Synthesis and antimicrobial activities of new mono and bisphenyl linked bispyrazole and bispyrazolone derivatives

Hemal B. Mehta; Priyank K. Patel; Bharat C. Dixit; Ritu B. Dixit

doi:10.1016/j.arabjc.2013.07.019

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Original article

10 (

2_suppl

); S1901-S1912

doi:

10.1016/j.arabjc.2013.07.019

Synthesis and antimicrobial activities of new mono and bisphenyl linked bispyrazole and bispyrazolone derivatives

Hemal B. Mehta^{^a}, Priyank K. Patel^{^a}, Bharat C. Dixit^{^b}, Ritu B. Dixit^{^a,⁎}

a Ashok and Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences, New Vallabh Vidyanagar 388121, Gujarat, India

b Chemistry Departments, V. P. and R. P. T. P Science College, Affiliated to Sardar Patel University, Vallabh Vidyanagar 388120, Gujarat, India

⁎Corresponding author. ritsdixit@yahoo.co.in (Ritu B. Dixit)

Received: 2012-1-24, Accepted: 2013-7-17, Published: 2013-05-01

Disclaimer:
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.

Peer review under responsibility of King Saud University.

Abstract

The entitled bispyrazole and bispyrazolone compounds (4a–4t) were synthesized in good yield using a simplified experimental procedure under both conventional and microwave heating from easily available starting materials. The structure of synthesized bispyrazole and bispyrazolone compounds (4a–4t) was established with the help of physico-chemical analysis and various spectroscopic techniques like FT-IR, Mass, ¹H NMR and ¹³C NMR. The results of analyses are in good agreement with the proposed structure of all the synthesized compounds. Further, all the synthesized compounds were evaluated for their antimicrobial (antibacterial and antifungal) activities using various species like Bacillus subtilis, Escherichia coli, Aspergillous niger and Aspergillous flavus by using the agar cup method. The results of antimicrobial screening showed that compounds have mild to moderate activity. However, compounds 4g and 4h have shown good activity among all the tested compounds.

Keywords

Bispyrazole

Bispyrazolone

Antimicrobial activities

Microwave

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1 Introduction

Pyrazole and pyrazolone derivatives are important synthons and reagents in organic synthesis and have found applications with numerous pharmacological activities, like analgesic, anti-inflammatory, antipyretic, antidiabetic, antibacterial, antiarrhythmic, tranquilizer, muscle relaxant, psychoanaleptic, anticonvulsant, monoamine epoxidase inhibitor, antianxiety etc. (Badawey and Ashmawey, 1998; Geronikaki et al., 2004; Gürsoy et al., 2000; Haddad et al., 2004; Kees et al., 1996; Tanitame et al., 2004 ). Further, pyrazoles and pyrazolones have been found to be useful in agrochemicals, dyestuffs and with other diversified applications (Elmorsi and Hassanein, 1999; Foulds, 1998; Ito et al., 2001; Kepe et al., 1998; Yang et al., 2000 ).

To date, there are many reports available describing the synthesis of pyrazole and pyrazolone derivatives (Batten and Robson, 1998; Liu et al., 2004; Majumder et al., 2009; Uzoukwu et al., 1998; Zhang et al., 2010; Zheng et al., 2009, 2010 ). However, there are only few reports on the synthesis of bispyrazole and bispyrazolone derivatives (Deb et al., 2009; Mabkhoot, 2009; Niknam et al., 2010; Tewari et al., 2010; Veettil and Haridas, 2009 ).

In recent years, the application of microwave assisted reactions in organic synthesis has received considerable attention. Compared to conventional heating, microwave irradiation often gives enhanced reaction rates and decreases the formation of byproducts (Alvarez et al., 2006; Dos Santos et al., 2004; Marquez et al., 2006 ). Microwave irradiation has been used for many organic reactions such as pericyclic (Srikrishna and Nagaraju, 1992), cyclization (Rama Rao et al., 1992), aromatic substitution (Laurent et al., 1994), oxidation (Gedye et al., 1986), alkylation (Yulin and Yuncheng, 1994), decarboxylation (Jones and Chapman, 1993), radical reactions (Bose et al., 1991), condensation (Sharma et al., 2011), and peptide synthesis (Yu et al., 1992).

Perusal of the above literature survey reveals that among the available reports, there are no reports in which two pyrazole or pyrazolone moieties are linked by mono and bisphenyl linkage in a single molecular framework. Therefore, we have been prompted for the synthesis of new bispyrazole and bispyrazolone derivatives based on aromatic diamines under conventional as well as microwave heating conditions. All the synthesized compounds were checked for their biological (antibacterial and antifungal) activities.

2 Results and discussion

2.1

2.1 Chemistry

The simpler and easily available diphenylic diamines [diaminodiphenyl sulphon–DAPSON (1a), diaminodiphenyl ether–DDE (1b) and diaminodiphenyl methane–DDM (1c)] were preferred as precursors, and were first tetra azotized and then coupled with 1,3-diones (acetyl acetone (2a)/methyl acetoacetate (2b)) to form hydrazono compounds (3a–3f), which upon cyclization with hydrazine derivatives (hydrazine hydrate and phenyl hydrazine) under conventional and microwave heating condition, produced entitled diphenylic bispyrazole (4a–4f) and bispyrazolone (4g–4l) derivatives respectively in quantitative yield, as shown in Scheme 1.

