一锅两步策略高效合成3-芳基-4-(芳硫基)-1H-吡唑-5-胺衍生物

doi:10.6023/cjoc202107045

摘要/Abstract

建立了3-氧代-3-芳基丙腈、肼基甲酸甲酯(或水合肼)和芳基磺酰肼的一锅两步反应. 在I₂和N-碘代丁二酰亚胺(NIS)的作用下, 通过环化、磺基化和脱酯基化反应构建了一系列3-芳基-4-(芳硫基)-1H-吡唑-5-胺化合物. 该方法具有良好的原子经济性、温和的反应条件、广泛的底物适用范围和克级规模的合成. 此外, 还对3-芳基-4-(芳硫基)-1H-吡唑-5-胺产物的进一步转化进行了研究.

关键词: 一锅两步, 1H-吡唑-5-胺, 环化, 亚磺酰化

One-pot two-step reaction of 3-oxo-3-arylpropanenitriles, methyl hydrazinecarboxylate (or hydrazine hydrate), and arylsulfonyl hydrazides has been established, and a series of 3-aryl-4-(arylthio)-1H-pyrazol-5-amines were constructed by sequential cyclization, sulfenylation, and removal of COOMe group under the action of I₂ and N-iodo-succininide (NIS), respectively. The method represents good atomic economy, mild reaction conditions, broad substrate scope, and gram-scale synthesis. Moreover, the further transformations of 3-aryl-4-(arylthio)-1H-pyrazol-5-amine products were also investigated.

Key words: one-pot two-step, 1H-pyrazol-5-amine, cyclization, sulfenylation

引用此文

冯易浇, 何静, 韦玥婷, 汤婷, 李春天, 刘平. 一锅两步策略高效合成3-芳基-4-(芳硫基)-1H-吡唑-5-胺衍生物[J]. 有机化学, 2022, 42(1): 226-234.

Yijiao Feng, Jing He, Yueting Wei, Ting Tang, Chuntian Li, Ping Liu. One-Pot Two-Step Strategy for Efficient Synthesis of 3-Aryl-4-(arylthio)-1H-pyrazol-5-amines Derivatives[J]. Chinese Journal of Organic Chemistry, 2022, 42(1): 226-234.

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图/表 8

Scheme 1. Multicomponent reactions of β-ketonitriles with hydrazides

Entry	Catalyst (mol%)	Solvent/mL	Yield^b/%
1	—	EtOH	Trace
2	NIS (50)	EtOH	84
3	NIS (20)	EtOH	85
4	NIS (10)	EtOH	86
5	NIS (5)	EtOH	67
6	I₂ (10)	EtOH	97
7	I₂ (5)	EtOH	92
8	TBAI (10)	EtOH	Trace
9	I₂ (10)	1,4-Dixoane	57
10	I₂ (10)	DCE	64
11	I₂ (10)	DMSO	45
12	I₂ (10)	DMF	34
13	I₂ (10)	THF	56
14^c	I₂ (10)	EtOH	85

Table 1. Optimization of cyclization reactiona

Entry	[I] source (mol%)	T/℃	Yield^b/%
1	—	80	19
2	I₂(50)	80	78
3	KI (50)	80	54
4	NH₄I (50)	80	46
5	TBAI (50)	80	38
6	NIS (50)	80	88
7	NIS (30)	80	82
8	NIS (70)	80	87
9	NIS (50)	60	30
10	NIS (50)	100	75
11^c	NIS (50)	80	94
12^d	NIS (50)	80	70

Table 2. Optimization of sulfonation reactiona

Table 3. One-pot two-step reaction of 3-oxo-3-arylpropaneni- trile, NH2NHCOOMe and ArSO2NHNH2a

Table 4. One-pot two-step reaction of 3-oxo-3-arylpropaneni- trile, NH2NH2•H2O and ArSO2NHNH2a

Scheme 2. Gram-scale synthesis and transformations of 5a Reaction conditions: (i) 1a (6 mmol), 2a (9 mmol), EtOH (5 mL), I2 (10 mol%), room temperature, 16 h; (ii) 4a (2.5 equiv.), NIS (50 mol%), 80 ℃, 20 h; (iii) 5a (0.2 mmol), m-CPBA (0.6 mmol), CHCl3 (2 mL), 65 ℃, 18 h; (iv) 5a (0.2 mmol), (E)-chalcone (0.4 mmol), KOH (0.4 mmol), DMF (1 mL), 110 ℃, 20 min; (v) 5a (0.2 mmol), PhCHO (0.3 mmol), Et3N (0.4 mmol), DTBP (0.6 mmol), NH4I (0.2 mmol), toluene (2 mL), 130 ℃, 12 h.

