Triton B Catalyzed Rapid and Mild Synthetic Protocol for both Henry Reaction of Isatin and Michael Reaction of Chalcone with Nitroalkane

Abstract

A highly efficient and general synthetic protocol for both Henry and Michael reactions was developed using metal-free catalyst Triton B (benzyltrimethylammonium hydroxide) and isatins and chalcones, respectively. This methodology is inexpensive, the reagents are easy to handle, and the approach offers wide functional group tolerance of isatins and chalcones. The base catalyst Triton B is less toxic, recyclable, and reusable. This efficient method reduces reaction times, minimizes reagent excess, avoids chromatography, and is aligned with sustainable chemistry principles, offering eco-friendly applications in diverse industries.

Keywords

phase-transfer catalyst - Triton B (benzyltrimethylammonium hydroxide) - Henry reaction - Michael addition - rapid synthesis

Publication History

Received: 03 January 2024

Accepted after revision: 06 April 2024

Article published online:
23 April 2024

• References:

• 1 Zhang Y, Li ZJ, Xu HS, Zhang Y, Wang W. RSC Adv. 2011; 1: 389
• 2 Khetmalis YM, Shivani M, Murugesan S, Sekhar KV. G. C. Biomed. Pharmacother. 2021; 141: 111842
• 3 Ziarani GM, Javadi F, Mohajer F. Curr. Org. Chem. 2021; 25: 779
• 4 Singh J, Sharma A. Adv. Synth. Catal. 2021; 363: 4284
• 5 Khan M, Yousaf M, Wadood A, Junaid M, Ashraf M, Alam U, Khan KM. Bioorg. Med. Chem. 2014; 22: 3441
• 6 Suthar SK, Bansal S, Alam MM, Jaiswal V, Tiwari A, Chaudhary A, Joseph A. Bioorg. Med. Chem. Lett. 2015; 25: 5281
• 7 Paul S, Roy A, Deka SJ, Panda S, Srivastava GN, Trivedi V, Manna D. MedChemComm 2017; 8: 1640
• 8 Shaw S, White JD. Chem. Rev. 2019; 119: 9381
• 9 Liu M, Gui D, Deng P, Zhou H. Molecules 2019; 24: 1471
• 10 Zhang G, Zhu C, Liu D, Pan J, Zhang J, Hu D, Song B. Tetrahedron 2017; 73: 129
• 11 Bai XF, Xu Z, Xia CG, Zheng ZJ, Xu LW. ACS Catal. 2015; 5: 6016
• 12 Halland N, Hazell RG, Jørgensen KA. J. Org. Chem. 2002; 67: 8331
• 13 Blay G, Hernandez-Olmos V, Pedro JR. Org. Lett. 2010; 12: 3058
• 14 Ballini R, Barboni L, Bosica G, Fiorini D. Synthesis 2002; 2725
• 15 Corey EJ, Zhang FY. Org. Lett. 2000; 2: 4257
• 16 Adib M, Ayashi N, Heidari F, Mirzaei P. Synlett 2016; 1738
• 17 Li S, Xie Z, Bian X, Wang C. J. Chem. Res. 2007; 660
• 18 Owolabi IA, Chennapuram M, Seki C, Okuyama Y, Kwon E, Uwai K, Nakano H. Bull. Chem. Soc. Jpn. 2019; 92: 696
• 19 Wujkowska Z, Zawisza A, Leśniak S, Rachwalski M. Tetrahedron 2019; 75: 230
• 20 Meshram HM, Ramesh P, Kumar AS, Swetha A. Tetrahedron Lett. 2011; 52: 5862
