Synthesis of Some New 1,3,4-Thiadiazole, Thiazole and Pyridine Derivatives Containing 1,2,3-Triazole Moiety.

In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and pyrazolylthioamide to give 1,3-thiazoles derivatives. Subsequently, 3-phenyl2-en-1-one was used to synthesize substituted pyridines and substituted nicotinic acid ester. The latter was converted to its azide compound which was reacted with aromatic amines and phenol to give substituted urea and phenylcarbamate containing 1,2,3-triazole moiety. The newly synthesized compounds were established by elemental analysis, spectral data and alternative synthesis whenever possible.

1. Introduction

In synthesis, 1,2,3-triazoles are useful building blocks and are additionally important due to their broad range of biological activities [1,2]—they are stable to moisture, oxygen, light and metabolic process. A series of novel 1,2,3-triazoles were synthesized [3] and found to have cytotoxic activity against human cancer cell lines such as U937, THP-1, HL60 and B16-F10. The 1,3,4-thiadiazole ring is one of the most important and well-known heterocyclic nuclei, as a common and integral feature of a variety of natural products and medicinal agents. As a core structural component, 1,2,4-thiadiazole is present in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, antitubercular and antinociceptive agents [4,5]. Thiazoles display a broad range of biological activities and are found in many potent biologically active molecules such as antimicrobial, antifungal and antineoplastic drugs [6]. However, they are mostly known for their anticancer [7] and antimicrobial [8] activities. Also, pyridine derivatives, including those bearing various heterocyclic nuclei, have shown potent pharmacological properties, including antifungal [9,10], antitubercular [11], antimalarial [12], antibacterial [13], antimicrobial [14], or insecticide [15]. We report here the synthesis of new 1,3,4-thiadiazoles, 5-arylazothiazoles, and pyridines containing 1,2,3-triazole moiety.

2. Results

Treatment of 1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one (1) [16] with methyl or benzyl carbodithioate [16,17] in 2-propanol gave the corresponding methyls 2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinecarbodithioate (2a) [17] and benzyl 2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinecarbodithioate (2b) [18], respectively (Scheme 1). Structures 2a and 2b were elucidated by elemental analyses, spectral data and chemical transformation. Thus, treatment of 2a or 2b with ethyl 2-chloro-2-(2-phenylhydrazono)acetate (3a) in ethanolic triethylamine at room temperature gave one isolated product formulated as ethyl 5-((1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazono)-4-phenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (7a) (Scheme 1). The latter was confirmed by elemental analysis, spectral data, and an alternative synthesis route. Thus, ethyl 5-hydrazono-4-phenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (8) [19] was reacted with compound 1, in 2-propanol to give a product identical in all aspects (m.p., mixed m.p., and spectra) with 7a.

Scheme 1

Synthesis of 1,3,4-thiadiazoles 7a,b.

In light of these results, the mechanism outlined in Scheme 1 seems to be the most plausible pathway for the formation of 7a from the reaction of the 2a (or 2b) with 3a. The reaction involves initial formation of thiohydrazonate 5, which undergoes intermolecular cyclization as soon as it is formed to yield the intermediate 6 or via 1,3-dipolar cycloaddition of nitrilimine 4a (generated in situ from 3a with triethylamine) to the C=S double bond of 2. The formations of 5 and 6 are similar to the reactions of hydrazonoyl halides with 1-phenyl-1,4-dihydrotetrazole-5-thione [20] and 5-phenyl-1,3,4-thiadiazole-2(3H)-thione [21]. Intermediate 6 was converted to 7 by elimination of methanthiol (or benzylthiol). Analogously, treatment of the appropriate 2a (or 2b) with 3b gave 2,3-dihydro-1,3,4-thiadiazoles 7b, in good yield (Scheme 1).

After 2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinecarbothioamide (9) [21] was reacted with hydrazonyl chloride 3c in ethanolic triethylamine under reflux to give the corresponding(2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)-4-phenyl-5-(phenyldiazenyl)thiazole (11b) in quantitative yield (Scheme 2), structure 11b was confirmed by elemental analysis, spectral data and alternative synthesis. Thus, 2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)-4-phenylthiazole (12) [22], prepared from reaction of 1 with 2-hydrazinyl-4-phenylthiazole (13) [23], or reaction of 9 with ω-bromoacetophenone [21], was coupled with benzenediazonium chloride in ethanolic sodium acetate at 0–5 °C to furnish a product identical in all aspects (m.p., mixed m.p., and spectra) to 11b. Analogously, treatment of 9 with the appropriate 3b,d,e gave thiazole derivatives 11a,c,d respectively, in good yields (Scheme 2).

Scheme 2

Synthesis of thiazoles 11a–d.

A similar treatment of 9 with ethyl 2-chloro-2-(2-phenylhydrazono)acetate (3a) in ethanolic triethylamine gave 2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)-5-(2-phenylhydrazono)thiazol-4(5H)-one (14a) (Scheme 3). Structure 14a was elucidated by elemental analysis, spectral data and an alternative synthetic route. Thus, treatment of benzenediazonium chloride with 2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)thiazol-4(5H)-one (15), prepared via reaction of 9 with ethyl chloroacetate in boiling ethanol, in a cold ethanolic sodium acetate solution, afforded a product identical in all aspects (m.p., mixed m.p., and spectra) with 14a.

Scheme 3

Synthesis of thiazolone 14a–d.

Analogously, the appropriate arenediazonium chloride was coupled with 15 in ethanolic sodium acetate afforded (2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)-5-(2-arylhydrazono)thiazol-4(5H)-one 14b and 14c; respectively (Scheme 3). Also, compound 15 was reacted with benzaldehyde in ethanol in the presence of a catalytic amount of piperidene, giving 5-(benzylidene)-2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)thiazol-4(5H)-one (16).

Treatment of 3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (17) [24,25] with the appropriate α-keto-hydrazonoyl halides 3a,c,e,f in ethanolic triethylamine afforded 5-(aryldiazenyl)-4-substituted-2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-1H-pyrazol-1-yl)-5-(aryldiazenyl)-4-substituted thiazole 20a–d, respectively (Scheme 4). Structures 20a–d were elucidated via elemental analyses, spectral data and alternative synthetic routes. Thus, 2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazole (21) was coupled with benzenediazonium chloride in ethanolic sodium acetate solution at 0–5 °C, affording a product identical in all aspects (m.p., mixed m.p., and spectra) with 20b.

Scheme 4

The 2-(3-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-5-(aryldiazenyl)-4-substituted thiazole 20a–d.

In the light of these results, the mechanism outlined in Scheme 4 seems to be the most plausible pathway for the formation of 20 from the reaction of 17 with 3. The reaction involves initial formation of thiohydrazonate 18, which undergoes cyclization as soon as it is formed to yield the intermediate 19. The latter suffers dehydration to the final product 20.