Proposed synthetic route for the synthesis of entitled compounds 4a–4l. Reagents and conditions: (i) Tetraazotization-NaNO2, H2SO4, 0–5 °C; (iia) Coupling-Acetylacetone, 0–5 °C; (iib) Coupling–Methyl acetoacetate, 0–5 °C; (iiia) Cyclization-hydrazine hydrate, EtOH, MW or Δ; (iiib) Cyclization-phenyl hydrazine, AcOH, MW or Δ; (iiic) Cyclization-hydrazine hydrate, EtOH, MW or Δ; (iiid) Cyclization-phenyl hydrazine, AcOH, MW or Δ.

However, experimentation with monophenylic diamines (1,3- or 1,4- phenylene diamine), results in complex reaction mass upon tetra azotization and the results were not reproducible in our hands. Therefore, we have attempted another path to synthesize monophenylic derivatives (4m–4t); for that, the nitro derivatives of aniline [m-nitroaniline (1d) and p-nitroaniline (1e)] were first diazotized and coupled with 2a and 2b to produce hydrazono compounds (3m, 3n and 3q, 3r), which were further cyclized likewise to form mono phenylic linked pyrazole (5m–5p) and pyrazolone (5q–5t) derivatives. The nitro functionality in 5m–5t was reduced using sodium polysulphide to produce corresponding amines (6m–6p and 6q–6t), which were again diazotized and coupled with 2a and 2b, and further cyclized under both conventional and microwave heating yielding entitled mono phenylic linked bispyrazole or bispyrazolone compounds (4m–4p and 4q–4t). The synthetic path is given in Scheme 2.

Proposed synthetic route for the synthesis of entitled compounds 4m–4t. (ia) Diazotization-NaNO2, H2SO4, 0–5 °C & Coupling-Acetylacetone, 0–5 °C; (ib) Diazotization-NaNO2, H2SO4, 0–5 °C & Coupling-Methyl acetoacetate, 0–5 °C; (iia) Cyclization-hydrazine hydrate, EtOH, MW or Δ/Cyclization-phenyl hydrazine, AcOH, MW or Δ; (iiia)=(iiib)=(iiic) Sodium polysulphide, 30 min, 60 °C; (iva) Diazotization-NaNO2, H2SO4, 0–5 °C & Coupling-Acetylacetone, 0–5 °C; (ivb) Diazotization-NaNO2, H2SO4, 0–5 °C & Coupling-Methyl acetoacetate, 0–5 °C; (va) Cyclization-hydrazine hydrate, EtOH, MW or Δ; (vb) Cyclization-phenyl hydrazine, AcOH, MW or Δ; (vc) Cyclization-hydrazine hydrate, EtOH, MW or Δ/Cyclization-phenyl hydrazine, AcOH, MW or Δ.

All the hydrazono derivatives (3a–3f, 3m, 3n, 3q, 3r and 7m–7t) were also cyclized using microwave heating to obtain pyrazole and pyrazolone derivatives. Comparison of both conventional and microwave synthetic methods has been included in Table 1, which indicates an increase in yields and lowering of reaction time by following microwave heating.

Table 1 Comparison of time consumed and yield obtained under conventional and microwave heating.

Sr. no.	Substitution		Conventional heating		Microwave heating
Sr. no.	R/phenyl	R₁	Time (h)	Yield (%)	Time (min.)	Yield (%)	Power (watt)
4a	SO₂	H	2.5	83	12	89	210
4b	SO₂	Ph	5	79	23	84	490
4c	O	H	3	70	13	83	210
4d	O	Ph	5.5	78	26	79	490
4e	CH₂	H	3	68	15	77	245
4f	CH₂	Ph	6	66	28	80	490
4g	SO₂	H	2	55	12	63	210
4h	SO₂	Ph	4	48	20	59	490
4i	O	H	2.5	46	13	60	210
4j	O	Ph	4.5	42	22	58	560
4 k	CH₂	H	3	73	14	83	210
4 l	CH₂	Ph	5	64	24	85	490
4 m	m–Substituted phenyl ring	H	3	75	12	81	245
4n	m–Substituted phenyl ring	Ph	6	68	26	77	490
4o	p–Substituted phenyl ring	H	3.5	72	15	80	245
4p	p–Substituted phenyl ring	Ph	6.5	62	26	73	560
4q	m–Substituted phenyl ring	H	2	47	14	64	210
4r	m–Substituted phenyl ring	Ph	5	44	23	49	560
4s	p–Substituted phenyl ring	H	2.5	49	13	59	245
4t	p–Substituted phenyl ring	Ph	6	39	22	48	560

The decomposition temperatures of all the synthesized compounds 4a–4t, 5m–5t, 6m–6t and 7m–7t are ranging from 180–235, 210–280, 195–235, 190–290 °C respectively, were checked with the help of a digital melting point apparatus and were uncorrected. All the compounds have characteristic color from yellow to reddish brown shade. The structure of the synthesized compounds was confirmed by using various characterization techniques like elemental analysis, infrared (FT-IR), mass and nuclear magnetic resonance (¹H NMR and ¹³C NMR) spectroscopy. The elemental and mass spectroscopic analysis for all the synthesized compounds showed that, calculated and observed values are in good agreement with each other.

