Introduction

Triazoles, in particular 1,2,4-triazoles, are privileged structural constituents of many pharmaceutical agents as well as natural products [1, 2]. Amino-1,2,4-triazoles, a subclass of 1,2,4-triazoles, are widely used in materials chemistry, medicinal chemistry [3], and synthetic chemistry as synthons [4]. Selected 1,2,4-triazoles with biological activities are depicted in Fig. 1 [5]. Since all triazoles are of synthetic origin and there is no triazole ring system detected as yet in nature, the development of new methodologies for the synthesis of functionalized triazoles continues to be an active area of research in fine chemistry. Among the conventional approaches developed over the past decades for the construction of the triazole skeleton [6,7,8], the most commonly used include the reaction of acyl hydrazides with isothioureas [9], oxidative coupling of N,N-dimethylguanidine with benzonitrile [10], and [3 + 2]-cycloaddition reaction of nitrile ylides with diazonium salts [11].

Fig. 1
figure 1

Selected 1,2,4-triazoles with biological activities

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Guanidines can be categorized as organic super bases due to the resonance stability of their conjugated acids [12]. Thus, they are expected to catalyze base-mediated organic reactions and can be widely and easily modified into a variety of chiral bases [13]. Guanidine derivatives serve as building blocks in various drugs, natural products, and agrochemicals [14,15,16]. Finally, neutral guanidines have found themselves as good supporting ligands in organometallic and coordination chemistry [17]. In continuation of our work on the developments of new routes to construct azole system via nitrile imines [18,19,20], we now report a [3 + 2] dipolar cycloaddition/elimination process for the synthesis of 1,2,4-triazoles.

Results and discussion

Our initial studies focused on searching for an optimal reaction condition to generate N,N-dimethyl-1,3-diphenyl-1H-1,2,4-triazol-5-amine (3a) using N-phenylbenzohydrazonoyl chloride (1a) [21] and tetramethylguanidine (2a, TMG) as reaction substrates (Table 1). Initially, the reaction between 1a and TMG was conducted in the presence of Et3N in MeCN at room temperature. After 3 h, the product 3a was isolated in 90% yield. The regioselective formation of 3a was confirmed on the basis of its 13C NMR spectrum, which exhibited two signals at 159.2 and 159.3 ppm for the N–C=N moieties. Thus, the isomeric 1,2,3-triazol derivative (see Table 1) is ruled out because it is expected to show only one carbon signal for its N–C=N carbon atom above 150 ppm. In order to optimize the reaction conditions for the formation of 3a, the effects of solvent and base were studied. Thus, a survey of different solvents such as THF, DMSO, DMF, and CH2Cl2 was made. As shown in Table 1, the best yield was obtained in MeCN. Then, different bases such as K2CO3, DABCO, DBU, and Cs2CO3 were examined. None of these bases were superior compared to Et3N. Thus, the optimum reaction condition for preparation of 3a is equimolar amounts of 1a and 2a in MeCN at 25 °C.

Table 1 Optimization of the reaction conditions for synthesis of 1,2,4-triazole 3a
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The scope of the present method was further explored by the utilization of a range of hydrazonoyl chlorides. As shown in Table 2, the reactivity of substrates 3 with different substituents on the nitrogen and carbon atoms was almost the same and the reactions proceeded smoothly, giving the desired products with satisfactory yields.

Table 2 Synthesis of highly substituted 1,2,4-triazoles 3
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The structures of products 3a–g were deduced from their IR, 1H NMR, and 13C NMR spectral data. For example, the 1H NMR spectrum of 3a exhibited a sharp singlet for the two methyl groups at about 2.87 ppm and aromatic protons appeared at δ = 7.35–8.15 ppm. The 13C NMR spectrum of 3a exhibited 11 signals in agreement with the proposed structure. The mass spectrum of 3a displayed the molecular ion peak at m/z = 264. The NMR spectra of compounds 3b–g are similar to those of 3a, except for the substituents, which showed characteristic signals in the appropriate regions of the spectra.