Treatment of 17 with 3b in ethanolic triethylamine gave 2-(3-(5-methyl-1-(p-tolyl)-n class="Chemical">1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-5-(2-phenylhydrazono)thiazol-4(5H)-one (22) in a good yield. Structure 22 was confirmed by elemental analysis and spectral data.

Next, treatment of compound 23 with each of ethyl acetoacetate, acetylacetone, malononitrile, ethyl cyanoacetate, cyanothioacetamide and benzoylacetonitrile in acetic acid containing ammonium acetate afforded pyridine derivatives 24–29, respectively (Scheme 5). Structures 24–29 were elucidated on the basis of elemental analysis, spectral data and chemical transformation (cf. Experimental and Scheme 5). 1H-NMR spectrum of 24 showed signals at δ = 1.34 (t, 3H, CHCH2O), 2.4 (s, 3H, 4-CH3C6H4), 2.60 (s, 3H, CH3, pyridine H-2), 2.69 (s, 3H, CH3, triazole H-5), 4.2 (q, 2H, CH3CHO), 7.27–7.73 (m, 9H, ArH’s), 7.90 (s, 1H, pyridine H-5).

Scheme 5

Synthesis of substituted pyridine derivatives 24–29.

Thus, treatment of 24 with hydrazine hydrate in boiling n class="Chemical">ethanol gave 2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinohydrazide (31) in a good yield. Structure 31 was elucidated via elemental analyses, spectral data and chemical transformation. Compound 31 was reacted with each of acetylacetone, ethyl acetoacetate, or with sodium nitrite in the presence of acetic acid to give 32, 33 and azido 34, respectively (Scheme 6).

Scheme 6

Synthesis of pyrazoles, urea, quinazoline and carbamate.

Meanwhile, each of the compounds 32 and 33 were reacted with benzenediazonium chloride in ethanolic sodium acetate solution, giving (3,5-dimethyl-4-(phenyldiazenyl)-1H-pyrazol-1-yl)-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)methanone (35a) and 5-methyl-2-[2-methyl-6-(5-methyl-1-(p-tolyl)-1H-[1,2,3]triazol-4-yl)-4-phenylpyridine-3-carbonyl]-4-(phenyl-hydrazono)-2,4-dihydro-pyrazol-3-one (36a) (Scheme 6). The structure of compounds 35a and 36a were confirmed by alternative synthesis, by treatment of the hydrazide 31 with each of 3-(2-phenylhydrazono)pentane-2,4-dione (37a) [26] and ethyl 3-oxo-2-(phenylhydrazono)butanoate (37b) [27] in boiling acetic acid for products identical in all aspects (m.p., mixed m.p., and spectra) with 35a and 36a, respectively.

Analogously, p-tolyldiazonium chloride was reacted with each 32 and 33, giving (3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)methanone (35b) and 5-methyl-2-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinoyl)-4-(2-(p-tolyl)-hydrazono)-2,4-dihydro-3H-pyrazol-3-one (36b), respectively (Scheme 6).

Azido(n class="Chemical">2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)methanone (34) can be converted into urea derivatives, 38a,b and 3-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)quinazoline-2,4(1H,3H)-dione (39) by being boiled with the appropriate aromatic amines, or anthranilic acid in dry dioxane, respectively. Also, phenyl 2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-ylcarbamate 40 can be obtained by boiling the azido 34 with phenol in dry benzene (Scheme 6).

3. Materials and Methods

All meeting points were determined on an electro thermal Gallen Kamp melting point apparatus (Laim George, Calgary, AB, Canada) and are uncorrected. IR (cm−1) spectra were recorded on KBr disk on a FTIR-8201 spectrophotometer (Shimadzu, Tokyo, Japan). 1H-NMR and 13C-NMR spectra were measured in deuterated dimethyl sulfoxide (DMSO-d6) using a Varian Gemini 300 NMR spectrometer (Varian, Inc., Karlsruhe, Germany). Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX mass spectrometer (Tokyo, Japan) at 70 eV. Measurements of the elemental analysis were carried out at the Microanalytical Centre of Cairo University, Giza, Egypt. All reactions were followed by TLC (Silica gel, Merck, Kenilworth, NJ, USA). Hydrazonoyl halides were prepared as previously reported [28,29,30,31]

3.1. Alkyl 2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-ethylidene)hydrazine-1-carbodithioate and

A mixture of 1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4yl)ethanone (1) [16] (1 g, 5 mmol) and n class="Chemical">alkyl carbodithioate (5 mmol) in 2-propanol (20 mL) was refluxed for 30 min. The reaction mixture was cooled and the resulting solid was collected and crystallized from the proper solvent to give 2a,b.

Methyl 2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-ethylidene)hydrazine-1-carbodithioate (2a). Buff crystals from n class="Chemical">ethanol: yield: 75% , m.p.: 186 °C, FT-IR (KBr, cm−1): 3522 (NH), 3064 (CH), 1603 (C=N), 1561 (C=C); 1H-NMR (300 MHz, DMSO-d6): δ = 2.36 (s, 3H, CH3), 2.45 (s, 3H, CH3), 2.50 (s, 3H, CH3), 3.20 (s, 3H, CH3), 7.38–7.51 (m, 4H, ArH’s) and 12.4 (s, br, 1H, NH). Anal. Calcd. For C14H17N5S2 (319.46) C, 52.64; H, 5.36; N, 21.92; S, 20.07 Found C, 52.70; H, 5.40; N, 21.90; S, 20.18.

Benzyl 2-(1-(5-methy-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-ethylidene)hydrazine-1-carbodithioate (2b). Buff crystals from DMF: yield 75%, m.p.: 324 °C, FT-IR (KBr, cm−1): 3421 (NH), 3052 (CH), 1611 (C=N), 1553 (C=C); 1H-NMR (300 MHz, DMSO-d6): δ = 2.41 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.73 (s, 3H, CH3), 3.28 (s, 2H, CH2), 7.39–7.47 (m, 9H, ArH’s) and 12.35 (s, br, 1H, NH). Anal. Calcd. For C20H21N5S2 (395.54) C, 60.73; H, 5.35; N, 17.71; S, 16.21 Found C, 60.69; H, 5.32; N, 17.68; S, 16.30.

3.2. 5-((1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene-4-phenyl-4,5-dihydro-1,3,4-thiadiazole-derivatives ,

Method A: Triethyl amine (0.75 mL, 0.5 g, 5 mmol) was added dropwise with stirring to a mixture of the appropriate n class="Chemical">alkyl carbodithioate 2a or 2b (5 mmol) and the appropriate hydrazonoyl halides 3a,b [27,28,29,30] (5 mmol) in ethanol (20 mL). The resulting solid which formed after 30 min was collected and crystallized from the proper solvent to give the corresponding thiadiazole derivatives 7a,b.

