Novel Benzothiophene-Based Fluorescent Dye Exhibiting a Large Stokes Shift

Abstract

We report a simple two-step method for the synthesis of a novel highly fluorescent benzothiophene-based dye comprising five fused rings and exhibiting a large Stokes shift (Δλ = 152 nm or Δν = 5482 cm^–1 in ethanol). Structural features of the obtained compound allow easy functionalization of the carbon core and open new possibility for the development of a series of new classes of fluorescent dyes.

Key words

fluorescence - benzothiophenes - fluorescent dye - Stokes shift - oxidative coupling

Publication History

Received: 24 August 2021

Accepted after revision: 01 October 2021

Article published online:
19 October 2021

• References and Notes

• 1a Kim D, Jeong K, Kwon JE, Park H, Lee S, Kim S, Park SY. Nat. Commun. 2019; 10: 3089
• 1b Svechkarev D, Mohs AM. Curr. Med. Chem. 2019; 26: 4042
• 2 Gonçalves MS. T. Chem. Rev. 2009; 109: 190
• 3a Capodilupo AL, Fabiano E, De Marco L, Ciccarella G, Gigli G, Martinelli C, Cardone A. J. Org. Chem. 2016; 81: 3235
• 3b Eom YK, Kang SH, Choi IT, Kim E, Kim J, Ju MJ, Kim HK. RSC Adv. 2015; 5: 80859
• 4a Ormond AB, Freeman HS. Materials 2013; 6: 817
• 4b Kamkaew A, Hui Lim S, Boon Lee H, Voon Kiew L, Yong Chung L, Burgess K. Chem. Soc. Rev. 2013; 42: 77
• 5 Lehmann M, Lichtner G, Klenz H, Schmoranzer J. J. Biophotonics 2016; 9: 161
• 6a Aaron J.-J, Mechbal Z, Adenier A, Parkanyi C, Kozmik V, Svoboda J. J. Fluoresc. 2002; 12: 231
• 6b Lô C, Aaron J.-J, Kozmík V, Svoboda J, Brochon J.-C, Na L. J. Fluoresc. 2010; 20: 1037
• 7 Jiao C, Huang K.-W, Wu J. Org. Lett. 2011; 13: 632
• 8a Ni Y, Wu J. Org. Biomol. Chem. 2014; 12: 3774
• 8b Lim SH, Thivierge C, Nowak-Sliwinska P, Han J, van den Bergh H, Wagnières G, Burgess K, Lee HB. J. Med. Chem. 2010; 53: 2865
• 9 Bröring M, Krüger R, Link S, Kleeberg C, Köhler S, Xie X, Ventura B, Flamigni L. Chem. Eur. J. 2008; 14: 2976
• 10a Melandri D, Montevecchi PC, Navacchia ML. Tetrahedron 1999; 55: 12227
• 10b Montevecchi PC, Navacchia ML. Phosphorus, Sulfur Silicon Relat. Elem. 2000; 166: 201
• 11 Typical Procedure for the Synthesis of Methyl 6,7-Dimethoxybenzo[b]thiophene-3-carboxylate (2)To the solution of thiol 1 (2.60 g, 15.27 mmol) in acetonitrile (150 mL) methyl propiolate (2.7 mL, 30.54 mmol) and AIBN (0.50 g, 3.1 mmol) were added under argon atmosphere. A yellow solution was stirred for 2 h under reflux. Liquids were evaporated in vacuo to obtain a yellow oil. The crude product was purified by column chromatography on silica gel (hexane–EtOAc from 50:1 to 15:1) to obtain 2 (1.35 g, 5.4 mmol, 35%) as colorless needles; R_f = 0.57 (hexane–EtOAc = 7:3).Analytical Data for 2 ¹H NMR (300 MHz, CDCl₃): δ = 8.25 (1 H, d, J = 8.6 Hz), 8.22 (1 H, s), 7.18 (1 H, d, J = 8.9 Hz), 4.03 (3 H, s), 3.96 (3 H, s), 3.93 (3 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 163.4, 148.9, 142.9, 135.4, 134.8, 132.2, 127.3, 120.1, 113.8, 60.7, 57.0, 51.8. ESI-HRMS: m/z calcd for С₁₂H₁₃O₄S⁺ [M + H]⁺: 253.0529; found: 253.0538.
• 12 Sarhan AA. O, Bolm C. Chem. Soc. Rev. 2009; 38: 2730
• 13 Synthesis of 1-Methoxycarbonyl-4,5,9,10-tetramethoxy-6-oxo-6H-phenantro[6,5-b:1,10-b′c′]dithiophene (3)A mixture of compound 2 (50.0 mg, 0.198 mmol), FeCl₃ (64.3 mg, 0.396 mmol), and DCE (0.5 mL) was stirred in a sealed tube under argon atmosphere for 2 h at 85 °С. After cooling to r.t. 1 M HCl (3 mL) was added, and the mixture was extracted with DCM (3 × 2 mL). Combined organic layers were washed with water (3 × 2 mL), brine (3 × 2 mL), dried over Na₂SO₄, and evaporated under reduced pressure. The residue was purified by flash column chromatography (hexane–EtOAc = 7:3) to obtain 3 as an orange solid (45 mg, 0.096 mmol, 97%). R_f = 0.35 (hexane–EtOAc = 7:3).Analytical Data for 3 ¹H NMR (300 MHz, CDCl₃): δ = 8.55 (1 H, s), 8.23 (1 H, s), 7.40 (1 H, s), 4.18 (3 H, s), 4.15 (3 H, s), 4.05 (3 H, s), 3.96 (3 H, s), 3.56 (3 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 179.5, 165.3, 150.9, 149.4, 147.1, 144.6, 141.4, 136.2, 135.1, 132.9, 132.8, 131.6, 131.0, 129.7, 128.4, 127.6, 122.7, 113.1, 62.0, 61.4, 61.0, 57.2, 52.2. ESI-HRMS: m/z calcd for С₁₂H₁₃O₄S⁺ [M + H]⁺: 471.0567; found: 471.0559.
• 14 Bolt YaV, Tsarkova AS, Baleeva NS. Russ. J. Bioorg. Chem. 2020; 46: 1289
• 15a Araneda JF, Piers WE, Heyne B, Parvez M, McDonald R. Angew. Chem. Int. Ed. 2011; 50: 12214
• 15b Benniston AC, Winstanley TP. L, Lemmetyinen H, Tkachenko NV, Harrington RW, Wills C. Org. Lett. 2012; 14: 1374
• 15c Bertolino CA, Caputo G, Barolo C, Viscardi G, Coluccia S. J. Fluoresc. 2006; 16: 221
• 15d Gong Y.-J, Zhang X.-B, Mao G.-J, Su L, Meng H.-M, Tan W, Feng S, Zhang G. Chem. Sci. 2016; 7: 2275
• 15e He X, Wang Y, Wang K, Chen M, Chen S. Anal. Chem. 2012; 84: 9056
• 15f Wu W.-B, Wang M.-L, Sun Y.-M, Huang W, Cui Y.-P, Xu C.-X. J. Phys. Chem. Solids 2008; 69: 76
• 15g Yuan L, Lin W, Chen H. Biomaterials 2013; 34: 9566