The regioselective formation of substituted triazole derivatives 3 can be explained by a plausible mechanism depicted in Scheme 1. Presumably, the initial event is elimination of HCl by Et3N, which leads to the formation of nitrile imine intermediate 4. This 1,3-dipolar intermediate is ceased by TMG to yield adduct 5, which undergoes subsequent loss of dimethylamine to generate product 3.

Scheme 1
scheme 1

A plausible mechanism for the regioselective formation of 1,2,4-triazoles derivatives 3

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To extend the scope of this reaction, we used cyanoguanidine (6) as the guanidine derivatives. As shown in Table 3 (entries 1–4), the reaction of 6 with 1 gave a mixture of 2-(1,3-diaryl-1H-1,2,4-triazol-5-yl)guanidine (7) and 1,3-diaryl-1H-1,2,4-triazol-5-amine (8). However, when a nitro group existed in the substrate, only a single product (namely 7e or 7f) was obtained (Table 3, entries 5 and 6). Products 8e and 8f were not observed in the proton NMR spectra of the reaction mixtures. The absence of these products in the reaction mixture can be explained by reduction of reactivity of the nitrile imine intermediate as a result of the presence of a nitro group. These less reactive nitrile imines are more selective toward the nitrile group of 6 and lead to the formation of 7 via the more stable “aromatic” transition state I compared to II (see Fig. 2).

Table 3 Synthesis of highly substituted 1,2,4-triazoles 7 and 8
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Fig. 2
figure 2

Transition states I and II for the formation of products 7 and 8, respectively

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The formation of 3-amino-1,2,4-triazoles 7 and 8 can be explained by a plausible mechanism depicted in Scheme 1. The initial event may be generation of nitrile imine intermediate 4 by elimination of HCl from 1. Intermediate 4 can be ceased by the cyano group of 6 to generate intermediate 9, which is in equilibrium with its tautomer 7 (route a). As shown in Scheme 1, in route b, 1,3-dipolar cycloaddition reaction involves the imino double bond of 6 to give intermediate 10, which is converted to product 8 by elimination of cyanamide (Scheme 2).

Scheme 2
scheme 2

Plausible mechanism for the formation of 1,2,4-triazoles derivatives 7 and 8

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In summary, we have developed an operational approach for the synthesis of functionalized 3-amino-1,2,4-triazoles in MeCN at 25 °C. Thus, the nitrile imines generated in situ from hydrazonoyl chlorides were seized by guanidine derivatives featuring the synthesis of triazoles in good yields and excellent regioselectivity. The reaction proceeds through a cascade [3 + 2] cycloaddition and elimination sequence. This methodology offers a simple and efficient strategy to construct structurally diverse 1,2,4-triazos from readily available starting materials in a one-step fashion under mild condition.

Experimental section

General remarks

All purchased solvents and chemicals had analytical grade and were used without further purification. Melting points: Electrothermal-9100 apparatus. IR (KBr) spectra: Shimadzu-IR-460 spectrometer; ν in cm−1. 1H NMR (500 MHz, 300 MHz) and 13C NMR (125 MHz, 75 MHz) spectra were obtained using Bruker DRX-500 Avance and Bruker DRX-300 Avance spectrometers. All NMR spectra were recorded at room temperature in CDCl3. Chemical shifts are reported in parts per million (δ) downfield from an internal TMS reference. Coupling constants are reported in hertz (Hz), and standard abbreviations were used to indicate spin multiplicities. Mass spectra were recorded on a Finnigan-MAT-8430EI-MS mass spectrometer, at an ionization potential 70 eV, in m/z (rel. %). Elemental analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer.