Ethyl 5-((-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-4-phenyl-4,5n class="Chemical">-dihydro-1,3,4-thiadiazole-2-carboxylate (7a). Yellow crystals from acetic acid Yield: 70%, m.p.: 205–207 °C; FT-IR (KBr, cm−1): 3047 (CH), 1708 (CO), 1616 (C=N), 1573 (C=C) ; 1H-NMR (300 MHz, CDCl3): δ = 1.59 (t, 3H, CH2-CH), 2.48 (s, 3H, CH3), 2.64 (s, 3H, CH3), 2.71 (s, 3H, CH3), 4.50 (q, 2H, CH-CH3), and 7.26–8.18 (m, 9H, AH’s); MS (El, m/z (%)): 461 (M+,100), 433 (20), 400 (80), 289 (20), 243 (20), 184 (30), 91 (30), 80 (100), 64 (40); Anal. Calcd. For C23H23N7SO2 (461.55), C, 59.85; H, 5.02; N, 21.24; S, 6.95 Found C, 59.90; H, 5.12; N, 21.34; S, 6.99

1(5-((1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-4-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one (7b). Yellow crystals from ethanol. Yield: 80%, m.p.: 270–271 °C; FT-IR (KBr, cm−1): 2924 (CH),1678 (CO), 1616 (C=N), 1573 (C=C); 1H-NMR (300 MHz, CDCl3): δ = 2.48 (s, 3H, CH3), 2.63 (s, 3H, CH3), 2.65 (s, 3H, CH3), 2.71 (s, 3H, CH3), and 7.26–8.14 (m, 9H, ArH’s); 13C-NMR in CHCl3 δ = 9.4 (5-CH3 triazole), 13.9 (=CH3), 19.9 (4-CH3C6H4), 24.7 (CH3CO), 123.3, 125.4, 127.2, 127.8, 129.3, 130.2, 132.4, 139.7, 140.7, 142.33, 147.8, 152.7, 163.8, 189.1 (CO), MS (El, m/z (%)): 431 (M+, 100), 403 (5), 370 (10), 360 (30), 301 (10), 259 (15), 194 (55), 184 (3), 172 (40), 91 (50), 80 (100), 64 (50); Anal. Calcd. For C22H21N7OS (431.52), C, 61.23; H, 4.91; N, 22.72; S, 7.43 Found C, 61.40; H, 4.89; N, 22.80; S, 7.80

Alternative synthesis of Ethyl 5-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene-4-phenyl-4,5n class="Chemical">-dihydro-1,3,4-thiadiazole-2-carboxylate (7a).

Method B: A mixture of ethyl 5-hydrazono-4-phenyl-4,5-dihydro-1,3,4-thiadiazole-2-carboxylate (8) [18] (1.3 g, 5 mmol) and n class="Chemical">1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethanone (1) (1 g, 5 mmol) in 2-propanol were heated for 30 min. The crude solid that was collected and crystallized from ethanol gave a product identical in all aspects (m.p., mixed m.p. and spectra) with 7a.

3.3. 2-(2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene-hydrazinyl-thiazole derivatives –

Method A: A mixture of 9 (1.4 g, 5 mmol), the appropriate hydrazonoyl halides 3b–e (5 mmol) and n class="Chemical">triethylamine (0.5 g, 0.7 mL, 5 mmol) in ethanol was heated under reflux for 3 h. The resulting solid that was collected and recrystallized gave thiazole derivatives 11a–d.

4-Methyl-2-(2-((E)-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-5-((E)-phenyldiazenyl)n class="Chemical">thiazole (11a). Orange crystals from acetic acid; Yield: 75%, m.p.: 255 °C; FT-IR (KBr, cm−1): 3417 (NH), 3032 (CH), 1600 (C=C); 1H-NMR (300 MHz, CDCl3): δ = 2.48 (s, 3H, CH3), 2.59 (s, 3H, CH3), 2.65 (s, 3H, CH3), 3.3 (s, 3H, CH3), 6.96–7.55 (m, 9H, ArH’s) and 9.18 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 12.9, 13.7, 20.8, 114.4, 121.6, 123.8, 129.0, 129.6, 129.9, 130.4, 139.1, 139.6, 146.2, 154.6, 160.1, 164.9. Anal. Calcd. For C22H22N8S (430.54): C, 61.37; H, 5.15; N, 26.03; S, 7.4 Found C, 61.40; H, 5.10; N, 26.13; S, 7.50.

2-(2-((E)-1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-phenyl-5-((E)-phenyldiazenyl)n class="Chemical">thiazole (11b). Orange crystals from ethanol, Yield: 70%, m.p.: 245 °C; FT-IR (KBr, cm−1): 3417 (NH), 3074 (CH), 1578 (C=C); 1H-NMR (300 MHz, DMSO-d6): δ = 2.45 (s, 3H, CH3), 2.49 (s, 3H, CH3), 3.30 (s, 3H, CH3), 7.32–8.28 (m, 14H, ArH’s) and 10.71 (s, br, 1H, NH). Anal. Calcd. For C27H24N8S (492.61): C, 65.83; H, 4.91; N, 22.75; S, 6.51; Found C, 65.79, N, 22.78, S, 6.561.

4-Methyl-2-(2-((E)-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-5-((Z)-p-tolyldiazenyl)n class="Chemical">thiazole (11c). Gray crystals from acetic acid, Yield: 70%, m.p.: 250 °C; FT-IR (KBr, cm−1): 3421 (NH), 3020 (CH), 1593 (C=C); 1H-NMR (300 MHz, DMSO-d6): δ = 2.30 (s, 3H, CH3), 2.44 (s, 3H, CH3), 2.58 (s, 3H, CH3), 2.65 (s, 3H, CH3), 2.75 (s, 3H, CH3), 7.15–7.53 (m, 8H, ArH’s), 10.54 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 12.9, 13.7, 20.8, 21.5, 114.2, 122.0, 123.8, 129.0, 129.6, 129.9, 136.8, 139.4, 139.8, 146.8, 151.6, 156.8, 164.7. Anal. Calcd. For C23H24N8S (444.57), C, 62.14; H, 5.44; N, 25.21; S, 7.21 Found C, 62.15; H, 5.55; N, 25.25; S, 7.30.

5-((Z)-(4-Chlorophenyl)diazenyl)-4-methyl-2-(2-((E)-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)n class="Chemical">thiazole (11d). Red crystals from ethanol, Yield: 70%, m.p.: 240 °C; FT-IR (KBr, cm−1): 3387 (NH), 3089, 3028 (CH), 1585 (C=C) ; 1H-NMR (300 MHz, DMSO-d6): δ = 2.49 (s, 3H, CH3), 2.58 (s, 3H, CH3), 2.65 (s, 3H, CH3), 3.30 (s, 3H, CH3), 7.34–7.54 (m, 8H, ArH’s) and 10.65 (s, br, 1H, NH). Anal. Calcd. For C22H21N8S (464.99), C, 56.83; H, 4.55; N, 24.10; S, 6.90 Found C, 56.89; H, 4.60; N, 24.15; S, 6.85.