Scheme 3. Control experiments

Scheme 4. Proposed reaction mechanism

参考文献 50

[1]	Daidone, G.; Maggio, B.; Plescia, S.; Raffa, D.; Musiu, C.; Milia, C.; Perra, G.; Marongiu, M. E. Eur. J. Med. Chem. 1998, 33, 375. doi: 10.1016/S0223-5234(98)80004-4
[2]	Penning, T. D.; Talley J. J.; S. R. Bertenshaw, S. R.; J. S. Carter, J. S.; Collins, P. R.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha, J. W.; Miyashiro, J. M.; Rogers, R. S.; Rogier, D. S.; Yu, S. S.; Anderson, G. G.; Burton, E. G.; Cogburn, J. N.; S. A. Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C. J. Med. Chem. 1997, 40, 1347. pmid: 9135032
[3]	Elvin, L. A.; John, E. C.; Leon, C. G.; John, J. L.; Harry, E. R. J. Med. Chem. 1964, 7, 259. doi: 10.1021/jm00333a004
[4]	Fancelli, D.; Berta, D.; Bindi, S.; Cameron, A.; Cappella, P.; Carpinelli, P.; Catana, C.; Forte, B.; Giordano, P.; Giorgini, M. L.; Mantegani, S.; Marsiglio, A.; Meroni, M.; Moll, J.; Pittala, V.; Roletto, F.; Severino, D.; Soncini, C.; Storici, P.; Tonani, R.; Varasi, M.; Vulpetti, A.; Vianello, P. J. Med. Chem. 2005, 48, 3080. pmid: 15828847
[5]	(a) Pevarello, P.; Brasca, M. G.; Orsini, P.; Traquandi, G.; Longo, A.; Nesi, M.; Orzi, F.; Piutti, C.; Sansonna, P.; Varassi, M.; Cameron, A.; Vulpetti, A.; Roletto, F.; Alzani, R.; Ciomei, M.; Alanese, C.; Pastori, W.; Marsiglio, A.; Pesenti, E.; Fiorentini, F.; Bischoff, R.; Mercurio, C. J. Med. Chem. 2005, 48, 2944. pmid: 15828833
	(b) Kuma, Y.; Sabio, G.; Bain, J.; Shpiro, N.; Márquez, R.; Cuenda, A. J. Biol. Chem. 2005, 280, 19472. doi: 10.1074/jbc.M414221200 pmid: 15828833
[6]	Bagley, M. C.; Davis, T.; Dix, M. C.; Widdowson, M. C.; Kipling, D. Org. Biomol. Chem. 2006, 4, 4158. pmid: 17312972
[7]	Dong, J. J.; Li, Q. S.; Wang, S. F.; Li, C. Y.; Zhao, X.; Qiu, H. Y.; Zhao, M. Y.; Zhu, H. L. Org. Biomol. Chem. 2013, 11, 6328. doi: 10.1039/c3ob40776d
[8]	Wang, S. F.; Yin, Y.; Zhang, Y. L.; Mi, S. W.; Zhao, M. Y.; Lv, P. C.; Wang; B. Z.; Zhu, H. L. Eur. J. Med. Chem. 2015, 93, 291. doi: 10.1016/j.ejmech.2015.02.018
[9]	(a) Allah, A. G. G.; Hefny, M. M.; Salih, El-Basiouny, M. S. Corrosion 1989, 45, 574. doi: 10.5006/1.3577875
	(b) Allah, A. G.; Badawy, M. W.; Reham, H. H.; Abou-Romia, M. M. J. Appl. Electrochem. 1989, 19, 928. doi: 10.1007/BF01007942
