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Article

Synthesis of New Bis-1,2,4-Triazole Derivatives

by
Olcay Bekircan
* and
Hakan Bektas
Department of Chemistry, Giresun Faculty of Arts and Sciences, Karadeniz Technical University, 28049, Giresun, Turkey
*
Author to whom correspondence should be addressed.
Molecules 2006, 11(6), 469-477; https://doi.org/10.3390/11060469
Submission received: 10 May 2006 / Revised: 20 June 2006 / Accepted: 21 June 2006 / Published: 21 June 2006
Browse Figures
Versions Notes

Abstract

:
A series of new 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 4 were prepared in good yields by  treatment of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 2 with certain bis-aldehydes 1. Compounds 4 were reduced with NaBH4 to afford the corresponding 1,2/1,3-bis[o-(N-methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 5. All new compounds were characterized by IR, 1H-NMR, 13C-NMR and mass spectral data.

Introduction

1,2,4-triazoles and their derivatives are found to be associated with various biological activities such as anticonvulsant [1,2], antifungal [3,4,5], anticancer [6,7,8,9], antiinflammatory [10,11,12] and antibacterial properties [13,14,15,16]. Several compounds (Figure 1) containing 1,2,4-triazole rings are well known as drugs. For example, fluconazole is used as an antimicrobial drug [17], while vorozole, letrozole and anastrozole are non-steroidal drugs used for the threatment of cancer [18] and loreclezole is used as an anticonvulsant [19].
Molecules 11 00469 g001 550
Figure 1.
Figure 1.
Molecules 11 00469 g001
Furthermore, in recent years some Schiff base derivatives of 1,2,4-triazoles and their reduced derivatives have been also found to possess pharmacological activities [20,21,22,23,24,25,26]. These biological data prompted us to synthesize some new bis-1,2,4-triazole derivatives, and in the present study, a novel series of bis-Schiff base derivatives resulting from the reaction of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 3 with bis-aldehydes 1 and their corresponding reduced derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR and mass spectral data.

Results and Discussion

The syntheses of the 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane/propane derivatives 4 were accomplished according to the reactions shown in Scheme 1, Scheme 2 and Scheme 3. First, bis-aldehydes 1 were synthesized using a published method [27], as indicated in Scheme 1. 3-Aryl-5-phenyl-4-amino-4H-1,2,4-triazoles 3 were obtained from the reaction of ethyl benzoate benzoylhydrazone derivatives 2 with hydrazine using the published method shown in Scheme 2 [28]. Finally reactions of compounds 1 and 3 afforded the desired compounds 4 (Scheme 3). In general, reduction of imine type compounds is possible [26,29], but attempts to reduce imines such as 4 may also lead to a reduction of the heterocyclic ring. For this reason, the selective reduction of the imino group present in compounds 4 without affecting the heterocyclic ring was another aim of the study. Thus, a general and convenient method using NaBH4 as a selective reducing agent was employed for the synthesis in good yields of the 1,2/1,3-bis[o-(N-methylamino-3-aryl,5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 5 (Scheme 3).
Molecules 11 00469 g002 550
Scheme 1.
Scheme 1.
Molecules 11 00469 g002
Molecules 11 00469 g003 550
Scheme 2.
Scheme 2.
Molecules 11 00469 g003
Molecules 11 00469 g004 550
Scheme 3.
Scheme 3.
Molecules 11 00469 g004
In the IR spectra of compounds 4 the characteristic C=N absorption bands appeared at 1597 cm-1. The 1H-NMR signals for the -N=CH group were observed at δ 8.23-8.70 ppm. The 13C-NMR signals for the –N=CH- group were recorded at δ 164 ppm. Reduced compounds 5 showed IR absorption bands around 3245-3290 cm-1 (υNH). The 1H-NMR signals for the -NH-CH2- group of these compounds were observed as a doublet or strong singlet at around δ 3.55-3.75 ppm and the proton signals of –NH-CH2- groups were recorded as a triplet or strong singlet between δ 6.95-7.08 ppm. The NH-CH2- carbon signals of compounds 5 were recorded at δ 48 ppm in the 13C-NMR. In addition to this, in the 13C-NMR the triazole C3 and C5 of the bis-Schiff base derivatives 4 were observed between δ 148-149 ppm and the triazole C3 and C5 signals of the reduced compounds 5 were observed between δ 152-153 ppm.

