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Efficient one pot synthesis of triazolotriazine, pyrazolotriazine, triazole, isoxazole and pyrazole derivatives

  • Eman A. El Rady EMAIL logo
Published/Copyright: September 21, 2012
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 18 Issue 4

Abstract

3-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (1) was used as a starting material for synthesis of functionalized heterocyclic derivatives mentioned in the title.

Keywords: 4-arylhydrazono-2,3-dihydroisoxazolone; 3-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile; pyrazolotriazine; 1,2,3-triazole; triazolopyrimidine; triazolotriazine

Introduction

Cyanoacetyl derivatives are versatile and highly reactive reagents in the synthesis of various heterocyclic compounds (Zayed et al., 1985; Ahmed et al., 1996; Elgemeie et al., 2004; Said et al., 2006; Samir et al., 2011), such as pyrazoles (Badawy et al., 1990; Daidone et al., 1998; Finn et al., 2003; Ma et al., 2010), triazoles (Wamhoff, 1984; Kadaba, 1988; Katritzky et al., 1994; El Sayed and Khodairy, 1998a,b; Zhu et al., 2000; Khodairy, 2001) and triazines (Bork et al., 2003; Khersonsky and Chang, 2004). In continuation of our efforts directed towards the application of simple and efficient procedures for the synthesis of heterocyclic compounds (Abd El Latif et al., 2002; El Rady et al., 2004, 2006, 2008), we wish to report the results of our investigation on the chemistry of 3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (1).

Results and discussion

The reaction of 3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (1) with 2-phenylenediamine, 2-aminophenol and 5-amino-1,2,4-triazole in refluxing toluene results in the displacement of the 3,5-dimethylpyrazole moiety from substrate 1 to give known benzimidazol-2-yl-acetonitrile (3a), benzoxazol-2-yl-acetonitrile (3b) (Khalafalh et al., 1995) and 7-amino-[1,2,4]triazolo[1,5-a]pyrimidine-5(4H)-one (6) (Levin et al., 1964; Tenor and Kroeger, 1964), respectively, as shown in Scheme 1. The structure of the reaction products were confirmed based on spectral and analytical data and comparison with the authentic samples (3a,b and 6). It can be suggested that compounds 3a,b are formed via aminolysis reaction of compound 1 followed by cyclization of the resultant intermediate product 2. Compound 4 would be expected to form via cycloaddition of 2, which was not the case. Product 6 is formed through the intermediary of 5 which undergoes cyclization in the last step. The IR spectrum of compound 6 shows intense bands at 1710, 3210 and 3440 cm-1 due to carbonyl, imino and amino groups, respectively. The 1H NMR spectrum of 6 shows singlets at δ 2.59, 7.31, 7.53 and 8.39 ppm due to amino, pyrimidine, triazole and imino protons, respectively. The mass spectrum of 6 shows a molecular ion peak at m/z 151.

Scheme 1
Scheme 1

By contrast, reactions of 1 with 5-amino-[1,2,4]tri­azole and 5-amino-3-phenylpyrazole in the presence of sodium nitrite and hydrochloric acid afforded the respective ­pro­ducts 8a and 8b (Scheme 2). The IR spectra of these compounds show intense bands at 1695–1698 and 3445–3448 cm-1 due to carbonyl and amino groups, respectively. The 1H NMR of 8a shows a singlet at δ 2.31 for the two methyl groups, a singlet at δ 5.32 for NH2 and two singlets at δ 7.12 and δ 7.14 ppm due to the two protons of pyrazole and triazole. The mass spectrum of 8a shows a molecular ion peak at m/z 257.

Scheme 2
Scheme 2

Direct coupling of the substrate 1 with aryldiazonium chlorides gives the corresponding 2(arylhydrazono)-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile derivatives 9a–f in good yields. Treatment of 9a–f with hydrazine hydrate in boiling ethanol containing few drops of piperidine afforded the corresponding products 11a–f through the intermediary of 10 (Scheme 3). The spectral data for 11 are in full agreement with the proposed structure.

Scheme 3
Scheme 3

By contrast, the reaction of 9a–f with hydroxyl­amine hydrochloride in boiling ethanol/piperidine gave product 13a–f that crystallized directly from the mixture. Related reactions are known (Hafez et al., 1980; Kandeel et al., 1980). The intermediary of 12 can be suggested (Scheme 4).