FT-IR spectra for all the synthesized compounds showed the important IR bands at appropriate frequencies as expected (Pavia et al., 2008). The IR spectra of all nitro pyrazole/pyrazolone (5m–5t), amino pyrazole/pyrazolone (6m–6t), hydrazones (3a–3f, 3m, 3n, 3q, 3r, 7m–7t) and bispyrazole or bispyrazolone compounds (4a–4t) showed that they resemble each other in their general shape, though certain characteristic differences have been observed. In case of nitro compounds (5m–5t) it showed characteristic band ranging from 1520 to 1550 cm⁻¹ due to the presence of the NO₂ group that disappears after reduction (6m–6t). One of the significant differences to be expected between the IR spectrum of the hydrazono and bispyrazole compounds (4a–4f, 4m–4p) is that in case of hydrazono compound there is presence of more bands in the region of 1706–1788 cm⁻¹ due to the presence of the C⚌O group that disappears after formation of the pyrazole ring. However, in case of bispyrazolone these bands persist even after formation of the pyrazolone ring but in decreased amount. This is also explained by the fact that the band of C⚌N stretching vibration of pyrazole and pyrazolone rings appeared at lower frequency around 1450 cm⁻¹ in the IR spectrum of hydrazono compounds. Further, weak bands at 980, 780 and 660 cm⁻¹ are corresponding to the presence of the phenyl ring. Thus, all of these characteristic features of the FT-IR studies supported the formation of pyrazole and pyrazolone ring containing compounds. In the, ¹H NMR spectra of intermediates (5m–5t), (6m–6t) and (7m–7t), signals for aliphatic protons of the methyl (CH₃) group in pyrazole or pyrazolone ring system appeared as singlets between δ 2.21 and 4.20 ppm. In case of hydrogens of primary amines (6m–6t), they signalled from δ 6.12 to 6.42 ppm as a singlet. Protons of hydrazono group(s) of compounds 5m, 5o, 5q–5t, 6m, 6o, 6q–6t and 7m–7t appeared as singlets in down field region from δ 9.62 to 10.68 ppm; but in pyrazolone compounds proton attached to the nitrogen of the pyrazolone ring appeared as broad singlet in most down field range from δ 11.69 to 11.86 ppm. Whereas in entitled compounds 4a–4t, three protons of the methyl (CH₃) group of pyrazole or pyrazolone ring system gave signals between δ 2.24 and 2.70 ppm and appeared as a singlet. In addition the signal appeared at little lower field attributed to two protons of methylene (Ar–CH₂–Ar) group present in 4e, 4f, 4k and 4l, and appeared at around δ 3.80 ppm. Aromatic protons of all the compounds resonated in the region of δ 6.73–7.98 ppm. Further, comparison of signals of equivalent aromatic protons in compounds containing sulphone and ether linkage (4a, 4b, 4g, 4h and 4c, 4d, 4i, 4j) appeared at higher δ values to those of methylene linkage (4e, 4f, 4k and 4l). Signals due to protons of hydrazono group(s) appeared as singlet in down field region around δ 10 ppm. In the case of bispyrazolone compounds (4g, 4i, 4k, 4q and 4s) signals due to protons of two hydrazono linkages are distinguished as; among these two protons attached to the nitrogen of the pyrazolone ring appeared as slightly broadened singlet in most down field region at around δ 12.95 ppm, and protons of hydrazono group(s) gave singlet in a higher field region around δ 9.95 ppm.

¹³C NMR spectra of all the synthesized intermediates and entitled compounds were also consistent with the proposed structure. Likewise all the compounds also have specific signals for aliphatic carbons attached to carbon between δ 11.1–27.5 ppm, and δ 41–50.5 ppm for the aliphatic carbons attached to one or more heteroatom or the aromatic ring. For aromatic carbons of ring, it is between δ 116.8 and 137.4 ppm and aromatic carbon attached with heteroatom ranging between δ 142.3 and 161.8 ppm, especially carbons of conjugated ketone group gave signals around δ 198 ppm.

2.2

2.2 Antibacterial and antifungal activity

All the synthesized entitled compounds (4a–4t) were also subjected for their antimicrobial (antibacterial and antifungal) activities against different bacterial species (Bacillus subtilis and Escherichia coli) and fungal spores (Aspergillou niger and Aspergillous flavus) using the agar-cup method (Cruickshank et al., 1975; Jagani et al., 2011) at a concentration of 200 μg/mL. The benzylpenicillin and imidil were used as standard drugs and solvent DMSO was used as control. The results of the measured zone of inhibition in mm for all synthesized compounds are summarized in Table 2.

Table 2 Antimicrobial activity of synthesized compounds (4a–4t).