Conclusions

In this study, a convenient method was established for the synthesis in good yields of bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy] alkane derivatives 4a-f and bis[o-(N-methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy] alkane derivatives 5a-f. The twelve new bis-(4H-1,2,4-triazole) derivatives synthesized in the study are expected to exhibit some biological activities and these results will be reported in due course.

Experimental

General

Melting points were determined on a Barnstead Electrothermal melting point apparatus and are uncorrected. 1H-NMR and 13C-NMR spectra (δ, ppm) were recorded on a Varian-Mercury 200 MHz spectrophotometer using tetramethylsilane as the internal reference. The IR spectra (υ, cm-1) were obtained with a Perkin-Elmer 1600 FTIR spectrometer in KBr pellets. The mass spectra were recorded on a MicroMass Quattro LC-MS/MS (70 eV) spectrometer. The necessary chemicals were purchased from Merck and Fluka.

Synthesis of bis-aldehydes 1a-b

Salicylaldehyde (0.01 mol) was dissolved in hot ethanolic KOH (prepared by dissolving 0.01 mol of KOH in 100 mL of absolute ethanol) and the solvent was then removed in vacuo. The residue was dissolved in DMF (25 mL) and the appropriate dihalide (0.005 mol) was added. The reaction mixture was refluxed for 5 minutes, during which KCl separated out. The solvent was then removed in vacuo and the remaining material was washed with water and crystallized from an appropriate solvent to give compounds 1a-b.
1,2-Bis(o-formylphenoxy)ethane (1a). Yield 68%; m.p. 129-130 °C (from ethanol; lit. [27] m.p. 129 °C).
1,3-Bis(o-formylphenoxy)propane (1b). Yield 70%; m.p. 99-100 °C (from ethanol; lit. [27] m.p. 99 °C).

Synthesis of hydrazones 2a-c

A solution of an appropriate hydrazide (0.01 mol) in absolute ethanol (25 mL) was added to a solution of iminoester hydrochloride (0.01 mol) in absolute ethanol (25 mL). The mixture was stirred for 6 h at 0-5 °C and subsequently for 2 h at room temperature. The reaction mixture was then poured into a beaker containing cold water (40 mL) and ice (10 g). The precipitate formed was washed with ice-water (50 mL), dried and the product was recrystallized from from 2:1 benzene-petroleum ether to give compounds 2a-c.
Ethyl benzoate benzoylhydrazone (2a). Yield 79%; m.p. 120-121 °C (lit. [28] m.p. 121°C).
Ethyl p-methylbenzoate benzoylhydrazone (2b). Yield 84%; m.p. 77-78 °C (lit. [26] m.p. 78 °C).
Ethyl p-chlorobenzoate benzoylhydrazone (2c). Yield 72%; m.p. 80-81 °C; IR: 3199 (N-H), 1637 (C=O), 1613 (C=N), 702, 730, 759, 839 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1.37 (t, 3H, CH3), 4.10 (q, 2H, CH2), 7.44-7.75 (m, 5H, Ar-H), 8.13 (m, 4H, Ar-H),10.79 (s, 1H, NH).

Synthesis of amino compounds 3a-c

Compounds 2 (0.005 mol) were added to a solution of hydrazine hydrate (0.01 mol) in 1-propanol (50 mL) and the mixture was refluxed for 24 h. On cooling, a precipitate was formed. This product was filtered and, after drying, was washed with benzene (20 mL). The product was then recrystallized from an appropriate solvent to give compounds 3a-c.
4-Amino-3,5-diphenyl-4H-1,2,4-triazole (3a). Yield 80%; m.p. 264-265 °C (from 1-propanol; lit. [28], m.p. 265 °C).
4-Amino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole (3b). Yield 85%; m.p. 283-284 °C (from 1-propanol; lit. [26], m.p. 284 °C).
4-Amino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazole (3c). Yield 68%; m.p. 284-285 °C (from ethyl acetate; lit. [28], m.p. 285 °C).

