Transition-Metal-Free and Photocatalyst-Free Sulfenylation of Halopyrazolamines under Visible-Light Irradiation via Electron Donor–Acceptor Complexes

Abstract

A new approach was developed for the thiolation of halogenated pyrazole-5-amines under blue LED irradiation in metal-free conditions. This efficient and practical approach enabled the generation of thiolated pyrazol-5-amine building blocks of medicinal significance. This straightforward technique permits photochemical thiolation by an electron donor–acceptor by two distinct processes; formation of a charge-transfer complex through a halogen bond or π–π interaction based on various halogenated pyrazolamines, depending on the HOMO–LUMO energy gap of the C–X bond. The reaction of halogenated pyrazol-5-amines with thiophenol derivatives proceeded in good to excellent yields. The formation of a π–π complex or halogen bonding between the halopyrazolamine and the thiolate anion was confirmed by UV/visible spectroscopy.

Key words

pyrazolamines - EDA - metal-free reaction - photochemical reaction - thiolation

Publication History

Received: 09 June 2023

Accepted after revision: 24 July 2023

Accepted Manuscript online:
24 July 2023

Article published online:
31 August 2023

• References and Notes

• 1a Comprehensive Organic Chemistry: The Synthesis and Reactions of Organic Compounds: Sulphur, Selenium, Silicon, Boron, Organometallic Compounds, Vol. 3. Jones DN. Pergamon; Oxford: 1979
• 1b Liu L, Stelmach JE, Natarajan SR, Chen M.-H, Singh SB, Schwartz CD, Fitzgerald CE, O’Keefe SJ, Zaller DM, Schmatz DM, Doherty JB. Bioorg. Med. Chem. Lett. 2003; 13: 3979
• 1c Gangjee A, Zeng Y, Talreja T, McGuire JJ, Kisliuk RL, Queener SF. J. Med. Chem. 2007; 50: 3046
• 2a Liu G, Huth JR, Olejniczak ET, Mendoza F, Fesik SW, DeVries P, Leitza S, Reilly EB, Okasinski GF, Fesik SW, von Geldern TW. J. Med. Chem. 2001; 44: 1202
• 2b DeMartino G, Edler MC, La Regina G, Coluccia A, Barbera MC, Barrow D, Nicholson RI, Chiosis G, Brancale A, Hamel E, Artico M, Silvestri R. J. Med. Chem. 2006; 49: 947
• 2c Beletskaya IP. Ananikov V. P. Chem. Rev. 2011; 111: 1596
• 2d Scott KA, Njardarson JT. Top. Curr. Chem. 2018; 376: 5
• 3a Boyd DA. Angew. Chem. Int. Ed. 2016; 55: 15486
• 3b Rahate AS, Nemade KR, Waghuley SA. Rev. Chem. Eng. 2013; 29: 471
• 3c Ríos M.-C, Portilla J. Chemistry 2022; 4: 940
• 3d Afsina CM. A, Aneeja T, Neetha M, Anilkumar G. Curr. Org. Synth. 2021; 18: 197
• 4 Bekhit AA, Nasralla SN, El-Agroudy EJ, Hamouda N, Abd El-Fattah H, Bekhit SA, Amagase K, Ibrahim TM. Eur. J. Pharm. Sci. 2022; 168: 106080