Compound code	Zone of Inhibition (mm)
	Bacteria		Fungi
	B. subtilis	E. coli	A. niger	A. flavus
4a	23	25	24	20
4b	21	24	20	19
4c	19	20	22	18
4d	18	17	19	17
4e	16	18	18	15
4f	15	16	17	15
4g	24	27	23	21
4h	24	26	24	19
4i	20	20	21	19
4j	19	19	20	19
4k	18	19	18	18
4l	16	18	19	17
4m	13	12	12	11
4n	12	12	11	11
4o	13	14	12	13
4p	12	13	13	14
4q	15	15	13	14
4r	14	15	12	13
4s	15	15	14	13
4t	14	14	13	15
Control (DMSO)	10	10	10	10
Benzylpenicillin	25	28	–	–
Imidil	–	–	27	22

2.2.1

2.2.1 Structural activity relationship (SAR)

Among all the compounds, 4n is the least active against microorganisms. By comparing it with 4p compound 4n is different by the meta substituted form instead of para substituted form. Replacement of meta phenylene system by para shows that there is no markable increase in the activity of compound. By comparing 4n with 4f, results showed that; replacement of meta phenylene system by the 4,4′-diphenylene methane group gives little bit increased activity. Now, if we compare 4n with 4d the structural difference is only at meta phenylene linkage by 4,4′-oxydiphenylene functionality, it showed an increase in activity. Although, replacement of meta phenylene system by the 4,4′-sulphonyldiphenylene (4b) group showed highest activity among all similar structures. Therefore, it was concluded that incorporation of DAPSON core in basic structure of bispyrazole and bispyrazolone scaffold resulted to increase the activity up to a higher extent.

Further, if replacements have been made from 4n and related structures 4b, 4d, 4f, 4p at the 3,5-dimethyl-1-phenylpyrazole ring by removing the phenyl ring attached to nitrogen, their respective analogous 4m, 4a, 4c, 4e and 4o respectively showed a slight increased activity. Therefore, it was concluded that elimination of the phenyl ring from the entitled compounds resulted for their better activity.

If replacement have been made at 3,5-dimethyl-1H-pyrazole (4a, 4c, 4e, 4m and 4o) or 3,5-dimethyl-1-phenylpyrazole (4b, 4d, 4f, 4n and 4p) rings in respective compounds by 3-methyl-1H-pyrazol-5(4H)-one (4g, 4i, 4k, 4q and 4s) and 3-methyl-1-phenyl-pyrazol-5(4H)-one (4h, 4j, 4l, 4r, 4t) ring systems, there was also a slight raise spotted in activity with similar compounds. It showed that the pyrazole ring with ketone substitution in place of methyl served improved activity.

Among all the screened compounds 4a, 4g, 4h show good activity, compound 4b, 4c, 4i, 4j show moderate activity and rest of compounds show less activity.

3 Experimental

The progress of the reaction was monitored by TLC plates on aluminium sheets coated with silica gel 60 F₂₅₄ (Meark) using hexane:ethyl acetate:methanol (8:5:2) mixture as mobile phase and by viewing the spot under UV light. Decomposition point (uncorrected) for all the synthesized compounds was assessed using a digital melting point apparatus. Elemental analysis for each compound was carried out with the help of CARLO ERBA-1108 elemental analyser. Mass spectral analysis was carried out using Thermo fisher Scientific, MS-LCQ Fleet instrument. FT-IR spectra were recorded in KBr pellets on Shimadzu 8400 s spectrometer in the range of frequency 400–4000 cm⁻¹. NMR spectra were recorded on Bruker 400 MHz instrument using DMSO-d₆ both as a solvent and internal standard. Microwave experiments were carried out at atmospheric pressure in a glass vessel equipped with a reflux condenser, using a scientific microwave reactor (700 W Catalyst™ Systems, Model: Cata-R).

3.1

3.1 Experimental procedure for the synthesis of entitled compounds (4a–4l)

3.1.1

3.1.1 General procedure for the synthesis of diphenylic bishydrazono compounds (3a–3f)

Compounds 3a–3c were prepared by the method reported in the literature (Furniss et al., 2004; Saleh et al., 2003). Accordingly, to the dispersion of DAPSON (1a) or DDE (1b) or DDM (1c) (0.0201 mol) in the conc. sulphuric acid (0.1450 mol) in 250 mL beaker, 20 mL sodium nitrite (0.0443 mol) was added over a period of 30 min. in the ice bath by maintaining temperature below 5 °C. Then, the obtained tetra azonium salt solution was coupled immediately with the solution of acetyl acetone (2a) (0.0443 mol) or methyl acetoacetate (2b) (0.0443 mol) dissolved in 15 mL methanol, and added slowly during 20 min. below 5 °C temperature. The reddish brown product (3a–3f) obtained was filtered, washed with water, dried in air and recrystallized using acetone.

3.1.2

3.1.2 General procedure for the synthesis of diphenylic bispyrazole or bispyrazolone compounds (4a–4l)

According to the method reported in the literature (Furniss et al., 2004), in 50 mL round bottomed flask 3a or 3b or 3c (0.004250 mol) in 20 mL of ethanol was reacted with hydrazine hydrate (0.0089 mol) in 15 mL of ethanol or phenyl hydrazine (0.0089 mol) in 20 mL CH₃COOH. The reaction mixture was then allowed to reflux for 2 h or 6 h respectively with continuous stirring. After refluxing, it was allowed to cool to room temperature. The yellowish product obtained, was filtered and recrystallized using acetone.

