Synthesis and fluorescent properties of coumarin-benzimidazole and coumarin

Abstract

Two coumarin-benzimidazole hybrids and two coumarin-phenanthroimidazole conjugates were conveniently synthesized and characterized. The UV–vis absorption, emission spectra, absolute quantum yields, and fluorescence lifetimes of these compounds in diluted dichloromethane solutions were measured.

Keywords

absorption benzimidazole coumarin fluorescence phenanthroimidazole

Coumarins have been widely studied not only for their various biological activities such as antibacterial, anti-HIV, and anticancer activities but also for their superior thermal stability and outstanding optical properties including high quantum yields, large Stokes shifts, and superior photostability. Thus, coumarin derivatives are extensively used as fluorescent whiteners, nonlinear optical chromophores, fluorescent probes, laser dyes, and solar energy collectors. Since their spectroscopic and photophysical properties can be easily modified by introducing substituents on the coumarin ring, the synthesis and application of coumarin derivatives have been attracting great interest.^1–3

Benzimidazole and phenanthroimidazole derivatives have also been extensively studied because of their synthetic utility and their variety of applications.^4,5 To our knowledge, coumarin-benzimidazole hybrids have been well studied due to their diversified properties. They are reported to exhibit various biological activities such as antitumor, antioxidant, and antihepatitis.⁶ They are also well-known laser dyes and have been investigated in many optical studies.⁷ However, studies on the optical properties and applications of coumarin-phenanthroimidazole conjugates in the literature are limited.⁸ Recently, we have synthesized coumarin-7, coumarin-30, and their 4-substituted regioisomers and found the UV–vis absorption and fluorescence emission properties of the isomers are different.^9,10 As a part of the foregoing research in our group, we present herein the concise synthesis and fluorescent properties of regioisomeric coumarin-benzimidazole and coumarin-phenanthroimidazole hybrids. As for the reported analogs,⁷ these synthesized compounds could be potentially used as laser dyes, environment-sensitive fluorescent probes, or dopants for organic light-emitting diodes.

Results and discussion

The synthesis of the target molecules was carried out as outlined in Scheme 1. As we have demonstrated previously in the synthesis of coumarin-7 and coumarin-30,^9,10 4-(diethylamino)salicylaldehyde (1) underwent the Wittig reaction with (ethoxycarbonylmethylene)triphenylphosphorane in ethanol under reflux condition to afford 7-(diethylamino)coumarin (2) in good yield. Subsequently, Vilsmeier–Haack reaction of coumarin 2 with N,N-dimethylformamide (DMF) and POCl₃ give rise to the intermediate 3-formylcoumarin 3 in high yield. On the other hand, m-diethylaminophenol (4) was subjected to the Pechmann reaction with ethyl acetoacetate in the presence of ZnCl₂ in ethanol under reflux condition to furnish the 4-methylcoumarin 5 in 82% yield. Compound 5 was oxidized to the 4-formylcoumarin 6 by treatment with SeO₂ in refluxing xylene in 58% yield. The intermediates 3-formylcoumarin 3 and 4-formylcoumarin 6 were then condensed with 2-aminodiphenylamine in the presence of ammonium acetate in ethanol at reflux to afford the desired coumarin-benzimidazole hybrids 7 and 8, respectively. It should be noted that compound 7 has been synthesized from 7-(diethylamino)coumarin-3-carboxylic acid and 2-aminodiphenylamine in two steps for evaluation in vitro as potent anticancer agent.¹¹ Moreover, intermediates 3 and 6 reacted respectively with 9,10-phenanthrenequinone, aniline, and ammonium acetate in acetic acid under reflux condition to give the coumarin-phenanthroimidazole hybrids 9 and 10. To the best of our knowledge, the synthesis of compounds 8, 9, and 10 have not been reported in the literature. These products were easily purified by column chromatography on silica gel and were characterized on the basis of spectroscopic data.

Scheme 1.

Synthesis of coumarin-benzimidazole and coumarin-phenanthroimidazole hybrids. Regents and conditions: (a) Ph₃P=CHCO₂Et, ethanol, reflux, 5 h, 72%; (b) DMF, POCl₃, 60°C, 7 h, 81%; (c) ethyl acetoacetate, ZnCl₂, ethanol, reflux, 5 h, 82%; (d) SeO₂, xylene, reflux, 10 h, 58%; (e) 2-aminodiphenylamine, ammonium acetate, ethanol, reflux, 7: 54%, 8: 49%; (f) 9,10-phenanthrenequinone, aniline, ammonium acetate, acetic acid, reflux, 9: 58%, 10: 43%.