Typical procedure for the synthesis of products 3

A mixture of hydrazonoyl chloride derivative 1 (1 mmol) and Et3N (0.101 g, 1 mmol) in MeCN (3 mL) was stirred at r.t. for 15 min. Then guanidine derivatives 2 (1 mmol) were added to the above mixture, and the reaction was stirred at r.t. for 3 h. After completion of the reaction (the progress of the reaction was followed by TLC), the solvent was removed under reduced pressure. The crude residue was purified by column chromatography [silica gel (230–400 mesh; Merck, n-hexane/AcOEt 3:1] to give the products 3a–3g

N,N-Dimethyl-1,3-diphenyl-1H-1,2,4-triazol-5-amine (3a)

Colorless powder, m.p.: 56–58 °C; Yield: 0.24 g (90%). IR (KBr) (νmax, cm−1): 3058, 2878, 2804, 1588, 1555, 1494, 1408, 1365. 1H NMR (500 MHz, CDCl3): δH = 2.87 (6 H, s, 2 Me), 7.37 (1 H, t, 3J = 7.5 Hz, Ar), 7.39 (1 H, t, 3J = 7.3 Hz, Ar), 7.44 (2 H, t, 3J = 7.3 Hz, Ar), 7.49 (2 H, t, 3J = 7.8 Hz, Ar), 7.68 (2 H, d, 3J = 8.1 Hz, Ar), 8.14 (2 H, d, 3J = 8.2 Hz, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 41.3 (2 Me), 123.9 (2 CH), 126.3 (2 CH), 127.7 (CH), 128.4 (2 CH), 128.9 (CH), 129.3 (2 CH), 131.3 (C), 138.9 (C), 159.2 (C=N), 159.3 (C=N). MS: m/z (%) = 264 (M+, 1), 249 (8), 194 (10), 118 (22), 103 (30), 91 (100), 77 (80). Anal. Calcd for C16H16N4 (264.33): C, 72.70; H, 6.10; N, 21.20%. Found: C, 73.08; H, 6.14; N, 21.55%.

3-(3-Chlorophenyl)-N,N-dimethyl-1-phenyl-1H-1,2,4-triazol-5-amine (3b)

Colorless powder, m.p.: 73–75 °C; Yield: 0.27 g (90%). IR (KBr) (νmax, cm−1): 3208, 2878, 1574, 1485, 1404, 1368. 1H NMR (300 MHz, CDCl3): δH = 2.86 (6 H, s, 2 Me), 7.33–7.35 (2 H, m, Ar), 7.37 (1 H, t, 3J = 7.4 Hz, Ar), 7.48 (2 H, t, 3J = 7.6 Hz, Ar), 7.64 (2 H, d, 3J = 8.2 Hz, Ar), 7.99 (1 H, t, 3J = 8.1 Hz, Ar), 8.13 (1 H, s, Ar). 13C NMR (75.0 MHz, CDCl3): δC = 41.2 (2 Me), 123.9 (2 CH), 124.3 (CH), 126.3 (CH), 127.8 (CH), 128.9 (CH), 129.3 (2 CH), 129.6 (CH), 133.1 (C), 134.4 (C), 138.7 (C), 158.0 (C=N), 159.3 (C=N). MS: m/z (%) = 298 (M+, 1), 283 (40), 269 (50), 228 (8), 207 (70), 118 (10), 91 (100), 77 (10), 64 (4). Anal. Calcd for C16H15ClN4 (298.77): C, 64.32; H, 5.06; N, 18.75%. Found: C, 64.75; H, 5.10; N, 19.19%.

