Metal-Free Synthesis of Thiocyanated Aminonitroalkenes and 2-Aminothiazoles/selenazoles from β-Aminonitroalkenes and N‑Thio/Selenocyanatosaccharin

Abstract

A convenient and efficient protocol has been developed for the synthesis of thiocyanated aminonitroalkenes and 2,4,5-trisubstituted thiazoles/selenazoles from β-aminonitroalkenes and N‑thio/selenocyanatosaccharin. This method features simple operation, mild reaction conditions, short reaction time, good functional group compatibility, and metal-free characteristics. The broad applications of polysubstituted thiazoles/selenazoles in organic and medicinal chemistry make this protocol much more practical.

Key words

2-aminothiazoles - β-aminonitroalkenes - N‑thiocyanatosaccharin

Publication History

Received: 25 July 2022

Accepted after revision: 23 August 2022

Accepted Manuscript online:
23 August 2022

Article published online:
21 November 2022

• References and Notes

• 1 Castanheiro T, Suffert J, Donnard M, Gulea M. Chem. Soc. Rev. 2016; 45: 494
• 2 Brown SP, Smith AB. J. Am. Chem. Soc. 2015; 137: 4034
• 3 Melzig L, Rauhut CB, Naredi-Rainer N, Knochel P. Chem. Eur. J. 2011; 17: 5362
• 4 Lu X, Wang H, Gao R, Sun D, Bi X. RSC Adv. 2014; 4: 28794
• 5 Gonda J, Martinková M, Raschmanová J, Balentová E. Tetrahedron: Asymmetry 2006; 17: 1875
• 6a Ali SH, Sayed AR. Synth. Commun. 2021; 51: 670
• 6b dos Santos GC, Martins LM, Bregadiolli BA, Moreno VF, da Silva Filho LC, da Silva BH. S. T. J. Heterocycl. Chem. 2021; 58: 2226
• 6c Petrou A, Fesatidou M, Geronikaki A. Molecules 2021; 26: 3166
• 6d Liu Y, He P, Zhang Y, Zhang X, Liu J, Du Y. J. Org. Chem. 2018; 83: 3897
• 6e Ling C, Zheng Z, Jiang X, Zhong W, Li S. Bioorg. Med. Chem. Lett. 2010; 20: 5123
• 7a Turan-Zitouni G, Altıntop MD, Özdemir A, Kaplancıklı ZA, Çiftçi GA, Temel HE. Eur. J. Med. Chem. 2016; 107: 288
• 7b Luzina EL, Popov AV. Eur. J. Med. Chem. 2009; 44: 4944
• 7c Sharma PC, Bansal KK, Sharma A, Sharma D, Deep A. Eur. J. Med. Chem. 2020; 188: 112016
• 7d Srivastava PC, Robins RK. J. Med. Chem. 1983; 26: 445
• 8a Moradi AV, Peyghan AA, Hashemian S, Baei MT. Bull. Korean Chem. Soc. 2012; 33: 3285
• 8b Rouf A, Tanyeli C. Eur. J. Med. Chem. 2015; 97: 911
• 9a Liu R, Huang Z, Murray MG, Guo X, Liu G. J. Med. Chem. 2011; 54: 5747
• 9b Koketsu M, Ishihara H. Curr. Org. Chem. 2003; 7: 175
• 10 Siddiqui N, Ahsan W. Eur. J. Med. Chem. 2010; 45: 1536
• 11 Kouatly O, Geronikaki A, Kamoutsis C, Hadjipavlou-Litina D, Eleftheriou P. Eur. J. Med. Chem. 2009; 44: 1198
• 12 Arora P, Narang R, Nayak SK, Singh SK, Judge V. Curr. Org. Chem. 2016; 25: 1717
• 13 Kumar Y, Green R, Borysko KZ, Wise DS, Wotring LL, Townsend LB. J. Med. Chem. 1993; 36: 3843
• 14a Sekiguchi A, Nishina A, Kimura H, Fukumoto R. h, Kogami M, Ishihara H, Koketsu M. Biol. Pharm. Bull. 2006; 29: 1404