• 5 Radulović NS, Nikolić MG, Mladenović MZ, Ranđelovic P, Stojanović NM, Stojanović-Radić Z, Jovanović L. Appl. Organomet. Chem. 2022; 36: e6514
• 6 Chen Y, Fu X.-D, Mu H.-P, Qin X.-F, Wan R. J. Chem. Res. 2014; 38: 272
• 7 Naim M, Alam O, Nawaz F, Alam MJ, Alam P. J. Pharm. BioAllied Sci. 2016; 8: 2
• 8a Mantzanidou M, Pontiki E, Hadjipavlou-Litina D. Molecules 2021; 26: 3439
• 8b Lyalin BV, Sigacheva VL, Kudinova AS, Neverov SV, Kokorekin AV, Petrosyan AV. Molecules 2021; 26: 4749
• 8c Kim MM, Ruck RT, Zhao D, Huffman MA. Tetrahedron Lett. 2008; 49: 4026
• 9a Yan K, Yang D, Sun P, Wei W, Liu Y, Li G, Lu S, Wang H. Tetrahedron Lett. 2015; 56: 4792
• 9b Dotsey EY, Jung K, Basit A, Wei D, Daglian J, Vacondio F, Armirotti A, Mor M, Piomelli D. Chem. Biol. 2015; 22: 619
• 10a Saeed A, Channar PA. J. Heterocycl. Chem. 2015; 54: 780
• 10b Yan K, Yang D, Wei W, Lu S, Li G, Zhao C, Zhang Q, Wang H. Org. Chem. Front. 2016; 3: 66
• 11a Bhowmik A, Yadav M, Fernandes RA. Org. Biomol. Chem. 2020; 18, 2447
• 11b Guo Y, Quan Z.-J, Da Y.-Z, Zhang Z, Wang X.-C. RSC Adv. 2015; 5: 45479
• 12a Hosseinian A, Kheirollahi Nezhad PD, Ahmadi S, Rahmani Z, Monfared A. J. Sulfur Chem. 2018; 40: 88
• 12b Jia F, He J, Wei Y, Wei Y, Liu Y, Gu Y, Vaccaro L, Liu P. Mol. Catal. 2022; 528: 112485
• 12c Xu M, Zhang XH, Zhong P. Synth. Commun. 2012; 42: 3472
• 12d Guo Y, Zhong S, Wei L, Wan J.-P. Beilstein J. Org. Chem. 2017; 13: 2017
• 13a Sundaravelu N, Sangeetha S, Sekar G. Org. Biomol. Chem. 2021; 19: 1459
• 13b Mondal S, Khan AT. Synthesis 2022; 54: 4521
• 13c Xu X.-M, Chen D.-M, Wang Z.-L. Chin. Chem. Lett. 2020; 31: 49
• 14a Kosugi M, Shimizu T, Migita T. Chem. Lett. 1977; 1423
• 14b Tanimoto K, Ohkado R, Iida H. J. Org. Chem. 2019; 84: 14980
• 14c Sun P, Yang D, Wei W, Jiang L, Wang Y, Dai T, Wang H. Org. Chem. Front. 2017; 4: 1367
• 14d Liu X, Cui H, Yang D, Dai S, Zhang T, Sun J, Wei W. RSC Adv. 2016; 6: 51830
• 15 Migita T, Shimizu T, Asami Y, Shiobara J, Kato Y, Kosugi M. Bull. Chem. Soc. Jpn. 1980; 53: 1385
• 16 Duan Z, Ranjit S, Zhang P, Liu X. Chem. Eur. J. 2009; 15: 3666
• 17 Eichman CC, Stambuli JP. J. Org. Chem. 2009; 74: 4005
• 18 Jiang Z, She J, Lin X. Adv. Synth. Catal. 2009; 351: 2558
• 19a Wang S, Wang H, König B. J. Am. Chem. Soc. 2021; 143: 15530
• 19b Ghosh S, Pyne P, Ghosh A, Choudhury S, Hajra A. Org. Biomol. Chem. 2023; 21: 1591
• 20a Vara BA, Li X, Berritt S, Walters CR, Petersson EJ, Molander GA. Chem. Sci. 2018; 9: 336
• 20b Cai S, Xu Y, Chen D, Li L, Chen Q, Huang M, Weng W. Org. Lett. 2016; 18: 2990
• 20c Srivastava V, Singh PK, Srivastava A, Singh PP. RSC Adv. 2020; 10: 20046
• 20d Paul S, Das S, Choudhuri T, Sikdar P, Bagdi AK. J. Org. Chem. 2023; 88: 4187
