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An Efficient Approach for the Synthesis of Triazole Conjugated Pyrazole Chalcone Derivatives

  • Venkataramana Rupireddy
  • Venkata Ramana Reddy ChittireddyEmail author
  • Ashok Dongamanti
Original Article
  • 16 Downloads

Abstract

An important intermediate, 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde in the synthesis of target compounds was synthesized using 2,4-dihydroxyacetophenone as starting synthon by adopting two different click chemistry synthetic protocols. Later the intermediate was further converted into a new series of triazole conjugated pyrazole chalcones from various acetophenones in the presence of potassium hydroxide under microwave irradiation and conventional methods.

Graphic Abstract

Keywords

Pyrazole-4-carbaldehyde 1,2,3-Triazole Chalcones Vilsmeier–Haack reagent Click reactions Microwave irradiation 

1 Introduction

Triazoles and their derivatives are an important class of heterocyclic compounds, which play a vital role in the synthesis of active pharmaceutical ingredients. Among these, 1,2,3-triazoles have attracted the attention of medicinal chemists due to their ability to serve as pharmacophores and linkers in conjugating the two biologically potent scaffolds [1]. The 1,2,3 triazole derivatives are known to show wide range of biological activities such as antiallergic [2], antibacterial [3, 4] anti-HIV [5, 6] cytotoxic [7, 8], anti-cancer [9], antifungal [10, 11], antimalarial [12] and Anti-Prostate Cancer [13]. The 1, 2, 3-Triazole derivatives also used as synthetic intermediates, dyes, photo stabilizers, photographic materials and agrochemicals. During recent years, a good amount of research has been carried out on triazoles synthesis by adopting click reaction [14, 15].

The Pyrazole derivatives are known to play an integrated role in agrochemicals and pharmaceuticals. The phenyl substituted pyrazole moiety is present in several drugs such as Deracoxib, Celecoxib [16], Rimonabant [17], Lonazolac [18], phenazone COX-2 inhibitor [19] and Viagra. Most of the phenylpyrazole based drugs are used as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), similarly, chalcones were reported to possess many useful properties as cytotoxic, antitumor, anti-inflammatory [20], anticancer [21], and antimicrobial [22] activities. In view of the profound biological significance of these scaffolds, it is intended to couple these chemical entities in a single molecule to get new molecular entities. Accordingly, we report the synthesis of 3-(3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazol-4-yl)-1-aryl-propenones under simple, convenient and mild reaction conditions by using microwave (MW) irradiation method [23].

2 Results and Discussion

The titled heterocyclic derivatives 8a–g were synthesised in two synthetic routes (Scheme 1). Initially, the key intermediate 7 in this synthetic protocol has been synthesized. In the route-1, 2,4-dihydroxyacetophenone was reacted with phenyl hydrazine in ethanol under reflux to afford 2,4-dihydroxy phenyl hydrazine 1 [23], in 95% yield, which was further treated with Vilsmeier–Haack reagent (DMF/POCl3) in DMF at 0 °C to room temperature for 1 h to afford 3-(2,4-dihydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 2 [24], in 35% yield. The intermediate 2 upon propargelation with propargylbromide and K2CO3 in acetone formed 3 in 80% yield. Further, the compound 3 was allowed by a click reaction to react with benzyl azide, triethylamine and CuI in DMF at rt for 1 h resulted in the formation of 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 7 in 55% yield. To improve the yield of compound 7 and study of reactivity of the intermediates by using same reagent In the route-1, we observed low yields at step-2a and step-4a, because of the 2,4 dihydroxy phonolic group and some of the pyrazole aldehyde compound may be degraded in the click reaction. To improve the yield of compound 7, we proposed alternate route-2, in which we first synthesized 1,2,3-triazole followed by pyrazole aldehyde.
Scheme 1

Synthesis of 1-[7-(1-benzyl-1H-[1,2,3] triazol-4-ylmethoxy-2,2-dimethyl-chroman-6-yl]-3-aryl-propenones