	(c) Badawy, W. A.; Hefny, M. M.; El-Egamy, S. S. Corrosion 1990, 46, 978. doi: 10.5006/1.3585055
	(d) Abou-Romia, M. M.; Abd El-Rahaman, H. A.; El-Sayed, H. A. M. Bull. Electrochem. 1990, 6, 757.
[10]	Joshi, K. C.; Pathak, V. N.; Garg, U J. Heterocycl. Chem. 1979, 16, 1141. doi: 10.1002/jhet.v16:6
[11]	Hanefeld, U.; Rees, C. W.; White, A. J. P. J. Chem. Soc., Perkin Trans. 1996, 1, 1545.
[12]	(a) Dodd, D. S.; Martinez, R. L.; Kamau, M.; Ruam, Z.; Kirk, K. V.; Cooper, C. B.; Hermsmeier, M. A.; Traeger, S. C., Poss, M. A.; J. Comb. Chem. 2005, 7, 584. doi: 10.1021/cc049814s
	(b) Villemin, D.; Benalloum, A. Synth. Commun. 1991, 21, 1. doi: 10.1080/00397919108020783
[13]	Ioannidou, H. A.; Koutentis, P. A. Tetrahedron 2009, 65, 7023. doi: 10.1016/j.tet.2009.06.041
[14]	Bagley, M. C.; Davis, T.; Dix, M. C.; Widdowson, C. S.; Kipling, D. Org. Biomol. Chem. 2006, 4, 4158. pmid: 17312972
[15]	Su, W. N.; Lin, T. P.; Cheng, K. M.; Sung, K. C.; Lin, S. K.; Wong, F. F. J. Heterocycl. Chem. 2010, 47, 831. doi: 10.1002/jhet.343
[16]	Kim, B. R.; Sung, G. H.; Ryu, K. E.; Lee, S. G.; Yoon, H. J.; Shin, D. S.; Yoon, Y. J. Chem. Commun. 2015, 51, 9201. doi: 10.1039/C5CC02020D
[17]	Zora, M.; Kivrak, A. J. Org. Chem. 2011, 76, 9379. doi: 10.1021/jo201685p
[18]	Reddy, G. J.; Latha, D.; Rao, K. S. Org. Prep. Proced. Int. 2004, 36, 494. doi: 10.1080/00304940409356638
[19]	Kirkham, J. D.; Edeson, S. J.; Stokes, S.; Harrity, J. P. Org. Lett. 2012, 14, 5354. doi: 10.1021/ol302418b pmid: 23025502
[20]	Senadi, G. C.; Hu, W. P.; Lu, T. Y.; Garkhedkar, A. M.; Vandavasi, J. K.; Wang, J. J. Org. Lett. 2015, 17, 1521. doi: 10.1021/acs.orglett.5b00398
[21]	Ma, C.; Wen, P.; Li, J.; Han, X.; Wu, Z.; Huang, G. Adv. Synth. Catal. 2016, 358, 1073. doi: 10.1002/adsc.201500767
[22]	(a) Suryakiran, N.; Reddy, T. S.; Latha, K. A.; Prabhakar, P.; Yadagiri, K.; Venkateswarlu, Y. J. Mol. Catal. A: Chem. 2006, 258, 371. doi: 10.1016/j.molcata.2006.07.054 pmid: 29977390
	(b) Suryakiran, N.; Ramesh, D.; Venkateswarlu, Y. Green Chem. Lett. Rev. 2007, 1, 73. doi: 10.1080/17518250701771909 pmid: 29977390
	(c) Everson, N.; Yniguez, K.; Loop, L.; Lazaro, H.; Belanger, B.; Koch, G.; Bach, J.; Manjunath, A.; Schioldager, R.; Law, J.; Grabenauer, M.; Eagon, S. Tetrahedron Lett. 2019, 60, 72. doi: 10.1016/j.tetlet.2018.11.060 pmid: 29977390
