Categories: C-N Bond Formation >
Synthesis of amidines
2,2,2-Trifluoro- and trichloroethyl imidates, which are easily prepared by reaction of a nitrile and a trihaloethanol in the presence of HCl, are excellent reagents for the preparation of amidines under mild reaction conditions.
S. Caron, L. Wei, J. Douville, A. Ghosh, J. Org. Chem., 2010, 75, 945-947.
A method for the Pd-catalyzed N-arylation of both aryl and alkyl amidines with a wide range of aryl bromides, chlorides, and triflates proceeds in short reaction times and with excellent selectivity for monoarylation. A one-pot synthesis of quinazoline derivatives via Pd-catalyzed N-arylation followed by addition of an aldehyde to the crude reaction mixture is also demonstrated.
M. A. McGowan, C. Z. McAvoy, S. L. Buchwald, Org. Lett., 2012, 14, 3800-3803.
Microwave reactions of primary and secondary amines with imidoylbenzotriazoles gave various polysubstituted amidines in good yields. Convenient preparations of a variety of amides and imidoylbenzotriazoles have also been developed using microwave irradiation under mild conditions and short reaction times.
A. R. Katritzky, C. Cai, S. K. Singh, J. Org. Chem., 2006, 71, 3375-3380.
The reaction of hexamethyldisilazane with formamides and sulfonamides provides sulfonylformamidines. This protocol can also be applied for arylformamidine formation with anilines as substrates under optimized conditions. The advantages of this method are high efficiency, good yields, and applicability in large-scale operations.
Y.-C. Chou, W.-H. Lin, X.-Y. Lin, C.-L. Kuo, W.-Q. Zeng, I.-C. Lu, C.-F. Liang, J. Org. Chem., 2022, 87, 15327-15332.
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.
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.
A catalyst-free hydroamination of N,N-disulfonyl ynamides with amines gives N-sulfonylamidines. Alkyl amines react with N,N-disulfonyl ynamides under mild conditions, whereas aryl amines require higher temperatures.
Y. Kong, L. Yu, J. Cao, Synthesis, 2014, 46, 183-188.
A silver-catalyzed or metal-free thermally promoted denitrogenation of N-sulfonyl-1,2,3-triazoles enables a highly efficient synthesis of N-sulfonylamidines in the presence of amines.
Y. Feng, W. Zhou, G. Sun, P. Liao, X. Bi, X. Li, Synthesis, 2017, 49, 1371-1379.
A N-trifluoromethylation of nitriles with PhICF3Cl followed by DMAP-catalyzed capture with N-, O-, or S-centered nucleophiles enables an efficient synthesis of a wide range of N-CF3 amidines, imidates, and thioimidates.
R. Z. Zhang, W. Huang, R. X. Zhang, C. Xu, M. Wang, J. Sun, Org. Lett., 2022, 24, 2393-2398.
Organic azides are easily and chemoselectively reduced to the corresponding amines by reaction with dichloroindium hydride under very mild conditions. γ-Azidonitriles give pyrrolidin-2-imines in an outstanding cyclization.
L. Benati, G. Bencivenni, R. Leardini, D. Nanni, M. Minozzi, P. Spagnolo, R. Scialpi, G. Zanardi, Org. Lett., 2006, 8, 2499-2502.
Copper-catalyzed cross-coupling reactions of amidine salts with aryl iodides give monoarylated amidines in good yields under ligand-free conditions. DMF was the superior solvent for the N-arylation of benzamidines, while MeCN was used in the formation of N-aryl amidines in good yield.
M. Cortes-Salva, C. Garvin, J. C. Antilla, J. Org. Chem., 2011, 76, 1456-1459.