3-(4-Chlorophenyl)-N,N-dimethyl-1-phenyl-1H-1,2,4-triazol-5-amine (3c)

Colorless powder, m.p.: 79–81 °C; Yield: 0.27 g (89%). IR (KBr) (νmax, cm−1): 3058, 2922, 1594, 1487, 1348, 764. 1H NMR (500 MHz, CDCl3): δH = 2.86 (6 H, s, 2 Me), 7.36–7.39 (3 H, m, Ar), 7.48 (2 H, t, 3J = 7.5 Hz, Ar), 7.64 (2 H, d, 3J = 8.1 Hz, Ar), 8.04 (2 H, d, 3J = 8.5 Hz, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 41.3 (2 Me), 123.9 (2 CH), 127.6 (2 CH), 127.8 (CH), 128.6 (2 CH), 129.3 (2 CH), 129.8 (C), 134.8 (C), 138.7 (C), 158.3 (C=N), 159.3 (C=N). MS: m/z (%) = 298 (M+, 1), 283 (35), 269 (50), 228 (12), 207 (70), 118 (15), 91 (100), 77 (10), 64 (15). Anal. Calcd for C16H15ClN4 (298.77): C, 64.32; H, 5.06; N, 18.75%. Found: C, 64.79; H, 5.09; N, 19.17%.

3-(4-Fluorophenyl)-N,N-dimethyl-1-phenyl-1H-1,2,4-triazol-5-amine (3d)

Colorless powder, m.p.: 43–45 °C; Yield: 0.24 g (86%). IR (KBr) (νmax, cm−1): 3054, 2924, 1580, 1497, 1410, 1365. 1H NMR (500 MHz, CDCl3): δH = 2.86 (6 H, s, 2 Me), 7.11 (2 H, dd, 3J = 8.78, 8.78 Hz, Ar), 7.37 (1 H, t, 3J = 7.5 Hz, Ar), 7.48 (2 H, t, 3J = 7.9 Hz, Ar), 7.65 (2 H, t, 3J = 7.4 Hz, Ar), 8.11 (2 H, dd, 3J = 8.9, 5.5 Hz, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 41.3 (2 Me), 115.3 (d, 2JC-F = 21.5 Hz), 123.9 (2 CH), 127.5 (d, 4JC-F = 3.2 Hz), 127.7 (CH), 128.2 (d, 3JC-F = 8.3 Hz), 129.3 (2 CH), 138.8 (C), 158.4 (C=N), 159.3 (C=N), 163.4 (d, 1JC-F = 250 Hz). MS: m/z (%) = 282 (M+, 1), 267 (33), 253 (10), 212 (22), 121 (13), 91 (100), 77 (15). Anal. Calcd for C16H15FN4 (282.13): C, 68.07; H, 5.36; N, 19.85%. Found: C, 68.46; H, 5.39; N, 20.26%.

N,N-Dimethyl-1-phenyl-3-(p-tolyl)-1H-1,2,4-triazol-5-amine (3e)

Colorless powder, m.p.: 65–68 °C; Yield: 0.25 g (89%). IR (KBr) (νmax, cm−1): 3058, 2913, 2804, 1566, 1496, 1411, 1365. 1H NMR (500 MHz, CDCl3): δH = 2.40 (3 H, s, Me), 2.87 (6 H, s, 2 Me), 7.24 (2 H, d, 3J = 7.9 Hz, Ar), 7.36 (1 H, t, 3J = 7.5 Hz, Ar), 7.48 (2 H, t, 3J = 7.9 Hz, Ar), 7.68 (2 H, d, 3J = 7.4 Hz, Ar), 8.03 (2 H, d, 3J = 8.1 Hz, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 21.4 (Me), 41.3 (2 Me), 123.9 (2 CH), 126.2 (2 CH), 127.6 (CH), 128.5 (C), 128.1 (2 CH), 129.2 (2 CH), 138.8 (C), 138.9 (C), 159.2 (C=N), 159.3 (C=N). MS: m/z (%) = 279 (M+, 1), 263 (23), 249 (10), 208 (22), 118 (22), 91 (100), 77 (26). Anal. Calcd for C17H18N4 (279.15): C, 73.35; H, 6.52; N, 20.13%. Found: C, 73.81; H, 6.55; N, 20.45%.