• 14b Sekiguchi A, Nishina A, Kimura H, Fukumoto R. h, Kanoh K, Ishihara H, Koketsu M. Chem. Pharm. Bull. 2005; 53: 1439
• 15 Scott KA, Njardarson JT. Top. Curr. Chem. 2018; 376: 5
• 16a Pathania S, Rawal RK. Chem. Heterocycl. Compd. 2020; 56: 445
• 16b Chowdhury A, Patel S, Sharma A, Das A, Meshram P, Shard A. Chem. Heterocycl. Compd. 2020; 56: 455
• 16c Ali SH, Sayed AR. Synth. Commun. 2021; 51: 670
• 16d Borcea AM, Ionuț I, Crișan O, Oniga O. Molecules 2021; 26: 624
• 17a Mishra CB, Kumari S, Tiwari M. Eur. J. Med. Chem. 2015; 92: 1
• 17b Facchinetti V, Nery AC. S, Avellar MM, Gomes CR. B, de Souza MV. N, Vasconcelos TR. A. Curr. Org. Synth. 2015; 12: 140
• 18 Chen B, Guo S, Guo X, Zhang G, Yu Y. Org. Lett. 2015; 17: 4698
• 19 Duan X, Liu X, Cuan X, Wang L, Liu K, Zhou H, Chen X, Li H, Wang J. J. Org. Chem. 2019; 84: 12366
• 20a Seko S, Komoto I. J. Chem. Soc., Perkin Trans. 1 1998; 2975
• 20b Trost BM, Müller C. J. Am. Chem. Soc. 2008; 130: 2438
• 21 General Procedure for the Synthesis of Compound 1 To a mixture of the appropriate aldehyde (10 mmol) and nitromethane (0.61 g, 10 mmol) in methanol (10 mL) at 0 °C, a solution of NaOH in H₂O (0.48 g, 12 mmol in 2 mL, 1.2 equiv) was added dropwise. Further methanol (3–5 mL) was added and the resulting yellow slurry stirred at that temperature for 1 h. Water (10 mL) was added, and the clear yellow solution was poured into hydrochloric acid (4.7 mL concd hydrochloric acid in 10 mL H₂O) and stirred for 15 min. The aqueous mixture was extracted with DCM (3 × 15 mL), the combined organic layers dried over magnesium sulfate, and the solvent removed using a rotary evaporator. The residue was purified by column chromato­graphy. Triethylamine (0.7 mL, 5.0 mmol) was added to a solution of methoxylamine–HCl (0.42 g, 5.0 mmol) in dimethyl­formamide (8 mL) at 0 °C. β-Nitroalkene (5.0 mmol) was then added, and the resulting suspension was stirred at 0 °C for 15 min and at room temperature for 5 min. The precipitate was removed by filtration and washed with a small amount of DMF. The combined filtrate was transferred into an addition funnel and was added dropwise to a potassium tert-butoxide (1.12 g, 10 mmol) solution in DMF (12 mL) at 0 °C. The cooling bath was then removed, and the reaction mixture was stirred for 30 min at r.t. The reaction was quenched with saturated aq. NH₄Cl (30 mL). The solvents were distilled in vacuo, and the residue was dissolved in DCM. The obtained organic phase was washed with water and brine, dried over MgSO₄, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (DCM/ethyl acetate, 6:1) to afford the desired β-amino nitroolefin. The obtained spectroscopic data were in accordance with those previously published.
• 22 Chandran R, Pise A, Shah SK, Rahul D, Suman V, Tiwari KN. Org. Lett. 2020; 22: 6557
• 23 Wu D, Qiu J, Karmaker PG, Yin H, Chen F.-X. J. Org. Chem. 2018; 83: 1576