	(d) Kelada, M.; Walsh, J. M. D.; Devine, R. W.; McArdle, P.; Stephens, J. C. Beilstein J. Org. Chem. 2018, 14, 1222. doi: 10.3762/bjoc.14.104 pmid: 29977390
[23]	(a) Shaabani, A.; Nazeri, M. T.; Afshari, R. Mol. Diversity 2019, 23, 751. doi: 10.1007/s11030-018-9902-8
	(b) Sun, K.; Li, G.; Li, Y.; Yu, J.; Zhao, Q.; Zhang, Z.; Zhang, G. Adv. Synth. Catal. 2020, 362, 1947. doi: 10.1002/adsc.v362.10
[24]	Wang, P.; Xie, Z.; Hong, Z.; Tang, J.; Wong, O.; Lee, C. S.; Wong, N.; Lee, S. J. Mater. Chem. 2003, 13, 1894. doi: 10.1039/b302972g
[25]	Fan, W.; Ye, Q.; Xu, H. W.; Jiang, B.; Wang, S. L.; Tu, S. J. Org. Lett. 2013, 15, 2258. doi: 10.1021/ol4008266
[26]	Jiang, B.; Fan, W.; Sun, M. Y.; Ye, Q.; Wang, S. L.; Tu, S. J.; Li, G. J. Org. Chem. 2014, 79, 5258. doi: 10.1021/jo500823z pmid: 24833111
[27]	Tu, X. J.; Hao, W. J.; Ye, Q.; Wang, S. S.; Jiang, B.; Li, G.; Tu, S. J. J. Org. Chem. 2014, 79, 11110. doi: 10.1021/jo502096t
[28]	Simpkins, N. S. In Sulfones in Organic Synthesis, Ed.: Baldwin, J. E., Pergamon Press, Oxford, UK, 1993.
[29]	Asai, T.; Takeuchi, T.; Diffenderfer, J.; Sibley, D. L. Antimicrob. Agents Chemother.. 2002, 46, 2393. doi: 10.1128/AAC.46.8.2393-2399.2002
[30]	(a) Caddick, S.; Aboutayab, K.; West, R. Synlett 1993, 231. pmid: 30129769
	(b) Wei, W.; Bao, P.; Yue, H.; Liu, S.; Wang, L.; Li, Y.; Yang, D. Org. Lett. 2018, 20, 5291. doi: 10.1021/acs.orglett.8b02231 pmid: 30129769
	(c) Sun, P.; Yang, D.; Wei, W.; Jiang, M.; Wang, Z.; Zhang, L.; Zhang, H.; Zhang, Z.; Wang, Y.; Wang, H. Green Chem. 2017, 19, 4785. doi: 10.1039/C7GC01891F pmid: 30129769
[31]	Ragno, R.; Coluccia, A.; La Regina, G.; De Martino, G.; Piscitelli, F.; Lavecchia, A.; Novellino, E.; Bergamini, A.; Ciaprini, C.; Sinistro, A.; Maga, G.; Crespan, E.; Artico, M.; Silvestri, R. J. Med. Chem. 2006, 49, 3172. pmid: 16722636
[32]	Silvestri, R.; De Martino, G.; La Regina, G.; Artico, M.; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; La Colla, P. J. Med. Chem. 2003, 46, 2482. pmid: 12773052
[33]	Avis, I.; Martínez, A.; Tauler, J.; Zudaire, E.; Mayburd, A.; Abu- Ghazaleh, R.; Ondrey, F.; Mulshine, J. L. Cancer Res. 2005, 65, 4181. doi: 10.1158/0008-5472.CAN-04-3441
[34]	De Martino, G.; La Regina, G.; Coluccia, A.; Edler, M. C.; Barbera, M. C.; Brancale, A.; Wilcox, E.; Hamel, E.; Artico, M.; Silvestri, R. J. Med. Chem. 2004, 47, 6120. doi: 10.1021/jm049360d