Scheme 4
Scheme 4

Interestingly, the reaction of 9a–f with hydroxyl­amine hydrochloride in the presence of anhydrous sodium acetate, when conducted under more drastic conditions using boiling DMF, afforded the previously identified compounds 11a–f (Scheme 5).

Scheme 5
Scheme 5

The hydrazone 9a was also allowed to react with hydroxylamine hydrochloride in ethanol in the presence of sodium acetate to give 2-arylhydrazono-3-oxo-3-(3,5-dimethyl-1H-pyrazol-1-yl)-N-hydroxypropanamidine (14), which was isolated and fully characterized. The treatment of 14 in the presence of anhydrous sodium in DMF under reflux conditions caused cyclization to give 11a.

Finally, the reaction of 9a with malononitrile in acetic acid under reflux conditions yielded the unexpected new compound 17 (Scheme 6). It can be suggested that addition of the active methylene moiety of malononitrile to the cyano function of 9a generates the intermediate product 15 which undergoes intramolecular cyclization to generate another intermediate product 16 which is the final precursor to 17.

Scheme 6
Scheme 6

Experimental

General

Melting points were determined on a Gallenkamp electrothermal melting point apparatus and are uncorrected. IR spectra were recorded using potassium bromide pellets on a FTIR unit Bruker-vector 22 spectrophotometer. 1H and 13C NMR spectra were obtained at 300 MHz and 75 MHz, respectively, on a Varian Gemini NMR spectrometer. Electron-impact mass spectra were recorded on a Hewlett Packard MS-5988 spectrometer at 70 eV. Elemental analysis was carried out at the Micro Analytical Center of Cairo University, Egypt. Microbial assay using bacteria and fungi was performed in the Environment Studies Microbiology Laboratory, South Valley University, Faculty of Science, Aswan, Egypt.

General procedure for compounds 3a and 3b

A mixture of 1 (0.16 g, 1 mmol), 2-phenylenediamine (0.10 g, 1 mmol) or 2-aminophenol (0.10 g, 1 mmol) in 20 mL of dry toluene was heated under reflux for 3 h. The solvent was evaporated under reduced pressure and the residue was triturated with methanol. The resulting solid product was collected by filtration and crystallized from ethanol.

Benzimidazol-2-yl-acetonitrile (3a)

Mp 200–205°C (lit. mp 212–216°C, Khalafalh et al., 1995); MS: m/z 157 (M+). Anal. Calcd for C9H7N3 (157.17): C, 68.78; H, 4.49; N, 26.74. Found: C, 68.78; H, 4.56; N, 26.86.

Benzoxazol-2-yl-acetonitrile (3b)

Mp >300°C (lit. mp 310°C, Khalafalh et al., 1995); MS: m/z 158 (M+). Anal. Calcd for C9H6N2O (158.16): C, 68.35; H, 3.82; N, 17.71. Found: 68.44; H, 3.95; N, 17.91.

7-Amino-[1,2,4]triazolo[1, 5-a]pyrimidine-5(4H)-one (6)

A mixture of 1 (0.16 g, 1 mmol), 5-amino-1,2,4-triazole (0.09 g, 1 mmol) in 20 mL of dry toluene was heated under reflux for 3 h. The solvent was evaporated under reduced pressure and the residue was triturated with methanol. The resulting solid product was collected by filtration and crystallized from DMF/H2O; pale yellow powder; yield 0.10 g (65%); mp >300°C (lit. mp 330°C, Tenor and Kroeger, 1964); IR: νmax 1710 (CO), 3210 (NH), 3440 cm-1 (NH2); 1H NMR (CDCl3): δ 2.59 (s, 2H, NH2), 7.31 (s, H, CH-pyrimidine), 7.53 (s, 1H, CH-triazole), 8.39 (s, 1H, NH); 13C NMR (CDCl3): δ 85.2 (C-6), 130.1 (C-3a), 135.3 (C-2), 145.2 (C-7), 165.3 (C-5); MS: m/z 151 (M+, 20). Anal. Calcd for C5H5N5O (151.13): C, 39.74; H, 3.33; N, 46.34. Found: C, 39.85; H, 3.45; N, 46.46.

