Journal of Chemistry

Volume 2013 (2013), Article ID 296792, 6 pages

http://dx.doi.org/10.1155/2013/296792

Research Article

A Convenient Synthesis of C-3-Aryloxymethyl Imidazo[1,2-]Pyridine Derivatives

Sridevi Kona,¹ Rama Suresh Ravi,¹ Venkata N. R. Chava,² and Ramu Sridhar Perali¹

¹School of Chemistry, University of Hyderabad, Andhra Pradesh, Hyderabad 500046, India

²Department of Chemistry, AG & SG Siddhartha Arts and Science College, Andhra Pradesh, Vuyyuru 521165, India

Received 16 June 2012; Accepted 26 July 2012

Academic Editor: Marco Radi

Copyright © 2013 Sridevi Kona et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Imidazo[1,2-]pyridine-based tosylhydrazone was prepared and treated with K₂CO₃ in dioxane at 110°C to generate the corresponding carbene in situ. It was coupled with a variety of aryl alcohols in one pot to obtain a series of imidazo[1,2-]pyridine derivatives possessing aryl ether moiety at C-3 position.

1. Introduction

Imidazopyridines are important class of heterocyclic compounds. Synthesis of imidazo[1,2-a]pyridine derivatives has been the subject of considerable interest because of their wide range of pharmaceutical, biological, and medicinal applications [1–3]. The derivatives of this scaffold show a variety of therapeutic properties such as agonist of benzodiazepine receptor [4], α2/α3 binding site agonists [5], ligand for detecting β-amyloid [6] and also constitute orally active nonpeptide bradykinin B₂ receptor antagonists [7]. These derivatives have been found to possess antibacterial [8], antiviral [9, 10], anti-inflammatory [11], antiulcer [12], antitubercular [13], anticancer [14], antiparasitic [15], and antiprotozoa [16] activities, and so forth Moreover, it is also a core structure of several drugs such as zolimidine (1) (antiulcer), alpidem (2) (anxiolytic), and zolpidem (3) (selective benzodiazepine receptor agonist, for the treatment of insomnia) [17] (Figure 1) which are currently available in the market. As a result, various methods for the preparation of imidazo[1,2-a]pyridine derivatives were developed [18–20]. Gueiffier and coworkers reported that imidazo[1,2-a]pyridine derivatives particularly bearing a thioether side chain at 3-position were found to be very active against human cytomegalovirus (HCMV) and varicella-zoster virus (VZV) [9, 10]. In view of significant importance of 3-substituted imidazo [1,2-a]pyridine derivatives herein we report a convenient preparation of imidazo[1,2-a]pyridine derivatives possessing an aryl ether moiety at C-3 position.

Figure 1: Structures of some biologically active imidazo[1,2-a]pyridine derivatives.

2. Experimental Section

2.1. General

All the chemicals used were purchased from Aldrich Chemical Co and were used without further purification. Freshly distilled solvents were used. For TLC, aluminum plates coated with silica gel containing F254 indicator were used, and the spots were visualized by UV light and/or by exposing to iodine. Column chromatography was performed on silica gel 100–200 mesh, using EtOAc and hexanes mixture as eluent. The ¹H and ¹³C spectra were recorded using 5 mm tubes on a Bruker 400 MHz NMR spectrometer field strengths: 400 and 100 MHz, resp. in CDCl₃ solution (unless specified otherwise) with shifts referenced to SiMe₄ (¹H, ¹³C: ), respectively. All values were in Hz. IR spectra were recorded on a JASCO FT/IR 5300 spectrometer. Elemental (C, H, N) analysis was done using Perkin-Elmer 240C CHN FLASH EA analyzer. Melting points were determined by using a SUPERFIT hot-stage melting point apparatus and are uncorrected.

