Denitrosation of Aryl-N-nitrosamines by a Transnitrosation Strategy Using Ethanethiol and p-Toluenesulfonic Acid under Mild Reaction Conditions

Abstract

A convenient and practical route is reported for the denitrosation of aryl-N-nitrosamines under mild reaction conditions using ethanethiol and PTSA. The reactions proceeds at room temperature and the amines are obtained in good to excellent yields. Many functional groups that are susceptible to reduction were stable during the denitrosation. A broad substrate scope and easy operations are salient features of this method.

Key words

amines - nitrosamines - denitrosation - metal-free reaction - ethanethiol - transnitrosation

Publication History

Received: 12 November 2022

Accepted after revision: 11 December 2022

Accepted Manuscript online:
11 December 2022

Article published online:
11 January 2023

• References and Notes

• 1 Current address: Department of Chemistry, Mahant Darshan Das Mahila Mahavidyalaya, Muzaffarpur, Bihar-842002, India.
• 2 Current address: Department of Chemistry, Kashi Naresh Govt. PG College, Bhadohi, Uttar Pradesh, 221304, India.
• 3a Anselme J.-P. In N-Nitrosamines, Chap. 1. Anselme J.-P. ACS Symposium Series 101; American Chemical Society; Washington DC: 1979: 1
• 3b Nitrosamines and Related N-Nitroso Compounds . Loeppky RN, Michejda CJ. ACS Symposium Series 553; American Chemical Society; Washington DC: 1994
• 3c N-Nitroso Compounds: Occurrence and Biological Effects . Bartsch H, O’Neill IK, Castegnaro M, Okada M. IARC Scientific Publication 41; International Agency for Research on Cancer; Lyon: 1982
• 4a Lijinsky W. Cancer Metastasis Rev. 1987; 6: 301
• 4b Tricker AR, Preussmann R. Mutat. Res., Genet. Toxicol. Environ. Mutagen. 1991; 259: 277
• 4c Nitric Oxide Donors: For Pharmaceutical and Biological Applications . Wang PG, Cai TB, Taniguchi N. Wiley-VCH; Weinheim: 2005
• 4d Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ. Chem. Rev. 2002; 102: 1091
• 5a Kakeya H, Imoto M, Takahashi Y, Naganawa H, Takeuchi T, Umezawa K. J. Antibiot. 1993; 46: 1716
• 5b Li M, Shandilya SM, Carpenter MA, Rathore A, Brown WL, Perkins AL, Harki DA, Solberg J, Hook DJ, Pandey KK, Parniak MA, Johnson JR, Krogan NJ, Somasundaran M, Ali A, Schiffer CA, Harris RS. ACS Chem. Biol. 2012; 7: 506
• 5c Gnewuch CT, Sosnovsky G. Chem. Rev. 1999; 97: 829
• 5d Rossini AA, Like AA, Chick WL, Appel MC, Cahill GF. Jr. Proc. Natl. Acad. Sci. U.S.A. 1977; 74: 2485
• 5e Iimura H, Takeuchi T, Kondo S, Matsuzaki M, Umezawa H. J. Antibiot. 1972; 25: 497
• 6a Saavedra JE. Org. Prep. Proced. Int. 1987; 19: 85
• 6b Seebach D, Enders D. Angew. Chem., Int. Ed. Engl. 1975; 14: 15
• 6c Williams DL. H. Tetrahedron 1975; 31: 1343
• 6d Cikotiene I, Jonusis M, Jakubkiene V. Beilstein J. Org. Chem. 2013; 9: 1819
• 7a Entwistle ID, Johnstone RA. W, Wilby AH. Tetrahedron 1982; 38: 419
• 7b Schueler FW, Hanna C. J. Am. Chem. Soc. 1951; 73: 4996
• 7c Hartman WW, Roll LJ. Org. Synth. 1933; 13: 66
• 7d Hinmap RL, Hamm KL. J. Org. Chem. 1958; 23: 529