N,N-Dimethyl-3-(4-nitrophenyl)-1-phenyl-1H-1,2,4-triazol-5-amine (3f)

Colorless powder, m.p.: 122–125 °C; Yield: 0.28 g (90%). IR (KBr) (νmax, cm−1): 3058, 2927, 2804, 1593, 1508, 1413, 1336. 1H NMR (500 MHz, CDCl3): δH = 2.89 (6 H, s, 2 Me), 7.41 (1 H, t, 3J = 7.5 Hz, Ar), 7.51 (2 H, t, 3J = 8.1 Hz, Ar), 7.64 (2 H, d, 3J = 7.5 Hz, Ar), 8.23–8.31 (4 H, m, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 41.3 (2 Me), 123.8 (2 CH), 124.1 (2 CH), 126.9 (2 CH), 128.2 (CH), 129.4 (2 CH), 137.3 (C), 138.5 (C), 148.0 (C), 157.1 (C=N), 159.4 (C=N). MS: m/z (%) = 309 (M+, 1), 294 (33), 280 (10), 262 (8), 160 (8), 118 (15), 91 (100), 77 (10). Anal. Calcd for C16H15N5O2 (309.12): C, 62.13; H, 4.89; N, 22.64%. Found: C, 62.53; H, 4.91; N, 22.96%.

3-(4-Chlorophenyl)-N,N-dimethyl-1-(4-nitrophenyl)-1H-1,2,4-triazol-5-amine (3g)

Colorless powder, m.p.: 132–135 °C; Yield: 0.30 g (88%). IR (KBr) (νmax, cm−1): 3115, 2875, 2804, 1597, 1584, 1511, 1405, 1333. 1H NMR (500 MHz, CDCl3): δH = 2.93 (6 H, s, 2 Me), 7.42 (2 H, d, 3J = 8.5 Hz, Ar), 7.97 (2 H, d, 3J = 9.0 Hz, Ar), 8.06 (2 H, d, 3J = 8.5 Hz, Ar), 8.37 (2 H, d, 3J = 9.0 Hz, Ar). 13C NMR (125.7 MHz, CDCl3): δC = 41.8 (2 Me), 122.7 (2 CH), 124.9 (2 CH), 127.7 (2 CH), 128.7 (2 CH), 129.2 (C), 135.4 (C), 143.5 (C), 145.8(C), 159.3 (C=N), 160.1 (C=N). MS: m/z (%) = 343 (M+, 1), 328 (48), 314 (15), 273 (22), 207 (15), 192 (10), 149 (8), 139 (51), 91 (100). Anal. Calcd for C16H14ClN5O2 (343.08): C, 55.90; H, 4.10; N, 20.37%. Found: C, 56.23; H, 4.14; N, 20%.

Typical procedure for the synthesis of products 7 and 8

A mixture of hydrazonoyl chloride 1 (1 mmol) and Et3N (0.101 g, 1 mmol) in MeCN (3 mL) was stirred at r.t. for 15 min. Then guanidine 6 (1 mmol) was added to the above mixture, and the reaction was stirred at r.t. for 3 h. After completion of the reaction (the progress of the reaction was followed by TLC), the solvent was removed under reduced pressure. The crude residue was purified by column chromatography [silica gel (230–400 mesh); Merck, n-hexane/AcOEt 3:1] to give the products 7a–7f and 8a–8d.

Formation of products 7a and 8a in 1:1 ratio

Colorless powder; mp: 134–142 °C; IR (KBr) (νmax, cm−1): 3423, 3298, 3115, 1637, 1544, 1503, 1417, 1366, 752. MS: m/z (%) = 312 (M+, 1), 270 (M+, 1), 295 (15), 228 (20), 133 (15), 91 (100), 77 (18).