4-Methyl-N′-{(2-phenylimidazo[1,2-a]pyridine-3-yl)methylene}benzenesulfonohydrazide (8) . To a rapidly stirred suspension of toluenesulfonyl hydrazide (4.6 g, 24.7 mmol) in methanol (10 mL) a solution of aldehyde 7 (5 g, 22.5 mmol) in methanol (20 mL) portion wise for a period of 15 minutes was added. A mildly exothermic reaction occurred and the solution became transparent. Within 15–20 min the tosylhydrazone began to precipitate. After stirring for 1 h the mixture was filtered, and the filter cake was washed with small quantity of methanol. The obtained product 8 was dried and used in the next step without further purification. Yield: 7.65 g (98%; colorless solid); Mp 102–104; IR (, cm⁻¹): 3379, 2762, 1605, 1345, 1166, 947, 739; ¹H NMR (400 MHz, CDCl₃): 2.42 (s, 3H, CH₃), 7.02–7.06 (m, 1H, Ar-H), 7.32–7.54 (m, 8H, Ar-H), 7.76, (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.90, (d, ³J(H-H) = 8.0 Hz, 2H, Ar-H), 8.16 (s, 1H, Ar-H), 9.34 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 21.6, 114.1, 114.9, 117.2, 127.7, 127.9, 128.7₍₆₎, 128.7₍₄₎, 128.9, 129.2, 129.8, 132.7, 135.3, 140.3, 144.4, 146.8, 151.1; LC/MS: m/z 391 [M + H]⁺; Anal. Calcd. for C₂₁H₁₈N₄O₂S: C, 64.60; H, 4.65; N, 14.35. Found: C, 64.69; H, 4.60; N, 14.45.

General Procedure for the Synthesis Ether Derivatives: 2-Phenyl-3-(P-tolyloxymethyl)imidazo[1,2-a]pyridine (10a) . An oven-dried 10 mL round bottom flask was charged with tosylhydrazone 8 (391 mg, 1.0 mmol), p-cresol (216 mg, 2.0 mmol), and K₂CO₃ (483 mg, 3.5 equiv). The flask was evacuated for 5 min and filled with N₂. To this dioxane (4 mL) was added and contents were stirred at 110 for 12 h under nitrogen. After completion of the reaction (monitored by TLC), the mixture was cooled to room temperature and the solvent was evaporated by rotary evaporator to obtain the crude reaction mixture. To this, saturated solution of NaOH (5 mL) and dichloromethane (15 mL) were added subsequently and the layers were separated. The aqueous phase was extracted with dichloromethane ( mL). The combined organic layers were washed with NaOH solution ( mL), brine (mL) and then dried over anhydrous Na₂SO₄. The crude product was purified by column chromatography (hexane:EtOAc 6 : 4) to afford 10a. Yield 0.20 g (64%; colorless solid); Mp 116–118°C; IR (, cm⁻¹): 3015, 1507, 1358, 1225, 1034, 976, 739; ¹H NMR (400 MHz, CDCl₃): 2.32 (s, 3H, CH₃), 5.40 (s, 2H, CH₂), 6.86–6.92 (m, 3H, Ar-H), 7.12–7.49 (m, 6H, Ar-H), 7.70 (d, ³J(H-H) = 9.2 Hz, 1H, Ar-H), 7.77 (s, 1H, Ar-H), 7.79 (d, ³J(H-H) = 1.2 Hz, 1H, Ar-H), 8.16 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 20.5, 60.1, 112.7, 114.8, 115.5, 117.7, 124.2, 125.3, 128.2, 128.7, 130.1, 131.0, 133.9, 145.5, 146.2, 156.0; LC/MS: m/z 315 [M + H]⁺; Anal. Calcd. For C₂₁H₁₈N₂O: C, 80.23; H, 5.77; N, 8.91. Found: C, 80.32; H, 5.81; N, 8.79.