Fortunately, a single crystal of compound 7 was obtained from petroleum ether/ethyl acetate solution for X-ray analysis, whereby the molecular structure of this coumarin-benzimidazole hybrid was further confirmed. The compound 7 crystallized in the P2₁2₁2₁ space group pertaining to orthorhombic crystal system. The crystal structure of compound 7 is shown in Figure 1. The crystallographic data and experimental details are shown in Table 1. In this molecule, the benzimidazole skeleton is not coplanar with the coumarin ring, and the dihedral angle is 57.89°. The phenyl ring attached to the N atom is also not coplanar with the benzimidazole skeleton and the coumarin ring, and the dihedral angles are 71.42° and 60.10°, respectively. Crystallographic data for 7 has been deposited at the Cambridge Crystallo-graphic Data Centre with the deposition number CCDC 1911906. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.

Figure 1.

The molecular structure of compound 7.

Table 1

Crystallographic data of compound 7.

Parameters	7
Empirical formula	C₂₆H₂₃N₃O₂
Formula weight	409.47
Temperature (K)	183(8)
Wavelength (Å)	0.71073
Crystal system	Orthorhombic
Space group	P2₁2₁2₁
a (Å)	8.1750(6)
b (Å)	12.8801(9)
c (Å)	20.3443(17)
α (°)	90
β (°)	90
γ (°)	90
Volume (Å³)	2142.2(3)
Z	4
ρ_calc (g cm⁻³)	1.270
Absorption coefficient (mm⁻¹)	0.082
F(000)	864.0
Crystal size (mm³)	0.21 × 0.17 × 0.14
2Θ range for data collection (°)	6.64 to 52.04
Index ranges	–5 ⩽ h ⩽10
	–11 ⩽ k ⩽ 15
	–25 ⩽ l ⩽ 11
Reflections collected	5223
Independent reflections	3879 (R_int = 0.0408)
Data/restraints/parameters	3879/0/282
Goodness-of-fit on F²	1.072
Final R indices [I > 2σ (I)]	R₁ = 0.0606, wR₂ = 0.1297
R indices (all data)	R₁ = 0.0898, wR₂ = 0.1591
Largest diff. peak/hole/e (Å⁻³)	0.18/−0.24

The UV–vis absorption and fluorescence spectra of the synthesized compounds 7, 8, 9, and 10 in diluted dichloromethane solutions are presented in Figure 2. It is shown that the absorption maxima of these four compounds are located at 413, 409, 409, and 402 nm, respectively. The emission spectra of compound 7 exhibits blue-green emission with a maximum peak at 473 nm, and the compounds 8, 9, and 10 show green emissions with a maximum peak at 516, 490, and 512 nm, respectively. The Stoke shift values obtained for compounds 8 and 10 are larger than those for 7 and 9. It is probable that the changes in geometry between the ground state and the first excited singlet state of the 4-substituted hybrids are larger than those of the corresponding 3-substituted analogs.¹² In order to gather more information on fluorescence properties of the synthesized compounds, the absolute quantum yields and fluorescence lifetimes in dichloromethane solutions were also determined. The quantum yields determined were absolute values using an Integrating Sphere without reference standard. The photoluminescence decay lifetimes of the compounds 7, 8, 9, and 10 were measured to be 2.40, 7.76, 2.65, and 5.69 ns, respectively, and the decay profiles are given in Figure 3. Table 2 summarizes the photophysical data of the four compounds.

Figure 2.

Normalized absorption and emission spectra of compounds 7, 8, 9, and 10 in dichloromethane (1 × 10⁻⁵ mol L⁻¹).

Figure 3.

Fluorescence life time measurements of compounds 7, 8, 9, and 10 in dichloromethane.

Table 2.

Photophysical data of the synthesized compounds.

Compound	λ_abs (nm)	λ_em (nm)	Stokes shift (nm)	Φ_f (%)	τ (ns)
7	413	473	60	85.4	2.40
8	409	516	107	82.9	7.76
9	409	490	81	88.0	2.65
10	402	512	110	57.2	5.69

In conclusion, the facile synthesis of two coumarin-benzimidazole regioisomeric hybrids and two coumarin-phenanthroimidazole regioisomeric hybrids has been described. The UV–vis absorption, emission spectra, absolute quantum yields, and fluorescence lifetimes in diluted dichloromethane solutions of these compounds were determined. The results revealed that the photophysical properties of the 3-substituted hybrids are obviously different from those of the corresponding 4-substituted analogs. Applicability of these coumarin-benzimidazole and coumarin-phenanthroimidazole conjugates is yet to be established.