2-[3-(3-Chlorophenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]guanidine (7a)

Yield: 0.12 g (40%); 1H NMR (300 MHz, DMSO-d6): δH = 6.95 (4 H, br, 2 NH2), 7.26 (1 H, t, 3 J = 7.4 Hz, Ar), 7.37–7.48 (4 H, m, Ar), 8.00 (1 H, dd, 3J = 6.6, 1.9 Hz, Ar), 8.04 (1 H, s, Ar), 8.13 (2 H, d, 3J = 7.7 Hz, Ar).13C NMR (75 MHz, DMSO-d6): 121.9 (2 CH), 124.1 (CH), 125.2 (CH), 125.5 (CH), 128.5 (2 CH), 128.6 (CH), 130.5 (CH), 133.4 (C), 133.5 (C), 138.6 (C), 155.2 (C=N), 156.9 (C=N), 158.7 (C=N). Anal. Calc. for C15H13ClN6: (312.09): C, 57.60; H, 4.19; N, 26.87%.

3-(3-Chlorophenyl)-1-phenyl-1H-1,2,4-triazol-5-amine (8a)

Yield: 0.12 g (44%); 1H NMR (300 MHz, DMSO-d6): δH = 6.62 (2 H, br, NH2), 7.37–7.48 (3 H, m, Ar), 7.54 (2 H, t, 3J = 7.7 Hz, Ar), 7.62 (2 H, d, 3J = 7.5 Hz, Ar), 7.89 (1 H, dd, 3J = 6.6, 1.9 Hz, Ar), 7.91 (1 H, s, Ar). 13C NMR (75 MHz, DMSO-d6): 122.9 (2 CH), 124.0 (CH), 125.1 (CH), 127.3 (CH), 128.6 (CH), 129.4 (2 CH), 130.6 (CH), 133.3 (C), 133.4 (C), 137.1 (C), 155.5 (C=N), 158.4 (C=N). Anal. Calc. for C14H11ClN4: (270.07): C, 62.11; H, 4.10; N, 20.70%.

Formation of products 7b and 8b in 1:1 ratio

Colorless powder; mp: 130–138 °C; IR (KBr) (νmax, cm−1): 3427, 3296, 3101, 1635, 1548, 1500, 1411, 1366, 754. MS: m/z (%) = 312 (M+, 1), 270 (M+, 1), 295 (5), 228 (33), 133 (18), 91 (100), 77 (18).

2-[3-(4-Chlorophenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]guanidine (7b)

Yield: 0.13 g (42%); 1H NMR (500 MHz, CDCl3): δH = 6.66 (4 H, br, 2 NH2), 7.26 (1 H, t, 3J = 8.0 Hz, Ar), 7.40–7.44 (4 H, m, Ar), 7.92 (2 H, d, 3J = 8.0 Hz, Ar), 8.05 (2 H, d, 3J = 8.5 Hz, Ar).13C NMR (125 MHz, CDCl3): 123.4 (2 CH), 127.4 (2 CH), 128.3 (CH), 128.6 (2 CH), 129.9 (2 CH), 130.0 (C), 134.7 (C), 138.2 (C), 156.8 (C=N), 157.3 (C=N), 157.8 (C=N). Anal. Calc. for C15H13ClN6: (312.09): C, 57.60; H, 4.19; N, 26.87%.

3-(4-Chlorophenyl)-1-phenyl-1H-1,2,4-triazol-5-amine (8b)

Yield: 0.13 g (46%); 1H NMR (500 MHz, CDCl3): δH = 5.02 (2 H, br, NH2), 7.40–7.44 (3 H, m, Ar), 7.53 (2 H, t, 3J = 8.3 Hz, Ar), 7.56 (2 H, d, 3J = 7.3 Hz, Ar), 7.98 (2 H, d, 3J = 8.4 Hz, Ar). 13C NMR (125 MHz, CDCl3): 123.7 (2 CH), 126.7 (CH), 127.4 (2 CH), 128.6 (2 CH), 128.8 (2 CH), 129.4 (C), 135.1 (C), 136.7 (C), 154.3 (C=N), 158.4 (C=N). Anal. Calc. for C14H11ClN4: (270.07): C, 62.11; H, 4.10; N, 20.70%.