• 21a Herrera-Luna JC, Pérez-Aguilar MC, Gerken L, García Mancheño O, Jiménez MC, Pérez-Ruiz R. Chem. Eur. J. 2023; 29: e202203353
• 21b Granados A, Cabrera-Afonso MJ, Escolano M, Badir SO, Molander GA. Chem. Catal. 2022; 2: 898
• 21c Cai Y.-P, Nie F.-Y, Song Q.-H. J. Org. Chem. 2021; 86: 12419
• 22 Liu B, Lim C.-H, Miyake GM. J. Am. Chem. Soc. 2017; 139: 13616
• 23 Li T, Liang K, Tang J, Ding Y, Tong X, Xia C. Chem. Sci. 2021; 12: 15770
• 24 Jin Y, Yang H, Fu H. Chem. Commun. 2016; 52: 12909
• 25 Desiraju GR, Ho PS, Kloo L, Legon AC, Marquardt R, Metrangolo P, Politzer P, Resnati G, Rissanen K. Pure Appl. Chem. 2013; 85: 1711
• 26a Yang D, Yan K, Wei W, Li G, Lu S, Zhao C, Tian L, Wang H. J. Org. Chem. 2015; 80: 11073
• 26b Feng Y, He J, Wei Y, Xie J, Liu P. Eur. J. Org. Chem. 2022; e202200357
• 26c Livesley S, Trueman B, Robertson CM, Goundry WR. F, Morris JA, Aïssa C. Org. Lett. 2022; 24: 7015
• 27a Xu R, Wan J.-P, Mao H, Pan Y. J. Am. Chem. Soc. 2010; 132: 15531
• 27b Huang W.-K, Chen W.-T, Hsu I.-J, Han C.-C, Shyu S.-G. RSC Adv. 2017; 7: 4912
• 27c Zhang Q, Hu B, Zhao Y, Zhao S, Wang Y, Zhang B, Yan S, Yu F. Eur. J. Org. Chem. 2020; 1154
• 28a Yan K, Yang D, Wei W, Lu S, Li G, Zhao C, Zhang Q, Wang H. Org. Chem. Front. 2016; 3: 66
• 28b Zheng Y, Bian R, Zhang X, Yao R, Qiu L, Bao X, Xu X. Eur. J. Org. Chem. 2016; 3872
• 29a Yang D, Sun P, Wei W, Meng L, He L, Fang B, Jiang W, Wang H. Org. Chem. Front. 2016; 3: 1457
• 29b Jana A, Panday AK, Mishra R, Parvin T, Choudhury LH. ChemistrySelect 2017; 2: 9420
• 30a Babiola Annes S, Saritha R, Chandru K, Mandali PK, Ramesh S. J. Org. Chem. 2021; 86: 16473
• 30b Saritha R, Babiola Annes S, Perumal K, Shankar B, Ramesh S. J. Org. Chem. 2022; 87: 13856
• 31 Saritha R, Babiola Annes S, Ramesh S. RSC Adv. 2021; 11: 14079
• 32 3-Methyl-1-phenyl-4-(phenylsulfanyl)-1H-pyrazol-5-amine (5a); Typical Procedure A mixture of 4-iodopyrazol-5-amine 4a (0.299 g, 1 mmol), PhSH (0.330 g, 3 mmol), and Cs₂CO₃ (0.977 g, 3 mmol) with DMSO (3 mL) was irradiated with blue LED light (9 W) for 24 h in a closed vessel. When the reaction was complete (TLC), the mixture was extracted with EtOAc and H₂O. The combined organic layer was dried (Na₂SO₄), then purified by column chromatography [silica gel (60–120 mesh), EtOAc–hexane] to give a brown solid; yield: 227 mg (81%); mp 72–74 °C; R_f = 0.35 (20% EtOAc–hexane). 1H NMR (600 MHz, CDCl₃): δ = 7.54–7.45 (m, 2 H), 7.35 (tt, J = 6.0, 6.2 Hz, 1 H), 7.26–7.23 (m, 2 H), 7.11 (d, J = 6.0 Hz, 3 H), 4.22 (s, 2 H), 2.24 (s, 3 H).
• 33 Li T, Liang K, Tang J, Ding Y, Tong X, Xia C. Chem. Sci. 2021; 12: 15655