2-Phenyl-3-(o-tolyloxymethyl)imidazo[1,2-a]pyridine (10b) . Yield: 0.24 g (76%; colorless solid); Mp 110–112; IR (, cm⁻¹): 2924, 1458, 1233, 1192, 1117, 997, 750; ¹H NMR (400 MHz, CDCl₃): 2.21 (s, 3H, CH₃), 5.44 (s, 2H, CH₂), 6.87–6.84 (m, 3H, Ar-H), 7.19–7.32 (m, 3H, Ar-H), 7.41–7.50 (m, 3H, Ar-H), 7.71–7.79 (m, 3H, Ar-H), 8.18 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 16.3, 60.0, 111.5, 112.6, 115.7, 117.7, 121.3, 124.1, 125.3, 126.9, 127.4, 128.2, 128.7, 131.0, 133.9, 145.6, 156.2. LC/MS: m/z 315 [M + H]⁺; Anal. Calcd. For C₂₁H₁₈N₂O: C, 80.23; H, 5.77; N, 8.91. Found: C, 80.12; H, 5.72; N, 8.97.

3-((4-tert-Butylphenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10c) . Yield: 0.31 g (87%; colorless solid); Mp 134–136; IR (, cm⁻¹): 2948, 1607, 1507, 1233, 1181, 999, 737; ¹H NMR (400 MHz, CDCl₃): 1.33, (s, 9H, (CH₃)₃), 5.41, (s, 2H, CH₂), 6.87, (t, ³J(H-H) = 6.8 Hz, 1H, Ar-H), 6.98, (d, ³J(H-H) = 8.8 Hz, 2H, Ar-H), 7.28–7.49, (m, 6H, Ar-H), 7.70, (d, ³J(H-H) = 9.2 Hz, 1H, Ar-H), 7.79, (d, ³J(H-H) = 7.6 Hz, 2H, Ar-H), 8.15, (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 31.5, 34.1, 59.9, 112.6, 114.4, 115.5, 117.6, 124.1, 125.3, 126.4, 128.2, 128.7, 133.9, 144.4, 145.5, 146.2, 155.9; LC/MS: m/z 357 [M + H]⁺; Anal. Calcd. For. C₂₄H₂₄N₂O: C, 80.87; H, 6.79; N, 7.86. Found: C, 80.77; H, 6.75; N, 7.80.

3-((4-Methoyphenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10d) . Yield 0.29 g (88%; colorless solid); Mp 116–118; IR (, cm⁻¹): 3011, 1507, 1358, 1225, 1034, 976, 738; ¹H NMR (400 MHz, CDCl₃): 3.79 (s, 3H, OCH₃), 5.38 (s, 2H, CH₂), 6.84–6.95 (m, 5H, Ar-H), 7.29–7.49 (m, 4H, Ar-H), 7.71 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.77 (d, ³J(H-H) = 7.2 Hz, 2H, Ar-H), 8.17 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 55.8, 60.8, 112.7, 114.8, 115.7, 116.2, 117.7, 124.2, 125.3, 128.2, 128.7, 134.0, 145.6, 146.3, 152.2, 154.6; LC/MS: m/z 331 [M + H]⁺; Anal. Calcd. For C₂₁H₁₈N₂O₂: C, 76.34; H, 5.49; N, 8.48. Found: C, 76.43; H, 5.48; N, 8.45.

3-((4-Chlorophenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10e) . Yield: 0.28 g (84%; colorless solid); Mp 134–136; IR (, cm⁻¹): 3044, 2922, 1491, 1356, 1231, 984, 817, 735; ¹H NMR (400 MHz, CDCl₃): 5.41 (s, 2H, CH₂), 6.90 (s, 1H, Ar-H), 6.92 (s, 2H, Ar-H), 7.27–7.76 (m, 9H, Ar-H), 8.15 (d, ³J(H-H) = 5.6 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 60.3, 112.9, 115.0, 116.3, 117.8, 124.1, 125.5, 126.6, 128.4, 128.7, 128.8, 129.6, 133.8, 145.6, 146.5, 156.7; LC/MS: m/z 335 [M + H]⁺; Anal. Calcd. For C₂₀H₁₅ClN₂O: C, 71.75; H, 4.52; N, 8.37. Found: C, 71.65; H, 4.58; N, 8.31.