[35]	Funk, C. D. Nat. Rev. Drug Discovery 2005, 4, 664. doi: 10.1038/nrd1796
[36]	Kaneda, K.; Mitsudome, T. Chem. Rec. 2017, 17, 1. doi: 10.1002/tcr.201780101
[37]	Shen, C.; Zhang, P.; Sun, Q.; Bai, S.; Hor, T. A.; Liu, X. Chem. Soc. Rev. 2015, 44, 291. doi: 10.1039/C4CS00239C
[38]	Qiu, G.; Zhou, K.; Wu, J. Chem. Commun. 2018, 54, 12561. doi: 10.1039/C8CC07434H
[39]	Dong, D. Q.; Hao, S. H.; Yang, D. S.; Li, L. X.; Wang, Z. L. Eur. J. Org. Chem. 2017, 45, 6576.
	(a) Liu, Y.; Xiong, J.; Wei, L. Chin. J. Org. Chem. 2017, 37, 1667. (in Chinese) doi: 10.6023/cjoc201702009
	(刘云云, 熊进, 韦丽, 有机化学, 2017, 37, 1667.) doi: 10.6023/cjoc201702009
	(b) Xu, X. M.; Chen, D. M.; Wang, Z. L. Chin. J. Org. Chem. 2019, 39, 3338. (in Chinese) doi: 10.6023/cjoc201904068
	(徐鑫明, 陈德茂, 王祖利, 有机化学, 2019, 39, 3338.) doi: 10.6023/cjoc201904068
	(c) Chen, S. H.; Wang, M.; Jiang, X. F. Acta Phys.-Chim. Sin. 2019, 35, 954. (in Chinese) doi: 10.3866/PKU.WHXB201810044
	(陈世豪, 王明, 姜雪峰, 物理化学学报, 2019, 35, 954.)
	(d) Liu, Y. Y.; Xiong, J.; Wei, L. Chin. J. Org. Chem. 2017, 37, 1667. (in Chinese) doi: 10.6023/cjoc201702009
	(刘云云, 熊进, 韦丽, 有机化学, 2017, 37, 1667.) doi: 10.6023/cjoc201702009
	(e) Xu, X. M.; Yang, H. L.; Li, W. Z. Chin. J. Org. Chem. 2020, 40, 1912. (in Chinese) doi: 10.6023/cjoc201912044
	(徐鑫明, 杨翰林, 李文忠, 有机化学, 2020, 40, 1912.) doi: 10.6023/cjoc201912044
	(f) Xu, X. M.; Li, J. Z.; Wang, Z. L. Chin. J. Org. Chem. 2020, 40, 886. (in Chinese) doi: 10.6023/cjoc201910020
	(徐鑫明, 李家柱, 王祖利, 有机化学, 2020, 40, 886.) doi: 10.6023/cjoc201910020
	(g) Li, Y.; Wan, J. Chin. J. Org. Chem. 2020, 40, 3889. (in Chinese) doi: 10.6023/cjoc202005026
	(李毅, 万结平, 有机化学, 2020, 40, 3889.) doi: 10.6023/cjoc202005026
[40]	(a) Wang, L.; Zhang, M.; Zhang, Y.; Liu, Q.; Zhao, X.; Li, J.; Luo, Z.; Wei, W. Chin. Chem. Lett. 2020, 31, 67. doi: 10.1016/j.cclet.2019.05.041
	(b) Liu, Q.; Lv, Y.; Liu, R.; Zhao, X.; Wang, J.; Wei, W. Chin. Chem. Lett. 2021, 32, 136. doi: 10.1016/j.cclet.2020.11.059
	(a) Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123. doi: 10.1021/ar9502083
	(b) Dömling, A.; Ugi, I. Angew. Chem., nt. Ed. 2000, 39, 3168.
[41]	(a) Meng, N.; Lv, Y.; Liu, Q.; Liu, R.; Zhao, X.; Wei, W. Chin. Chem. Lett. 2021, 32, 258. doi: 10.1016/j.cclet.2020.11.034