In the route-2, the 2,4-dihydroxy acetophenone was propargylated to afford compound 4 [25] in 75% yield. Later, the intermediate 4 was converted into compound 5 [26] in 85% yield by click reaction, which was further reacted with phenyl hydrazine to give hydrazone derivative 6. The compound 6 was reacted with Vilsmeier–Haack reagent (DMF/POCl3) to afford 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 7 in 85% yield. Thus, the compound 7 was synthesised in good yields, following route-2. This key intermediate 7 was further used for the synthesis of various chalcone derivatives 8a–g (Fig. 1) under conventional (method A) and microwave (MWI) irradiation (method B) conditions in the presence of potassium hydroxide (Table 1). The green synthesis method, microwave assisted synthesis was found to be an efficient method over conventional methods.
Fig. 1

Structure of pyrazolechalcones. Substituted acetophenones: a Acetophenone, b 1-(p-tolyl)ethanone, c 1-(4-methoxyphenyl)ethanone, d 1-(3,4-dimethoxyphenyl)ethanone, e 1-(4-hydroxy phenyl)ethenone, f 1-(thiophen-2-yl)ethenone, g 1-(5-hydroxynaphthalen-2-yl)ethanone

Table 1

Substituents and yields of compounds 8ag obtained with conventional heating and microwave irradiation

Compound

Conventional method

Microwave method

Time (h)

Yield (%)a

Time (min)

Yield (%)a

8a

12

75

15

91

8b

14

78

10

93

8c

15

70

12

85

8d

12

68

10

75

8e

10

71

15

89

8f

10

80

20

93

8g

18

61

15

71

aIsolated yields

2.1 Proposed Mechanism for the Synthesis of 3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (Via Route-2)

The structure of the synthesized compound, 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 7 was confirmed by IR, 1H NMR, 13C NMR and LCMS spectral data. In the IR spectrum, the compound 7 showed absorption bands at 3134 cm−1 due to OH, 1715 cm−1 due to Pyrazole aldehyde, 1577 cm−1 due to C=N and 1509 cm−1 due to N=N groups respectively. The 1H NMR spectrum (400 MHz, DMSO-d6) exhibited two singlets at δ 5.15 and δ 5.63 correspond to O–CH2 and N–CH2–Ar protons. The two aromatic protons have appeared as a doublet at δ 6.64–6.67 ppm with a coupling constant 8.53 Hz and δ 7.46–7.48 ppm with a coupling constant 8.53 Hz respectively. Two singlets at δ 7.53 and δ 8.32 ppm correspond to triazole and pyrazole protons respectively. One singlet observed at δ 9.16 ppm is due to pyrazole aldehyde proton and another singlet appeared at δ 9.78 ppm due to Ar–OH. In the 13C NMR spectrum (100 MHz, DMSO-d6), the characteristic carbonyl carbon appeared at δ 185.92 ppm and another two carbons of O–CH2 and N–CH2 group appeared at δ 61.07 and 52.83 ppm respectively. The LCMS shows m/z 452 [M+H]+ appeared as base peak, which confirm the desired product 7.

The IR spectrum of compound 8a, showed characteristic peaks at 3028 cm−1 (Ar–OH), 1449 cm−1 (N=N of triazole), 1587 cm−1 (C=N of pyrazoline) and 1740 cm−1 (C=O of chalcone). The 1H NMR spectrum of chalcone, 8a showed characteristic signals at δ 7.45 ppm and at δ 7.96 ppm corresponding to Hα (d, J = 6.02 Hz), Hβ (d, J = 7.53 Hz) respectively and two singlets appeared at δ 7.58 and δ 8.35 ppm correspond to triazole and pyrazole protons respectively. In 13C NMR of 8a carbonyl carbon of chalcones appeared at δ 189.89. The LC–MS spectrum of 8a showed a molecular ion peak at (m/z) 554 (M+H)+.

3 Experimental Section

IR spectra were recorded on a Shimadzu FT-IR 8400 S spectrometer in KBr pellets. The 1H and 13C NMR spectra were recorded on a Bruker Avance-400 spectrometer (400 and 100 MHz, respectively) in CDCl3 and DMSO d6 using TMS as internal standard. All spectra measurements were carried out at room temperature. Mass spectra (ESI) were recorded on a Shimadzu GCMS-QP 1000 spectrometer. Elemental analyses were made on a KarloErba 1106 elemental analyser. Microwave reactions were carried out in a Milestone multi SYNTH series ATC-FO 300 multimode microwave reactor with a twin magnetron (2 × 800 W, 2.45 GHz) with a maximum delivered power of 1000 W in 10 W increments (pulsed irradiation). Melting points were determined in open capillary tubes and are uncorrected. Analytical TLC was performed on Merck precoated 60 F254 silica gel plates. Visualization was done by exposing to iodine vapour and UV. All the reagents and solvents used were obtained from commercial sources.