• 21 Chennapuram M, Subba Reddy UV, Seki C, Okuyama Y, Kwon E, Uwai K, Nakano H. Eur. J. Org. Chem. 2017; 1638
• 22 Chakraborty A, Ghosh T, Maiti DK, Majumdar S. ChemistrySelect 2019; 4: 1841
• 23 SaiPrathima P, Srinivas K, Rao MM. Green Chem. 2015; 17: 2339
• 24 Menapara T, Tak RK, Saravanan S, Kureshy RI, Noor-ul HK, Ganguly B, Si MK. Tetrahedron 2018; 74 (49) 7000
• 25 Meshram HM, Kumar DA, Goud PR, Reddy BC. Synth. Commun. 2009; 40 (01) 39
• 26 Vakulya B, Varga S, Csámpai A, Soós T. Org. Lett. 2005; 7: 1967
• 27 Suresh P, Pitchumani K. Tetrahedron: Asymmetry 2008; 19: 2037
• 28 Li Z, Lu H, Liu Z, Ma X. J. Chem. Sci. 2019; 131: 1
• 29 Zhao D, Ren H, Wang J, Yang Y, Zhao Y. Energy Fuels 2007; 21: 2543
• 30 Wechteti L, Mekni NH, Romdhani-Younes M. Heterocycl. Commun. 2018; 24: 187
• 31 Meshram HM, Goud PR, Reddy BC, Kumar DA. Synth. Commun. 2010; 40: 2122
• 32 Sabitha G, Bhikshapathi M, Nayak S, Srinivas R, Yadav JS. J. Heterocycl. Chem. 2011; 48: 267
• 33 Ooi T, Uematsu Y, Maruoka K. J. Am. Chem. Soc. 2006; 128: 2548
• 34 Lygo B, Andrews BI. Acc. Chem. Res. 2004; 37: 518
• 35 Albanese D. Catal. Rev.: Sci. Eng. 2003; 45: 369
• 36 Luthra SS, Yang X, dos Santos LM. F, White LS, Livingston AG. J. Membr. Sci. 2002; 201: 65
• 37 Vachon J, Lacour J. Chimia 2006; 60: 266
• 38 Sahiba N, Sethiya A, Teli P, Agarwal S. ACS Omega 2023; 8: 5877
• 39 Agarwal S, Sethiya A, Soni J, Sahiba N, Teli P. Appl. Organomet. Chem. 2022; 36: e6604
• 40 Ishikawa T, Mizuta T, Hagiwara K, Aikawa T, Kudo T, Saito S. J. Org. Chem. 2003; 68: 3702
• 41 Zade RN, Mude KM, Mude BM, More PS, Patange AN. Int. Res. J. Sci. Eng. 2017; A1: 163
• 42 Meshram HM, Eeshwaraiah B, Sreenivas M, Aravind D, Syama Sundar B, Yadav JS. Synth. Commun. 2009; 39: 1857
• 43 Bulbule VJ, Jnaneshwara GK, Deshmukh RR, Borate HB, Deshpande VH. Synth. Commun. 2001; 31: 3623
• 44 Chaturvedi D, Ray S. Monatsh. Chem. 2006; 137: 311
• 45 Goel V. Orient. J. Chem. 2012; 28: 1725
• 46 Talukdar M, Islam N, Begari E. Results Chem. 2023; 101215
• 47 Prathima PS, Srinivas K, Balaswamy K, Arundhathi R, Reddy GN, Sridhar B, Likhar PR. Tetrahedron: Asymmetry 2011; 22: 2099
• 48 Li S, Xie Z, Bian X, Wang C. J. Chem. Res. 2007; 660
• 49 Wang L, Zhang Q, Zhou X, Liu X, Lin L, Qin B, Feng X. Chem. Eur. J. 2010; 16: 7696
• 50a Synthesis of Compounds 3a–l and 5a–n; General Procedure: A mixture of nitroalkane 2 (1.5 mmol), substituted isatin 1 (1 mmol) or substituted chalcone 4 (1 mmol) and Triton B (40% solution in methanol, 1 mL) were stirred at ambient temperature for 2–3 minutes. The progress of the reaction was monitored by TLC (thin-layer chromatography). After complete conversion of the starting materials, the reaction mixture was extracted with diethyl ether (4 × 10 mL). Removal of the solvent under reduced pressure gave the analytically pure products 3 or 5 without column chromatography.
