Lei Yingjie, Shen Hongqin, Zhang Youlai, Ouyang Jie
(School of Chemistry & Chem. Engineering，Tianjin University of Technology，Tianjin 300191)

Abstract A convenient method to synthesize 2-(2-hydroxyphenyl) benzimidazole with substituent(s) X (X=H, NH₂, SO₃H, CH₂OH, ArN=N, mono-bromide and di-bromide ) via the reaction of substituted salicylaldehyde and o-phenylenediamine in the presence of manganese (Ⅲ) acetate was reported. The corresponding photo-physical properties were characterized by ultraviolet absorption and fluorescence spectra in methanol. Meanwhile, the fluorescent characteristics of these compounds were investigated on the basis of excited-state intramolecular proton transfer mechanism. Stokes’ shift and quantum yield were also derived.
Keywords Benzimidazole derivatives; Synthesis; Photo-physical properties

1. INTRODUCTION
Due to the intense emission property via excited-state intramolecular proton transfer (ESIPT), 2-(2-hydroxyphenyl) benzimidazole and its derivatives become a series of important fluorescent compounds, which are useful as a new kind of fluorescent probes^[1-2] as well as for the potential applications as molecular switches in logic or memory circuits^[3-4]. While the conventional method for preparation of 2-(2-hydroxyphenyl) benzimidazole is from salicylic acid and o-phenylenediamine in polyphospholic acid at high temperature (150-250ºC), they frequently give rather low yields ^[5]. With the aid of the previous research work ^[6], we have found that manganese triacetate is a highly effective oxidizing reagent for promoting condensations of substituted 2-hydroxybenzaldehydes and the corresponding aromatic 1, 2-diamines under milder reaction conditions. Herein, we wish to report the syntheses of six derivatives of 2-(2-hydroxyphenyl) benzimidazole by means of the one-pot oxidative condensation in the presence of manganese (III) acetate and to investigate some of their photo-physical properties.

2. EXPERIMENTAL
   2.1 Reagents and Apparatus
   All chemicals were obtained commercially and were used without further purification. Melting points were determined with an X-4 apparatus and were uncorrected. Infrared spectra were recorded with KBr pellets on a Nicolet Inpact 170S FT-IR spectrometer in the 4000-400 cm^-1region. Elemental analyses for C, H, and N were performed on a Perkin Elmer 240 element analyzer.¹HNMR spectra were measured on a Bruker DPX 300MHz in DMSO solutions with TMS as internal standard. UV spectra were taken on a UV-1600 spectrometer and the emission spectra were obtained on a Hitachi F-4500 fluorescence spectrophotometer.
   2.2 General Synthesis
   The general procedure for the reaction of substituted 2-hydroxybenzaldehydes with o-phenylenediamine in the presence of manganese triacetate was as follows (Scheme 1). A solution of o-phenylenediamine(6mmol) in DMF (25mL) was added dropwise to a mixture of substituted salicylaldehyde(12mmol) and  anhydrous methanol (25mL) with stirring. The resulting mixture was stirred for 2 h at room temperature. The obtained sediments were collected by filtration, washed with methanol and dried, followed with dissolving in 30 mL chloroform. Manganese (III) acetate(12mmol) in a mixture solvent of H₂O / HOAc was added to the former solution of chloroform and stirred for 12 h at room temperature. The residue was poured into 100 mL water, extracted with ethyl acetate and neutralized with a saturated solution of sodium bicarbonate. The filtrate was evaporated and the crude product was further purified by thin-layer chromatography (ethyl acetate/n-hexane, 1:1).