Experimental

Reagents and solvents were all from commercial sources and used without further purification. IR spectra were performed on a Digilab FTS-3000 FTIR spectrophotometer. ¹H NMR and ¹³C NMR spectra were recorded on either an Agilent Technologies DDZ 600 MHz or a Bruker Avance III 500 MHz spectrometer. Melting points were determined using a microscope apparatus and are uncorrected. High-resolution mass spectra (HRMS) were determined on a Bruker Daltonics APEX II 47e spectrometer. Single crystal X-ray diffraction measurements were made on a Bruker X8 APEX diffractometer working with graphite monochromated Mo Kα radiation. UV–vis absorption and fluorescence spectra were recorded on a Hitachi U-3900H spectrometer and on a Hitachi F7000 FL spectrophotometer, respectively. Fluorescent lifetimes and absolute quantum yields were recorded on a FLS920 type steady-state/transient fluorescence spectrometer (Edinburgh Instruments Ltd).

7-(Diethylamino)coumarin (2), 7-(diethylamino)-3-formylcoumarin (3), 7-(diethylamino)-4-methylcoumarin (5), and 7-(diethylamino)-4-formylcoumarin (6) were synthesized according to the procedures described previously.¹⁰

Synthesis of 7-(Diethylamino)-3-(1-phenyl-1H-benzo[d]imidazol-2-yl)coumarin (7)

7-(Diethylamino)-3-formylcoumarin (0.23 g, 0.94 mmol), ammonium acetate (0.45 g, 5.84 mmol), and N-phenyl-o-phenylenediamine (0.19 g, 1.03 mmol) were dissolved in ethanol (20 mL). The reaction mixture was stirred under reflux conditions for 5 h. After the completion of reaction, the solvent was evaporated under reduced pressure and the resulting mixture was dissolved in ethyl acetate (50 mL). The organic phase was washed with water (3 × 50 mL), dried over Na₂SO₄, and evaporated under vacuum. The resulting residue was purified by column chromatography over silica gel using petroleum ether/acetone (v/v = 6:1) as eluent to afford yellow solid product. Yield 0.21 g (54%), m.p. 220°C–221°C (lit.¹¹ m.p. 198°C–200°C). IR (KBr) cm⁻¹: 3059, 2978, 1710, 1525, 1452, 1384, 729. ¹H NMR (600 MHz, CDCl₃): δ/ppm 8.14 (s, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.48–7.27 (m, 9H), 6.59 (dd, J = 9.0 and 2.4 Hz, 1H), 6.41 (d, J = 2.4 Hz, 1H), 3.41 (q, J = 7.2 Hz, 4H), 1.20 (t, J = 7.2 Hz, 6H). ¹³C NMR (150 MHz, CDCl₃): δ/ppm 159.1, 157.3, 151.5, 149.1, 146.2, 142.7, 136.9, 136.6, 129.8, 129.4, 128.2, 126.3, 123.4, 122.8, 119.7, 111.1, 110.4, 109.1, 108.1, 97.1, 44.9, 12.4.

Synthesis of 7-(Diethylamino)-4-(1-phenyl-1H-benzo[d]imidazol-2-yl)coumarin (8)

Compound 8 was prepared from 7-(diethylamino)-4-formylcoumarin (0.15 g, 0.61 mmol) and N-phenyl-o-phenylenediamine (0.13 g, 0.71 mmol) by a method similar to that described for 7 as yellow solid. Yield 0.12 g (49%), m.p. 218°C–220°C. IR (KBr) cm⁻¹: 3049, 2943, 1724, 1600, 1494, 1357, 754. ¹H NMR (600 MHz, CDCl₃): δ/ppm 7.95 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.49–7.30. (m, 8H), 6.58 (dd, J = 9.0 and 2.4 Hz, 1H), 6.51 (d, J = 2.4 Hz, 1H), 5.81 (s, 1H), 3.42 (q, J = 7.2 Hz, 4H), 1.21 (t, J = 7.2 Hz, 6H). ¹³C NMR (150 MHz, CDCl₃): δ/ppm 161.0, 156.8, 150.9, 147.0, 143.5, 142.9, 136.2, 135.6, 130.0, 129.0, 128.4, 126.4, 124.5, 123.5, 120.6, 111.1, 110.9, 109.1, 107.0, 97.6, 44.8, 12.4. HRMS Calculated for C₂₆H₂₄N₃O₂ [M+H]⁺: 410.1863, Found: 410.1874.