Method B: Benzenediazonium chloride (5 mmol), prepared in the usual way from n class="Chemical">aniline (0.46 g, 5 mmol), hydrochloric acid (1.5 mL, 6 M) and sodium nitrite (0.35 g, 5 mmol), was added dropwise with stirring to a cold solution of 2-(2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-phenylthiazole (12) (1.9 g, 5 mmol) and sodium acetate (1.3 g, 10 mmol) in ethanol (30 mL) at 0–5 °C. The reaction mixture was stirred for 3 h in an ice bath and was left in refrigerator overnight. The solid was collect and crystallized from ethanol, giving a product identical (m.p., mixed mp and spectra) with 11b.

3.4. 2-(2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-phenylthiazole ()

Method A: A mixture of 9 (1.4 g, 5 mmol) and ω-bromoacetophenone (1 g, 5 mmol) in ethanol was refluxed for 4 h. The resulting solid that was collected and crystallized from n class="Chemical">ethanol gave a white crystal of 13, Yield: 75%, m.p. 290 °C (Lit. m.p. 273 °C [22]).

Method B: A mixture of 2-hydrazinyl-4-phenylthiazole (12) (1.76 g, 10 mmol), 1 (2.1 g, 5 mmol) in n class="Chemical">ethanol (20 mL) and conc. hydrochloric acid (2 drops) was heated under reflux for 15 min. The solid was collected and crystallized from ethanol giving a product identical in all aspects (m.p., mixed m.p., and spectra) with the above sample obtained by Method A.

3.5. (E)-5-(2-Arylhydrazono)-2-((Z)-2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)thiazol-4(5H)-one –

Method A: A mixture of 9 (1.4 g, 5 mmol), hydrazonoyl halide 3a (5 mmol) and n class="Chemical">triethylamine (0.5 g, 0.7 ml, 5 mmol) in ethanol was boiled under reflux for 3 h. The resulting solid was collected and recrystallized from acetic acid afforded by 14a

Method B: Dropwise addition of arenediazonium chlorides (5 mmol), which was prepared via reaction of the appropriate n class="Chemical">aniline, p-toluidine, p-chloroaniline (5 mmol), hydrochloric acid (1.5 mL, 6 M), sodium nitrite (0.37 g, 5 mmol) at 0–5 °C, to a mixture of 15 (1.64 g, 5 mmol) and sodium acetate (0.66 g, 5 mmol) in ethanol at 0–5 °C, while stirring. The reaction mixture was stirred for 3 h. The resulting solid was collected, washed with water and crystallized, giving 14a–c.

(E)-2-((Z)-2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-5-(2-phenylhydrazono)thiazol-4(5H)-one (14a). Yellow crystals from n class="Chemical">acetic acid, Yield 75%, m.p. 298–300 °C; FT-IR (KBr, cm−1): 3431, 3211 (2NH), 3051, 2920 (CH), 1581(C=C), 1659 (CO), 1604 (C=N); 1H-NMR (300 MHz, DMSO-d6): δ = 2.44 (s, 3H, CH3), 2.49 (s, 3H, CH3), 3.32 (s, 3H, CH3), 6.92–7.85 (m, 9H, ArH’s) 10.5 (s, br, 1H, NH) and 11.9 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 19.2, 21.0, 115.4, 122.0, 123.8, 127.7, 129.8, 130.1, 139.2, 139.8, 145.7, 146.3, 147.2, 159.4, 167.9, 176.1. Anal. Calcd. For C21H20N8SO (432.51), C, 58.32; H, 4.66; N, 25.91; S, 7.41 Found C, 58.30; H, 4.69; N, 25.80; S, 7.50.

(E)-2-((Z)-2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-5-(2-(p-tolyl)hydrazono)thiazol-4(5H)-one (14b). Brown crystals from n class="Chemical">ethanol, Yield: 80%, m.p. >300 °C; FT-IR (KBr, cm−1): 3437, 3267 (2NH), 2931 (CH), 1732 (CO), 1627 ν(C=N), 1573 ν(C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.26 (s, 3H, CH3), 2.47 (s, 3H, CH3), 2.49(s, 3H, CH3), 2.53 (s, 3H, CH3), 7.41–7.50 (m, 8H, ArH’s), 8.41 (s, br, 1H, NH) and 10.9 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 19.2, 20.6, 21.0, 117.4, 123.9, 128.6, 129.9, 130.2, 136.8, 139.2, 139.8, 145.2, 145.8, 146.3, 159.6, 167.9, 176.0. Anal. Calcd. For C22H22N8OS (446.54), C, 59.18; H, 4.97; N, 25.09; S, 7.18 Found C, 59.28; H, 4.89; N, 25.11; S, 7.28.

(E)-5-(2-(4-Chlorophenyl)hydrazono)-2-((Z)-2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)thiazol-4(5H)-one (14c). Pale brown crystals from ethanol, Yield: 70%, m.p.: 263–265 °C; FT-IR (KBr, cm−1): 3431,3108 (2NH), 2972 (CH), 1664 (CO), 1634 (C=N), 1H-NMR (300 MHz, DMSO-d6): δ = 2.42 (s, 3H, CH3), 2.53 (s, 3H, CH3), 3.30 (s, 3H, CH3), 7.42–7.51 (m, 8H, ArH’s), 8.32 (s, br, 1H, NH) and 11.99 (s, br, 1H, NH). Anal. Calcd. For C21H19N8OSCl (466.96), C, 54.02; H, 4.10; N, 24.00; S, 6.87; Cl, 7.59 Found: C, 54.12; H, 4.20; N, 24.05; S, 6.90.

3.6. (E)-2-(2-(1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)thiazol-4(5H)-one ()

A mixture of 9 (1.4 g, 5 mmol) and ethyl chloroacetate (0.61 g, 5 mmol) in ethanol was refluxed for 4 h. The resulting solid was collected and recrystallized from ethanol that gave white crystals of 15, Yield: 75%, m.p. 255 °C. FT-IR (KBr, cm−1): 3116 (NH), 2951 (CH), 1735 (CO), 1624 (C=N). 1H-NMR (300 MHz, DMSO-d6): δ = 2.46 (s, 3H, CH3), 2.54 (s, 3H, CH3), 3.30 (s, 3H, CH3), 3.87 (s, 2H, OCH2), 7.42–8.32 (m, 4H, ArH’s) and 11.97 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 19.1, 20.8, 37.1, 123.9, 129.7, 129.9, 139.2, 139.7, 146.0, 159.7, 168.0, 183.5. Anal. Calcd. For C15H16N6OS (328.40), C, 54.86; H, 4.91; N, 25.59; S, 9.76 Found: C, 54.90; H, 4.95; N, 25.34; S, 9.70.