Synthesis of bis-Schiff bases 4a-f

The corresponding bis-aldehyde (0.01 mol) was added to a solution of compound 3 (0.005 mol) in glacial acetic acid (20 mL) and the mixture was refluxed for 16 h. After cooling, the mixture was poured into a beaker containing ice-water (100 mL). The precipitate formed was filtered. After drying in vacuo, the product was recrystallized from 1:2 benzene-petroleum ether to give the desired compound.
1,2-Bis[o-(N-methylidenamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (4a). Yield 70%; m.p. 212-213 °C; IR: 1598 (C=N), 693, 770 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 3,98 (s, 4H, OCH2), Ar-H: [6,89-7,04 (m, 4H), 7,33 (m, 10H), 7,70 (m, 6H), 7.44-7.56 (m, 4H), 7,92-8,06 (m, 4H)], 8,23 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 164.44 (2C, N=CH), 149.87 (2C, triazole C3), 149.87 (2C, triazole C5), Ar-C: [158.20 (2C), 134.75 (2C), 129.55 (2C), 128.76 (8C), 128.27 (8C), 126.88 (4C), 126.23 (4C), 121.33 (2C), 119.39 (2C), 113.48 (2C)], 66.86 (2C, OCH2); LC-MS/MS, m/z (I, %) for C44H34N8O2 (m.w.: 706.81 g/mol): 729.26 [M+Na]+ (50), 707.25 [M+1]+ (30), 221.97 (100), 103.86 (60).
1,3-Bis[o-(N-methylidenamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (4b). Yield 72%; m.p. 189-190 °C; IR: 1595 (C=N), 694, 754 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1,65 (q, 2H, -CH2-), 3,77 (t, 4H, OCH2), Ar-H: [6,97-7,16 (m, 6H), 7,51 (m, 12H), 7,80 (m, 8H), 7,97 (m, 2H)], 8,67 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 164.73 (2C, N=CH), 150.00 (2C, triazole C3), 150.00 (2C, triazole C5), Ar-C: [158.36 (2C), 134.93 (2C), 129.60 (2C), 128.66 (8C), 128.23 (8C), 126.95 (4C), 126.48 (4C), 120.97 (2C), 119.29 (2C), 112.93 (2C)], 64.29 (2C, OCH2), 27.75 (C, CH2); LC-MS/MS, m/z (I, %) for C45H36N8O2 (m.w.: 720.83 g/mol): 743.18 [M+Na]+ (25), 721.23 [M+1]+ (60), 500.16 (12), 221.96 (100), 114.83 (28), 103.82 (32)
1,2-Bis[o-(N-methylidenamino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (4c).Yield 72%; m.p. 271-272 °C; IR: 1597 (C=N), 696, 721, 757, 823 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 2,52 (s, 6H, CH3), 4,00 (s, 4H, OCH2), Ar-H: [7,12 (m, 8H), 7,32 (bs, 6H), 7,49-7,68 (m, 10H), 7,94(m, 2H)], 8,25 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 164.34 (2C, N=CH), 149.90 (2C, triazole C3), 149.72 (2C, triazole C5), Ar-C: [158.45 (2C), 139.30 (2C), 134.72 (2C), 129.50 (2C), 129.16 (4C), 128.56 (4C), 128.09 (4C), 128.00 (4C), 126.93 (2C), 126.31 (2C), 123.42 (2C), 121.36 (2C), 119.50 (2C), 113.56 (2C)], 66.86 (2C, OCH2), 20.73 (2C, CH3); LC-MS/MS, m/z (I, %) for C46H38N8O2 (m.w.: 734.86 g/mol): 757.18 [M+Na]+ (100), 735.14 [M+1]+ (70), 555.17 (22), 503.05 (14), 288.99 (98), 251.00 (35), 104.75 (27).
