Synthesis and optical properties of novel 1,2,3-triazole derivatives possessing highly substituted imidazoles

Abstract

Reactions of 1,4,5-triaryl-2-(4-bromomethyl)phenyl-imidazoles with sodium azide in acetone give the corresponding azidomethyl derivatives, which on 1,3-dipolar cycloaddition with various terminal alkynes in the presence of CuI afford novel 1,2,3-triazole products. On the other hand, treatment of 2,4,5-triaryl-1-(4-hydroxyphenyl)-imidazoles with propargyl chloride in the presence of a base gives the corresponding propargyl ether derivatives, which under CuI-catalyzed 1,3-dipolar cycloaddition with benzyl azide produce 1,2,3-triazole derivatives. All the products are characterized from their spectroscopic data and most are evaluated for fluorescence emission. The optical parameters of the studied products are also reported.

Introduction

1,3-Dipolar cycloaddition of azides and alkynes, as one of the most powerful click reactions, offers an efficient methodology for the synthesis of 1,2,3-triazoles.^1–3 Several members of these azoles have been widely applied in diverse areas of chemistry such as medicinal and materials hemistry,^4–6 and also various streams of applied sciences.^7–12 The Cu(I)-catalyzed version of this coupling reaction, which was discovered by the groups of Sharpless and Meldal independently, increases the reaction rate and produces the 1,4-disubstituted triazoles regioselectively.^13,14 Continuing efforts and several modifications leading to the production of highly diverse derivatives highlight the special interest in this click reaction.^15–17

Polyaromatic molecules with several heterocyclic frameworks and high conjugation have attracted attention due to having high technology applications, especially in biological and optical systems.^18–21 Meanwhile, there are many reports on the synthesis of hybrid molecules containing a 1,2,3-triazole moiety with other heterocyclic compounds.^22,23 1,2,4,5-Tetraarylimidazole derivatives, which can be prepared by four-component condensation of aromatic aldehydes, benzil, primary amines and ammonium acetate,^24,25 have been recently reported by our group^26,27 to act as light-emitting backbones. According to our interest in the synthesis of new heterocyclic and polyaromatic systems containing a 1,2,3-triazole ring, ²⁸ herein we report Cu(I)-catalyzed cycloadditions between azidomethyl derivatives of 1,2,4,5-tetraarylimidazoles and terminal alkynes to afford new 1,2,3-triazole structures possessing polyaryl imidazole scaffolds. In addition, catalytic cyclizations of propargyloxy derivatives of the prepared tetraarylimidazoles with benzyl azide to diversify the products are also reported. All of the synthesized products are evaluated for their absorption and fluorescence emission properties.

Results and discussion

The starting compounds 1a and 1b were prepared by benzylic bromination of the corresponding 2-tolyl-1,4,5-triarylimidazoles ²⁶ and then treated with sodium azide in acetone to give the corresponding azidomethyl derivatives (Table 1). Cyclization of the azide intermediates with various alkynes in the presence of CuI (10 mol%) in tert-butyl alcohol at 70 °C gave the desired 1,2,3-triazole derivatives 2a–k. The commercial alkynes used such as phenyl acetylene, propargyl alcohol and dimethylacetylenedicarboxylate, afforded the products 2a–e in good to moderate yields (entries 1–5). The prepared 3-aryloxy-propyne derivatives, which were obtained by reactions of propargyl chloride with various phenolate salts,^29–32 were treated with the azidomethyl intermediates to afford the products 2f–j (entries 6–10). Finally, cyclization of N-(2-propynyl)aniline ³³ resulted in the aminomethyl-substituted triazole 2k (entry 11).

Table 1.

The synthesis of 1,2,3-triazole derivatives 2a–k.