(4-Amino-[1,2,4]triazolo[5,1-c][1,2,4]triazin-3-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (8a)

A solution of sodium nitrite (0.69 g, 1 mmol) in cold water (15 mL) was added dropwise during a period of 15 min to a mixture of 5-amino-[1,2,4]triazole (0.88 g, 1 mmol), ethanol (10 mL) and concentrated hydrochloric acid (3 mL). Then this mixture was added to 10 mL of a well-stirred cold ethanol solution of compound 1 (1.6 g, 1 mmol) and 2 g of anhydrous sodium acetate. The mixture was left overnight at room temperature. The precipitated solid product was collected by filtration, washed with water and crystallized from methanol; pale yellow powder, yield 0.09 g (60%); mp 195–199°C; IR (νmax, cm-1): 1695 (CO), 3445 (NH2); 1H NMR (CDCl3): δ 2.31 (s, 6H, 2 CH3), 5.22 (s, 2H, NH2), 7.12 (s, 1H, CH-4 pyrazole), 7.14 (s, 1H, CH-6 triazole); 13C NMR (CDCl3): δ 13.2 (CH3), 110.2 (C-4 pyrazole), 122.4 (C-5 pyrazole), 122.5 (C-3 pyrazole), 129.1 (C-6-triazine), 133.1 (C-8a), 175.2 (CO); MS: m/z 257 (M-1, 16). Anal. Calcd for C10H10N8O (258.24): C, 46.51; H, 3.90; N, 43.39. Found: C, 46.62; H, 3.99; N, 43.48.

(4-Amino-7-phenylpyrazolo[5,1-c][1,2,4]triazin-3-yl)(3,5-dimethyl-1H-pyrazol-1-yl) methanone (8b)

The reaction of 5-amino-3-phenyl-pyrazole (1.5 g, 1 mmol) was conducted using the procedure described above; solid buff, yield 0.09 g (58%); mp 180–184°C; IR (νmax, cm-1): 1698 (CO), 3448 (NH2); 1H NMR (CDCl3): δ ppm 2.52 (s, 6H, 2 CH3), 5.91 (s, 2H, NH2), 6.52 (s, 1H, CH-4 pyrazole), 7.72 (s, 1H, CH-8 pyrazole); 13C NMR (CDCl3): δ 13.2 (CH3), 95.5 (C-8), 103.2 (C-4 pyrazole), 122.4 (C-3 pyrazole), 122.5 (C-5 pyrazole), 127.3, 128.3, 129.3, 133.6 (Ph), 143.1 (C-3-triazine), 144.1 (C-4-triazine), 147.1 (C-7), 150.2 (C-8a), 175.4 (CO); MS: m/z 333 (M+, 30). Anal. Calcd for C17H15N7O (333.36): C, 61.25; H, 4.54; N, 29.41. Found: C, 61.32; H, 4.65; N, 29.54.

General procedure for synthesis of compounds 9a–f

To a solution of aromatic amine (1 mmol) in a mixture of 10 mL of ethanol and 3 mL of concentrated hydrochloric acid, sodium nitrite (0.69 g, 1 mmol) in 15 mL of ice water was added dropwise during a period of 15 min. The resulting solution was added to 10 mL of a well-stirred cold ethanol solution of compound 1 (1.6 g, 1 mmol) and anhydrous sodium acetate (2 g). The mixture was left overnight at room temperature. The solid product 9a–f was collected by filtration, washed with water and crystallized from ethanol.

2-Phenylhydrazono-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo­propanenitrile (9a)

Deep yellow powder; yield 0.11 g (73%); mp 120–124°C; IR (νmax, cm-1): 1698 (CO), 2215 (CN), 3120 (NH); 1H NMR (CDCl3): δ 2.60 (s, 6H, 2 CH3), 7.18 (s, 1H, pyrazole), 7.20–7.69 (m, 5H, Ar-H), 7.70 (s, 1H, NH); MS: m/z 267 (M+, 30). Anal. Calcd for C14H13N5O (267.29): C, 62.91; H, 4.90; N, 26.20. Found: C, 62.99; H, 5.12; N, 26.33.