3.1 Synthesis of 3-(2,4-Dihydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2)

A round-bottom flask was charged with 8 mL of DMF and cooled to 0 °C, phosphoryl chloride (10.33 mmol) was added drop wise under stirring. The mixture was stirred for 15 min at 0 °C, then a solution of 4-(1-(2-phenylhydrazono)ethyl) benzene-1,3-diol (1.0 g, 4.13 mmol) (1) in 2 mL of DMF was added. The reaction mixture was then stirred for 1 h at room temperature. After completion of the reaction (monitored by TLC; EtOAc/hexane, 1:2; v/v), the reaction mixture was poured in ice-cold water and was basified with aqueous NaHCO3 solution. The solid obtained was filtered and washed with water followed by n-pentane and dried under high vacuum to afford pure off white solid, 3-(2,4-dihydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2). Yield = 35%; m.p 160–162 °C; IR (ν cm−1) = 3376 (Ar–OH), 3117(Ar–H), 1740 (Pyrazole C=O) and 1628 (C=N); 1HNMR: (400 MHz, DMSO d6) δ (ppm) = 6.37 (1H, d, J = 8.28 Hz, Ar H), 6.45 (1H, s Ar H), 7.34–7.54 (5H, m, Ar H), 7.94–7.96 (2H, m, Ar H), 9.12 (1H, s, CHO), 9.77 (1H, s, Ar–OH); 13CNMR: (100 MHz, DMSO d6) δ (ppm) = 102.52, 110.24, 113.80, 119.42, 122.67, 128.52, 129.32, 131.55, 135.93, 142.52, 151.57, 158.51, 159.61, 185.92 (C=O); Found, %: C 68.51; H 4.28; N 9.93. C16H12N2O3. Calculated, %: C, 68.56; H, 4.32; N, 9.99; LCMS: 281.2 [M+H]+.

3.2 Synthesis of 3-(2-Hydroxy-4-(prop-2-yn-1-yloxy)phenyl)-1-phenyl-1H-pyrazole-4-carbal deyde (3)

To a stirred solution of 3-(2,4-dihydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2) (400 mg, 1.44 mmol) in dry acetone (20 mL) K2CO3 (3.142 mmol) and propargyl bromide (80% in toluene) (1.785 mmol) were added at room temperature. The reaction mixture was refluxed at 60 °C for 6 h and the progress of the reaction was monitored by TLC (EtOAc/hexane, 1:3 v/v). After completion of the reaction, acetone was distilled from the reaction mixture to get crude. Then 25 mL of ice cold water was added to the residue, the solid separated, filtered and washed with excess of water and dried under high vacuum to afford 3-(2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3) as Off white solid; Yield = 80%; mp 118–120 °C; IR (ν cm−1) = 3263 (C≡C–H), 3119 (Ar–OH), 2117 (C≡C), 1687 (Pyrazole C=O); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 2.56 (1H, s, C≡C–H), 4.75 (2H, s, O–CH2), 6.66–6.72 (2H, m, Ar H), 7.42–7.96 (1H, m, Ar H), 7.53–7.57 (2H, m, Ar H), 7.71–7.73 (2H, m, Ar H), 8.02 (1H, d, J = 8.53 Hz, Ar H), 8.56 (1H, s, Pyrazole-H), 10.16 (1H, s, CHO), 10.41 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 55.85 (O–CH2), 75.86 (C≡C), 78.18 (C≡C), 103.10, 107.23, 119.41, 122.80, 128.40, 129.93, 130.80, 133.15, 138.16, 152.57, 157.82, 159.90, 183.96 (Pyrazole CHO); Found, %: C 71.75; H 4.38; N 8.76. C19H14N2O3. Calculated, %: C, 71.69; H, 4.43; N, 8.80; LCMS: 318.9 [M+H]+, 300.9.