Entry	R1	R2	R3	Product	Yield (%)	Time (h)
1	H	Ph	H	2a	74	10
2	Cl	Ph	H	2b	72	10
3	H	CH2OH	H	2c	52	8
4	Cl	CH2OH	H	2d	56	8
5	Cl	COOCH3	COOCH3	2e	60	8
6	H	CH2OPh	H	2f	73	4
7	Cl	CH2OPh	H	2g	74	4
8	Cl		H	2h	61	10
9	Cl		H	2i	62	6
10	Cl		H	2j	65	5
11	Cl	CH2-NH-Ph	H	2k	59	7

To study the optical properties of the synthesized compounds, we recorded the UV-Vis and fluorescence spectra of some chosen products in dilute (10^-6 M) ethanolic solutions. Two absorbtion peaks appeared for each of the studied materials, one in the range of 223–234 nm and the other in the range of 284–296 nm (Table 2). Calculated molar extinction coefficients (ε_max) for the more intense peaks (223–234 nm) indicate strong π–π* transitions. The fluorescence emission spectra of the samples and the related descriptions are presented in Figure 1 and Table 2, respectively.

Figure 1.

The fluorescence spectra of dilute solutions (10^-6 M) of selected products 2 in ethanol.

Table 2.

Fluorescence and UV-Vis parameters of selected products 2.

Product	λmax (nm)	εmax (mol-1 Lcm-1 × 103)	λem (nm)	Stokes shift (cm-1) a	Φx
2a	223, 284	70	373	18034	0.088
2b	234, 294	72	379	16350	0.27
2d	226, 290	72	378	17792	0.38
2e	228, 295	60	360	16082	0.02
2g	227, 286	75	377	17527	0.20
2h	227, 285	69	378	17597	0.15
2j	227, 294	60	370	17025	0.02
2k	233, 296	62	444	20396	0.01

a

λ_max (cm^-1) – λ_em (cm^-1).

As seen, compound 2k containing an anilinomethyl group exhibits a longer absorption wavelength, λ_max, and also a longer emission wavelength, λ_em, relative to the other studied products. The emission quantum yields (Φ_x), which were determined by using equation (1) relative to 2-aminopyridine as standard (Φ = 0.6), show the highest value for compound 2d.

$${\mathrm{\Phi }}_{\mathrm{X}}=\left({\mathrm{A}}_{\mathrm{s}}\times {\mathrm{F}}_{\mathrm{x}}\times {\mathrm{n}}^2\mathrm{x}\times {\mathrm{\Phi }}_{\mathrm{s}}\right)/\left({\mathrm{A}}_{\mathrm{x}}\times {\mathrm{F}}_{\mathrm{s}}\times {\mathrm{n}}^2\mathrm{s}\right)$$

(1)

According to the equation, x is the symbol of the samples and s is the symbol of the standard, where Φ is the fluorescence quantum yield, F is the area under the fluorescence emission curves and A shows the absorbance at the excitation wavelength (270 nm), and n_x and n_s are the refractive indexes of ethanol and water (1.36 and 1.33, respectively).

The Stokes shifts of the synthesized compounds, calculated from the difference between the emission wavelength λ_em and the absorption wavelength λ_max, are relatively good, indicating low overlap between their absorption and emission spectra.

We then prepared the 1-(4-hydroxyphenyl)-2,4,5-triarylimidazoles 3a–j by four-component condensation of benzil, 4-aminophenol, aromatic aldehydes and ammonium acetate in the presence of toluene p-sulfonic acid. ²⁶ Substitution reactions of the phenols 3a–j with propargyl chloride in the presence of K₂CO₃ in dimethylformamide (DMF) afforded the corresponding propargyl ether intermediates. Subsequently, CuI-catalyzed cyclization of these ethers with benzyl azide gave the target 1,4-disubstituted triazoles 4a–j in good yields (Table 3).

Table 3.

The synthesis of 1,2,3-triazole derivatives 4a–j.

Entry	Ar	Product	Yield (%)
1	phenyl	4a	87
2	4-methylphenyl	4b	86
3	4-methoxyphenyl	4c	71
4	4-isopropylphenyl	4d	68
5	1-methylpyrrole-2-yl	4e	63
6	3-bromophenyl	4f	73
7	4-chlorophenyl	4g	91
8	thiophene-2-yl	4h	78
9	thiophene-3-yl	4i	68
10	4-fluorophenyl	4j	88

The optical behavior of the products obtained was also evaluated in dilute (10^-6 M) ethanolic solutions. Figure 2 shows the fluorescence spectra of the samples 4a–j. While all of the absorption wavelength values, λ_max, are almost the same, compound 4e containing a pyrrole ring exhibits a relatively long emission wavelength (λ_em). The calculated emission quantum yields relative to anthracene as a standard (Φ = 0.27) show the highest value for compound 4g with 4-chlorophenyl substitution (Table 4).

