Synthesis, Table of Contents Synthesis 2022; 54(07): 1793-1802DOI: 10.1055/a-1684-0308 paper Halogenations of 3-Aryl-1H-pyrazol-5-amines Jing He , Yueting Wei , Yijiao Feng , Chuntian Li , Bin Dai∗ , Ping Liu∗ Recommend Article Abstract Buy Article All articles of this category Abstract A direct C–H halogenation of 3-aryl-1H-pyrazol-5-amines using N-halogenosuccinimides (NXS; X = Br, I, Cl) in dimethyl sulfoxide at room temperature has been developed. This transformation provides an effective metal-free protocol for the synthesis of novel 4-halogenated pyrazole derivatives with moderate to excellent yields. The method utilizes NXS reagents as cheap and safe halogenating reagents under simple and mild reaction conditions, it has broad substrate scope, and can be used for gram-scale synthesis. The utility of this procedure is established by further transformations of the 4-halogenated products. Mechanism studies show that DMSO plays a dual role of catalyst and solvent. Key words Key wordshalogenation - metal-free - pyrazol-5-amine - synthesis - 4-halogenopyrazole - N-halogenosuccinimides - dimethyl sulfoxide Full Text References References 1 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845 2 MacBean C. The Pesticide Manual, 16th ed. British Crop Production Council; Alton: 2012 3a Janin YL. Chem. Rev. 2012; 112: 3924 3b Jedinák L, Cankař P. Eur. J. Org. Chem. 2016; 2016: 2013 3c Jedinák L, Zátopková R, Zemánková H, Šustková A, Cankař P. J. Org. Chem. 2017; 82: 157 3d Fu L, Xu Z, Wan JP, Liu Y. Org. Lett. 2020; 22: 9518 3e Pan Y, Gong Y, Song Y, Tong W, Gong H. Org. Biomol. Chem. 2019; 17: 4230 3f Xiong J, Zhong G, Liu Y. Adv. Synth. Catal. 2019; 361: 550 4 Lamberth C. Heterocycles 2007; 71: 1467 5 Clarke ED, Mallon LJ. In Modern Methods in Crop Protection Research . Jeschke P, Krämer W, Schirmer U, Witschel M. Wiley-VCH; Weinheim: 2012: 273 6 Lahm GP, Selby TP, Freudenberger JH, Stevenson TM, Myers BJ, Seburyamo G, Smith BK, Flexner L, Clark CE, Cordova D. Bioorg. Med. Chem. Lett. 2005; 15: 4898 7 Lahm GP, Stevenson TM, Selby TP, Freudenberger JH, Cordova D, Flexner L, Bellin CA, Dubas CM, Smith BK, Hughes KA, Hollingshaus JG, Clark CE, Benner EA. Bioorg. Med. Chem. Lett. 2007; 17: 6274 8 Clark DA, Lahm GP, Smith BK, Barry JD, Clagg DG. Bioorg. Med. Chem. 2008; 16: 3163 9 Lahm GP, Cordova D, Barry JD. Bioorg. Med. Chem. 2009; 17: 4127 10 Gregory V, Pasteris RJ. WO 2009055514, 2009 11 Morimoto K, Sato T, Yamamoto S, Takeuchi H. J. Heterocycl. Chem. 1997; 34: 537 12 Dunkel R, Elbe H.-L, Greul JN, Hartmann B, Gayer H, Seitz T, Wachendorff-Neumann U, Dahmen P, Kuck H.-K. WO 2006061215, 2006 13 Paruch K, Guzi TJ, Dwyer MP. WO 2009070567, 2009 14 Rouse M, Seefeld MA. WO 2010093885, 2010 15 Li H, Yuan J, Bakthavatchalam R, Hodgetts KJ, Apitosti SM, Mao CJ, Wustrow DJ, Guo Q. WO 2009012482, 2009 16 Bolea C. WO 2010079239, 2010 17a Zhao Z.-G, Wang Z.-X. Synth. Commun. 