Synthesis and Photophysical Properties of 3-(Trifluoromethyl)-2H-imidazo[5,1-a]isoquinolinium Chloride Derivatives

Abstract

A series of novel blue-light-emitting 2H-imidazo[5,1-a]isoquinolinium chloride derivatives were synthesized by the reaction of isoquinoline with trifluoroacetimidoyl chlorides and isocyanides in dry CH₂Cl₂ in excellent yields. Fluorescence studies showed that the compounds absorb UV radiation and then emit blue light at about 481 nm with moderate to good fluorescence quantum yields. These compounds also showed high Stokes shifts, and can be used to develop ­ultrasensitive fluorescent molecular probes to study a variety of biological events and processes.

Key words

fluorescence - imidazoisoquinolinium chlorides - trifluoroacetimidoyl chlorides - isoquinoline - isocyanides - molecular probes

• References and Notes

• 1 Swinboune FJ. Hunt JH. Klinkert G. Adv. Heterocycl. Chem. 1987; 23: 103
• 2 Kuhla DE. US 4163745, 1979
• 3 Bower JD. Ramage GR. J. Chem. Soc. 1955; 2834
• 4 Blatcher D. Middlemiss D. Tetrahedron Lett. 1980; 21: 2195
• 5 Paudler WP. Chao LC. Helmick SL. J. Heterocycl. Chem. 1972; 9: 1157
• 6 Sasaki K. Tsurumori A. Hirota T. J. Chem. Soc., Perkin Trans. 1 1998; 3851
• 7 Zimmer H. Glasgow GD. McClanahan M. Novinson T. Tetrahedron Lett. 1968; 9: 2805
• 8 Berthet J.-C. Nierlich M. Ephritikhine M. Eur. J. Org. Chem. 2002; 375
• 9 Mahmoud S. Sheha M. Aboul-Fadl T. Farag H. Arch. Pharm. (Weinheim, Ger.) 2003; 336: 258
• 10 Yavari I. Khalili G. Mirzaei A. Helv. Chim. Acta 2010; 93: 72
• 11a Rahmani F. Darehkordi A. Notash B. J. Fluorine Chem. 2014; 166: 84
• 11b Rahmani F. Darehkordi A. Synlett 2017; 28: 1224
• 11c Darehkordi A. Rahmani F. Hashemi V. Tetrahedron Lett. 2013; 54: 4689
• 11d Darehkordi A. Rahmani F. J. Fluorine Chem. 2016; 190: 41
• 12 Darehkordi A. Khabazzadeh H. Saidi K. J. Fluorine Chem. 2005; 126: 1140
• 13 Tamura K. Mizukami H. Maeda K. Watanabe H. Uneyama K. J. Org. Chem. 1993; 58: 32
• 14 Krasovitski BM. Bolotin BM. Organic Luminescent Materials . VCH; Weinheim: 1988
• 15 Zhu M. Yang C. Chem. Soc. Rev. 2013; 42: 4963
• 16a Adachi C. Baldo MA. Forrest SR. Lamansky S. Thompson ME. Kwong RC. Appl. Phys. Lett. 2001; 78: 1622
• 16b Adachi C. Kwong RC. Djurovich P. Adamovichi V. Baldo MA. Thompson ME. Forrest SR. Appl. Phys. Lett. 2001; 79: 2082
• 16c Adachi C. Baldo MA. Thompson ME. Forrest SR. J. Appl. Phys. 2001; 90: 5048
• 16d Sun Y. Giebink NC. Knanno H. Ma B. Thompson ME. Forrest SR. Nature 2006; 440: 908
• 17a Huang J. Sun N. Dong Y. Tang R. Lu P. Cai P. Li Q. Ma D. Qin J. Li Z. Adv. Funct. Mater. 2013; 23: 2329
• 17b Chien C.-H. Chen C.-K. Hsu F.-M. Shu C.-F. Chou P.-T. Lai C.-H. Adv. Funct. Mater. 2009; 19: 560