Figure 2.

The fluorescence spectra of dilute solutions (10^-6 M) of products 4a–j in ethanol.

Table 4.

Fluorescent and UV–Vis parameters of products 4a–j.

Product	λmax (nm)	εmax (mol-1 Lcm-1 × 103)	λem (nm)	Stokes shift (cm-1)	Φx
4a	270	27.6	380	10722	0.31
4b	280	25.2	390	10073	0.33
4c	280	22.8	390	10073	0.45
4d	280	24.8	390	10073	0.35
4e	280	23.4	420	11905	0.33
4f	280	21.6	380	9399	0.45
4g	280	25.4	390	10073	0.86
4h	280	20.0	390	10073	0.52
4i	280	23.4	390	10073	0.22
4j	280	23.2	380	9399	0.22

A single product was obtained from each of the above Cu(I) catalysed cycloaddition reactions and was identified by analogy with the literature as the 1,4-disubstituted triazole rather than the 1,5-disubstituted isomer. ³⁴ The triazole-H signal in the ¹H NMR spectra of the products 2a–k and 4a–j appeared at about δ 7.5 consistent with this hydrogen being attached to the 5-position of the triazole ring. Due to the resonance structures of triazole, the 1H NMR signal of H5 (in 1,4-disubstituted-triazoles) is always shifted considerably downfield compared to H4 (in 1,5-disubstituted-triazoles). ³⁵

Conclusion

In conclusion, we have reported the synthesis and optical properties of some novel tetraaryl imidazole derivatives possessing a 1,2,3-triazole ring. These products were prepared by CuI-catalyzed 1,3-dipolar cycloadditions of either azidomethyl derivatives of tetraaryl imidazoles with various commercial and prepared terminal acetylenes, or propargyloxy derivatives of tetraaryl imidazoles with benzyl azide. All the products were characterized from their spectroscopic data (supplemental material) and most of them were evaluated in view of their optical properties. Fluorescence spectra as well as the optical parameters (λ_max, ε_max, λ_em, quantum yields of emission and Stokes shifts) of the products have been reported. The highest values of emission quantum yields in two series of the products were obtained for compounds 2d and 4g, which both contain a 4-chlorophenyl group at 1- and 2- positions of imidazole ring, respectively.

Experimental

Melting points were measured on an Electrothermal MEL-TEMP apparatus (model 1202D). FTIR spectra were obtained with a Bruker Tensor 27 spectrometer; υ in cm^-1. ¹H NMR and ¹³C NMR spectra were recorded with a Bruker Spectrospin Avance 400 spectrometer operating at 400 and 100 MHz, respectively; chemical shifts are given in parts per million (ppm, δ) relative to tetramethylsilane or solvent peaks as internal standards [δ: CDCl₃: 7.26 ppm (¹H), 76 ppm (¹³C); DMSO-d₆: 2.50 ppm (¹H), 39.5 ppm (¹³C)]. Elemental analyses were measured using a Vario EL ΙΙΙ apparatus (Elementar Co.). UV-Vis spectra were recorded on an Analytic Jena Specorel 250 spectrometer. Preparative thin-layer chromatography (PLC) was performed with prepared glass-backed plates (20 × 20 cm², 500 μ) using silica gel (Merck Kieselgel 60 PF_{254 + 366}). Fluorescence emission spectra were acquired on a Jasco FP-750 spectrofluorimeter.

Synthesis of products 2a–k: general procedure

A mixture of bromide 1 (2 mmol) and sodium azide (0.13 g, 2 mmol) in acetone (3 mL) was stirred at room temperature for 24 h. The solid salt was filtered and the filtrate concentrated (using a rotary evaporator) to give the azidomethyl intermediate. A mixture of the dried azide (2 mmol), acetylene derivative (2 mmol), and CuI (10 mol%, 0.04 g) in tert-butylalcohol (4 mL) was heated at 70°C for 4–10 h. Filtering the mixture gave a solution which was concentrated under reduced pressure. The obtained crude product was purified by recrystallization from ethyl acetate (products 2a, 2b) or by preparative TLC (n-hexane-EtOAc, 20:7) (products 2c–k) (Table 1).