Scheme 1. Synthesis of 2-(2-hydroxyphenyl) benzimidazole and its derivatives

2.3 Ultraviolet and Fluorescent Spectra
All sample solutions were filtered through 0.45mm Teflon membrane filters to remove interfering dust particles or fibers. For all measurements the path length was 1 cm with a cell volume of 3.0 mL. The absorption and emission spectra of these compounds were measured in methanol and have been corrected for the spectral response of the detection system. Quantum yields were determined using quinine sulfate in 0.05mol/L H₂SO₄ as fluorescence standard (from measurements using 350 nm excitation wavelength, F= 0.577) which is then given by the equation as follows,

Where the subscript x or st represents the tested or the standard, F denotes the fluorescence quantum yield, F is the peak area under the fluorescence spectra, A is the absorbance intensity, n is an index of refraction of solvent used．

3. RESULT AND DISCUSSION
   3.1 Synthesis and Characterization
   The one-pot oxidative condensation involves the formation of a Schiff base, following with nucleophilic addition of the other amino group to the imide in the presence of manganese (Ⅲ) acetate to give a cyclic intermediate, which is converted to benzimidazoles by dehydrogenation^[7]. The specific details of the products are listed below.
   2-(1H-Benzoimidazo1-2-y1)-phenol(3a)．
   This compound was obtained as colorless microcrystals, y= 85%. mp 240-242ºC(lit. 241-242ºC);¹HNMR(DMSO-d₆)d：13.20(br s,2H,OH and NH), 8.10(dd,1H,ArH,J=1.6, 7.2Hz)，7.76 (d,1H,ArH, J=5.6Hz)，7.65(d,1H,ArH,J=5.6Hz)，7.44-7.32(m,3H,ArH)，7.10-7.04(m,2H,ArH)．
   4-Amino-2-(1H-benzoimidazol-2-yl)-phenol (3b)
   This compound was obtained as pale-yellow microcrystals, y= 60%. mp 262-264ºC; ¹HNMR(DMSO-d₆)d：13.01 (br s,2H,OH and NH), 7.66(dd,1H,ArH,J=1.6,7.2Hz)，7.55 (d,1H,ArH,J=5.6Hz),7.25(d,3H,ArH,J=5.6Hz),6.74(m,2H,ArH), 4.80 (s, 2H, NH₂)．Anal. Calcd. for：C₁₃H₁₁N₃O: C,69.32; H,4.92;N,18.66. Found：C, 69.22; H, 4.90; N, 18.59.
   3-(1H-Benzoimidazo1-2-y1)-4-hydroxy-benzenesulfonic acid (3c)．
   This compound was obtained as white-off microcrystals, y= 61%. mp > 300ºC; IR(KBr)n/cm-1: 3500-3000(-SO₃H, -OH, NH), 1609(C=C); ¹HNMR(DMSO-d₆) d：13.12~15.04 (br s, 3H, SO₃H, -OH and NH), 8.42(d, 1H, ArH, J=1.6Hz), 7.84 ~7.77 (m, 3H, ArH), 7.55~7.52 (m, 2H, ArH), 7.14~7.17(d, 1H, ArH, J=8.8Hz); Anal. Calcd. for：C₁₃H₁₀N₂O₄S: C,53.79; H,3.47;N,9.65. Found：C, 53.59; H, 3.42; N, 9.62.
   2-(1H-Benzoimidazo1-2-y1)-4-hydroxymethyl-phenol(3d)．
   This compound was obtained as pale-yellow microcrystals, y= 31%. mp 272-274ºC; IR(KBr)n/cm-1: 3534 (-OH), 3449（-NH），3419 (-CH₂OH), 1397,1428,1489（- Ar）; ¹HNMR(DMSO-d₆) d：13.21(br s, 2H, OH and NH), 8.05(d, 1H, ArH, J=1.6Hz), 7.66(dd,2H,ArH,J=3.2, 9.2Hz), 7.34(dd,1H,ArH,J=3.9, 9.2Hz), 7.30(d,1H,ArH，J=1.6Hz), 7.24(d, 1H, ArH，J=1.6Hz), 7.02(d, 1H, ArH, J=8.8Hz), 4.52(m, 2H, CH₂); 2.51(br t, 1H, OH). Anal. Calcd. for：C₁₄H₁₂N₂O₂: C,69.99; H,5.03;N,11.66. Found：C,69.84; H,5.01; N,11.60.
   2-(1H-benzoimidazol-2-yl)-4-phenylazo-phenol (3e)
   This compound was obtained as bright-yellow microcrystals, y= 85%. mp 252-254ºC; IR(KBr)n/cm-1: 3350 (-OH), 3449（-NH），1634,1589(-Ar), 1495(-N=N-); ¹HNMR(DMSO-d₆) d：13.69 (br s, 2H, OH and NH), 8.76 (d, 1H, ArH, J=1.6Hz), 7.98(dd,1H,ArH,J=3.2,9.2Hz), 7.90 (dd,2H,ArH,J=3.9,9.2Hz), 7.70(d,2H,ArH,J=1.6Hz), 7.64-7.55(m, 3H, ArH), 7.32(m, 2H,ArH), 7.24(m,1H,ArH). Anal. Calcd. for：C₁₉H₁₄N₄O: C,72.60; H,4.49; N,17.82. Found：C, 72.52; H, 4.45; N, 17.76.
   4-Bromo-2-(1H-benzoimidazol-2-yl)-phenol (3f)
   This compound was obtained as greenish yellow microcrystals, y= 63%. mp > 300ºC; IR(KBr)n/cm-1: 3446(-OH), 3334(-NH), 1634,1589(-Ar), 532(C-Br); ¹HNMR (DMSO-d₆) d：13.30 (br s, 2H, OH and NH), 8.30 (d, 1H, ArH, J=1.6Hz), 7.74 (d,1H,ArH,J=3.2Hz),7.63(d,1H,ArH,J=3.9Hz), 7.53(d,1H,ArH,J=1.6Hz), 7.31 (m, 2H, ArH), 7.02(m, 1H,ArH). Anal. Calcd. for：C₁₃H₉BrN₂O: C,54.00; H,3.14; N,9.69. Found：C,53.89; H,3.11; N,9.64.
   4, 6-Dibromo-2-(1H-benzoimidazol-2-yl)-phenol (3g)
   This compound was obtained as yellow needless microcrystals, y= 52%. mp 243-245ºC; IR(KBr)n/cm-1: 3446(-OH), 3398（-NH）,1634,1589(-Ar); ¹HNMR(DMSO-d₆) d：13.30 (br s, 2H, OH and NH), 7.70(d, 1H, ArH, J=1.6Hz), 7.63 (d,1H,ArH,J=3.9 Hz),7.44 (s,1H,ArH), 7.35 (s,1H,ArH), 7.26 (d, 1H, ArH, J=1.6Hz), 6.86(m, 1H,ArH). Anal. Calcd. for：C₁₃H₈Br₂N₂O: C,42.43; H,2.19; N,7.61. Found：C,42.39; H,2.16; N,7.59.
   3.2 Spectroscopic properties
   The absorption and emission spectra of these compounds were measured in methanol while quantum yields were determined using quinine sulfate in 0.05mol/L H₂SO₄ as the standard, the data were listed in Table 1．