3.1.2.1

3.1.2.1 4,4′–(2,2′–(4,4′–Sulphonylbis(4,1–phenylene))bis(hydrazin–2–yl–1–ylidene))bis(3,5–dimethyl–4H–pyrazole) (4a)

Yield: 1.58 g (83%). Decomposition temperature 194 °C. IR (KBr) ν max/cm^–1: 1325 (S⚌O Str.), 1535 (N⚌C Str.), 3078 (C–H Str.), 3467 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.65 (s, 12H, –CH₃), 7.85–8.10 (m, 8H, –CH_aro), 9.95 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): 22.2, 119.1, 128.4, 136.2, 138.9, 148.7, 161.6. MS (ESI, 70 eV): m/z 463.1 [M+H]⁺. Anal. Calcd. for C₂₂H₂₂N₈O₂S: C, 57.13; H, 4.79; N, 24.23; S, 6.93%. Found: C, 57.31; H, 4.47; N, 24.48; S, 7.07%.

3.1.2.2

3.1.2.2 4,4′-Sulphonylbis(4,1–phenylene)bis(diazene–2,1–diyl)bis(3,5–dimethyl–1–phenyl–1H–pyrazole) (4b)

Yield: 1.58 g (79%). Decomposition temperature 184 °C. IR (KBr) ν max/cm^–1: 1339 (S⚌O Str.), 1588 (C⚌N Str.), 3166 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.32 (s, 6H,–CH₃), 2.68 (s, 6H, –CH₃), 7.42–7.56 (m, 10H, –CH_aro), 7.70 (d, 4H, J = 7.6 Hz, –CH_aro), 7.93 (d, J = 7.6 4H, Hz, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.2, 13.1, 108.4, 125.3, 126.7, 128.8, 129.6, 130.5, 134.4, 138.7, 140.5, 143.0, 149.9. MS (ESI, 70 eV): m/z 615.1 [M+H]⁺. Anal. Calcd. for C₃₄H₃₀N₈O₂S: C, 66.43; H, 4.92; N, 18.23%. Found: C, 66.21; H, 5.19; N, 18.47%.

3.1.2.3

3.1.2.3 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2-yl-1-lidene))bis(3,5-dimethyl-4H-pyrazole) (4c)

Yield: 1.4 g (70%). Decomposition temperature 165 °C. IR (KBr) ν max/cm^–1: 1173 (C–O Str.), 1521 (C⚌N Str.), 3208 (C–H Str.), 3452 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.68 (s, 12H, –CH₃), 6.49–7.46 (m, 8H, –CH), 9.92 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 22.0, 118.5, 124.7, 135.3, 138.8, 146.9, 161.5. MS (ESI, 70 eV): m/z 415.2 [M+H]⁺. Anal. Calcd. for C₂₂H₂₂N₈O: C, 63.75; H, 5.35; N, 27.04%. Found: C, 63.62; H, 5.25; N, 27.27%.

3.1.2.4

3.1.2.4 4,4′-Oxybis(4,1-phenylene)bis(diazene-2,1-diyl)bis(3,5-dimethyl-1-phenyl-1H-pyrazole) (4d)

Yield: 1.56 g (78%). Decomposition temperature 180 °C. IR (KBr) ν max/cm^–1: 1289 (C–O Str.), 1591 (C⚌N Str.), 2881 (C–H Str.), 3187 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.29 (s, 6H, –CH₃), 2.63 (s, 6H, –CH₃), 7.18 (d, J = 7.6 Hz, 4H, –CH_aro), 7.39–7.48 (m, 10H, –CH_aro), 7.62 (d, J = 7.6 Hz, 4H, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.3, 13.2, 108.7, 119.1, 122.6, 125.4, 126.9, 128.5, 129.8, 138.6, 140.2, 151.2, 158.0. MS (ESI, 70 eV): m/z 567.2 [M+H]⁺. Anal. Calcd. for C₃₄H₃₀N₈O: C, 72.07; H, 5.34; N, 19.77%. Found: C, 71.89; H, 5.58; N, 19.60%.

3.1.2.5

3.1.2.5 bis(4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)methane (4e)

Yield: 1.36 g (68%). Decomposition temperature 173 °C. IR (KBr) ν max/cm^–1: 1574 (C⚌N Str.), 2932 (C–H Str.), 3011 (C–H Str.), 3395 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.35 (s, 12H, –CH₃), 3.78 (s, 2H, –CH₂), 6.38–7.16 (m, 8H, –CH_aro), 9.95 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 22.3, 42.4, 118.3, 123.7, 134.6, 138.5, 148.7, 161.5. MS (ESI, 70 eV): m/z 413.2 [M+H]⁺. Anal. Calcd. for C₂₃H₂₄N₈: C, 66.97; H, 5.86; N, 27.17%. Found: C, 67.19; H, 5.64; N, 27.22%.