1,3-Bis[o-(N-methylidenamino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (4d). Yield 62%; m.p. 229-230 °C; IR: 1597 (C=N), 697, 723, 765, 822 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 2.51 (s, 6H, CH3), 1,69 (q, 2H, -CH2-), 3,78 (t, 4H, OCH2), Ar-H: [6.98-7.13 (m, 4H), 7.24 (m, 4H), 7.49 (m, 10H), 7.78 (m, 3H), 7.82 (m, 3H), 7.98 (m, 2H)], 8.69 (s, 2H,CH); 13C-NMR (DMSO-d6) δ (ppm): 164.65 (2C, N=CH), 150.04 (2C, triazole C3), 149.87 (2C, triazole C5), Ar-C: [158.33 (2C), 139.25 (2C), 134.90 (2C), 129.52 (2C), 129.20 (4C), 128.62 (4C), 128.17 (4C), 128.11 (4C), 126.96 (2C), 126.54 (2C), 123.61 (2C), 120.94 (2C), 119.31 (2C), 112.88 (2C)], 64.26 (2C, OCH2), 27.72 (C, CH2), 20.68 (2C, CH3); LC-MS/MS, m/z (I, %) for C47H40N8O2 (m.w.: 748.89 g/mol): 771.20 [M+Na]+ (55), 749.24 [M+1]+ (40), 475.31 (42), 235.88 (15), 155.88 (26), 148.83 (32), 117.86(100).
1,2-Bis[o-(N-methylidenamino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy] ethane (4e). Yield 75%; m.p. 213-214 °C; IR υ (cm-1): 1598 (C=N), 695, 723, 758, 834 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 4,02 (s, 4H, OCH2), Ar-H: [7,01-7,10 (m, 3H), 7,30-7,37 (m, 6H), 7,42-7,55 (m, 10H), 7,64-7,73 (m, 3H), 7,81 (d, 3H), 7,94 (m, 1H)], 8,30(s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 164.68 (2C, N=CH), 149.85 (2C, triazole C3), 149.10 (2C, triazole C5), Ar-C: [158.47(2C), 134.85 (2C), 134.46 (2C), 129.74 (4C), 129.56 (4C), 128.74 (4C), 128.57 (4C), 128.17 (2C), 127.01 (2C), 126.07 (2C), 125.11 (2C), 121.36 (2C), 119.35 (2C), 113.51 (2C)], 66.87 (2C, OCH2); LC-MS/MS, m/z (I, %) for C44H32Cl2N8O2 (m.w.: 775.70 g/mol): 798.11 [M+Na]+ (20), 775.13 [M]+ (18), 255.93 (10), 166.84 (15), 164.84 (43), 134.83(100).
1,3-Bis[o-(N-methylidenamino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazol-4-yl)-phenoxy]propane (4f). Yield 77%; m.p. 189-190 °C; IR: 1597 (C=N), 690, 723, 757, 833 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1,69 (bs, 2H, -CH3-), 3,80 (bs, 4H, OCH2), Ar-H: [6,99-7,14 (m, 6H), 7,44-7,56 (m, 12H), 7,83-7,99 (m, 8H)], 8,70 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 163.88 (2C, N=CH), 149.08 (2C, triazol C3), 148.21 (2C, triazol C5), Ar-C: [157.41 (2C), 133.99 (2C), 133.47 (2C), 128.89 (4C), 127.78 (4C), 127.66 (4C), 127.24 (4C), 126.03 (2C), 125.35 (2C), 124.35 (2C), 124.23 (2C), 119.99 (2C), 118.25 (2C), 111.91 (2C)], 63.31 (2C, OCH2), 26.79 (CH2); LC-MS/MS, m/z (I, %) for C45H34Cl2N8O2 (m.w.: 789.72 g/mol): 811.19 [M+Na]+ (60), 789.31 [M]+ (56), 559.18 (13), 256.03 (53), 134.93 (84), 104.86 (100).