Formation of products 7c and 8c in 1:1 ratio

Colorless powder; mp: 179–185 °C; IR (KBr) (νmax, cm−1): 3447, 3183, 1608, 1540, 1500, 1417, 758. MS: m/z (%) = 296 (M+, 1), 253 (M+, 1), 279 (20), 212 (15), 121 (10), 91 (100), 77 (15).

2-[3-(4-Fluorophenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]guanidine (7c)

Yield: 0.13 g (43%); 1H NMR (500 MHz, CDCl3): δH = 6.59 (4 H, br, 2 NH2), 7.12 (2 H, d, 3J = 8.6 Hz, Ar), 7.25 (1 H, t, 3J = 7.4 Hz, Ar), 7.42 (2 H, t, 3J = 7.7 Hz, Ar), 7.93 (2 H, d, 3J = 8.0 Hz, Ar), 8.10 (2 H, dd, 3J = 8.6, 5.6 Hz, Ar).13C NMR (125 MHz, CDCl3): 115.5 (d, 2JC-F = 21.9 Hz), 123.4 (2 CH), 127.8 (d, 4JC-F = 3.2 Hz), 128.1 (d, 3JC-F = 8.3 Hz), 128.2 (CH), 128.6 (2 CH), 138.3 (C), 156.9 (C=N), 157.4 (C=N), 157.8 (C=N), 163.5 (d, 1JC-F = 250 Hz). Anal. Calc. for C15H13FN6: (296.12): C, 60.80; H, 4.42; N, 28.36%.

3-(4-Fluorophenyl)-1-phenyl-1H-1,2,4-triazol-5-amine (8c)

Yield: 0.13 g (49%); 1H NMR (500 MHz, CDCl3): δH = 5.02 (2 H, br, NH2), 7.11 (2 H, d, 3J = 8.6 Hz, Ar), 7.42 (1 H, t, 3J = 7.7 Hz, Ar), 7.53 (2 H, t, 3J = 7.7 Hz, Ar), 7.58 (2 H, d, 3J = 7.7 Hz, Ar), 8.04 (2 H, dd, 3J = 8.4, 5.5 Hz, Ar). 13C NMR (125 MHz, CDCl3): δC = 115.3 (d, 2JC-F = 21.9 Hz), 123.6 (2 CH), 126.5 (CH), 127.2 (d, 4JC-F = 3.2 Hz), 127.9 (d, 3JC-F = 8.3 Hz), 129.8 (2 CH), 136.8 (C), 154.2 (C=N), 158.6 (C=N), 163.3 (d, 1JC-F = 250 Hz). Anal. Calc. for C14H11FN4: (254.10): C, 66.13; H, 4.36; N, 22.04%.

Formation of products 7d and 8d in 5:2 ratio

Colorless powder; mp: 197–205 °C; IR (KBr) (νmax, cm−1): 3430, 3304, 3201, 2921, 1610, 1590, 1552, 1381, 755. MS: m/z (%) = 292 (M+, 1), 250 (M+, 1), 275 (5), 208 (20), 174 (50), 105 (20), 91 (100), 77 (40).

2-[1-Phenyl-3-(p-tolyl)-1H-1,2,4-triazol-5-yl]guanidine (7d)

Yield: 0.172 g (59%); 1H NMR (500 MHz, CDCl3): δH = 2.41 (3 H, s, Me), 6.90 (4 H, br, 2 NH2), 7.25–7.29 (3 H, m, Ar), 7.44 (2 H, t, 3J = 7.9 Hz, Ar), 7.96 (2 H, d, 3J = 8.0 Hz, Ar), 8.02 (2 H, d, 3J = 8.0 Hz, Ar).13C NMR (125 MHz, CDCl3): 21.4 (Me), 123.5 (2 CH), 126.0 (2 CH), 126.4 (CH), 128.6 (2 CH), 128.7 (C), 129.1 (2 CH), 134.5 (C), 138.7 (C), 157.1 (C=N), 157.6 (C=N), 157.8 (C=N). Anal. Calc. for C16H16N6: (292.14): C, 65.74; H, 5.52; N, 28.75%.