3-((4-Nitrophenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10f) . Yield 0.25 g (73%;  yellow colored solid); Mp 132–134; IR (, cm⁻¹): 2924, 1505, 1318, 1146, 1086, 754, 700. ¹H NMR (400 MHz, CDCl₃): 4.85 (s, 2H, CH₂), 6.89 (t, ³J(H-H) = 6.8 Hz, 1H, Ar-H), 7.04–7.17 (m, 3H, Ar-H), 7.29–7.36 (m, 7H, Ar-H), 7.66 (d, ³J(H-H) = 9.2 Hz, 1H, Ar-H), 8.41 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 52.4, 108.2, 112.8, 117.1, 124.8, 126.0, 127.9, 128.0(9), 128.0₍₀₎, 128.1, 129.6, 132.6, 134.0, 145.1, 145.6, 146.9; LC/MS: m/z 346 [M + H]⁺; Anal. Calcd. For C₂₀H₁₅N₃O₃: C, 69.56; H, 4.38; N, 12.17. Found: C, 69.45; H, 4.31; N, 12.25.

3-((2,4-Dimethylphenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10g) . Yield 0.26 g (79%; colorless solid); Mp 110–112; IR (, cm⁻¹): 2921, 1505, 1356, 1215, 1129, 984, 741; ¹H NMR (400 MHz, CDCl₃): 2.18 (s, 3H, CH₃), 2.30 (s, 3H, CH₃), 5.40 (s, 2H, CH₂), 6.83–6.98 (m, 3H, Ar-H), 7.02 (s, 1H, Ar-H), 7.28–7.50 (m, 4H, Ar-H), 7.72 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.79 (d, ³J(H-H) = 7.6 Hz, 2H, Ar-H), 8.16 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 16.2, 20.4, 60.1, 111.6, 112.5, 115.9, 117.6, 124.0, 125.2, 127.0, 127.1, 128.1, 128.7, 130.5, 131.8, 133.9, 145.4, 146.1, 154.1; LC/MS: m/z 329 [M + H]⁺; Anal. Calcd. for C₂₂H₂₀N₂O: C, 80.46; H, 6.14; N, 8.53. Found: C, 80.35, H, 6.18, N, 8.45.

3-((3,5-Dimethylphenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10h) . Yield: 0.31 g (95%; colorless solid); Mp: 126-128; IR (, cm⁻¹): 2919, 1593, 1502, 1404, 1294, 1154, 736; ¹H NMR (400 MHz, CDCl₃): 2.29 (s, 6H, (CH₃)₂), 5.43 (s, 2H, CH₂), 6.63 (s, 2H, Ar-H). 6.68 (s, 1H, Ar-H), 6.91 (t, ³J(H-H) = 6.8 Hz, 1H, Ar-H), 7.31–7.52 (m, 3H, Ar-H), 7.73 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.79–7.81 (m, 3H, Ar-H), 8.19 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 21.4, 59.6, 112.6, 112.7, 115.6, 117.6, 123.3, 124.2, 125.4, 128.2, 128.8₍₇₎, 128.8₍₁₎, 133.9, 139.5, 145.5, 146.1, 158.1; LC/MS: m/z 329 [M + 1]⁺; Anal. Calcd. for C₂₂H₂₀N₂O: C, 80.46; H, 6.14; N, 8.53. Found: C, 80.32; H, 6.19; N, 8.45.

3-((2,6-Dimethylphenoxy)methyl)-2-phenylimidazo[1,2-a]pyridine (10i) . Yield 0.21 g (64%; colorless solid); Mp 118–120; IR (, cm⁻¹): 2924, 1503, 1358, 1190, 1090, 955, 764; ¹H NMR (400 MHz, CDCl₃): 2.09 (s, 6H, (CH₃)₂), 5.31 (s, 2H, CH₂), 6.85–7.00 (m, 4H, Ar-H), 7.27–7.39 (m, 4H, Ar-H), 7.58 (d, ³J(H-H) = 7.2 Hz, 2H, Ar-H), 7.69 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 8.14 (d, ³J(H-H) = 6.4 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 16.5, 63.4, 112.5, 117.2, 117.6, 124.1, 124.4, 125.2, 128.0, 128.5, 128.7, 129.1, 131.1, 133.8, 145.3, 146.2, 155.6; LC/MS: m/z 329 [M + H]⁺; Anal. Calcd. for C₂₂H₂₀N₂O: C, 80.46; H, 6.14; N, 8.53. Found: C, 80.35; H, 6.22; N, 8.61.

