3,4-二取代-3-(二氟甲基)吡唑类化合物的构建

doi:10.6023/cjoc201912024

摘要/Abstract

二氟甲基在活性分子中可以起到氢键供体、生物电子等排体、亲脂性调节等作用，在药物和农药分子的设计中被广泛使用.3，4-二取代-3-（二氟甲基）吡唑骨架的发现及应用是该领域的一个突出代表，研究表明含有这类骨架的分子能够抑制琥珀酸脱氢酶（SDHIs），具有作为杀菌剂的潜力，目前市场上已有近十种农药分子含有3，4-二取代-3-（二氟甲基）吡唑结构单元，年销售额高达十几亿美元.按照所用含氟砌块的不同种类，对近二十年来3，4-二取代-3-（二氟甲基）吡唑类化合物的合成方法进行总结和展望.

关键词: 3,4-二取代-3-(二氟甲基)吡唑, 二氟甲基杂环化合物, 杀菌剂, 合成

The CHF₂ moiety has been widely utilized in the design of pharmaceuticals and agrochemicals, because this group can act as hydrogen-bonding donor to improve the binding selectivity of biologically active compounds, as a bioisostere to substitute for methyl, methoxy, hydroxy, amino and thiol groups, and as a lipophilic regulator to improve the liposolubility of the active compounds. For example, 3-difluoromethylpyrazole scaffolds are present in many organic compounds that exhibit important biological activities. In this content, there are nearly ten kinds of pesticide molecules on the market that contain 3,4-disubstituted-3-(difluoromethyl)pyrazole units, with annual sales of up to one billion dollars. In this review, the methods of construction of 3,4-disubstituted 3-difluoromethylpyrazoles will been briefly summarized that have been reported so far. Four different strategies including using fluorinated reagents as substrates, difluoroacetic acid and its derivatives as fluorine building blocks, difluorodiazonium and others as fluorine building blocks will be introduced.

Key words: 3,4-disubstituted-3-difluoromethylpyrazoles, difluoromethyl heterocyclic compounds, fungicides, synthesis

引用此文

曾俊良, 许志红, 马军安. 3,4-二取代-3-(二氟甲基)吡唑类化合物的构建[J]. 有机化学, 2020, 40(5): 1105-1116.

Zeng Junliang, Xu Zhihong, Ma Junan. Construction of 3,4-Disubstituted-3-(difluoromethyl)pyrazoles[J]. Chinese Journal of Organic Chemistry, 2020, 40(5): 1105-1116.