2-(p-Methylphenylhydrazono)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (9b)

Yellow powder; yield 0.11 g (70%); mp 125–129°C; IR (νmax, cm-1): 1700 (CO), 2210 (CN), 3122 (NH); 1H NMR (CDCl3): δ 2.50 (s, 6H, 2 CH3), 3.11 (s, 3H, CH3), 6.44 (d, 2H, J=6 Hz), 7.19 (s, 1H, pyrazole), 7.32 (d, 2H, J=6 Hz), 7.68 (s, 1H, NH);MS: m/z 281 (M+, 30). Anal. Calcd for C15H15N5O (281.32): C, 64.04; H, 5.37; N, 24.90. Found: C, 64.22; H, 5.55; N, 24.99.

2-(p-Methoxyphenylhydrazono)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (9c)

Yellow powder; yield 0.11 g (66%); mp 130–137°C; IR (νmax, cm-1): 1701 (CO), 2210 (CN), 3125 (NH); 1H NMR (300 MHz, CDCl3): δ ppm 2.30 (s, 6H, 2 CH3), 3.31 (s, 3H, OCH3), 6.42 (d, 2H, J=6 Hz), 7.10 (s, 1H, pyrazole), 7.22 (d, 2H, J=6 Hz), 7.71 (s, 1H, NH); MS: m/z 297 (M+, 25). Anal. Calcd for C15H15N5O2 (297.32): C, 60.60; H, 5.09; N, 23.56. Found: C, 60.75; H, 5.23; N, 23.73.

2-(p-Nitrophenylhydrazono)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (9d)

Orange powder; yield 0.10 g (60%); mp 180–184°C; IR (νmax, cm-1): 1698 (CO), 2205 (CN), 3127 (NH); 1H NMR (CDCl3): δ ppm 2.61 (s, 6H, 2 CH3), 6.54 (d, 2H, J=6 Hz), 7.20 (s, 1H, pyrazole), 7.22 (d, 2H, J=6 Hz), 7.72 (s, 1H, NH); MS: m/z 313 (M+1, 15). Anal. Calcd for C14H12N6O3 (312.28): C, 53.85; H, 3.87; N, 26.91. Found: C, 53.99; H, 3.99; N, 26.04.

2-(p-Chlorophenylhydrazono)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (9e)

Brown powder; yield 0.09 g (55%), 0.09 g; mp 150–154°C; IR (νmax, cm-1): 1698 (CO), 2205 (CN), 3128 (NH); 1H NMR (CDCl3): δ ppm 2.60 (s, 6H, 2 CH3), 6.21 (d, 2H, J=6), 7.18 (s, 1H, pyrazole), 6.98 (d, 2H, J=6 Hz), 7.70 (s, 1H, NH); MS: m/z 301 (M+, 15). Anal. Calcd for C14H12ClN5O (301.73): C, 55.73; H, 4.01; N, 23.21. Found: C, 55.87; H, 4.32; N, 23.37.

2-(p-Bromophenylhydrazono)-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (9f)

Yellow powder; yield 0.10 g (60%); mp 190–194°C; IR (νmax, cm-1): 1700 (CO), 2210 (CN), 3128 (NH); 1H NMR (CDCl3): δ 2.61 (s, 6H, 2 CH3), 6.54 (d, 2H, J=6 Hz), 7.19 (s, 1H, pyrazole), 7.22 (d, 2H, J=6 Hz), 7.64 (s, 1H, NH); MS: m/z 347 (M+1, 15). Anal. Calcd for C14H12BrN5O (346.18): C, 48.57; H, 3.49; N, 20.23. Found: C, 48.65; H, 3.65; N, 20.31.

General procedures for synthesis of (5-amino-2-aryl-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanones 11a–f

Method A

A mixture of 9a–f (1 mmol) and hydrazine hydrate (excess) in 20 mL of ethanol containing 0.3 mL of piperidine was heated under reflux for 3 h. The precipitated product was collected by filtration and crystallized from DMF/H2O.

Method B

A mixture of 9a–f (1 mmol) and hydroxylamine hydrochloride (0.67 g, 1 mmol) in 20 mL of DMF containing 0.3 g of anhydrous sodium acetate was heated under reflux for 8 h. After cooling, the mixture was poured onto ice. The product was collected by filtration, washed several times with cold water and crystallized from DMF/H2O.

Method C

A mixture of 14a (1 mmol) in 20 mL of DMF containing 0.3 g of anhydrous sodium acetate was heated under reflux for 9 h. After cooling, the mixture was poured onto ice. The product 11a was collected by filtration, washed several times with cold water and crystallized from DMF/H2O.