4-phenyl-1-[4-(1,4,5-triphenyl-1H-imidazol-2-yl)benzyl]-1H-1,2,3-triazole ( 2a ): 0.78 g (74%), Yellow crystals, mp 222-224°C, FTIR (KBR): ν 3057, 2924, 1598, 1490, 1441, 765, 695 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ 5.53 (s, 2H, CH₂), 7.03 (d, J = 7.1 Hz, 2H, ArH), 7.11 (d, J = 6.8 Hz, 2H, ArH), 7.16–7.33 (m, 12H, ArH), 7.38–7.45 (m, 4H, ArH), 7.57 (d, J = 7.2 Hz, 2H, ArH), 7.69 (s, 1H, triazole-H), 7.79 (d, J = 7.5 Hz, 2H, ArH); ¹³C NMR (100 MHz, CDCl₃): δ 52.7 (CH₂), 118.7, 124.6, 125.8, 126.4, 126.8, 127.11, 127.13, 127.20, 127.25, 127.3, 127.6, 127.8, 128.2, 128.4, 129.0, 129.4, 129.6, 129.9, 130.2, 133.7, 135.6, 144.9, 147.1. Anal. Calcd for С₃₆H₂₇N₅ (529.23): С, 81.64; Н, 5.14; N, 13.22; found: С, 81.32; Н, 4.86; N, 13.48.

Synthesis of products 4a–j: general procedure

A mixture of phenol 3 (1 mmol), propargyl chloride (1.2 mmol, 0.08 mL), and K₂CO₃ (1.2 mmol, 0.16 g) in dry DMF (3 mL) was heated at 60°C for 24 h. After cooling, water (30 mL) was added and the precipitated solid (propargyl ether) was filtered and washed with H₂O (30 mL). The dried propargyl ether derivative (1 mmol) was mixed with benzyl azide (1.2 mmol, 0.16 g) and CuI (10 mol%, 0.02 g) in dry ethanol (5 mL), and the mixture was heated at 75°C for 24 h. After cooling, the precipitated solid was filtered and washed with n-hexane (10 mL). The dried solid was recrystallized from ethyl acetate to give the triazole products 4a–j.

1-Benzyl-4-{[4-(2,4,5-triphenyl-1H-imidazol-1-yl)phenoxy]methyl}-1H-1,2,3-triazole ( 4a ): 0.48 g (87%), pale yellow solid, mp 111–113°C, FTIR (KBr): ν 3045, 2928, 1603, 1508, 1469, 1237, 843, 694 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ 5.10 (s, 2H, CH₂-N), 5.54 (s, 2H, CH_2-O), 6.82 (d, J = 6.7 Hz, 2H, ArH), 6.95 (d, J = 6.7 Hz, 2H, ArH), 7.11 (dd, J = 7.8, 1.7 Hz, 2H, ArH), 7.19-7.29 (m, 11H, ArH), 7.36-7.39 (m, 3H, ArH), 7.44 (dd, J = 7.6, 1,7 Hz, 2H, ArH), 7.51 (s, 1H, triazol-H), 7.59 (d, J = 8.3 Hz, 2H, ArH); ¹³C NMR (100 MHz, CDCl₃): δ 53.3 (CH₂-N), 61.1 (CH₂-O), 113.9, 121.6, 125.6, 126.4, 126.9, 127.1, 127.2, 127.3, 127.9, 128.2, 128.5, 129.3, 129.4, 129.5, 130.0, 133.3, 137.1, 142.9, 156.8. Anal. Calcd for С₃₇H₂₉N₅O (559.66): С, 79.40; Н, 5.22; N, 12.51; found: С, 79.71; Н, 5.50; N, 12.28.

Supplemental Material

Supporting_information_PDF – Supplemental material for Synthesis and optical properties of novel 1,2,3-triazole derivatives possessing highly substituted imidazoles

Supplemental material, Supporting_information_PDF for Synthesis and optical properties of novel 1,2,3-triazole derivatives possessing highly substituted imidazoles by Zarrin Ghasemi, Arezoo Mirzaie, Roqhayeh Arabzadeh, Zahra Fathi and Ameneh Abolghassemi Fakhree in Journal of Chemical Research