3.7. (E)-5-Benzylidene-2-((E)-2-(1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethylidene)-hydrazinyl)thiazol-4(5H)-one ()

A mixture of 15 (1.6 g, 5 mmol) and benzaldehyde (0.53 g, 5 mmol) in n class="Chemical">ethanol and catalytic amount of piperidine (5 drops) was refluxed for 3 h. The resulting solid was collected and recrystallized from acetic acid affording white crystals of 16, Yield: 80%, m.p.: 283 °C. FT-IR (KBr, cm−1): 3124 (NH), 2974 (CH), 1705 (CO), 1624 (C=N). 1H-NMR (300 MHz, DMSO-d6): δ = 2.49 (s, 3H, CH3), 2.54 (s, 3H, CH3), 3.30 (s, 3H, CH3), 7.42–7.51 (m, 10H, ArH’s and = CH) and 11.91 (s, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.1, 19.1, 20.8, 123.9, 129.2, 129.7, 129.9, 130.7, 132.5, 138.2, 139.3, 139.6, 146.2, 159.8, 167.8, 174.1. Anal. Calcd. For C22H20N6SO (416.51), C, 63.44; H, 4.84; N, 20.18; S, 7.70 Found: C, 63.50; H, 4.90; N, 20.20; S, 7.75.

3.8. 5-(Aryldiazenyl)-4-substituted-2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-yl)thiazole –,

Method A: A mixture of 17 (1.9 g, 5 mmol), the appropriate hydrazonoyl halides 3a,c,e,f or 3b (5 mmol) and n class="Chemical">triethyl amine (0.5 mg, 0.75 mL, 5 mmol) in ethanol (20 mL) was heated under reflux for 4 h. The resulting solid was collected and recrystallized, giving thiazole derivatives 20a–d and 21.

Method B: Benzenediazonium chloride (5 mmol) which was prepared via reaction of n class="Chemical">aniline (0.55 g, 5mmol), hydrochloric acid (3 mL, 6 M), and sodium nitrite (0.35 g, 5 mmol) was added dropwise, with stirring, to a cold solution of 21. The reaction mixture was stirred for 3 h .The resulting solid was collected, washed with water and crystallized from ethanol, giving 20b.

(E)-4-Methyl-2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5n class="Chemical">-dihydro-1H-pyrazol-1-yl)-5-(phenyldiazenyl)thiazole (20a). Orange crystals from acetic acid, Yield: 75%, m.p.: 235 °C; FT-IR (KBr, cm−1): 3045, 2926, 2860 (CH), 1653 (C=N), 1587 (C=C); 1H-NMR (300 MHz, DMSO-d6): δ = 2.49 (s, 3H, CH3), 2.56 (s, 3H, CH3), 2.70 (s, 3H, CH3), 3.72–3.74 (dd, 1H, Hb), 3.78 (dd, 1H, Ha), 5.78 (dd, 1H, Hx) and 7.26–7.76 (m, 14H, ArH’s). 13C-NMR (DMSO-d6) δ = 8.1, 12.82, 21.0, 33.2, 63.6, 114.8, 121.7, 123.8, 127.5, 129.1, 129.5, 129.8, 130.1, 130.7, 130.9, 139.2, 139.7, 144.8, 149.6, 154.1, 161.1. MS (El, m/z (%)): 518 (M+, 100), 489 (5), 413 (2), 273 (15), 184 (20), 170 (15), 144 (25), 91 (35%), 77 (70), 65 (17). Anal. Calcd. For C29H26N8S (518.65), C, 67.16; H, 5.05; N, 21.61; S, 6.18 Found C, 67.26; H, 5.10; N, 21.69; S, 6.28.

(E)-2-(3-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5n class="Chemical">-dihydro-1H-pyrazol-1-yl)-4-phenyl-5-(phenyldiazenyl)thiazole (20b). Red crystals from acetic acid, Yield: 70%, m.p.: 275 °C; FT-IR (KBr, cm−1): 3043, 2924 (CH), 1666 (C=N); 1H-NMR (300 MHz, CDCl3): δ = 2.49 (s, 3H, CH3), 2.71 (s, 3H, CH3), 3.73–3.78 (dd, 1H, Hb), 4.18 (dd, 1H, Ha) 5.82 (dd, 1H, Hx), and 7.33–8.18 (m, 19H, ArH’s), 13C-NMR (DMSO-d6) δ = 8.1, 12.82, 21.0, 33.2, 63.6, 108.7, 121.7, 123.8, 126.7, 127.4, 128.2, 128.7, 128.2, 129.8, 129.9, 130.1, 130.4, 130.9, 133.1, 136.2, 139.1, 139.7, 144.7, 154.7, 168.0 MS (El, m/z (%): 580 (M+, 85), 551 (30), 447 (10), 367 (30), 133 (40), 91(50), 77(100), 65(20). Anal. Calcd. For C34H28N8S (580.72), C, 70.32; H, 4.86; N, 19.30; S, 5.52 Found C, 70.22; H, 4.75; N, 19.20; S, 5.56.

(E)-4-Methyl-2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5n class="Chemical">-dihydro-1H-pyrazol-1-yl)-5-(p-tolyldiazenyl)thiazole (20c). Red crystals from acetic acid, Yield: 70%, m.p.: 240 °C; FT-IR (KBr, cm−1): 3039, 2926 (CH), 1658 (C=N); 1H-NMR (300 MHz, CDCl3): δ = 2.40 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.60 (s, 3H, CH3), 2.72 (s, 3H, CH3), 3.5–3.6 (dd, 1H, Hb), 4.1–4.2 (dd, 1H, Ha), 5.61–5.64 (dd, 1H, Hx) and 6.81–8.17 (m, 13H, ArH’s). Anal. Calcd. For C30H28N8S (532.68), C, 67.65; H, 5.30; N, 2.04; S, 6.02 Found C, 67.72; H, 5.34; N, 2.14; S, 6.12.

(E)-5-((4-Chlorophenyl)diazenyl)-4-methyl-2-(3-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5n class="Chemical">-dihydro-1H-pyrazol-1-yl)thiazole (20d). Red crystals from ethanol, Yield:65%, m.p.: 220 °C; FT-IR (KBr, cm−1): 3037, 2926 (CH), 1670 (C=N); 1H-NMR (300 MHz, CDCl3): δ = 2.48 (s, 3H, CH3), 2.56 (s, 3H, CH3), 2.69 (s, 3H,CH3), 3.63–3.72 (dd, 1H, Hb), 4.11–4.21 (dd, 1H, Ha), 5.64–5.70 (dd, 1H, Hx) and 6.81–7.71 (m, 13H, ArH’s). Anal. Calcd. For C29H25N8SCl (553.09), C, 62.98; H, 4.56; N, 20.26; S, 5.80; Cl, 6.41 Found C, 62.85; H, 4.55; N, 20.30; S, 5.89.

3.9. 2-(3-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenylthiazole ()

A mixture of 17 (1.85 g, 5 mmol) and ω-bromoaceophenone (1 g, 5 mmol) in ethanol was refluxed for 4 h. The resulting solid was collected and crystallized from n class="Chemical">ethanol giving white crystals of 21, Yield: 75%, m.p. 220 °C (Lit. m.p. 193 °C [25]).