(5-Amino-2-phenyl-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11a)

Red crystals; yield 73%; mp 260–264°C; IR (νmax, cm-1): 1669 (CO), 3419 (NH2); 1H NMR (DMSO-d6): δ 2.51 (s, 6H, 2 CH3), 2.40 (s, 2H, NH2), 7.15–7.65 (m, 6H, Ar-H + CH-pyrazole); 13C NMR (CDCl3): δ 13.12 (CH3), 101.23 (C-4 pyrazole), 122.23 (C-5 pyrazole), 122.25 (C-3 pyrazole), 128.2, 129.2, 132.1 (Ph), 140.3 (C-4 triazole), 140.4 (C-5 triazole), 170.1 (CO); MS: m/z 282 (M+, 30). Anal. Calcd for C14H14N6O (282.30): C, 59.56; H, 5.00; N, 29.77. Found: C, 59.68; H, 5.12; N, 29.98.

(5-Amino-2-p-tolyl-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11b)

Red crystals; yield 66%; mp 265–269°C; IR (νmax, cm-1): 1694 (CO), 3420 (NH2); 1H NMR (DMSO-d6): δ 2.55 (s, 6H, 2 CH3), 2.56 (s, 3H, CH3), 2.34 (s, 2H, NH2), 6.44 (d, 2H, J=6 Hz), 7.15 (s, 1H, CH-pyrazole), 7.22 (d, 2H, J=6 Hz); MS: m/z 296 (M+, 30). Anal. Calcd for C15H16N6O (296.33): C, 60.80; H, 5.44; N, 28.36. Found: C, 60.99; H, 5.56; N, 28.47.

(5-Amino-2-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11c)

Yellow powder; yield 0.18 g (60%); mp 250–254°C; IR (νmax, cm-1): 1690 (CO), 3430 (NH2). 1H NMR (DMSO-d6): δ 2.66 (s, 6H, 2 CH3), 2.71 (s, 3H, CH3), 2.38 (s, 2H, NH2), 6.12 (d, 2H, J=6 Hz), 7.18 (s, 1H, CH-pyrazole), 7.34 (d, 2H, J=6 Hz); MS, m/z (%)=312 (M+, 30). Anal. Calcd for C15H16N6O2 (312.33): C, 57.68; H, 5.16; N, 26.91. Found: C, 57.77; H, 5.29; N, 26.99.

(5-Amino-2-(4-nitrophenyl)-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11d)

Brown powder; yield 0.18 g (60%); mp 230–234°C; IR (νmax, cm-1): 1692 (CO), 3430 (NH2); 1H NMR (DMSO-d6): δ ppm 2.61 (s, 6H, 2 CH3), 2.48 (s, 2H, NH2), 6.12 (d, 2H, J=6 Hz), 7.22 (s, 1H, CH-pyrazole), 7.44 (d, 2H, J=6 Hz); MS: m/z 327 (M+, 20). Anal. Calcd for C14H13N7O3 (327.30): C, 51.38; H, 4.00; N, 29.96. Found: C, 51.47; H, 4.12; N, 30.11.

(5-Amino-2-(4-chlorophenyl)-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11e)

Brown powder; yield 0.21 g (55%); mp 310–314°C; IR (νmax, cm-1): 1698 (CO), 3435 (NH2); 1H NMR (DMSO-d6): δ 2.62 (s, 6H, 2 CH3), 2.42 (s, 2H, NH2), 6.34 (d, 2H, J=6 Hz), 7.12 (s, 1H, CH-pyrazole), 7.33 (d, 2H, J=6 Hz); MS: m/z 316 (M+, 40). Anal. Calcd for C14H13ClN6O (316.75): C, 53.09; H, 4.14; N, 26.53. Found: C, 53.32; H, 4.25; N, 26.76.

(5-Amino-2-(4-bromophenyl)-2H-1,2,3-triazol-4-yl)(3,5-dimethyl-1H-pyrazol-1-yl)methanone (11f)

Red powder; yield 0.18 g (50%); mp 280–284°C; IR (νmax, cm-1): 1693 (CO), 3440 (NH2); 1H NMR (DMSO-d6): δ 2.71 (s, 6H, 2 CH3), 2.53 (s, 2H, NH2), 6.12 (d, 2H, J=6 Hz), 7.23 (s, 1H, CH-pyrazole), 7.44 (d, 2H, J=6 Hz); MS: m/z 361 (M+, 25). Anal. Calcd for C14H13BrN6O (361.20): C, 46.55; H, 3.63; N, 23.27. Found: C, 46.63; H, 3.74; N, 23.35.

