Halogenations of 3-Aryl-1H-pyrazol-5-amines

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

halogenation - metal-free - pyrazol-5-amine - synthesis - 4-halogenopyrazole - N-halogenosuccinimides - dimethyl sulfoxide

Publication History

Received: 12 October 2021

Accepted after revision: 02 November 2021

Accepted Manuscript online:
02 November 2021

Article published online:
06 December 2021

• 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