2007; 37: 137 17b Fu L, Bao X, Li S, Wang L, Liu Z, Chen W, Xia Q, Liang G. Tetrahedron 2017; 73: 2504 18a Mykhailiuk PK. Chem. Rev. 2021; 121: 1670 18b Luo JF, Xu X, Zhao YC, Liang HZ. Chin. J. Org. Chem. 2017; 37: 2873 18c Zeng ZG, Sang XK, Yuan B, Wu MH, Zhang YW. Chin. J. Org. Chem. 2021; 41: 959 18d Petrone DA, Ye J, Lautens M. Chem. Rev. 2016; 116: 8003 18e Liu D, Zhu YY, Gu SX, Chen FE. Chin. J. Org. Chem. 2021; 41: 1002 18f Liao G, Shi BF. Acta Chim. Sin. 2015; 73: 1283 18g Tang RJ, Milcent T, Crousse B. J. Org. Chem. 2018; 83: 930 18h Udavant RN, Yadav AR, Shinde SS. Eur. J. Org. Chem. 2018; 2018: 3432 18i Stefani HA, Pereira CM. P, Almeida RB, Braga RC, Guzen KP, Cella R. Tetrahedron Lett. 2005; 46: 6833 18j Olsen KL, Jensen MR, MacKay JA. Tetrahedron Lett. 2017; 58: 4111 19a Song S, Li X, Wei J, Jiao N. Nat. Catal. 2020; 3: 107 19b Fosu SC. C, Hambira M, Chen AD, Fuchs JR, Nagib DA. Chem 2018; 5: 417 19c Tanemura K, Suzuki T, Nishida Y, Satsumabayashi K, Horaguchi T. Chem. Lett. 2003; 32: 932 19d Xiong X, Yeung YY. ACS Catal. 2018; 8: 4033 19e Wang M, Zhang Y, Wang T, Wang C, Xue D, Xiao J. Org. Lett. 2016; 18: 1976 19f Maddox SM, Nalbandian CJ, Smith DE, Gustafson JL. Org. Lett. 2015; 17: 1042 19g Zhang L, Hu X. Chem. Sci. 2017; 8: 7009 19h Rodriguez RA. C, Pan M, Yabe Y, Kawamata Y, Eastgate MD, Baran PS. J. Am. Chem. Soc. 2014; 136: 6908 19i Luo T, Tian SH, Wan J, Liu YY. Curr. Org. Chem. 2021; 25: 1180 19j Lin Y, Wan J, Liu Y. New J. Chem. 2020; 44: 8120 19k Li ZH, Fiser B, Jiang BL, Li JW, Xu BH, Zhang SJ. Org. Biomol. Chem. 2019; 17: 3403 19l Ma XT, Zhou KJ, Ren MJ, Wang MY, Yu J. Chin. J. Org. Chem. 2019; 39: 2796 19m Majetich G, Hicks R, Reister S. J. Org. Chem. 1997; 62: 4321 19n Li Y, Wan J. Chin. J. Org. Chem. 2020; 40: 3889 20 Jiang B, Ning Y, Fan W, Tu SJ, Li G. J. Org. Chem. 2014; 79: 4018 21a Wei Y, Liu P, Liu Y, He J, Li X, Li S, Zhao J. Org. Biomol. Chem. 2021; 19: 3932 21b Yang Z, He J, Wei Y, Li W, Liu P, Zhao J, Wei Y. Org. Biomol. Chem. 2020; 18: 9088 21c Yang Z, He J, Wei Y, Li W, Liu P. Org. Biomol. Chem. 2020; 18: 3360 21d Liu Y, Wei Y, Yang Z, Li Y, Liu Y, Liu P. Org. Biomol. Chem. 2021; 19: 5191 21e Wei YT, Liu YL, He J, Li XZ, Liu P, Zhang J. Tetrahedron 2020; 76: 131646 21f Wei Y, He J, Liu Y, Xu L, Vaccaro L, Liu P, Gu Y. ACS Omega 2020; 5: 18515 21g Chen L, Zhang J, Wei Y, Yang Z, Liu P, Zhang J, Dai B. Tetrahedron 2019; 75: 130664 21h Zhang J, Wang Z, Chen L, Liu Y, Liu P, Dai B. RSC Adv. 2018; 8: 41651 21i Chen L, Liu P, Wu J, Dai B. Tetrahedron 2018; 74: 1513 21j Li Y, Yang Z, Liu Y, Liu Y, Gu Y, Liu P. Mol. Catal. 2021; 511: 111747 21k Feng Y, He J, Wei Y, Tang T, Li C, Liu P. Chin. J. Org. Chem. 2021; in press 21l Liu Y, Yang Z, Li Y, Liu Y, Liu P. Chin. J. Org. Chem. 2021; in press 21m He J, Wei Y, Li X, Dai B, Liu P. Synthesis 2021; in press; DOI: 22 Cresswell AJ, Eey TC. S, Denmark SE. Nat. Chem. 2015; 7: 146 23 Samanta RC, Yamamoto H. J. Am. Chem. Soc. 2017; 139: 14605 24 Sakakura A, Ukai A, Ishihara K. Nature 2007; 445: 900 25 Seidl FJ, Min C, Lopez JA, Burns NZ. J. Am. Chem. Soc. 2018; 140: 15646 Supplementary Material Supplementary Material Supporting Information