3.1.2.6

3.1.2.6 bis(4-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)methane (4f)

Yield: 1.32 g (66%). Decomposition temperature 199 °C IR (KBr) ν max/cm^–1: 1562 (C⚌N Str.), 2906 (C–H Str.), 3196 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.27 (s, 6H, –CH₃), 2.66 (s, 6H, –CH₃), 3.82 (s, 2H, –CH₂), 7.28 (d, J = 7.8 Hz, 4H, –CH_aro), 7.41–7.64 (m, 10H, –CH_aro), 7.82 (d, J = 7.8 Hz, 4H, –CH_aro). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.1, 13.2, 42.0, 108.5, 125.3, 125.9, 127.4, 129.8, 130.2, 131.6, 138.3, 140.4, 142.3, 150.2. MS (ESI, 70 eV): m/z 565.3 [M+H]⁺. Anal. Calcd. for C₃₅H₃₂N₈: C, 74.44; H, 5.71; N, 19.84%. Found: C, 73.69; H, 7.50; N, 19.69%.

3.1.2.7

3.1.2.7 4,4′-(2,2′-(4,4′-Sulphonylbis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4g)

Yield: 1.46 g (73%). Decomposition temperature 198 °C. IR (KBr) ν max/cm^–1: 1368 (S⚌O Str.), 1540 (C⚌N Str.), 1766 (C⚌O Str.), 2888 (C–H Str.), 3065 (C–H Str.), 3453 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.38 (s, 6H, –CH₃), 7.88–8.11 (m, 8H, –CH_aro), 9.51 (s, 2H, –NH), 12.99 (br. s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 17.6, 120.5, 127.2, 130.8, 132.8, 147.3, 150.1, 162.6. MS (ESI, 70 eV): m/z 467.1 [M+H]⁺. Anal. Calcd. for C₂₀H₁₈N₈O₄S: C, 51.50; H, 3.89; N, 24.02; S, 6.87%. Found: C, 51.72; H, 3.91; N, 23.88; S, 6.93%.

3.1.2.8

3.1.2.8 4,4′-(2,2′-(4,4′-Sulphonylbis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4h)

Yield: 1.28 g (64%). Decomposition temperature 205 °C. IR (KBr) ν max/cm^–1: 1315 (S⚌O Str.), 1593 (C⚌N Str.), 1740 (C⚌O Str.), 2931 (C–H Str.), 3173 (C–H Str.), 3440 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.39 (s, 6H, –CH₃), 7.37– 8.12 (m, 18H, –CH_aro), 9.36 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 13.4, 120.7, 121.9, 127.1, 128.8, 129.5, 130.2, 133.4, 139.7, 148.1, 148.9, 162.4. MS (ESI, 70 eV): m/z 619.1 [M+H]⁺. Anal. Calcd. for C₃₂H₂₆N₈O₄S: C, 62.12; H, 4.24; N, 18.11; S, 5.18%. Found: C, 62.46; H, 4.11; N, 18.23; S, 5.33%.

3.1.2.9

3.1.2.9 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2–yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4i)

Yield: 1.5 g (75%). Decomposition temperature 169 °C. IR (KBr) ν max/cm^–1: 1144 (C–O Str.), 1515 (C⚌N Str.), 1706 (C⚌O Str.), 2910 (C–H Str.), 3220 (C–H Str.), 3450 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.46 (s, 6H, –CH₃), 7.21–7.96 (m, 8H, –CH_aro), 9.52 (s, 2H, –NH), 12.95 (br. s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 17 .5, 115.4, 116.3, 125.4, 128.8, 144.2, 148.4, 162.6. MS (ESI, 70 eV): m/z 419.1 [M+H]⁺. Anal. Calcd. for C₂₀H₁₈N₈O₃: C, 57.41; H, 4.34; N, 26.78%. Found: C, 57.56; H, 4.72; N, 26.51%.

3.1.2.10

3.1.2.10 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4j)

Yield: 1.48 g (74%). Decomposition temperature 200 °C. IR (KBr) ν max/cm^–1: 1278 (C–O Str.), 1580 (C⚌N Str.), 1735 (C⚌O Str.), 2870 (C–H Str.), 3180 (C–H Str.), 3412 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.30 (s, 6H, –CH₃), 7.25–7.87 (m, 18H, –CH_aro), 9.31 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.7, 116.3, 116.7, 118.6, 124.9, 127.6, 128.7, 129.3, 139.7, 144.5, 147.3, 162.5. MS (ESI, 70 eV): m/z 571.2 [M+H]⁺. Anal. Calcd. for C₃₂H₂₆N₈O₃: C, 67.36; H, 4.59; N, 19.64%. Found: C, 67.58; H, 4.38; N, 19.59%.

3.1.2.11

3.1.2.11 4,4′-(2,2′-(4,4′-Methylenebis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4k)

Yield: 1.44 g (72%). Decomposition temperature 186 °C. IR (KBr) ν max/cm^–1: 1597 (C⚌N Str.), 1756 (C⚌O Str.), 3018 (C–H Str.), 3206 (C–H Str.), 3360 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.37 (s, 6H, –CH₃), 3.79 (s, 2H, –CH₂), 7.12–7.93 (m, 8H, –CH_aro), 9.50 (s, 2H, –NH), 12.92 (br. s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 12.1, 44.7, 115.9, 122.6, 129.3, 132.1, 141.7, 149.1, 161.5. MS (ESI, 70 eV): m/z 417.1 [M+H]⁺. Anal. Calcd. for C₂₁H₂₀N₈O₂: C, 60.57; H, 4.84; N, 26.91%. Found: C, 60.36; H, 5.02; N, 26.74%.