General procedure for synthesis of 4-arylhydrazono-5-imino-2,3-dihydroisoxazol-3(2H)-ones 13a–f

A mixture of 9a–f (1 mmol), hydroxylamine hydrochloride (1 mmol) and piperidine (0.3 mL) in 20 mL of ethanol was heated under reflux for 3 h. The solid product 13a–f was collected by filtration and crystallized from DMF/H2O.

5-Imino-4-phenylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13a)

Yellow powder; yield 0.18 g (70%); mp 255–259°C (lit. mp 245°C; Hafez et al., 1980; lit. mp 238°C; Kandeel et al., 1980); IR (νmax, cm-1): 1711 (CO), 3293 (NH); 1H NMR (CDCl3): δ 7.22–7.92 (m, 7H, Ar-H + 2 NH); 13C NMR (CDCl3): δ 77.2 (C-4), (128.1, 128.8, 128.9) (Ph), 145.2 (C-5), 176.2 (CO); MS: m/z 204 (M+, 25). Anal. Calcd for C9H8N4O2 (204.19): C, 52.94; H, 3.95; N, 27.44. Found: C, 52.99; H, 4.12; N, 27.57.

5-Imino-4-p-tolylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13b)

Orange powder; yield 0.16 g (55%); mp 290–292°C; IR (νmax, cm-1): 1715 (CO), 3294 (NH); 1H NMR (CDCl3): δ 3.10 (s, 3H, CH3), 6.21 (d, 2H, J=6 Hz), 7.33 (s, 2H, 2 NH), 7.44 (d, 2H, J=6 Hz); MS: m/z 218 (M+, 30). Anal. Calcd for C10H10N4O2 (218.22): C, 55.04; H, 4.62; N, 25.68. Found: C, 55.13; H, 4.71; N, 25.73.

5-Imino-4-p-methoxyphenylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13c)

Red powder; yield 0.15 g (50%); mp 270–274°C; IR (νmax, cm-1): 1712 (CO), 3293 (NH); 1H NMR (CDCl3): δ 3.20 (s, 3H, OCH3), 6.11 (d, 2H, J=6 Hz), 7.32 (s, 2H, 2 NH), 7.47 (d, 2H, J=6 Hz); MS: m/z 234 (M+, 25). Anal. Calcd for C10H10N4O3 (234.21): C, 51.28; H, 4.30; N, 23.92. Found: C, 51.36; H, 4.42; N, 23.99.

5-Imino-4-p-nitrophenylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13d)

Golden crystals; yield 60%, 0.18 g; mp 220–224°C; IR (νmax, cm-1): 1711(CO), 3295 (NH); 1H NMR (CDCl3): δ 6.19 (d, 2H, J=6 Hz), 7.24 (s, 2H, 2 NH), 7.38 (d, 2H, J=6 Hz); MS, m/z (%)=249 (M+, 30). Anal. Calcd for C9H7N5O4 (249.19): C, 43.38; H, 2.83; N, 28.11. Found: C, 43.43; H, 2.90; N, 28.23.

5-Imino-4-p-chlorophenylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13e)

Brown powder; yield 52%, 0.15 g; mp 240–244°C; IR (νmax, cm-1): 1710 (CO), 3290 (NH); 1H NMR (CDCl3): δ 6.24 (d, 2H, J=6. Hz), 7.36 (s, 2H, 2 NH), 7.41 (d, 2H, J=6 Hz); MS: m/z 238 (M+, 20). Anal. Calcd for C9H7CLN4O2 (238.63): C, 45.30; H, 2.96; N, 23.48. Found: C, 45.39; H, 2.99; N, 23.56.

5-Imino-4-p-bromophenylhydrazono-2,3-dihydroisoxazol-3(2H)-one (13f)

Red powder; yield 0.18 g (50%); mp 235–239°C; IR (νmax, cm-1): 1711 (CO), 3298 (NH), 3448 (NH2); 1H NMR (CDCl3): δ 2.42 (s, 2H, NH2), 6.27 (d, 2H, J=6 Hz), 7.36 (s, 2H, 2 NH), 7.40 (d, 2H, J=6 Hz); MS: m/z 283 (M+, 15). Anal. Calcd for C9H7BrN4O2 (283.08): C, 38.19; H, 2.49; N, 19.79. Found: C, 38.22; H, 2.54; N, 19.84.