1-Phenyl-3-(p-tolyl)-1H-1,2,4-triazol-5-amine (8d)

Yield: 0.069 g (32%); 1H NMR (500 MHz, CDCl3): δH = 2.41 (3 H, s, Me), 5.82 (2 H, br, NH2), 7.28 (2 H, t, 3J = 7.5 Hz, Ar), 7.42 (1 H, t, 3J = 7.3 Hz, Ar), 7.53 (2 H, t, 3J = 8.0 Hz, Ar), 7.59 (2 H, d, 3J = 7.9 Hz, Ar), 7.96 (2 H, d, 3J = 8.0 Hz, Ar). 13C NMR (125 MHz, CDCl3): 21.4 (Me), 123.4 (2 CH), 126.1 (2 CH), 128.1 (CH), 129.0 (C), 129.2 (2 CH), 129.8 (2 CH), 135.1 (C), 138.4 (C), 154.0 (C=N), 159.5 (C=N). Anal. Calc. for C15H14N4: (250.12): C, 71.98; H, 5.64; N, 22.38%.

2-[3-(4-Nitrophenyl)-1-phenyl-1H-1,2,4-triazol-5-yl]guanidine (7e)

Yellow powder, m.p.: 189–192 °C; Yield: 0.26 g (82%). IR (KBr) (νmax, cm−1): 3320, 3251, 1629, 1597, 1504, 1337, 1256, 1102, 501. 1H NMR (300 MHz, DMSO-d6): δH = 7.00 (4 H, br, 2 NH2), 7.28 (1 H, t, 3J = 7.4 Hz, Ar), 7.46 (2 H, t, 3J = 8.0 Hz, Ar), 8.13 (2 H, d, 3J = 7.9 Hz, Ar), 8.25–7.32 (4 H, m, Ar). 13C NMR (75 MHz, DMSO-d6): δC = 122.0 (2 CH), 124.0 (2 CH), 125.9 (CH), 126.5 (2 CH), 128.6 (2 CH), 137.4 (C), 138.5 (C), 147.3 (C), 154.8 (C=N), 158.5 (C=N), 158.9 (C=N). MS: m/z (%) = 323 (M+, 1), 306 (15), 281 (12), 231 (11), 91 (100), 77 (5). Anal. Calcd for C15H13N7O2 (323.11): C, 55.72; H, 4.05; N, 30.33%.

2-[3-(4-Chlorophenyl)-1-(4-nitrophenyl)-1H-1,2,4-triazol-5-yl]guanidine (7f)

Yellow powder, m.p.: 227–230 °C; Yield: 0.28 g (78%). IR (KBr) (νmax, cm−1): 3318, 3241, 1633, 1597, 1503, 1333, 1258, 1102, 842. 1H NMR (300 MHz, DMSO-d6): δH = 7.15 (4 H, br, 2 NH2), 7.53 (2 H, d, 3J = 8.5 Hz, Ar), 8.07 (2 H, t, 3J = 8.5 Hz, Ar), 8.28 (2 H, d, 3J = 9.3 Hz, Ar), 8.65 (2 H, d, 3J = 9.3 Hz, Ar). 13C NMR (75 MHz, DMSO-d6): δC = 120.6 (2 CH), 124.4 (2 CH), 127.7 (2 CH), 128.7 (2 CH), 129.6 (C), 134.0 (C), 143.5 (C), 143.8 (C), 156.7 (C=N), 158.8 (C=N), 159.7 (C=N). MS: m/z (%) = 357 (M+, 1), 294 (33), 281 (10), 262 (8), 91 (100), 77 (10). Anal. Calcd for C15H12ClN7O2 (357.07): C, 50.36; H, 3.38; N, 27.41%.