Table 1．Photo-physical characteristics of the 2-(2-hydroxyphenyl) benzimidazole derivatives

Table1 clearly demonstrates that all of the title compounds display an intense fluorescence emission with a quantum yield ranging 0.03 to 0.69 for total fluorescence and show certain large Stokes shifts from 124 to 167 nm, which are the typical emission properties of excited-state intramolecular proton transfer (ESIPT) fluorophore^[8].
As for the dependence between the structure of hydroxyaryl and benzimidazole groups, it can be found that the photo-physical properties are significantly influenced by donor or acceptor substitutents. When an electron-withdrawing group is attached to the benzene ring of 2-hydroxyphenyl group at C-4 position (and C-5), such as compounds of 3c, 3e, 3f (3g), their maximum absorption wavelength (except for 3c, which was nearly unchanged) and maximum emission wavelength were toward a bathochromic shift. The absorption coefficients e was enlarged with the corresponding increasing of 16-23 nm Stokes shift approximately. However, their quantum yields were decreased relative to those of the parent compound 3a, especially in the case of compound 3e where the quantum yield was only 0.03, which indicates that phenylazo is a poor substituent to the 2-(2-hydroxyphenyl) benzimidazole fluorophore.
On the other hand, when a donor substitutent, such as an amino group, is attached to the benzene ring of 2-hydroxyphenyl group at C-4 position 3b, its maximum absorption wavelength and maximum emission wavelength were increased, but absorption coefficient (e), Stokes shift and quantum yield were decreased relative to those of the parent compound 3a. In the case of hydroxymethyl group attached to the benzene ring of 2-hydroxyphenyl group at C-4 position 3d, however，except for its quantum yield, the maximum absorption wavelength, maximum emission wavelength, absorption coefficient (e)and Stokes shift were increased relative to those of compound 3a, which may be partly caused by the inductive effect from the oxygen with the hydroxymethyl group.
3.3 Dependence of Normal and Tautomer Emission on the Structure
It is known that 2-(2-hydroxyphenyl) benzimidazole is with the dual emission characteristics at room temperature, which is called normal and tautomer respectively ^[9-10]. The normal emission is led by two intramolecular hydrogen bonded rotamers I and II in which the former is more stable and cannot be inter-convertible in the excited singlet state. However, only rotamer II on excited can undergo excited-state intramolecular proton transfer (ESIPT) to form a tautomer III in the ground state which gives rise to the tautomer emission with large Stokes shift (Scheme 2)．