3.1.2.12

3.1.2.12 4,4′-(2,2′-(4,4′-Methylenebis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4l)

Yield: 1.24 g (62%). Decomposition temperature 177 °C. IR (KBr) ν max/cm^–1: 1556 (C⚌N Str.), 1745 (C⚌O Str.), 2954 (C–H Str.), 3231 (C–H Str.), 3410 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.41 (s, 6H, –CH₃), 3.81 (s, 2H, –CH₂), 7.2–7.85 (m, 18H, –CH_aro), 9.61 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.5, 44.2, 116.8, 118.5, 121.4, 127.3, 129.8, 130.2, 133.1, 142.7, 147.4, 161.2. MS (ESI, 70 eV): m/z 569.2 [M+H]⁺. Anal. Calcd. for C₃₃H₂₈N₈O₂: C, 69.70; H, 4.96; N, 19.71%. Found: C, 69.47; H, 5.12; N, 19.68%.

3.2

3.2 Experimental procedure for the synthesis of entitled compounds (4m–4t)

3.2.1

3.2.1 Monophenylic hydrazono derivatives (3m, 3n, 3q, 3r)

Compounds 3m, 3n or 3q, 3r were prepared from 3-nitroaniline (1d) or 4-nitroaniline (1e) using the method available in the literature (Furniss et al., 2004; Saleh et al., 2003). Accordingly, 1d or 1e (0.0362 mol) was dissolved in conc. sulphuric acid (0.1303 mol), and NaNO₂ (0.0398 mol) was dissolved in 30 mL water respectively. These two solutions were kept in ice bath for 10 min. below 5 °C and then NaNO₂ solution was added dropwise to the solution of 1d or 1e over a period of 20 min. with constant stirring, by maintaining same temperature. The diazonium salt of 1d or 1e generated was immediately used for coupling reaction with acetyl acetone or methyl acetoacetate (0.0398 mol). It was taken in methanol and was added dropwise to the solution of diazonium salt over a period of 20 min. with continuous stirring below 5 °C. Upon completion of the addition the reaction mass was allowed to come to room temperature with stirring. The product (3m, 3n or 3q, 3r) obtained was washed with water, dried and recrystallized using acetone.

3.2.2

3.2.2 Monophenylic pyrazole or pyrazolone derivatives (5m–5t)

According to the literature method (Furniss et al., 2004), compound 3m, 3n (0.0120 mol) was treated with the hydrazine hydrate (0.0132 mol) in 25 mL of ethanol and 3q, 3r (0.0120 mol) was treated with phenyl hydrazine (0.0132 mol) in 20 mL of CH₃COOH in a 100 mL round bottom flask and stirred well for 5 min. Further, it was refluxed for 3 h or 6 h respectively and finally allowed to obtain room temperature. The yellowish product (5m–5t) thus obtained was filtered and recrystallized using acetone.

3.2.2.1

3.2.2.1 3,5-Dimethyl-4-(2-(3-nitrophenyl)hydrazono)-4H-pyrazole (5m)

Yield: 6.37 g (71%). Decomposition temperature 234 °C. IR (KBr) ν max/cm^–1: 1488 (C⚌N Str.), 1520 (N⚌O Str.), 1742 (C⚌O Str.), 2916 (C–H Str.), 3144 (C–H Str.), 3428 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 3.29 (s, 6H, –CH₃), 7.42–7.62 (m, 4H, –CH_aro), 9.62 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 18.7, 108.4, 114.7, 118.9, 131.1, 135.3, 144.7, 150.1, 159.2. MS (ESI, 70 eV): m/z 246.3 [M+H]⁺. Anal. Calcd. for C₁₁H₁₁N₅O₂: C, 53.87; H, 4.52; N, 28.56%. Found: C, 53.84; H, 4.55; N, 28.60%.

3.2.2.2

3.2.2.2 3,5-Dimethyl-4-((3-nitrophenyl)diazenyl)-1-phenyl-1H-pyrazole (5n)

Yield: 7.03 g (60%). Decomposition temperature 247 °C. IR (KBr) ν max/cm^–1: 1472 (C⚌N Str.), 1533 (N⚌O Str.), 1757 (C⚌O Str.), 2925 (C–H Str.), 3101 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.27 (s, 3H, –CH₃), 2.66 (s, 3H, –CH₃), 7.64–7.98 (m, 9H, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 10.9, 13.1, 108.2, 123.8, 124.4, 125.5, 127.3, 128.7, 130.1, 131.9, 135.6, 138.2, 140.6, 144.8, 151.3. MS (ESI, 70 eV): m/z 322.1 [M+H]⁺. Anal. Calcd. for C₁₇H₁₅N₅O₂: C, 63.54; H, 4.71; N, 21.79%. Found: C, 63.32; H, 4.93; N, 21.61%.