3.3 Synthesis of 3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (7)

To a stirred solution of 3-(2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl)-1-phenyl-1H-pyrazole-4-carb aldehyde (3) (360 mg, 1.13 mmol) in DMF benzyl azide (1.35 mmol), triethylamine (1.35 mmol) and CuI (0.15 mmol) were added at room temperature. The reaction mixture was stirred for 2 h at room temperature and the progress of the reaction was monitored by TLC (EtOAc/hexane, 1:3 v/v). The reaction mixture filtered through Celite pad and the filtrate was evaporated under reduced pressure to afford crude, which was dissolved in ethyl acetate, washed with saturated brine solution and dried over Na2SO4 filtered and concentrated under reduced pressure to obtained crude, which was purified by (60;120 silica gel) column chromatography eluting with ethyl acetate and n-hexane to afford 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (7). Off white solid; Yield =55%; mp = 155–156 °C; IR (ν cm−1) = 3134 (Ar–OH), 2884 (Ar–H), 1663 (Pyrazole C=O), 1577 (C=N), 1509 (N=N) and 1281 (C–O–C); 1HNMR: (400 MHz, DMSO d6) δ (ppm) = 5.15 (2H, s, N–CH2), 5.63 (2H, s, O–CH2), 6.62 (1H, s, Ar H), 6.65 (1H, d, J = 8.53 Hz, Ar H), 7.33–7.42 (7H, m, Ar H), 7.47 (1H, d, J = 8.53 Hz, Ar H), 7.53–7.57 (2H, m, triazole-H and Ar H), 7.96–7.98 (2H, m, Ar H), 8.32 (1H, s, Pyrazole-H), 9.16 (1H, s Pyrazole CHO), 9.78 (1H, s, Ar OH); 13CNMR: (100 MHz, DMSO d6) δ (ppm) = 52.83 (N–CH2), 61.07 (O–CH2), 102.35, 105.95, 111.43, 119.08, 122.67, 124.69, 127.40, 127.92, 128.13, 128.74, 129.61, 130.89, 131.55, 135.95, 138.68, 142.86, 151.57, 156.17, 159.90, 185.92 (C=O); Found, %: C 69.22; H, 4.64; N, 15.46. C26H21N5O3: Calculated, %: C, 69.17; H, 4.69. N, 15.51; LCMS: 491.1, 452.1 [M+H]+, 434.1.

3.4 Synthesis of 1-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)ethanone (5)

To a stirred solution of 1-(2-hydroxy-4-(prop-2-yn-1-yloxy)phenyl)ethanone (4) (1.0 g, 5.26 mmol), benzylazide (5.26 mmol), triethylamine (6.31 mmol) and CuI (0.52 mmol) were added at room temperature. The reaction mixture was stirred for 2 h at room temperature and the progress of the reaction was monitored by TLC (EtOAc/hexane, 1:3 v/v). The reaction mixture filtered through Celite pad and the filtrate was evaporated under reduced pressure to afford crude, which was dissolved in ethyl acetate, washed with saturated brine solution and dried over Na2SO4 filtered and concentrated under reduced pressure to obtained crude, which was purified by (60;120 silica gel) column chromatography eluting with ethyl acetate and n-hexane to afford 1-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl) ethanone (5). Off white solid; Yield =85%; mp 130–132 °C; IR (ν cm−1) = 3283 (Ar–OH), 2942 (Ar H), 1697 (C=O), 1498 (N=N), 1246 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 2.55 (3H, s acetyl CH3), 5.19 (2H, s, N–CH2), 5.54 (2H, s, O–CH2), 6.48 (1H, s, Ar H), 6.50 (2H, dd, J = 7.02 Hz, CH2), 7.27–7.29 (2H, m, Ar H), 7.37–7.39 (3H, m, Ar H), 7.50 (1H, s, triazole H), 7.63 (1H, d, J = 9.53 Hz, Ar H), 12.71 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 26.19, 54.25 (N–CH2), 62.04 (O–CH2), 101.01, 107.64, 114.27, 122.76, 128.70, 128.83, 129.13, 132.40, 134.28, 143.42, 164.51, 165.00, 202.61 (C=O); Found, %: C 66.94; H 5.20; N 12.07. C18H17N3O3: Calculated, %: C 66.86; H 5.30; N 13.00; LCMS: 365.0, 323.9 [M+H]+.