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参考文献

[1] (a) Yossi, Z.; Gali, S. M.; Dina, Y.; Anat, B.; Dafna, A.; Daniele, M.; Shlomi, E.; Shahaf, K.; Nissan, A.; Moran, M.; Eytan, G.; Sigal, S. J. Med. Chem. 2019, 62, 5628.
(b) Dai, J.-L.; Lei, W.-L.; Liu, Q. Acta Chim. Sinica 2019, 77, 911(in Chinese). (戴建玲, 雷文龙, 刘强, 化学学报, 2019, 77, 911.)
(c) Fu, X.-P.; Xiao, Y.-L.; Zhang, X.-G. Chin. J. Chem. 2018, 36, 143.
(d) Damian, E. Y.; Sebastian, B. V.; Postigo. A. Chem.-Eur. J. 2017, 23, 14676.
(e) Ni, C.-F.; Zhu, L.-G.; Hu, J.-B. Acta Chim. Sinica 2015, 73, 90(in Chinese). (倪传法, 朱林桂, 胡金波, 化学学报, 2015, 73, 90.)
(f) Yang, Y.; You, Z.; Qing, F. Acta Chim. Sinica 2012, 70, 2323(in Chinese). (杨义, 游正伟, 卿凤翎, 化学学报, 2012, 70, 2323.)
(g) O'Hagan, D.; Wang, Y.; Skibinski, M.; Slawin, A. M. Z. Pure Appl. Chem. 2012, 84, 1587.
(h) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529.
(i) Erichson, J. A.; McLoughlin, J. I. J. Org. Chem. 1995, 60, 1626.
[2] Mcloughlin, J. I.; Louis, St.; Metz, S. C. US 2005223526, 1992.
[3] (a) Zierke, T.; Maywald, V.; Rack, M.; Smidt, S. P.; Keil, M.; Wolf, B.; Koradin, C. WO 2009133179, 2009.
(b) Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins, P. W.; Doctor, S.; Greveto, M. J.; Lee, L. F.; Malecha, J. W.; Miyashiro, J. M.; Rogers R. S.; Rogier, D. J.; Yu, S. S.; Anderson, G. D.; Burton, E. G.; Gregory, S. A.; Icoboldt, C. M.; Perkus, W. E.; Seibert, K. A.; Veenhuizen, W.; Zhang, Y. Y.; Isakson, P. C. J. Med. Chem. 1997, 40, 1347.
(c) Liu, X.-H.; Zhao, W.; Shen, Z.-H.; Xing, J.-H.; Xu, T.-M.; Peng, W.-L. Eur. J. Med. Chem. 2017, 125, 881.
[4] (a) Qiu, S.-S.; Bai, Y.-L. Modern Agrochem. 2014, 6, 1(in Chinese). (仇是胜, 柏亚罗, 现代农药, 2014, 6, 1.)
(b) Qiu, S.-S.; Bai, Y.-L. Modern Agrochem. 2015, 14, 1(in Chinese). (仇是胜, 柏亚罗, 现代农药, 2015, 14, 1.)
[5] Xiao, H. World Pestic. 2007, 39, 12(in Chinese). (筱禾, 世界农药, 2007, 39, 12.)
[6] Lantzsch, R.; Pazenok, S.; Memmel, F. WO 2005044804, 2005.
[7] Syngenta Participations AG EP 2008996, 2008.
[8] Kremsner, J. M.; Rack, M.; Pilger, C.; Kappe, C. O. Tetrahedron Lett. 2009, 50, 3665.
[9] Bolea, C.; Celanire, S.; Boudou, C.; Tang, L.; Rocher, J. P.; Liverton, N. J. WO 2012009009, 2012.
[10] Fan, X.-B.; Lin, X.-J.; Xu, X.-M.; Huang, C.; Shen, Q.-F. CN 104016920, 2014.
[11] Sakamoto, R.; Kashiwagi, H.; Maruoka, K. Org. Lett. 2017, 19, 5126.
[12] Zhang, Y.; Chen, Z.; Nie, J.; Zhang, F.-G.; Ma, J.-A. J. Org. Chem. 2019, 84, 7148.
[13] (a) Liu, C.-B.; Meng, W.; Li, F.; Wang, S.; Nie, J.; Ma, J.-A. Angew. Chem., Int. Ed. 2012, 51, 6227.
(b) Wang, S.; Nie, J.; Zheng, Y.; Ma, J.-A. Org. Lett. 2014, 16, 1606.
(c) Zhang, F.-G.; Wei, Y.; Yi, Y. P.; Ma, J.-A. Org. Lett. 2014, 16, 3122.
(d) Chen, Z.; Zheng, Y.; Ma, J.-A. Angew. Chem., Int. Ed. 2017, 56, 4569.
[14] Li, L.-F.; Xu, G. Y.; Zhao, D.-J.; Chen, M.; Wang, Y. Fine Chem. Intermed. 2011, 43(6), 17.
[15] Oharu, K.; Kumai, S. EP 0694523, 1995.
[16] Nishimiya, T.; Fuku, A.; Okamoto, S. WO 2008078479, 2008.
[17] Talley, J. J.; Penning, T. D.; Collins, P. W.; Rogier, D. J.; Malecha, J. W.; Miyachiro, J. M.; Bertenshaw, S. R.; Khanna, I. K.; Granets, M. J.; Rogers, R. S.; Carter, J. S.; Docter, S. H.; Yu, S. S. WO 9515316, 1995.
[18] (a) Singh, S. P.; Kumar, D.; Batra, H.; Naithani, R.; Rozas, I.; Elguero, J. Can. J. Chem. 2000, 78, 1109.
(b) Sloop, J. C. Bumgardner, C. L.; Loehle, W. D. J. Fluorine Chem. 2002, 118, 135.
[19] Norris, T.; Colon-Cruz, R.; Ripin, D. H. B. Org. Biomol. Chem. 2005, 3, 1844.
[20] Gosselin, F.; O'Shea, P. D.; Webster, R. A.; Reamer, R. A.; Tillyer, R. D.; Grabowski, E. J. J. Synlett 2006, 19, 3267.
[21] Gewehr, M.; Muller, B.; Grote, T.; Grammenos, W.; Schwogler, A.; Rheinheimer, J.; Blettner, G.; Schafer, P.; Schieweck, F.; Werner, F.; Rether, J.; Strathmann, S.; Stierl, R.; Scherer, M. WO 2005123690, 2005.