3-((2-tert-Butyl-4-methylphenoxy)methyl)-2-phenyl-imidazo[1,2-a]pyridine (10j) . Yield 0.30 g (81%; colorless solid); Mp 144–146; IR (, cm⁻¹): 2957, 1499, 1362, 1219, 1094, 1004, 731; ¹H NMR (400 MHz, CDCl₃): 1.32 (s, 9H, (CH₃)₃), 2.35 (s, 3H, CH₃), 5.38 (s, 2H, CH₂), 6.87 (t, ³J(H-H) = 6.8 Hz, 1H, Ar-H), 6.94 (d, ³J(H-H) = 8.4 Hz, 1H, Ar-H), 7.04 (d, ³J(H-H) = 8.0 Hz, 1H, Ar-H), 7.19 (s, 1H, Ar-H), 7.27–7.48 (m, 4 H, Ar-H), 7.74 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.82 (d, ³J(H-H) = 7.6 Hz, 2H, Ar-H), 8.12 (d, ³J(H-H) = 6.8 Hz, 1 H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 20.8, 29.8, 34.7, 59.4, 111.5, 112.6, 115.7, 117.7, 123.8, 125.3, 127.2, 127.9, 128.1, 128.6, 128.7, 130.0, 133.8, 138.1, 145.5, 146.1, 155.0; LC/MS: m/z 371 [M + H]⁺; Anal. Calcd. for C₂₅H₂₆N₂O: C, 81.05; H, 7.07; N, 7.56. Found: C, 81.13; H, 7.12; N, 7.48.

3-((2,4-Di-tert-butylphenoxy)methyl)-2-phenylimidazo [1,2-a]pyridine (10k) . Yield 0.34 g (84%; colorless solid); Mp 164–166; IR (, cm⁻¹): 2961, 1495, 1360, 1229, 1092, 993, 737; ¹H NMR (400 MHz, CDCl₃): 1.33 (s, 9H, (CH₃)₃), 1.35 (s, 9H, (CH₃)₃), 5.39 (s, 2H, CH₂), 6.87 (t, ³J(H-H) = 6.8 Hz, 1H, Ar-H), 6.97 (d, ³J(H-H) = 8.4 Hz, 1H, Ar-H), 7.23–7.47 (m, 6H, Ar-H), 7.74 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 7.81 (d, ³J(H-H) = 7.2 Hz, 2H, Ar-H), 8.11 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 29.9, 31.6, 34.4, 35.1, 59.4, 111.0, 112.6, 115.8, 117.8, 123.4, 123.9, 124.4, 125.3, 128.2, 128.7, 128.8, 133.9, 137.7, 143.4, 145.6, 146.3, 154.9; LC/MS: m/z 413 [M + H]⁺; Anal. Calcd. For C₂₈H₃₂N₂O: C, 81.51; H, 7.82; N, 6.79. Found: C, 81.46; H, 7.88; N, 6.71.

3-(Mesityloxymethyl)-2-phenylimidazo[1,2-a]pyridine (10l) . Yield 0.26 g (76%; colorless solid); Mp 126–128; IR (, cm⁻¹): 2917, 1482, 1358, 1198, 1142, 961, 747; ¹H NMR (400 MHz, CDCl₃): 2.07 (s, 6H, (CH₃)₂), 2.26 (s, 3H, CH₃), 5.28 (s, 2H, CH₂), 6.81 (s, 2H, Ar-H), 6.85–6.89 (m, 1H, Ar-H), 7.26–7.31 (m, 1H, Ar-H), 7.37–7.42 (m, 3H, Ar-H), 7.58–7.61 (m, 2H, Ar-H), 7.70 (d, ³J(H-H) = 8.8 Hz, 1H, Ar-H), 8.18 (d,³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 16.4, 20.7, 63.5, 112.6, 117.4, 117.6, 124.2, 125.3, 128.0, 128.5, 128.8, 129.7, 130.7, 133.7, 133.9, 145.3, 146.2, 153.3; LC/MS: m/z 343 [M + H]⁺; Anal. Calcd. for C₂₃H₂₂N₂O: C, 80.67; H, 6.48; N, 8.18. Found: C, 80.59; H, 6.41; N, 8.25.