3.5 Synthesis of (5-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-(1-(2-phenylhydrazono)ethyl) phenol (6)

1-(4-((1-Benzyl-1H-1, 2, 3-triazol-5-yl) methoxy)-2-hydroxy phenyl) ethanone (5) (1.44 g, 4.45 mmol) in 15 mL of ethanol was added to Phenyl hydrazine (5.34 mmol) at room temperature and the reaction mixture was refluxed for 2 h. After completion of the reaction (as indicated by TLC; EtOAc/hexane, 1:1 v/v), the mixture was cooled to room temperature. The solid obtained was filtered and washed with ethanol followed by n-pentane and dried under high vacuum to afford pure off white solid of (5-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-(1-(2-phenyl hydrazono)ethyl) phenol (6). Off white solid; Yield = 92%; mp 140–142 °C; IR (ν cm−1) = 3226 (NH), 3160 (Ar–OH), 2942(Ar H), 1635 (C=N), 1501 (N=N) and 1247 (C–O–C); 1HNMR: (400 MHz, DMSO d6) δ (ppm) = 2.35 (3H, s, acetyl CH3), 5.14 (2H, s, N–CH2), 5.62 (2H, s, O–CH2), 6.55–6.56 (2H, m, Ar H), 6.80–6.82 (1H, d, J = 7.28 Hz, Ar H), 7.01–7.03 (2H, m, Ar H), 7.25–7.48 (7H, m, Ar H), 7.47 (1H, d, J = 9.53 Hz, Ar H), 8.30 (1H, s, Pyrazole-H), 9.39 (1H, s, NH), 13.16 (1H, s, Ar–OH); 13CNMR: (100 MHz, DMSO d6) δ (ppm) = 13.08, 52.80 (N–C), 61.05 (O–C), 102.25, 105.90, 112.29, 113.92, 119.44, 124.64, 127.91, 128.12, 128.32, 128.72, 129.23, 135.93, 142.81, 145.09, 148.40, 158.90, 159.12; Found, %: C 69.78; H 5.58; N 16.90. C24H23N5O2: Calculated, %: C 69.72; H 5.61; N 16.94; LCMS: 455.0, 414.1 [M+H]+, 365.0, 323.9.

3.6 Synthesis of 3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (7)

A round-bottom flask was charged with 5 mL of DMF and cooled to 0 °C, to which phosphoryl chloride (9.05 mmol) was added dropwise under stirring. The mixture was stirred for 15 min at 0 °C and a solution of phenyl hydrazone (1.7 g, 4.11 mmol) (6) in 1 mL of DMF was added and further stirred for 30 min at 0 °C and for 30 min at room temperature. After completion of the reaction (monitored by TLC; EtOAc/hexane, 1:3 v/v), the mixture was poured into ice water. The solid separated on basification with aqueous NaHCO3 was filtered and washed with water followed by n-pentane to afford off white solid product of 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl) methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (7). Yield = 85%.

3.7 General Procedure for the Preparation of 1-[7-(1-Benzyl-1H-[1,2,3]triazol-4-ylmethoxy-2,2-dimethyl-chroman-6-yl]-3-aryl-propenones 8a–g

3.7.1 Conventional Heating Method

To a stirred solution of 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (7) (0.1 g, 0.22 mmol) in ethanol (10 mL), acetophenone (0.26 mmol) and pellets of KOH (0.55 mmol) were added. The reaction mixture was stirred for 12 h at room temperature. After completion of the reaction (monitored by TLC; EtOAc/hexane, 1:1 v/v), the mixture was poured into ice water and neutralized with 2 N HCl. The solid obtained was filtered and washed with water followed by n-pentane to afford pure pale yellow solid of 3-(3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl) methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one (8a) 0.09 g, Yield = 85%.