• 17c Tonzola CJ. Kulkarni AP. Gifford AP. Kaminsky W. Jenekhe SA. Adv. Funct. Mater. 2007; 17: 863
• 17d Chen W.-C. Yuan Y. Wu G.-F. Wei H.-X. Tang L. Tong Q.-X. Wong F.-L. Lee C.-S. Adv. Opt. Mater. 2014; 2: 626
• 18 Rusakowicz R. Testa AC. J. Phys. Chem. 1968; 72: 2680
• 19 Meech SR. Phillips D. J. Photochem. 1983; 23: 193
• 20 Ulrich G. Nastasi F. Retailleau P. Puntoriero F. Ziessel R. Campagna S. Chem. Eur. J. 2008; 14: 4381
• 21 Haugland P. Molecular Probes: Handbook of Fluorescent Probes and Research Chemicals. Interchim; Eugene: 1992
• 22 3-(Trifluoromethyl)-2H-imidazo[5,1-a]isoquinolinium chlorides 4a–j; General Procedure The appropriate isocyanide derivative 3 (1 mmol) was added to a magnetically stirred solution of isoquinoline (1; 1 mmol) and the appropriate 2,2,2-trifluoroacetimidoyl chloride derivative 2 (1 mmol) in CH₂Cl₂ (10 mL) at r.t. The mixture was then stirred for the appropriate time until the reaction was complete. The solvent was removed under reduced pressure, and the residue was washed with hot EtOAc. 1-(Cyclohexylamino)-2-(4-methylphenyl)-3-(trifluoromethyl)-2H-imidazo[5,1-a]isoquinolin-4-ium Chloride (4a) white solid; yield: 431 mg (94%); mp 231–232 °C. IR (KBr): 3417, 3074, 2925, 2850 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.74 (d, J = 8.4 Hz, 1 H), 8.55 (d, J = 7.6 Hz, 1 H), 8.12 (d, J = 8.4 Hz, 1 H), 7.94–7.81 (m, 3 H), 7.60 (d, J = 8.4 Hz, 2 H), 7.55 (d, J = 8.4 Hz, 2 H), 5.78 (d, J = 7.6, 1 H, NH), 2.74–2.68 (m, 1 H, CH cyclohexyl), 2.49 (s, 3 H, CH₃), 1.66–1.45 (m, 5 H), 1.19–0.95 (m, 5 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 21.44 (Me), 25.20, 25.41, 33.87, 57.99, 117.41 (q, J = 270 Hz, CF₃), 118.40 (q, J = 41 Hz, C-CF₃), 120.32, 122.51, 122.73, 122.88, 127.12, 128.19, 128.96, 129.61, 130.26, 130.46, 130.90, 135.86, 142.01. Anal. Calcd for C₂₅H₂₅ClF₃N₃: C, 65.28; H, 5.48; 12.39; N, 9.14. Found: C, 65.22; H, 5.37; N, 9.15. 1-(Cyclohexylamino)-3-(trifluoromethyl)-2-[2-(trifluoromethyl)phenyl]-2H-imidazo[5,1-a]isoquinolin-4-ium Chloride (4b) white solid; yield: 477 mg (93%); mp 263–265 °C; IR (KBr): 3401, 3151, 2931, 2855 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.67 (d, J = 8.4 Hz, 1 H), 8.59 (d, J = 7.2 Hz, 1 H), 8.23–8.05 (m, 5 H), 7.98–7.84 (m, 3 H), 6.18 (d, J = 8.8 Hz, 1 H, NH), 2.81–2.73 (m, 1 H, CH cyclohexyl), 1.90–1.26 (m, 5 H), 1.07–0.87 (m, 5 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 25.27, 25.38, 25.54, 34.14, 34.34, 58.76, 117.16 (q, J = 270 Hz, CF₃), 117.45 (q, J = 41 Hz, C-CF₃), 119.13, 120.10, 120.13, 120.23 (q, J = 272 Hz, CF₃), 122.50, 123.65, 123.90, 126.43 (q, J = 31 Hz, C-CF₃), 127.26, 128.71, 128.75, 128.87, 129.17, 130.61, 131.06, 131.55, 133.76, 134.72, 137.27. Anal. Calcd for C₂₅H₂₂ClF₆N₃: C, 58.43; H, 4.31; N, 8.18. Found: C, 58.34; H, 4.26; N, 8.14.