2-Phenyl-3-((pyridine-4-yloxy)methyl)imidazo[1,2-a]pyridine (10m) . Yield 0.19 g (63%; colorless solid); Mp 102-103; IR (, cm⁻¹): 2923, 1505, 1302, 1142, 1084, 669, 546; ¹H NMR (400 MHz, CDCl₃): 4.87 (s, 2H, CH₂), 6.95–7.74 (m, 12H, Ar-H), 8.47 (d, ³J(H-H) = 6.8 Hz, 1H, Ar-H); ¹³C NMR (100 MHz, CDCl₃): 52.6, 108.4, 113.1, 117.3, 125.0, 126.3, 128.1, 128.2, 128.3, 128.8, 128.9, 129.8, 134.1, 145.3, 145.7; LC/MS: m/z 302 [M + H]⁺; Anal. Calcd. For C₁₉H₁₅N₃O: C, 75.73; H, 5.02; N, 13.94. Found: C, 75.63; H, 5.10; N, 13.85.

3. Results and Discussion

Towards the synthesis of 3-substituted imidazo[1,2-a]pyridine derivatives, we were attracted by recent reports on the use of tosylhydrazones in C–C and C–O bond formation under metal-free reaction conditions [21–24].

2-Phenyl-imidazo[1,2-a]pyridine 6 was synthesized by refluxing 2-aminopyridine 4 and bromoacetophenone 5 in ethanol for 4 h. Vilsmeier-Haack formylation of 6 provided aldehyde 7 [9, 10] in excellent yield. Treatment of 7 with tosylhydrazide lead to the required hydrozone precursor 8 which was used for etherification reaction (Scheme 1).

Scheme 1: Synthesis of imidazo[1,2-a]pyridine-derived tosylhydrazone precursor.

We first examined the reaction of tosyl hydrazone 8 with p-cresol 9a in the presence of K₂CO₃ as a base in dioxane solvent at 110. We were pleased to find that the reaction proceeded smoothly to afford the corresponding ether, 10a in 95% yield. The scope of the reaction was further carried out using various monosubstituted phenols (Table 1 entries 1–5). Irrespective of the electronic and steric factors of the substituents all the reactions provided the corresponding ethers (10b-10f) in excellent yield (73–88%). Similarly, the disubstituted phenols (Table 1 entries 6–10) and the trisubstituted phenol (entry 11) also provided the corresponding imidazo[1,2-a]pyridine derivatives bearing an ether side chain at 3-position (10g-10l). Interestingly, reaction of tosylhydrazone 8 with 4-hydroxypyridine also afforded the corresponding ether derivative 10 m in 63% yield.

Table 1: Scope of the synthesis of C-3-aryl ether substituted 2-phenyl imidazo[1,2-a]pyridines 10a–10m. aReaction conditions: Tosylhydrazone 8 (1.0 mmol), phenol (2.0 mmol), K₂CO3 (3.5 mmol) dioxane (4.0 mL), 110°C, 12 h. byield refers to pure and isolated.

Serial no.
Ether
Yield (%)
Serial no.
Ether
Yield (%)

1

76
7

95

2

87
8

64

3

88
9

81

4

84
10

84

5

73
11

76

6

79
12

63

4. Conclusion

In conclusion, we have demonstrated a convenient method for the synthesis of C-3 aryl ether derivatives of imidazo[1,2-a]pyridine via insertion reaction of in situ generated diazocompound with various phenols. This method is fairly general and provides access for the synthesis of aryl ether imidazo[1,2-a]pyridine compounds. The bioactivity assays of these derivatives against HCV and VZV are under progress.

Acknowledgment

S. Kona and V. chara thank UGC networking resource centre to carryout research work at University of Hyderabad.

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