3.7.2 Microwave Irradiation Method

A mixture of 3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxy phenyl)-1-phenyl-1H-pyrazole-4-carb aldehyde (7) (0.1 g, 0.22 mmol) acetophenone (0.26 mmol) and powdered KOH (0.55 mmol) in ethanol (2.5 mL) was taken into a quartz tube and inserted into a screw-capped Teflon vial and then subjected to microwave irradiation (180 W) for 15 min. After completion of the reaction (monitored by TLC; EtOAc/hexane, 1:1 v/v), the mixture was poured into ice water and neutralized with 2 N HCl. The solid obtained was filtered and washed with water followed by n-pentane to afford pure pale yellow solid of 3-(3-(4-((1-benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one (8a). 0.11 g Yield = 91%.

3.8 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one (8a)

Pale yellow solid; mp 145–148 °C; IR (ν cm−1) = 3028 (Ar–OH), 2935(Ar H), 1740 (C=O), 1587 (C=N), 1449 (N=N) and 1218 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 5.22 (2H, s, N–CH2), 5.55 (2H, s O–CH2), 6.62 (1H, dd, J = 8.53 Hz, Ar–H), 6.71 (1H, d, J = 2.51 Hz, Ar H), 7.29–7.31 (2H, m, Ar H), 7.36–7.42 (5H, m, Ar H), 7.45 (1H, d, J = 6.02 Hz, olefinic Hα), 7.50–7.53 (5H, m, Ar H), 7.58 (1H, s, triazole-H), 7.71–7.73 (2H, m, Ar H), 7.96 (1H, d, J = 7.53 Hz, olefinic Hβ), 8.01–8.03 (2H, m, Ar H), 8.35 (1H, s, Pyrazole-H), 10.25 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 54.22 (N–CH2), 62.07 (O–CH2), 102.95, 107.07,109.99, 118.22, 118.97, 122.58, 122.63, 126.84, 127.53, 128.90, 128.35, 128.39, 128.62, 128.77, 129.11, 129.70, 132.82, 134.40, 135.07, 137.94, 138.52,144.27, 151.06, 157.34, 159.90, 189.89 (C=O); Found, %: C 73.71; H, 4.60; N, 15.41. C34H27N5O3: Calculated, %: C, 73.76; H, 4.92; N, 12.65; LCMS: 576.2, 554.3 [M+H]+, 383.1, 243.1.

3.9 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(p-tolyl)prop-2-en-1-one (8b)

Pale yellow solid; mp 150–152 °C; IR (ν cm−1) = 3132 (Ar–OH), 2951 (Ar–H), 2874 (Ar–CH3), 1687 (C=O), 1589 (C=N), 1450 (N=N), and 1254 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 2.44 (3H, s, CH3), 5.22 (2H, s, N–CH2), 5.55 (2H, s, O–CH2), 6.62 (1H, dd, J = 8.53 Hz, Ar H), 6.71 (1H, d, J = 2.51 Hz, Ar H), 7.30–7.57 (13H, m, Ar H and triazole-H), 7.72 (2H, d, J = 7.78 Hz, Ar H), 7.94–8.01 (3H, m, Ar H), 8.34 (1H, s, Pyrazole-H), 10.27 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 21.67, 54.26 (N–CH2), 62.13 (O–CH2), 102.96, 107.12, 110.05, 118.36, 119.03,122.62, 122.74, 126.81, 127.54, 128.13, 128.28, 128.57, 128.80, 129.14, 129.36, 129.74, 134.43, 134.63, 135.38, 138.61, 143.75, 144.33, 151.04, 157.37,159.90, 189.37 (C=O); Found, %: C 74.01; H, 5.12; N, 12.30. C35H29N5O3: Calculated, %: C, 74.06; H, 5.15; N, 12.34; LCMS: 606.3, 568.3 [M+H]+, 434.0.