• 7e Browne DL, Harrity JP. A. Tetrahedron 2010; 66: 553
• 7f Stewart FH. C. Chem. Rev. 1964; 64: 129
• 8a Chaudhary P, Kandasamy J, Macabeo AP. G, Tamargo RJ. I, Lee YR. Adv. Synth. Catal. 2021; 363: 2037
• 8b Liu B, Fan Y, Gao Y, Sun C, Xu C, Zhu J. J. Am. Chem. Soc. 2013; 135: 468
• 8c Liu BQ, Song C, Sun C, Zhou SG, Zhu J. J. Am. Chem. Soc. 2013; 135: 16625
• 8d Wang C, Huang Y. Org. Lett. 2013; 15: 5294
• 8e Chen J, Chen P, Song C, Zhu J. Chem. Eur. J. 2014; 20: 14245
• 8f Gao T, Sun P. J. Org. Chem. 2014; 79: 9888
• 8g Wu Y, Feng L.-J, Lu X, Kwong FY, Luo H.-B. Chem. Commun. 2014; 50: 15352
• 8h Xie F, Qi Z, Yu S, Li X. J. Am. Chem. Soc. 2014; 136: 4780
• 8i Yu S, Li X. Org. Lett. 2014; 16: 1200
• 8j Li D.-D, Cao Y.-X, Wang G.-W. Org. Biomol. Chem. 2015; 13: 6958
• 8k Dong J, Wu Z, Liu Z, Liu P, Sun P. J. Org. Chem. 2015; 80: 12588
• 8l Wu Y, Sun L, Chen Y, Zhou Q, Huang J.-W, Miao H, Luo H.-B. J. Org. Chem. 2016; 81: 1244
• 9a Teuten EL, Loeppky RN. Org. Biomol. Chem. 2005; 3: 1097
• 9b Zhang J, Jiang J, Li Y, Wan X. J. Org. Chem. 2013; 78: 11366
• 9c Leoppky RN, Tomasik W. J. Org. Chem. 1983; 48: 2751
• 10 Jones EC. S, Kenner J. J. Chem. Soc. 1932; 711
• 11 Kano S, Tanaka Y, Sugino E, Shibuya S, Hibino S. Synthesis 1980; 741
• 12 Alper H, Edward JT. Can. J. Chem. 1970; 48: 1543
• 13 Enders D, Hassel T, Pieter R, Renger B, Seebach D. Synthesis 1976; 548
• 14a Chaudhary P, Gupta S, Muniyappan N, Sabiah S, Kandasamy J. Green Chem. 2016; 18: 2323
• 14b Chaudhary P, Gupta S, Sureshbabu P, Sabiah S, Kandasamy J. Green Chem. 2016; 18: 6215
• 14c Chaudhary P, Gupta S, Muniyappan N, Sabiah S, Kandasamy J. J. Org. Chem. 2019; 84: 104
• 14d Chaudhary P, Korde R, Gupta S, Sureshbabu P, Sabiah S, Kandasamy J. Adv. Synth. Catal. 2018; 360: 556
• 14e Sureshbabu P, Azeez S, Chaudhary P, Kandasamy J. Org. Biomol. Chem. 2019; 17: 845
• 14f Chauhan S, Chaudhary P, Singh AK, Verma P, Srivastava V, Kandasamy J. Tetrahedron Lett. 2018; 59: 272
• 14g Azeez S, Chaudhary P, Sureshbabu P, Sabiah S, Kandasamy J. Org. Biomol. Chem. 2018; 16: 8280
• 15 N-Benzylaniline (2a); Typical Procedure N-Benzyl-N-nitrosoaniline (1a; 1.0 mmol, 1.0 equiv) was stirred in DCM (3 mL) for 5 min at room temperature, then PTSA (0.3 equiv) and ethanethiol (2.0 equiv) were added, and the mixture was stirred until the reaction as complete (TLC). The mixture was then diluted with DCM and washed with H₂O. The organic layer was dried (Na₂SO₄), concentrated, and purified by column chromatography [silica gel, hexane–EtOAc (92:8)] to give a pale-yellow viscous liquid; yield: 164 mg (89%); R_f = 0.62.¹H NMR (500 MHz, CDCl₃): δ = 7.26–7.19 (m, 4 H), 7.18–7.13 (m, 1 H), 7.08–7.04 (m, 2 H), 6.61 (td, J = 7.4, 1.0 Hz, 1 H), 6.50 (dd, J = 8.6, 0.9 Hz, 2 H), 4.18 (s, 2 H), 3.85 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 148.0, 139.3, 129.1, 128.5, 127.4, 127.1, 117.4, 112.7, 48.1.
• 16 Inami K, Kondo S, Ono Y, Saso C, Mochizuki M. Bioorg. Med. Chem. 2013; 21: 7853
• 17 Yi S.-L, Li M.-C, Hu X.-Q, Mo W.-M, Shen Z.-L. Chin. Chem. Lett. 2016; 27: 1505