Synthesis of reduced rompounds 5a-f

The corresponding compound 4a-f (0.005 mol) was dissolved in dried methanol (50 mL) and NaBH4 (0.01 mol) was added in small portions to this solution. The mixture was refluxed for 20 min and then allowed to cool. After evaporation at 30-35 °C under reduced pressure, the solid residue was washed with cold water. After drying in vacuo, the solid product was recrystallized from an appropriate solvent (1:1 ethanol-water, unless otherwise noted) to afford the desired compound.
1,2-Bis[o-(N-methylamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (5a). Yield 85%; m.p. 242-243 °C; IR: 3245 (NH), 1600 (C=N), 692, 720, 756 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 3.63 (d, 4H, -NH-CH2), 3.86 (s, 4H, OCH2), 6.95 (t, 2H, NH), Ar-H: [6.70 (d, 6H), 7.09-7.16 (m, 2H), 7.42 (m, 12H), 7.85-7.90 (m, 8H); 13C-NMR (DMSO-d6) δ (ppm): 153.57 (2C, triazole C3), 153.57 (2C, triazole C5), Ar-C: [156.20 (2C), 130.02 (2C), 129.47 (4C), 129.05 (2C), 128.29 (8C), 127.68 (8C), 126.97 (4C), 123.41 (2C), 120.11 (2C), 111.47 (2C)], 65.96 (2C, OCH2), 48.78 (2C,CH2-NH); LC-MS/MS, m/z (I, %) for C44H38N8O2 (m.w.: 710.84 g/mol): 733.22 [M+Na]+ (15), 711.22 [M+1]+ (35), 490.18 (8), 269.02 (11), 221.96 (28), 147.85 (100).
1,3-Bis[o-(N-methylamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (5b). Yield 74%; m.p. 216-217 °C; IR: 3253 (NH), 1601 (C=N), 694, 717, 745 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1.88 (q, 2H, -CH2-), 3.55 ( bs, 4H, OCH2 + 4H, -NH-CH2 ), 7.04 ( m, 2H, 2NH + 2H, Ar-H ), Ar-H: [6.66 (m, 4H), 7.47 (bs, 14H), 7.94 (bs, 8H); 13C-NMR (DMSO-d6) δ (ppm): 153.65 (2C, triazole C3), 153.65 (2C, triazole C5), Ar-C: [156.24 (2C), 129.96 (2C), 129.54 (4C), 129.07 (2C), 128,34 (8C), 127.76 (8C), 127.07 (4C), 123,31 (2C), 119.81 (2C), 111.09 (2C)], 63.90 (2C, OCH2), 48.87 (2C, CH2-NH), 28.17 (CH2); LC-MS/MS, m/z (I, %) for C45H40N8O2 (m.w.: 724.87 g/mol): 747.26 [M+Na]+ (95), 725.28 [M+1]+ (100), 272.98 (52), 234.97 (100), 104.86 (16).
1,2-Bis[o-(N-methylamino-3-p-tolyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (5c). Yield 79%; m.p. 192-193 °C; IR: 3261(NH), 1601(C=N), 690, 729, 748, 820 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 2.29 (s, 6H, CH3), 3.64 (d, 4H, -NH-CH2-), 3.88 (s, 4H, OCH2), 6.92 (t, 2H, NH), Ar-H: [6.72 (d, 4H), 7.22 (d, 4H), 7.37-7.43 (m, 10H), 7.78-7.87 (m, 8H); 13C-NMR (DMSO-d6) δ (ppm): 153.51 (2C, triazole C3), 153.47 (2C, triazole C5), Ar-C: [156.23 (2C), 139.15 (2C), 130.03 (2C), 129.40 (2C), 129.04 (2C), 128.92 (4C), 128.23 (4C), 127.71 (4C), 127.53 (4C), 127.05 (2C), 124.20 (2C), 123.48 (2C), 120.14 (2C), 111.48 (2C)], 65.98 (2C, OCH2), 48.76 (2C, CH2-NH), 20.80 (2C, CH3); LC-MS/MS, m/z (I, %) for C46H42N8O2 (m.w.: 738.65 g/mol): 740.30 [M+2]+ (55), 739.23 [M+1]+ (100), 414.95 (12), 370.13 (15), 216.93 (16), 156.88 (38).