Synthesis of 7-(Diethylamino)-3-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)coumarin (9)

7-(Diethylamino)-3-formylcoumarin (0.21 g, 0.86 mmol), 9, 10-phenanthrenequinone (0.22 g, 1.05 mmol), aniline (0.12 g, 1.30 mmol), and ammonium acetate (0.20 g, 2.60 mmol) were dissolved in acetic acid (20 mL). The reaction mixture was refluxed under nitrogen for 12 h. After completion, the reaction mixture was cooled to room temperature and was poured into water (100 mL) and extracted with dichloromethane (3 × 100 mL). The combined organic phase was dried over Na₂SO₄. After filtering, the filtrate was evaporated under reduced pressure. The resulting residue was purified by chromatography on silica gel using petroleum ether/ethyl acetate/dichloromethane (v/v/v = 3:1:1) as the eluent to afford yellow solid product. Yield 0.25 g (58%), m.p. 261°C–263°C. IR (KBr) cm⁻¹: 2987, 1718, 1608, 1519, 1355, 1136, 754. ¹H NMR (500 MHz, DMSO-d₆): δ 8.94 (d, J = 8.5 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 8.64 (dd, J = 8.0 and 1.5 Hz, 1H), 8.24 (s, 1H), 7.79–7.34. (m, 10H), 7.16 (dd, J = 8.0 and 1.5 Hz, 1H), 6.73 (dd, J = 8.5 and 2.5 Hz, 1H), 6.51 (d, J = 2.5 Hz, 1H), 3.43 (q, J = 7.0 Hz, 4H), 1.12 (t, J = 7.0 Hz, 6H). ¹³C NMR (125 MHz, DMSO-d₆): δ 159.3, 156.7, 151.4, 147.6, 147.2, 137.3, 136.4, 130.2, 129.8, 129.7, 128.7, 128.5, 127.6, 127.5, 127.2, 126.7, 125.7, 125.4, 124.5, 123.7, 122.3, 121.9, 120.2, 109.9, 109.4, 107.0, 96.3, 44.2, 12.3. HRMS Calculated for C₃₄H₂₈N₃O₂ [M+H]⁺: 510.2176, Found: 510.2189.

Synthesis of 7-(Diethylamino)-4-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)coumarin (10)

Compound 10 was prepared from 7-(diethylamino)-4-formylcoumarin (0.26 g, 1.06 mmol), 9,10-phenanthrenequinone (0.27 g, 1.28 mmol), aniline (0.15 g, 1.61 mmol), and ammonium acetate (0.24 g, 3.12 mmol) by a method similar to that described for 9 as yellow solid. Yield 0.23 g (43%), m.p. 240°C–242°C. IR (KBr) cm⁻¹: 2974, 1708, 1622, 1407, 1355, 1276, 1141, 758. ¹H NMR (500 MHz, DMSO-d₆): δ 8.96 (d, J = 8.5 Hz, 1H), 8.91 (d, J = 8.5 Hz, 1H), 8.66 (dd, J = 8.0 and 1.5 Hz, 1H), 7.81–7.36 (m, 10H), 7.13 (dd, J = 8.5 and 1.5 Hz, 1H), 6.69 (dd, J = 9.5 and 2.5 Hz, 1H), 6.55 (d, J = 2.5 Hz, 1H), 6.05 (s, 1H), 3.43 (q, J = 7.0 Hz, 4H), 1.12 (t, J = 7.0 Hz, 6H). ¹³C NMR (125 MHz, DMSO-d₆): δ 159.9, 156.1, 150.7, 145.5, 143.8, 137.0, 136.6, 130.4, 130.1, 128.8, 128.7, 128.6, 127.8, 127.7, 127.6, 126.8, 126.6, 126.1, 125.8, 124.6, 123.8, 122.2, 122.0, 120.4, 110.4, 109.1, 106.8, 96.8, 44.0, 12.3. HRMS Calculated for C₃₄H₂₈N₃O₂ [M+H]⁺: 510.2176, Found: 510.2185.

Footnotes

Acknowledgements

We thank the Instrument Analysis Center of Lanzhou Jiaotong University.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Xiaolong Wang

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Synthesis and fluorescent properties of coumarin-benzimidazole and coumarin–phenanthroimidazole hybrids

Abstract

Keywords

Results and discussion

Experimental

Synthesis of 7-(Diethylamino)-3-(1-phenyl-1H-benzo[d]imidazol-2-yl)coumarin (7)

Synthesis of 7-(Diethylamino)-4-(1-phenyl-1H-benzo[d]imidazol-2-yl)coumarin (8)

Synthesis of 7-(Diethylamino)-3-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)coumarin (9)

Synthesis of 7-(Diethylamino)-4-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)coumarin (10)

Footnotes

Acknowledgements

Declaration of conflicting interests

Funding

ORCID iD

References