Scheme 2 Three tautomers of 2-(2-hydroxyphenyl) benzimidazole

Meanwhile, in order to assessment the dependence of normal and tautomer emission on the structure of 2-(2-hydroxyphenyl) benzimidazole and its derivatives, quantum yield of the normal emission(F_N) and quantum yield of the tautomer emission(F_T) as well as a corresponding ratio (F_N/F_T) of the title compounds were evaluated in methanol at 25ºC(Figure 1), the data were listed in Table 2.

Figure 1 The fluorescent spectra of compounds 3b-3g in methanol at 25 ºC.

Table 2 Quantum yields of F_N and F_T for 2-(2-hydroxyphenyl) benzimidazole derivatives

From Table 2, it can be found that when an electron-donating group is attached to the benzene ring of 2-hydroxyphenyl group，such as 3b and 3d，the electron density of lone pair within the OH of 2-hydroxyphenyl group is increased comparison to that of the parent compound 3a, so that the population of the rotamer I will increase and leads to the relative enhancement of the normal emission along with the corresponding large F_N/F_T ratio values.
On the contrary，when an electron-withdrawing group to the benzene ring of 2-hydroxyphenyl group at C-4 position (and C-5), such as compounds of 3e and 3f (3g), the ratio of F_N/F_T is less than that of the parent compound 3a because of the decreasing of electron density of the oxygen atom on OH,thus the population of rotamer II, which is responsible for the tautomer emission, becomes more predominant. Except for the poor quantum yield of compound 3e, which may be act as a p-donating resonance contribution as well as s-accepting inductive component, in the case of these derivatives, a high intensity emission with a high Stokes shift due to ESIPT transform is produced.
However, the ratio of F_N/F_T in compound 3c is unusually higher than that of the parent compound 3a, even more than those with electron-donating substituents. How to explain this phenomenon is undergoing further investigation. What’s more, to increase the solubility of 2-(2-hydroxyphenyl) benzimidazole, we functionalized this fluorophore with a sulfo group. Fortunately, the results showed that modification with sulphonation, 2-(2-hydroxyphenyl) benzimidazole derivative 3c can be solved in water at room temperature easily, which may have a bright future in fluorescent molecular sensor applications.

4. CONCLUSION
   Six derivatives of 2-(2-hydroxyphenyl) benzimidazole have been prepared via the reaction of substituted salicylaldehyde and o-phenylenediamine in the presence of manganese (III) acetate. The corresponding photo-physical properties have been carried out based on the ultraviolet absorption and fluorescence spectra in methanol, and the results show that the fluorescent characteristics of these compounds are typical to the excited-state intramolecular proton transfer mechanism. Meanwhile, solubility test shows that modification with a sulfo group to 2-(2-hydroxyphenyl) benzimidazole can improve the solubility in water at room temperature easily.

ACKNOWLEDGEMENT    The project was supported by the National Science Foundation of China (NSFC, No.20771082).

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