3.10 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(4-methoxyphenyl)prop-2-en-1-one (8c)

Off white solid; mp 162–164 °C; IR (ν cm−1) = 3132 (Ar–OH), 1684 (C=O), 1610 (C=C), 1459 (N=N) and 1221 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 3.90 (3H, s, –OCH3), 5.22 (2H, s, N–CH2), 5.55 (2H, s, O–CH2), 6.62 (1H, d, J = 9.03 Hz, Ar H), 6.71 (1H, s Ar H) 6.97–7.00 (2H, m, Ar H), 7.29–7.77 (11H, m, Ar H and triazole-H), 7.96–8.04 (3H, m, Ar H), 7.99 (1H, m, Ar H), 8.32 (1H, s Pyrazole-H), 10.23 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 54.17 (N–CH2), 55.42 (O–CH3), 62.02 (O–CH2), 102.91, 106.98, 110.05, 113.81, 118.33, 118.86, 119.53, 122.41, 122.65, 126.78, 127.39, 128.05, 128.72, 129.07, 129.64, 129.68, 130.67, 130.76, 134.50, 134.07, 134.40, 138.50, 144.23, 150.86, 157.31, 159.86,163.47, 189.98 (C=O); Found, %:C 71.09; H 4.97; N 11.95. C35H29N5O4; Calculated, %: C 72.03; H 5.01; N 12.00; LCMS: 606.3, 584.12 [M+H]+.

3.11 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one (8d)

Off white solid; mp 158–160 °C; IR (ν cm−1) = 3124 (Ar–OH), 2933 (Ar H), 1629 (C=O), 1593 (C=C), 1508 (N=N) and 1265 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 3.97 (6H, s, 2CH3), 5.22 (2H, s, N–CH2), 5.55 (2H, s, O–CH2), 6.62 (1H, d, J = 8.53 Hz, Ar H), 6.71 (1H, s, Ar H), 6.93 (1H, d, J = 6.27 Hz, Ar H), 7.30–7.72 (15H, m, Ar H and triazole-H), 7.99 (1H, d, J = 14.81 Hz, =CH), 8.33 (1H, s Pyrazole-H), 10.25 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 52.76 (N–CH2), 55.48 (O–CH3), 55.69 (O–CH3), 61.05 (O–CH2), 102.25, 105.62, 110.47, 110.80, 112.28, 118.35, 119.28, 119.68, 122.63, 124.61, 126.70, 127.87, 128.06, 128.69, 129.59, 130.62, 131.71, 134.81, 135.92, 139.08, 142.85, 148.68, 151.28, 152.95, 156.19, 159.65, 186.95 (C=O); Found, %: C, 70.55; H, 5.04; N, 11.36. C36H31N5O5. Calculated, %: C, 70.46; H, 5.09; N, 11.41; LCMS: 636.2, 614.3 [M+H]+.

3.12 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(4-hydroxyphenyl)prop-2-en-1-one (8e)

Yellow solid; mp 138–140 °C; IR (ν cm−1) = 3134 (Ar–OH), 3024 (H Ar), 1739 (C=O), 1630 (C=C), 1573 (C=N), 1490 (N=N) and 1206 (C–O–C); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 5.23 (2H, s, N–CH2), 5.56 (2H, s, O–CH2), 6.66 (1H, dd, J = 8.53 Hz, Ar H), 6.71 (1H, d, J = 2.51 Hz, Ar H), 6.94 (1H, t, J = 15.09 Hz, Ar H), 7.04 (1H, d, J = 8.53 Hz, Ar H), 7.29–7.31 (2H, m, Ar H), 7.38–7.40 (4H, m, Ar H), 7.49–7.57 (6H, m, Ar H, and triazole-H), 7.73 (2H, m, Ar H), 7.88 (1H, dd, J = 8.53 Hz, Ar H), 8.10 (1H, d, J = 15.30 Hz, =CH), 8.38 (1H, s, Pyrazole-H), 10.12 (1H, s, Ar–OH); 12.86 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 54.29 (N–CH2), 62.17 (O–CH2), 103.13, 107.21, 109.96, 118.70, 118.85, 118.89, 119.11, 120.53, 122.67, 127.17, 127.73, 128.16, 128.84, 129.18, 129.46, 129.80, 134.46, 135.79, 136.40, 138.55, 144.33, 151.33, 157.42, 160.10, 163.65, 193.15 (C=O); Found, %: C, 71.63; H, 4.74; N, 12.26. C34H27N5O4: Calculated, %: C, 71.69; H, 4.78; N, 12.30. LCMS: 570.3 [M+H]+, 434.2, 324.7,156.0.