1,3-Bis[o-(N-methylamino-3-p-tolyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (5d). Yield 78%; m.p. 181-182 °C; IR: 3249 (NH), 1601 (C=N), 692, 729, 749, 823 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 2.33 (s, 6H, CH3), 1.89 (q, 2H, ­-CH2-), 3.76 ( bs, 4H, OCH2 + 4H, -NH-CH2), 7.04 (t, 2H, NH), Ar-H: [6.63-6.74 (m, 6H), 7.11-7.16 (m, 2H), 7.26-7.37 (m, 5H), 7.45 (m, 5H), 7.82-7.93 (m, 8H)]; 13C-NMR (DMSO-d6) δ (ppm): 153.57 (2C, triazole C3), 153.48 (2C, triazole C5), Ar-C: [156.25 (2C), 139.22 (2C), 129.97 (2C), 129.44 (2C), 129.05 (2C), 128.94 (4C), 128.28 (4C), 127.77 (4C), 127.62 (4C), 127.12 (2C), 124.29 (2C), 123.37 (2C), 119.82 (2C), 111.06 (2C)], 63.93 (2C, OCH2), 28.19 (C, CH2), 48.82 (2C, CH2-NH), 20.83 (2C, CH3); LC-MS/MS, m/z (I, %) for C47H44N8O2 (m.w.: 752.85 g/mol): 775.23 [M+Na]+ (65), 753.33 [M+1]+ (100), 235.94 (5), 105.02 (5).
1,2-Bis[o-(N-methylamino-3-p-chlorophenyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (5e). Yield 69%; m.p. 219-220 °C (from 1:2 ethanol-water); IR: 3249 (NH), 1601 (C=N), 689, 729, 749, 833 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 3.63 (bs, 4H, -NH-CH2-), 3.89 (bs, 4H, -OCH2), 6.99 (bs, 2H, NH), Ar-H: [6.71 (bs ,6H), 7.14 (bs, 2H), 7.45 (bs, 10H), 7.88 (m, 8H); 13C-NMR (DMSO-d6) δ (ppm): 153.81 (2C, triazole C3), 152.65 (2C, triazole C5), Ar-C: [156.21 (2C), 134.27 (2C), 130.20 (2C), 129.65 (2C), 129.35 (4C), 129.17 (4C), 128.41 (4C), 128.30 (4C), 127.66 (2C), 126.79 (2C), 125.69 (2C), 123.29 (2C), 120.14 (2C), 111.40 (2C)], 65.95 (2C, OCH2), 48.79 (2C, CH2-NH); LC-MS/MS, m/z (I, %) for C44H36Cl2N8O2 (m.w.: 778.24 g/mol): 801.12 [M+Na]+(48), 779.15 [M+1]+ (18), 747.26 (21), 725.22 (20), 214.93 (13), 164.84 (43), 134.83 (100).
1,3-Bis[o-(N-methylamino-3-p-chlorophenyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (5f). Yield 72%; m.p. 126-127 °C (from 1:2 ethanol-water); IR: 3291(NH), 1601(C=N), 690, 734, 754, 835 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1.89 (bs, 2H, -CH2-), 3.75 ( bs, 4H, OCH2 + 4H, -NH-CH2 ), 7.08 ( m,2H, 2NH + 2H, Ar-H ), Ar-H: [6.65(m, 6H), 7.50 (m, 10H), 7.93 (m, 8H)]; 13C-NMR (DMSO-d6) δ (ppm): 153.81 (2C, triazole C3), 152.78 (2C, triazole C5), Ar-C: [156.21 (2C), 134.29 (2C), 130.11 (2C), 129.68 (2C), 129.44 (4C), 129.15 (2C), 128.45 (4C), 128.30 (4C), 127.69 (4C), 126.90 (2C), 125.78 (2C), 123.17 (2C), 119.78 (2C), 110.94 (2C)], 64.20 (2C, OCH2), 48.82 (2C, CH2-NH), 28.19 (C, CH2); LC-MS/MS, m/z (I, %) for C45H38Cl2N8O2 (m.w.: 792.25 g/mol): 815.26 [M+Na]+ (100), 793.25 [M+1]+ (45), 563.18 (28), 283.10 (12), 34.93 (15).

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Bekircan, O.; Bektas, H. Synthesis of New Bis-1,2,4-Triazole Derivatives. Molecules 2006, 11, 469-477. https://doi.org/10.3390/11060469

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Bekircan O, Bektas H. Synthesis of New Bis-1,2,4-Triazole Derivatives. Molecules. 2006; 11(6):469-477. https://doi.org/10.3390/11060469

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Bekircan, Olcay, and Hakan Bektas. 2006. "Synthesis of New Bis-1,2,4-Triazole Derivatives" Molecules 11, no. 6: 469-477. https://doi.org/10.3390/11060469

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