An efficient three-component preparation of 4-acylpyrazoles
Pyrazoles constitute an essential class of natural and synthetic heterocyclic compounds exhibiting a wide range of pharmacological activities. [1] Wan and Coll. published very recently an efficient three-component preparation of 4-acylpyrazoles starting from alkyl and aryl (including heteroaryl) N,N-dimethylenaminones, hydrazine hydrochlorides in DMSO as solvent, as well as C1 source, in the presence of a catalytic amount of molecular iodine and 5 equivalents of Selectfluor (see Scheme below). [2]
This methodology displays a broad substrate tolerance, more than 30 4-acylpyrazole derivatives have been prepared in 50-90% yields. A plausible mechanism for this DMSO-based pyrazole ring formation is discussed.
[1] (a) V. Kumar, K. Kaur, G. K. Gupta, A. K. Sharma, Eur. J. Med. Chem. 2013, 69, 735-753. (b) G. Ş. Küçükgüzel, S. Şenkardeş, Eur. J. Med. Chem. 2015, 97, 786-815. (c) A. Schmidt, A. Dreger, Curr. Org. Chem. 2011, 15, 1423-1463.
[2] H. Guo, L. Tian, Y. Liu, J.-P. Wan, Org. Lett. 2022, 24, 228-233.
Scientist in Chemical Sciences at Paraza Pharma Inc.
1y5 equivalents of Selectfluor at 90 °C in DMSO is probably the last thing I would recommend to try ... From the corresponding EROS page. "Solubility [...] DMSO (reacts rapidly and exothermically)." "exothermic decomposition can occur at temperatures >80 ◦C)" That sounds enough of a definitive no-go for safety reasons to me.