	(b) Gui, Q. W.; Wang, B. B.; Zhu, S.; Li, F. L., Zhu, M. X..; Yi, M.; Yu, J. L.; Wu, Z.-L.; He, W. M. Green Chem. 2021, 23, 4430. doi: 10.1039/D1GC01017D
	(c) Wu, Y.; Chen, J.Y.; Ning, J.; Jiang, X.; Deng, J.; Deng, Y.; Xu, R.; He, W. M. Green Chem. 2021, 23, 3950. doi: 10.1039/D1GC00562F
	(d) Wang, S. C.; Liu, P. Y.; Chen, Y. X.; Shen, Z. J.; Hao, W. J.; Tu, S. J.; Jiang, B. Chem. Commun. 2021, 57, 7966. doi: 10.1039/D1CC02973H
	(e) Li, Q. X.; Li, M. W.; Shi, S. Q.; Ji, X. S.; He, C. L.; Jiang, B.; Hao, W. J. Chin. J. Org. Chem. 2020, 40, 384. (in Chinese) doi: 10.6023/cjoc201909041
	(李庆雪, 李梦伟, 时绍青, 季晓霜, 何春兰, 姜波, 郝文娟, 有机化学, 2020, 40, 384.) doi: 10.6023/cjoc201909041
	(f) Zhang, T. S.; Hao, W. J.; Wang, R.; Wang, S. C.; Tu, S. J.; Jiang, B. Green Chem. 2020, 22, 4259. doi: 10.1039/D0GC00771D
[42]	Sun, J.; Qiu, J. K.; Zhu, Y. L.; Guo, C.; Hao, W. J.; Jiang, B.; Tu, S. J. J. Org. Chem. 2015, 80, 8217. doi: 10.1021/acs.joc.5b01280
[43]	Sun, J.; Qiu, J. K.; Jiang, B.; Hao, W. J.; Guo, C.; Tu, S. J. J. Org. Chem. 2016, 81, 3321. doi: 10.1021/acs.joc.6b00332
[44]	Wei, Y.; Liu, P.; Liu, Y.; He, J.; Li, X.; Li, S.; Zhao, J. Org. Biomol. Chem. 2021, 19, 3932. doi: 10.1039/D1OB00438G
[45]	(a) Chen, L. J.; Zhang, J.; Wei, Y. T.; Yang, Z.; Liu, P.; Zhang, J; Dai, B. Tetrahedron 2019, 75, 130664. doi: 10.1016/j.tet.2019.130664
	(b) Wei, Y. T.; He, J.; Liu, Y. L.; Xu, L.; Vaccaro, L.; Liu, P.; Gu, Y. L. ACS Omega 2020, 5, 18515. doi: 10.1021/acsomega.0c02590
	(c) Wei, Y. T.; Liu, Y. L.; He, J.; Li, X. Z.; Liu, P.; Zhang, J. Tetrahedron 2020, 76, 131646. doi: 10.1016/j.tet.2020.131646
	(d) He, J.; Wei, Y. T.; Li, X. Z.; Dai, B.; Liu, P. Synthesis 2022, 54, 490. doi: 10.1055/a-1592-6394
[46]	(a) Yang, F. L.; Wang, F. X.; Wang, T. T.; Wang, Y. J.; Tian, S. K. Chem. Commun. 2014, 50, 2111. doi: 10.1039/c3cc48961b
	(b) Yang, F. L.; Tian, S. K. Angew. Chem., Int. Ed. 2013, 52, 1.
[47]	Yang, F. L.; Yang, G.; Yu, B. K.; Jin, Y. X.; Tian, S. K. Adv. Synth. Catal. 2016, 358, 3368. doi: 10.1002/adsc.v358.21
[48]	Zhang, J.; Li, W.; Liu, Y.; Liu, P. ChemistrySelect 2020, 5, 5497. doi: 10.1002/slct.v5.19
[49]	Talla, A.; Driessen, B.; Straathof, N. J.; Milroy, L. G.; Brunsveld, L.; Hessel, V.; Noel, T. Adv. Synth. Catal, 2015, 357, 2180. doi: 10.1002/adsc.v357.10
[50]	Lv, Y.; Luo, J.; Ma, Y.; Dong, Q.; He, L. Org. Chem. Front. 2021, 8, 2461. doi: 10.1039/D1QO00112D