• 50b Characterization Data for Compound 3a: Yield: 98%; light-brown solid; mp 135–140 °C; R_f = 0.40 (40% EtOAc/hexane). ¹H NMR (500 MHz, DMSO-d ₆): δ = 10.58 (s, 1 H, NH), 7.41 (d, J = 7.3 Hz, 1 H, ArH), 7.28 (td, J = 7.7, 1.1 Hz, 1 H, ArH), 7.00 (td, 1 H, ArH), 6.86 (d, J = 7.7 Hz, 1 H, ArH), 6.78 (s, 1 H, OH), 5.02 (q, 2 H, CH₂NO₂). ¹³C NMR (126 MHz, DMSO-d ₆): δ = 176.38, 143.03, 130.74, 128.37, 125.16, 122.30, 110.52, 78.92, 73.27. HRMS (ESI+): m/z calcd for [C₉H₈N₂O₄ + H]⁺: 209.0562; found: 209.0544.
• 50c Characterization Data for Compound 3b: Yield: 95%; off-white solid; mp 169–174 °C; R_f = 0.38 (40% EtOAc/hexane). ¹H NMR (500 MHz, DMSO-d ₆): δ = 10.73 (s, 1 H, NH), 7.65 (d, J = 2.0 Hz, 1 H, ArH), 7.47 (dd, J = 8.3, 2.1 Hz, 1 H, ArH), 6.90 (s, 1 H, OH), 6.83 (d, J = 8.3 Hz, 1 H, ArH), 5.09 (q, 2 H, CH₂NO₂). ¹³C NMR (126 MHz, DMSO-d ₆): δ = 175.99, 142.45, 133.34, 130.99, 128.16, 113.89, 112.52, 78.33, 73.09. HRMS (ESI+): m/z calcd for [C₉H₇BrN₂O₄ + H]⁺: 286.9667; found: 286.9641.
• 50d Characterization Data for Compound 5a: Yield: 98%; colorless solid; mp 87–90 °C; R_f = 0.36 (15% EtOAc/hexane). ¹H NMR (500 MHz, DMSO-d ₆): δ = 7.94 (d, J = 7.2 Hz, 2 H, ArH), 7.64 (t, J = 7.4 Hz, 1 H, ArH), 7.52 (t, J = 7.7 Hz, 2 H, ArH), 7.38 (d, J = 7.3 Hz, 2 H, ArH), 7.30 (t, J = 7.6 Hz, 2 H, ArH), 7.23 (t, J = 7.3 Hz, 1 H, ArH), 4.99 (dd, J = 12.9, 5.6 Hz, 1 H, CHNO₂), 4.87 (dd, J = 12.9, 9.8 Hz, 1 H, CHNO₂), 4.05 (dq, J = 9.7, 6.8 Hz, 1 H, CH), 3.55 (qd, J = 18.0, 7.0 Hz, 2 H, CH₂). ¹³C NMR (126 MHz, DMSO-d ₆): δ = 197.91, 140.49, 136.86, 133.88, 129.20, 128.95, 128.39, 128.26, 127.68, 80.15, 41.61, 39.71. HRMS (ESI+): m/z calcd for [C₁₆H₁₅NO₃ + H]⁺: 270.1130; found: 270.1160.
• 50e Characterization Data for Compound 5b: Yield: 98%; off-white solid; mp 45–48 °C; R_f = 0.38 (15% EtOAc/hexane). ¹H NMR (500 MHz, DMSO-d ₆): δ = 7.93 (d, 2 H, ArH), 7.65 (t, J = 7.4 Hz, 1 H, ArH), 7.53 (t, J = 7.7 Hz, 2 H, ArH), 7.43 (d, J = 8.5 Hz, 2 H, ArH), 7.37 (d, 2 H, ArH), 5.00 (dd, J = 13.0, 5.5 Hz, 1 H, CHNO₂), 4.87 (dd, J = 13.0, 9.8 Hz, 1 H, CHNO₂), 4.05 (dq, 1 H, CH), 3.56 (qd, 2 H, CH₂). ¹³C NMR (126 MHz, DMSO-d ₆): δ = 197.75, 139.57, 136.77, 133.94, 132.30, 130.27, 129.23, 128.89, 128.39, 79.92, 41.42, 39.11. HRMS (ESI+): m/z calcd for [C₁₆H₁₄ClNO₃ + H]⁺: 304.0740; found: 304.0733.