[22] (a) Wu, Z.-B.; Hu, D.-Y.; Kuang, J.-Q.; Cai, H.; Wu, S. X.; Xue, W. Molecules 2012, 17, 14205.
(b) Sun, J.-L.; Zhou, Y.-M. Molecules 2015, 20, 4383.
(c) Liu, X.-H.; Zhao, W.; Shen, Z.-H.; Xing, J.-H.; Xu, T.-M.; Peng, W.-L. Eur. J. Med. Chem. 2017, 125, 881.
(d) Qiao, L.; Zhai, Z.-W.; Cai, P.-P.; Tan, C.-X.; Weng, J.-Q.; Han, L.; Liu, X.-H.; Zhang Y.-G. J. Heterocycl. Chem. 2019, 56, 2536.
[23] Dochnahl, M.; Keil, M.; Gotz, R. WO 2011054733, 2010.
[24] Huang, X.-Y.; Shang, Y.; Wang, L.-P.; Wang, W. Agrochemicals 2018, 57(10), 703.
[25] Rack, M.; Smidt, S. P.; Lohr, S.; Keil, M.; Dietz, J.; Rheinheimer, J.; Grote, T.; Zierke, T.; Lohmann, J. K.; Sukopp, M. WO 2008053043, 2008.
[26] Bowden, M.; Gott, B. D.; Jackson, D. A. WO 2009000442, 2009.
[27] Iaroshenko, V. O.; Specowius, V.; Vlach, K.; Vilches-Herrera, M.; Ostrovskyi, D.; Mkrtchyan, S.; Villinger, A.; Langer, P. Tetrahedron 2011, 67, 5663.
[28] Braun, M. J.; Jaunzems, J. WO 2012010692, 2012.
[29] Sosnovskikh, V. Y.; Irgashev, R. A. Moshkin, V. S. Kodess, M. I. Russ. Chem. Bull. 2008, 57, 2146.
[30] Lantzsch, R.; Wolfgang, J.; Pazenok, S. WO 2005042468, 2004.
[31] Zierke, T.; Maywald, V.; Rack, M.; Smidt, S. P.; Keil, M.; Wolf, B.; Koradin, C. US 20110040096, 2009.
[32] Zierke, T.; Rheinheimer, J.; Rack, M.; Smidt, S. P.; Altenhoff, A. G.; Schmidt-Leithoff, J.; Challand, N. WO 2008145740, 2008.
[33] Pazenok, S.; Lui, N.; Heinrich, J. D.; Wollner, T. WO 2009106230, 2009.
[34] Wang, M.-C.; Li, Q.-Y.; Luo, Z.-B. CN 107663172, 2016.
[35] Gilman, H.; Jones, R. G. J. Am. Chem. Soc. 1943, 65, 1458.
[36] (a) Morandi, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2011, 50, 9085.
(b) Morandi, B.; Carreira, E. M. Org. Lett. 2011, 13, 5984.
(c) Morandi, B.; Carreira, E. M. Angew. Chem., Int. Ed. 2010, 49, 938.
(d) Artamonov, O. S.; Mykhailiuk, P. K.; Voievoda, N. M.; Volochnyuk, D. M.; Komarov, I. V. Synthesis 2010, 443.
(e) Li, F.; Nie, J.; Sun, L.; Ma, J.-A. Angew. Chem., Int. Ed. 2013, 52, 6255.
(f) Peng, X.; Xiao, M.-Y.; Zeng, J.-L.; Zhang, F.-G.; Ma, J.-A. Org. Lett. 2019, 21, 4808.
(g) Zhang, Z.-Q.; Zheng, M.-M.; Xue, X.-S.; Marek, I.; Zhang, F.-G.; Ma, J.-A. Angew Chem., Int. Ed. 2019, 58, 18191.
[37] Mykhailiuk, P. K. Angew Chem., Int. Ed. 2015, 54, 6558.
[38] Mertens, L.; Hock, K. J.; Koenigs, R. M. Chem.-Eur. J. 2016, 22, 9542.
[39] Li, J.; Yu, X.-L.; Cossy, J.; Lv, S.-Y.; Mykhailiuk, P. K.; Wu, Y. Eur. J. Org. Chem. 2017, 266.
[40] Britton, J.; Jamison, T. F. Angew. Chem., Int. Ed. 2017, 56, 8823.
[41] Zeng, J.-L.; Chen, Z.; Zhang, F.-G.; Ma, J.-A. Org. Lett. 2018, 20, 4562.
[42] Linderman, R. J.; Kirollos, K. S. Tetrahedron Lett. 1989, 30, 2049.
[43] (a) Hamper, B. C. J. Fluorine Chem. 1990, 48, 123.
(b) Hamper, B. C.; Kurtzweil, M. L.; Beck, J. P. J. Org. Chem. 1992, 57, 5680.
[44] (a) England, D. C.; Melby, L. R.; Dietrich, M. A.; Lindsey, R. V. J. Am. Chem. Soc. 1960, 82(19), 5116.
(b) Wakselman, C. Tordeux, M. J. Chem. Soc., Chem. Commun. 1975, 956.
(c) Sergiy P.; Florence G.; Grégory L.; Norbert L.; Jean-Pierre, V,; Frédéric, R. L. Eur. J. Org. Chem. 2013, 4249.
(d) Etienne, S.; Baptiste, R.; Armen, P.; Jean-Pierre, V.; Sergii, P.; Frédéric, R. L. Org. Lett. 2015, 17(18), 4510.
(e) Etienne, S. Grégory, L.; Jean-Pierre, V.; Norbert, L.; Sergiy, P.; Frédéric, R. L. Eur. J. Org. Chem. 2018, 3792.
[45] Nett, M.; Grote, T.; Lohmann, J. K.; Dietz, J.; Smidt, S. P.; Rack, M.; Zierke, T. WO 2008152138, 2008.
[46] Pazenok, S.; Lui, N.; Neeff, A. WO 2008022777, 2008.
[47] Nett, M.; Grote, T.; Lohmann, J. K.; Dietz, J.; Smidt, S. P.; Rack, M.; Zierke, T. US 2010084994, 2010.