3.10. 2-(3-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)5–phenyl-4,5-dihydro-1H-pyrazole-1-yl)-5-(2-phenyl-hydrazono)thiazol-4(5H)-one ()

A mixture of 4,5-dihydro-3-(5-methyl-1-(p-tolyl)-n class="Chemical">1H-1,2,3-triazol-4-yl)-5-phenyl-pyrazol-1-carbothioamide (17) (1.9 g, 5 mmol) and ethyl 2-chloro-2-(2-phenylhydrazono)acetate (3b) (1.1 g, 5 mmol) in ethanol (20 mL) was heated under reflux for 3 h. The resulting solid was collected and recrystallized from acetic acid, giving 22 as pale orange crystals. Yield 75%, m.p. 294–296 °C, FT-IR (KBr, cm−1): 3437 (NH), 3049, 2929 (CH), 1695 (CO), 1658 (C=N). 1H-NMR (300 MHz, CDCl3): δ = 2.48 (s, 3H, CH3), 2.65 (s, 3H, CH3), 3.73–3.85 (dd, 1H, Hb), 4.09–4.19 (dd, 1H, Ha), 5.77–5.81 (dd, 1H, Hx), 7.26–7.38 (m, 15H, ArH’s and NH). 13C-NMR (DMSO-d6) δ = 8.1, 12.82, 21.0, 33.2, 67.2, 115.3, 122.3, 123.9, 127.0, 127.8, 128.7, 129.8, 129.9, 130.7, 139.1, 139.7, 144.0, 144.6, 146.7, 149.5, 156.6, 175.1. Anal. Calcd. For C28H24N8OS (520.62): C, 64.60; H, 4.65; N, 21.52; S, 6.16. Found, C, 64.67; H, 4.70; N, 21.60; S, 6.19.

3.11. 6-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridine derivatives ()–()

General procedure: A mixture of 23 (1.5 g, 5 mmol), the appropriate acetylacetone, n class="Chemical">ethyl acetoacetate, ethyl cyanoacetate, cyanothioacetamide, malononitrile, benzoylacetonitrile and ammonium acetate (0.38 g, 5 mmol) in acetic acid (10 mL) was heated under reflux for 4 h. The resulting solid was filtered, washed with water and crystallized from the proper solvent, giving pyridine derivatives 24–29.

Ethyl 2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinate (24). Yellow crystals from n class="Chemical">ethanol, yield 85% m.p.: 195 °C, FT-IR (KBr, cm−1): 3035, 2953 (CH); 1660 (CO), 1629 (C=N); 1579 (C=C); 1H-NMR (300 MHz, CDCl3): δ = 1.34 (t, 3H, CH2CH), 2.42 (s, 3H, CH3), 2.60 (s, 3H, CH3), 2.69 (s, 3H, CH3), 4.20 (q, 2H, CHCH3), 7.27–7.73 (m, 10H, ArH’s and pyridine H-5). 13C-NMR (DMSO-d6) δ = 11.5, 13.82, 20.9, 23.5, 61.7, 63.6, 93.3, 118.6, 123.0, 125.3, 125.8, 129.4, 129.8, 133.6, 134.52, 142.4, 146.0, 154.3, 167.9, 175. MS (El, m/z (%): 412 (M+, 15), 395 (10), 384 (50), 325 (30), 342 (10), 247 (70), 132 (100), 103 (80), 91 (90), 77 (40), 65 (55). Anal. Calcd. for C25H24O2N4 (412.49), C, 72.80; H, 5.86; N,13.60. Found: C, 72.86; H, 5.90; N, 13.65.

1-(2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)ethan-1-one (25). Orange crystals from n class="Chemical">acetic, yield 70% m.p.: 190 °C, FT-IR (KBr, cm−1): 3002, 2949 (CH); 1737 (CO); 1614 (C=N); 1579 (C=C). 1H-NMR (300 MHz, CDCl3): δ = 2.09 (s, 3H, CH3), 2.43 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.66 (s, 3H, CH3) and 7.26–8.14 (m, 10H, ArH’s and pyridine H-5), MS (El, m/z (%): 384 (M+2, 20), 369 (10), 354 (60), 341 (70), 247 (40), 194 (35), 144 (15), 132 (95), 91 (99), 77 (40), 65 (60). Anal. Calcd. For C24H22ON4, (382.47): C, 75.37; H, 5.80; N, 14.65. Found C, 75.47; H, 5.95; N, 14.75.

2-Amino-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)4–phenyln class="Chemical">pyridine-3-carbonitrile (26). Yellow crystals from acetic acid, Yield 75%, m.p.: 197 °C, FT-IR (KBr, cm−1): 3427, 3224 ν(NH2); 3002, 2954 ν(CH); 2276 ν(CN); 1635 ν(C=N); 1581 ν(C=C), 1H-NMR ( 300 MHz, CDCl3): δ = 2.46 (s, 3H, CH3), 2.65 (s, 3H, CH3), 6.95 (s, br, 2H, NH2), 7.26–8.14 (m, 10H, ArH’s and pyridineH-5). 13C-NMR (DMSO-d6) δ = 11.5, 20.9, 63.6, 91.7, 97.8, 118.4, 118.8, 121.3, 127.5, 128.8, 129.7, 133.52, 133.7, 140.3, 142.5, 150.6, 160.7, 166. MS (EI, m/z (%)): 366 (M+, 60), 351 (30), 338 (40), 247 (50), 194 (0), 144 (30), 132 (70), 103 (50), 91 (70), 80 (100), 64 (50). Anal. Calcd. for C22H18N6 (366.43), C,72.11; H, 4.95; N, 22.94 Found: C, 72.15; H, 4.85; N, 22.88.

6-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-2-oxo-4-phenyl-pyridine-3-carbonitrile (27). Yellow crystals from n class="Chemical">acetic acid. Yield 75%, m.p. 193 °C, FT-IR (KBr, cm −1): 3433 (NH), 3043, 2929 (CH); 1668 (CO), 1643 (C=N), 1581 (C=C); 1H-NMR (300 MHz, CDCl3): δ = 2.47 (s, 3H, CH3), 2.65 (s, 3H, CH3), 7.26–8.14 (m, 10H, ArH’s and pyridine H-5), 11.65 (s, br, 1H, NH), MS (El, m/z (%)): 368 (M+1, 40), 304 (10), 247 (65), 194 (55), 132 (100), 115 (30), 103 (70), 91 (85), 77 (40), 65 (50). Anal. Calcd. For C22H17N5O (367.41), C, 71.92; H, 4.66; N, 19.06 Found: C, 71.89; H, 4.65; N, 19.16.

