Electrochemical/I– Dual-Catalyzed Access to Sulfonated Pyrazoles under External Oxidant-Free Conditions
Jing Ma‡
,
Jianjing Yang‡
,
Kelu Yan
,
Boju Luo
,
Kexin Huang
,
Ziling Wu
,
Yumeng Zhou
,
Shuyun Zhu
,
Xian-En Zhao
,
Jiangwei Wen∗
This work was supported by the National Natural Science Foundation of China (No. 21902083, 22076097) and the Natural Science Foundation of Shandong Province (No. ZR2020QB130). This work was also supported by the Talent Program Foundation of Qufu Normal University (No. 6132 and 6125).
An electrochemical/I– dual-catalyzed access to sulfonated pyrazoles from pyrazolones and sodium sulfites under external oxidant-free conditions has been developed. This established electrochemical reaction works smoothly under external oxidant-free conditions and has the advantages of good functional group tolerance, easy to gram-scale synthesis, delivering up to 95% yield for 35 examples.
2 McGrath, N. A.; Brichacek, M.; Njardarson, J. T. J. Chem. Educ. 2010, 87, 1348; https://njardarson.lab.arizona.edu/content/top-pharmaceuticals-poster (accessed June 1, 2023).
17General Procedure In an oven-dried undivided three-necked flask (25 mL) equipped with a stir bar, a (0.25 mmol), b (0.5 mmol), and NH4I (30 mol%, 10.8 mg) were combined and added. The flask was equipped with carbon rod as the anode, Pt plate (1 × 1 cm2) as the cathode and was then charged with nitrogen. Under the protection of nitrogen, CH3CN/H2O (6.3 mL, v = 3: 0.1) was slowly injected into the reaction flask. The reaction mixture was stirred and electrolyzed at a constant current of 10 mA under room temperature for 2 h. When the reaction was finished and monitored by TLC, the solution was concentrated in a vacuum and the pure product 1c-35c was obtained by flash column chromatography on silica gel. 1H and 13C NMR and other analytical data of compounds 1c, 2c, 5c, 9c, 10c–14c, 16c, 19c, 22c–24c, 27c–29c, 31c, 32c are reported in the literature.11,121-(4-Methoxyphenyl)-3-methyl-4-tosyl-1H-pyrazol-5-ol (3c)Synthesized in accordance with the general procedure for electrochemical/I– dual-catalyzed access to sulfonated pyrazoles performed in an undivided cell, using 2-(4-methoxyphenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (3a, 0.25 mmol, 51.0 mg), sodium 4-methylbenzenesulfinate (2b, 0.5 mmol, 89.0 mg), and NH4I (30 mol%, 10.8 mg) with CH3CN/H2O (6.3 mL, v = 3: 0.1) as the solvent. The reaction mixture was stirred and electrolyzed at a constant current of 10 mA under room temperature for 2 h. The desired product (yield 74.4 mg, 0.21 mmol, 83%) was obtained as a white solid; mp 127–130 °C. 1H NMR (500 MHz, DMSO): δ = 7.87 (d, J = 7.9 Hz, 2 H), 7.82 (d, J = 9.0 Hz, 2 H), 7.29 (d, J = 6.8 Hz, 2 H), 6.85 (d, J = 7.9 Hz, 2 H), 3.71 (s, 3 H), 2.33 (s, 3 H), 2.17 (s, 3 H). 13C NMR (126 MHz, DMSO): δ = 160.3, 156.2, 145.5, 143.0, 142.5, 133.4, 129.7, 126.1, 121.3, 114.0, 97.2, 55.6, 21.3, 14.6. HRMS (EI): m/z calcd for C18H18N2O4S [M + H]+: 359.1061; found: 359.1060.
