu, W. Dai, Y. Xie, X. Liu, G. Wu, Synthesis, 2021, 53, 2889-2896.
Amidines can be prepared by reducing acylated amidoximes with potassium formate. This method has proved to be very simple and effective.
K. Nadrah, M. Sollner Dolenc, Synlett, 2007, 1257-1258.