6-(5-Methy-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-2-thioxo-pyridine-3-carbonitrile (28). Orange crystals from n class="Chemical">acetic acid, Yield 70%, m.p. 278 °C, FT-IR (KBr, cm−1): 3437 (NH); 3037, 2920 (CH); 2211 (CN), 1584 (C=C), 1615 (C=N), 1H-NMR (300 MHz, CDCl3): δ = 2.41 (s, 3H, CH3), 2.49 (s, 3H, CH3), 4.47–8.12 (m, 10H, ArH’s, pyridine H-5), 15.45 (S, br, 1H, NH). 13C-NMR (DMSO-d6) δ = 8.5, 20.9, 108.4, 112.2, 118.3, 123.2, 128.8, 129.7, 129.9, 130.4, 135.4, 135.8, 137.4, 139.4, 139.8, 150.3, 150.7, 177.8. MS (El, m/z (%)): 383 (M+, 40), 303 (5), 247 (50), 194 (50), 132 (100), 103 (60), 90 (100), 77 (50), 68 (60). Anal. Calcd. For C22H17N5S (383.48), C, 68.91; H, 4.47; N, 18.26; S, 8.36. Found C, 68.89; H, 4.37; N, 18.30 S, 8.46.

(2-Amino-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)(phenyl)-methanone (29). Pale yellow crystals from n class="Chemical">ethanol, Yield 70%, m.p.: 183 °C, FT-IR (KBr, cm−1): 3431, 3330 (NH2); 2972, 2925 (CH), 1659 (CO); 1596 (C=C). 1H-NMR (300 MHz, CDCl3): δ = 2.49 (s, 3H, CH3), 2.56 (s, 3H, CH3), 6.93 (s, br, 2H, NH2), 7.26–8.12 (m, 15H, ArH’s and pyridine H-5). Anal. Calcd. For C28H23N5O (445.53), C, 75.49; H, 5.20; N, 15.72 Found C, 75.39; H, 5.40; N, 15.65.

3.12. 2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinohydrazide ()

Equimolar amounts of ethyl 6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl pyridine-3-carboxylate (24) (2.2 g, 5 mmol) and hydrazine hydrate (1 mL, 10 mmol) in ethanol (10 mL) were refluxed for 5 h. The resulting solid was collected and recrystallized, giving 31 as white crystals from ethanol, Yield 89%, m.p. 145 °C, FT-IR (KBr, cm−1): 3431, 3335 (NH2); 2960, 2923 (CH); 1662 (CO); 1572 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.24 (s, br, 2H, NH2), 2.42 (s, 3H, CH3), 2.60 (s, 3H, CH3), 2.97 (s, 3H, CH3), 10.20 (s, br, 1H, NH), 7.11–7.61 (m, 10H, ArH’s and pyridine H-5). Anal. Calcd. For C23H22·N6O (398.42): C, 69.33; H, 5.57; N, 21.09 Found C, 69.35; H, 5.60; N, 21.19.

3.13. (3,5-Dimethyl-1H-pyrazol-1-yl)(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl)methanone () and 5-Methyl-2-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridine-3-carbonyl)-2,4-dihydropyrazol-3-one ()

Equimolar amounts of 31 and the appropriate acetylacetone or n class="Chemical">ethyl acetoacetate (4 mmol for each) in ethanol (10 mL), with two drops of acetic acid, were refluxed for 4 h. The resulting solid was collected and recrystallized from ethanol, giving the corresponding products 32 and 33, respectively.

(3,5-Dimethyl-1H-pyrazol-1-yl)(n class="Chemical">2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl) methanone (32). White crystals from ethanol, Yield 80%, m.p. 207 °C, FT-IR (KBr, cm−1): 3032, 2961, 2941, 2839 (CH); 1641 (CO); 1589 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.41 (s, 3H, CH3) 2.48 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.57 (s, 3H, CH3), 2.70 (s, 3H, CH3), 7.21–7.57 (m, 11H, ArH’s, pyridine H-5 and pyrazole H-4). Anal. Calcd. For C28H26·N6O (462.56): C, 72.71; H, 5.67; N, 18.17 Found C, 72.80; H, 5.81; N, 18.27.

5-Methyl-2-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-n class="Chemical">pyridine-3-carbonyl)-2,4-dihydropyrazol-3-one (33). White crystals from ethanol, Yield 80%, m.p. 217 °C, FT-IR (KBr, cm−1): 3434 (OH); 2976, 2925 ν(CH); 1682 (CO); 1609 (C=N), 1575 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.21 (s, 3H, CH3) 2.48 (s, 3H, CH3), 2.57 (s, 3H, CH3), 2.62 (s, 3H, CH3), 4.67 (s, 2H, pyrazoline H-4), 7.19–7.52 (m, 10H, ArH’s, pyridine H-5). Anal. Calcd. For C27H24N6O2 (464.53): C, 69.81; H, 5.21; N, 18.09 Found C, 69.91; H, 5.33; N, 18.19

3.14. Azido (2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl)-methanone ()

To a stirred solution of 31 (5 mmol) in acetic acid (15 mL) at 0–5 °C, sodium nitrite was added portion-wise until effervescence ended. The reaction mixture was stirred for 1 h. The resulting solid was collected, filtered, washed with water and recrystallized, giving the azido derivative 34. Buff crystals from acetic acid, yield (86%) m.p. 160 °C, FT-IR (KBr, cm−1): 2964, 2924 (CH); 1641 (CO), 1609 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.44 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.69 (s, 3H, CH3), 7.17–7.57 (m, 10H, ArH’s and pyridine H-5). Anal. Calcd. For C23H19N7O (409.49): C, 67.47; H, 4.68; N, 23.95 Found C, 67.50; H, 4.70; N, 23.99.

3.15. 4-(Aryldiazenyl-3,5-dimethylpyrazol-1-yl)(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl]methanone (, ) and 4-(Arylyhydrazono)-5-methyl-2(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-carbonyl)-2,4-dihydropyrazol-3-one (, )

Dropwise addition of the appropriate arenediazonium chloride (5 mmol), which was prepared via reaction of appropriate n class="Chemical">aniline or p-toluidine (5 mmol), hydrochloric acid (1.5 mL, 6M) and sodium nitrite (0.37 g, 5 mmol) at 0–5 °C, to a mixture of the appropriate 32 or 33 (5 mmol) and sodium acetate (1.3 g, 5 mmol) in ethanol (30 mL) at 0–5 °C while stirring the reaction mixture was stirred for 3 h. The resulting solid was collected, washed with water and recrystallized from acetic acid, giving 35a, 35b, 36a and 36b, respectively.

(E)-(3,5-Dimethyl-4-(phenyldiazenyl)-1H-pyrazol-1-yl)(n class="Chemical">2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)methanone (35a). Orange crystals from acetic acid, Yield 70%, m.p. 170 °C, FT-IR (KBr, cm−1): 2925 (CH); 1722 (CO); 1608 (C=N), 1566 (C=C): 1H-NMR (300 MHz, DMSO-d6): δ = 2.28 (s, 3H, CH3) 2.44 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.60 (s, 3H, CH3), 2.69 (s, 3H, CH3) and 7.17–7.97 (m, 15H, ArH’s, pyridine H-5). Anal. Calcd. For C34H30N8O (566.67): C, 72.07; H, 5.34; N, 19.77 Found C, 72.16; H, 5.29; N, 19.88

(E)-(3,5-Dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)(n class="Chemical">2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)methanone (35b). Orange crystals from acetic acid, Yield 70%,m.p. 175 °C, FT-IR (KBr, cm−1): 2966, 2924 (CH); 1722 (CO); 1647 (C=N); 1605 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.25 (s, 3H, CH3) 2.44 (s, 3H, CH3), 2.49 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.69 (s, 3H, CH3), 2.71 (s, 3H, CH3) and 7.17–7.98 (m, 14H, ArH’s, pyridine H-5). Anal. Calcd. For C35H32N8O (580.70): C, 72.39; H, 5.55; N, 19.30 Found C, 72.49; H, 5.66; N, 19.40.