2-Phenylhydrazono-3-oxo-3-(3,5-dimethyl-1H-pyrazol-1-yl)-N-hydroxy-propanamidine (14)

A solution of 9a (1 mmol), hydroxylamine (0.67 g, 1 mmol) and 0.3 g of anhydrous sodium acetate in 20 mL of ethanol was heated under reflux for 5 h. After cooling, the mixture was poured onto ice. The product 14 was collected by filtration, washed several times with cold water and crystallized from DMF/H2O; deep yellow powder; yield 0.12 g (45%); mp 160–164°C; IR (νmax, cm-1): 1700 (CO), 3110 (NH), 3450 (NH2), 3480 (OH); 1H NMR (CDCl3): δ 2.71 (s, 6H, 2 CH3), 3.51 (s, 2H, NH2), 7.31 (s, 1H, pyrazole), 7.33–7.98 (m, 5H, Ar-H + NH), 10.21 (s, 1H, OH); MS: m/z 300 (M+, 30). Anal. Calcd for C14H16N6O2 (300.32): C, 55.99; H, 5.37; N, 27.98. Found: C, 56.09; H, 5.45; N, 28.12.

4-Acetamido-3-(3,5-dimethyl-1H-pyrazol-1-yl)carbonyl-1-phenyl-1H-pyrazole-5-carbonitrile (17)

A mixture of 1 (0.16 g, 1 mmol), malononitrile (0.07 g, 1 mmol) in 20 mL of acetic acid was heated under reflux for 6 h. The solvent was evaporated under reduced pressure and the residue was triturated with methanol. The solid product 17 was collected by filtration and crystallized from the methanol; yellow crystals; yield 0.06 g (35%); mp 210–214°C; IR (νmax, cm-1): 1669, 1700 (CO), 2220 (CN), 3245 (NH); 1H NMR (CDCl3): δ 2.34 (s, 1H, NH), 2.56 (s, 3H, CH3), 7.25–7.99 (m, 6H, Ar-H + CH pyrazole); MS: m/z 347 (M-1, 26). Anal. Calcd for C18H16N6O2 (348.36): C, 62.06; H, 4.63; N, 24.12. Found: C, 62.22; H, 4.76; N, 24.32.

Corresponding author: Eman A. El Rady, South Valley University, Faculty of Science, Chemistry Department, Aswan 81528, Egypt

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Received: 2012-5-9
Accepted: 2012-6-22
Published Online: 2012-09-21
Published in Print: 2012-10-01

©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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https://doi.org/10.1515/hc-2012-0072
Keywords for this article
4-arylhydrazono-2,3-dihydroisoxazolone; 3-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile; pyrazolotriazine; 1,2,3-triazole; triazolopyrimidine; triazolotriazine
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Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Preliminary Communication
  4. Synthesis of novel NHC-pyrrole-NHC C-N-C Pincer proligands
  5. Research Articles
  6. Synthesis of new tetracyclic paullone derivatives as potential CDK inhibitors
  7. Keto furanylidene building blocks from silyl ethers of monoalkynylated β-keto carbonyls with iron(III) chloride hexahydrate-iodine
  8. Synthesis of perhydro-N-(2,2-disubstituted-3-aminopropyl) heterocycles as potentially bioactive compounds and fragments for combinatorial chemistry
  9. Pirfenidone structural isosteres: design, synthesis and spectral study
  10. Synthesis and characterization of new metallophthalocyanines bearing macrocyclic N3O2 groups on peripheral positions
  11. Synthesis and antimicrobial evaluation of substituted benzimidazolyl fluoroquinolones under conventional and microwave irradiation conditions
  12. Synthesis of novel 2,6-bis(5-t-butylbenzo[b]furan-2-ylcarbonyl)pyridines
  13. An efficient synthesis of 2-substituted benzoxazoles using cerium(III) chloride/sodium iodide as catalyst
  14. Efficient one pot synthesis of triazolotriazine, pyrazolotriazine, triazole, isoxazole and pyrazole derivatives
  15. Synthesis of novel trifluoromethyl-containing heterocycle-fused troponoid compounds
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