Categories: Synthesis of N-Heterocycles >
Synthesis of pyridazines
A Lewis acid-mediated inverse electron demand Diels-Alder reaction between 3-monosubstituted s-tetrazine and silyl enol ethers provides functionalized pyridazines, including 3-bromo-pyridazines, with high regiocontrol.
S. D. Schnell, J. A. González, J. Sklyaruk, A. Linden, K. Gademann, J. Org. Chem., 2021, 86, 12008-12023.
An unexpected C-C bond cleavage in the absence of metal enables an efficient approach toward 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from simple and commercially available 1,3-dicarbonyl compounds and methyl ketones.
Q. Gao, Y. Zhu, M. Lian, M. Liu, J. Yuan, G. Yin, A. Wu, J. Org. Chem., 2012, 77, 9865-9870.
Cu(II)-catalyzed aerobic 6-endo-trig cyclizations provide 1,6-dihydropyridazines and pyridazines via the judicious choice of reaction solvent. Whereas 1,6-dihydropyridazines were obtained in good yields with MeCN as the reaction solvent, employment of AcOH directly afforded pyridazines in good yields.
Z. Fan, Z. Pan, L. Huang, J. Cheng, J. Org. Chem., 2019, 84, 4236-4245.
A copper-promoted 6-endo-trig cyclization of readily available β,γ-unsaturated hydrazones enables an efficient synthesis of a series of 1,6-dihydropyridazines with good yields, high functional group tolerance, and remarkable regioselectivity under mild conditions. Importantly, the 1,6-dihydropyridazines can be efficiently converted to biologically important pyridazines in the presence of NaOH.
Y.-Q. Guo, M.-N. Zhao, Z.-H. Ren, Z.-H. Guan, Org. Lett., 2018, 20, 3337-3340.
A TBAI/K2S2O8-promoted [4 + 2] annulation of ketene N,S-acetals, and N-tosylhydrazones provides a variety of trisubstituted pyridazines in good yields. The method offers a broad substrate scope and a good functional group tolerance.
Z. Liu, J. Lou, J. Xiao, Org. Lett., 2021, 23, 1606-1610.
An aza-Diels-Alder reaction of 1,2,3-triazines with 1-propynylamines enables a highly regioselective synthesis of 6-aryl-pyridazin-3-amines in high yields under neutral conditions. This reaction offers good functional group compatibility, broad substrate scope and simple, metal-free, and neutral reaction conditions.
T. Kodama, I. Sasaki, H. Sugimura, J. Org. Chem., 2021, 86, 8926-8932.
The synthesis of pyridazinium salts was achieved from readily available phenylazosulfonates in a single reaction step via the formation of short-lived phenyldiazenes, which undergo a rapid cycloaddition to furans to give the desired products after elimination of water.
S. Gradl, J. Köckenberger, J. Oppl, M. Schiller, M. R. Heinrich, J. Org. Chem., 2021, 86, 6228-6238.