(E)-5-Methyl-2-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinoyl)-4-(phenyldiazenyl)-2,4-dihydro-3H-pyrazol-3-one (36a). Orange crystals from acetic acid, Yield 70%, m.p. 165 °C, FT-IR (KBr, cm−1): 3432 (OH); 2975, 2921 (CH); 1721 (CO); 1679 (C=N); 1584 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.31 (s, 3H, CH3) 2.43 (s, 3H, CH3), 2.58 (s, 3H, CH3), 2.69 (s, 3H, CH3), 4.35 (s, br, 1H, pyrazoline), 7.09–7.58 (m, 15H, ArH’s and pyridine H-5). 13C-NMR (DMSO-d6) δ = 9.6, 11.8, 20.8, 24.4, 115.3, 123.4, 125.7, 126.8, 128.4, 129.7, 130.4, 132.4, 133.3, 138.8, 139.5, 139.8, 140.8, 169.0, 171.2, 172.5, 170.0. Anal. Calcd. For C33H28N8O2 (568.64): C, 69.70; H, 4.96; N, 19.71 Found C, 69.65; H, 4.85; N, 19.72.

(E)-5-Methyl-2-(2-methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylnicotinoyl)-4-(p-tolyldiazenyl)-2,4-dihydro-3H-pyrazol-3-one (36b). Orange crystals from acetic acid, Yield 70%, m.p. 170 °C, FT-IR (KBr, cm−1): 2974, 2922 (CH); 1721 (C=O); 1649 (C=N); 1608 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.42 (s, 3H, CH3), 4.50 (s, 1H, pyrazoline), 2.49 (s, 3H, CH3), 2.57 (s, 3H, CH3), 2.69 (s, 3H, CH3), 2.71 (s, 3H, CH3), and 7.14–7.57 (m, 14H, ArH’s and pyridine H-5). Anal. Calcd. For C34H30N8O2 (582.67): C, 70.09; H, 5.19; N, 19.23 Found C, 70.19; H, 5.20; N, 19.10.

3.16. 1-(2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl)-3-substituted urea (, ) and 3-(2-Methyl-6-(methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl)quinazoline-2,4-(1H,3H)dione ()

A mixture of 34 (2 g, 5mmol) and appropriate aniline, n class="Chemical">p-toluidine, anthranilic acid (or methyl anthranilate) (5 mmol) in dry dioxane (20 mL) was refluxed for 4 h. The resulting solid that was collected and recrystallized from the proper solvent gave 38a, 38b and 39, respectively

1-(2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)-3-phenylurea (38a). White crystals from n class="Chemical">acetic acid yield 70%, m.p. 180 °C. FT-IR (KBr, cm−1): 3426 (NH); 2983, 2926 (CH); 1722 (CO); 1647 (C=N); 1594 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.43 (s, 3H, CH3) 2.59 (s, 3H, CH3), 2.71 (s, 3H, CH3), 7.44–7.97 (m, 15H, ArH’s and pyridine H-5), 8.88 (s, br, 2H, 2NH). Anal. Calcd. For C29H26N6O (474.57): C, 73.40; H, 5.52; N, 17.71 Found C, 73.37; H, 5. 63; N, 17.69.

1-(2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)-3-p-tolylurea (38b). White crystals from n class="Chemical">acetic acid yield 72%, m.p. 170–172 °C. FT-IR (KBr, cm−1): 3423 (NH); 2984, 2962, 2952 (CH); 1722 (CO); 1592 (C=C), 1H-NMR (300 MHz, DMSO-d6): δ = 2.44 (s, 3H, CH3) 2.49 (s, 3H, CH3), 2.60 (s, 3H, CH3), 2.71 (s, 3H, CH3), 7.27–7.98 (m, 14H, ArH’s and pyridine H-5), 8.90 (s, br, 2H, 2NH). Anal. Calcd. For C30H28N6O (488.60): C, 73.75; H, 5.17; N, 17.20 Found C, 73.80; H, 5.20; N, 17.30.

3-(2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenyl-pyridin-3-yl)-qninazoline-2,4-(1H,3H)dione (39). White crystals from acetic acid, yield 65%, m.p. 190 °C. FT-IR (KBr, cm−1): 3424 (NH); 2983, 2926, 2875 (CH); 1722 (CO); 1594 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.43 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.59 (s, 3H, CH3), 7.44–7.97 (m, 14H, ArH’s and pyridine H-5), 10.54 (s, br, 1H, NH), 13C-NMR (DMSO-d6) δ = 8.8, 20.5, 21.1, 114.2, 115.6, 117.2, 121.9, 123.7, 123.8, 128.5, 129.8, 132.7, 134.2, 134.6, 135.2, 137.8, 138.4, 138.7, 139.5, 140.2, 141.3. 144.2, 153.1, 158.6, 161.7, 164.6. Anal. Calcd. For C30H24N6O2 (500.56): C, 71.99; H, 4.83; N, 16.79 Found C, 71.89; H, 4.79; N, 16.85.

3.17. Phenyl 2-Methyl-6-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)-4-phenylpyridin-3-yl)-carbamate ()

A mixture of 34 (2 g, 5 mmol) and phenol (0.47 g, 5 mmol) in dry n class="Chemical">benzene (20 mL) was refluxed for 4 h. The resulting solid was collected and crystallized from ethanol, affording the corresponding 40, as buff crystals, yield 70%, m.p. 140–142 °C. FT-IR (KBr, cm−1): 3425 (NH); 2984, 2925, 2866 (CH); 1722 (CO); 1597 (C=C). 1H-NMR (300 MHz, DMSO-d6): δ = 2.44 (s, 3H, CH3) 2.49 (s, 3H, CH3), 2.69 (s, 3H, CH3), 7.33–7.97 (m, 15H, ArH’s and pyridine H-5), 11.65 (s, br, 1H, NH); Anal. Calcd. For C29H25N5O2 (475.55): C, 73.25; H, 5.30; N, 14.73; Found C, 73.35; H, 5.40; N, 14.85.

4. Conclusions

Compound 1 proved to be useful for synthesis of a new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles and pyridines containing 1,2,3-triazole moiety using hydrazonoyl halides as precursors. Also, compound 31 proved to be a useful precursor in the synthesis of various pyrazoles, urea and carbamate derivatives. The biological activities of the synthesized products will be reported in extended work.