3.13 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(thiophen-2-yl)prop-2-en-1-one (8f)

Yellow solid; mp 142–144 °C; IR (ν cm−1) = 3025 (Ar–OH), 2930 (Ar H), 1679 (C=O); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 5.22 s (2H, N–CH2), 5.56 s (2H, O–CH2), 6.54–6.71 m (2H, Ar H), 7.11 s (1H, Ar H), 7.28–7.30 m (3H, Ar H), 7.38 m (4H, Ar H), 7.52–7.61 m (5H, Ar H), 7.71–7.76 m (3H, Ar H and triazole-H), 7.84 (1H, dd, J = 8.53 Hz, Ar H), 8.04 (1H, d, J = 15.30 Hz, =CH), 8.35 (1H, s, Pyrazole-H), 10.23 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 54.25 (N–CH2), 62.13 (O–CH2), 103.00, 107.15,110.00, 118.65, 119.05, 122.32, 122.63, 127.58, 128.12, 128.27, 128.80, 129.14, 129.47, 129.74, 131.67, 133.88, 134.13, 134.34, 134.43,138.57,144.31, 145.31, 151.10, 157.36, 159.96, 191.56 (C=O); Found, %: C 68.64; H 4.47; N 12.49; S 5.70. C32H25N5O3S: Calculated, %: C 68.68; H 4.50; N 12.51; S 5.73; Mass: 560.01 [M+H]+, 434.0.

3.14 3-(3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(naphthalen-2-yl)prop-2-en-1-one (8g)

Pale yellow solid; mp 155–157 °C; IR (ν cm−1) = 3028 (Ar–OH), 2935(Ar H), 1689 (C=O); 1HNMR: (400 MHz, CDCl3) δ (ppm) = 5.20 (2H, s, N–CH2), 5.54 (2H, s, O–CH2), 6.57 (1H, dd, J = 8.78 Hz, Ar H), 6.70 (1H, d, J = 2.51 Hz, Ar H), 7.18 (1H, dd, J = 8.78 Hz, =CH), 7.28–7.29 (3H, m, Ar H), 7.36–7.38 (5H, m, Ar H), 7.48–7.55 (5H, m, Ar H), 7.66–7.70 (5H, m, Ar H and triazole-H), 7.79 (1H, d, J = 7.78 Hz, =CH), 8.01 (1H, d, J = 8.78 Hz, Ar H), 8.17 (1H, s, Ar H), 8.17 (1H, s, Pyrazole-H), 10.72 (1H, s, Ar–OH); 13CNMR: (100 MHz, CDCl3) δ (ppm) = 54.28 (N–CH2), 62.17 (O–CH2), 103.05, 107.17,110.08, 118.38, 119.08, 122.65, 122.74, 124.43, 126.86, 126.94, 127.60, 127.87, 128.16, 128.46, 128.65, 128.83, 129.48, 129.78, 129.92, 132.57, 134.47, 135.04, 135.36, 135.53, 138.63, 144.36, 151.15, 157.43, 159.98, 189.70 (C = O); Found, %: C, 75.58; H, 4.80; N, 11.56. C38H29N5O3: Calculated, %: C, 75.61; H, 4.84; N, 11.60; O, 7.95; LCMS: 604.4 [M+H]+, 626.5.

4 Conclusion

3-(4-((1-Benzyl-1H-1,2,3-triazol-5-yl)methoxy)-2-hydroxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 7 were synthesized in two synthetic routes from 2,4-dihydroxyacetophenone which was used for synthesis of new series of triazole conjugated pyrazole chalcones from various acetophenones in the presence of potassium hydroxide under microwave irradiation and conventional methods.

Notes

Acknowledgements

The authors are thankful to Jawaharlal Nehru Technological University Hyderabad for providing laboratory facilities and CFRD, Osmania University, Hyderabad for analytical facilities.

Supplementary material

42250_2019_103_MOESM1_ESM.doc (7.5 mb)
Supplementary material 1 (DOC 7696 kb)

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Copyright information

© The Tunisian Chemical Society and Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of ChemistryJawaharlal Nehru Technological University HyderabadHyderabadIndia
  2. 2.Department of ChemistryOsmania UniversityHyderabadIndia

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