3.2.2.3

3.2.2.3 3,5-Dimethyl-4-(2-(4-nitrophenyl)hydrazono)-4H-pyrazole (5o)

Yield: 6.15 g (69%). Decomposition temperature 210 °C. IR (KBr) ν max/cm^–1: 1493 (C⚌N Str.), 1512 (N⚌O Str.), 1752 (C⚌O Str.), 2911 (C–H Str.), 3155 (C–H Str.), 3474 (N–H Str.). ¹H–NMR (400 MHz, DMSO-d₆): δ 3.28 (s, 6H, –CH₃), 7.16 (d, J = 8.0 Hz, 2H, –CH_aro), 7.82 (d, J = 8.0 Hz, 2H, –CH_aro), 10.02 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 18.2, 112.5, 125.5, 135.3, 138.2, 147.7, 157.3. MS (ESI, 70 eV): m/z 246.1 [M+H]⁺. Anal. Calcd. for C₁₁H₁₁N₅O₂: C, 53.87; H, 4.52; N, 28.56%. Found: C, 53.90; H, 4.53; N, 28.60%.

3.2.2.4

3.2.2.4 3,5-Dimethyl-4-((4-nitrophenyl)diazenyl)-1-phenyl-1H-pyrazole (5p)

Yield: 6.88 g (58%). Decomposition temperature 253 °C; IR (KBr) ν max/cm^–1: 1478 (C⚌N Str.), 1541 (N⚌O Str.), 1785 (C⚌O Str.), 2944 (C–H Str.), 3186 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.31 (s, 3H, –CH₃), 2.69 (s, 3H, –CH₃), 7.59–7.64 (m, 5H, –CH_aro), 7.69 (d, J = 7.8 Hz, 2H, –CH_aro) 7.86 (d, J = 7.8 Hz, 2H, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.1, 13.3, 108.1, 124.6, 125.8, 126.9, 127.5, 130.2, 132.1, 135.4, 140.5, 144.2, 151. MS (ESI, 70 eV): m/z 322.2 [M+H]⁺. Anal. Calcd. for C₁₇H₁₅N₅O₂: C, 63.54; H, 4.71; N, 21.79%. Found: C, 63.31; H, 4.52; N, 21.90%.

3.2.2.5

3.2.2.5 3-Methyl-4-(20(3-nitrophenyl)hydrazono)-1H-pyrazol-5(4H)-one (5q)

Yield: 6.78 g (76%). Decomposition temperature 229 °C. IR (KBr) ν max/cm^–1: 1485 (C⚌N Str.), 1524 (N⚌O Str.), 1749 (C⚌O Str.), 2922 (C–H Str.), 3160 (C–H Str.), 3422 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.41 (s, 3H, –CH₃), 7.40–7.64 (m, 4H, –CH_aro), 10.12 (s, 1H, –NH), 11.82 (br. s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.2, 108.8, 114.5, 120.4, 127.7, 130.8, 143.3, 147.6, 149.4, 161.1; MS (ESI, 70 eV): m/z 248.4 [M+H]⁺. Anal. Calcd. for C₁₀H₉N₅O₃: C, 48.58; H, 3.67; N, 28.33%. Found: C, 48.54; H, 3.70; N, 28.30%.

3.2.2.6

3.2.2.6 3-Methyl-4-(2-(3-nitrophenyl)hydrazono)-1-phenyl-1H-pyrazol-5(4H)-one (5r)

Yield: 6.34 g (53%). Decomposition temperature 237 °C. IR (KBr) ν max/cm^–1: 1466 (C⚌N Str.), 1529 (N⚌O Str.), 1743 (C⚌O Str.), 2946 (C–H Str.), 3133 (C–H Str.), 3443 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.39 (s, 3H, –CH₃), 7.59–7.81 (m, 9H, –CH_aro), 9.92 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.0, 108.7, 114.5, 118.9, 120.5, 127.5, 128.2, 129.7, 131.1, 141.3, 144.4, 147.7, 149.2, 161.9. MS (ESI, 70 eV): m/z 324.3 [M+H]⁺. Anal. Calcd. for C₁₆H₁₃N₅O₃: C, 59.44; H, 4.05; N, 21.66%. Found: C, 59.47; H, 4.10; N, 21.64%.

3.2.2.7

3.2.2.7 3-Methyl-4-(2-(4-nitrophenyl)hydrazono)-1H-pyrazol-5(4H)-one (5s)

Yield: 5.5 g (61%). Decomposition temperature 246 °C. IR (KBr) ν max/cm^–1: 1483 (C⚌N Str.), 1539 (N⚌O Str.), 1747 (C⚌O Str.), 2911 (C–H Str.), 3153 (C–H Str.), 3435 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.38 (s, 3H, –CH₃), 7.09 (d, J = 8.0 Hz, 2H, –CH_aro), 7.77 (d, J = 8.0 Hz, 2H, –CH_aro), 10.17 (s, 1H, –NH), 11.86 (br. s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.8, 114.7, 124.2, 129.5, 138.7, 147.6, 150.2, 161.1; MS (ESI, 70 eV): m/z 248.1 [M+H]⁺. Anal. Calcd. for C₁₀H₉N₅O₃: C, 48.58; H, 3.67; N, 28.33%. Found: C, 48.60; H, 3.62; N, 28.34%.

3.2.2.8

3.2.2.8 3-Methyl-4-(2-(4-nitrophenyl)hydrazono)-1-phenyl-1H-pyrazol-5(4H)-one (5t)

Yield: 6.1 g (52%). Decomposition temperature 278 °C. IR (KBr) ν max/cm^–1: 1479 (C⚌N Str.), 1530 (N⚌O Str.), 1761 (C⚌O Str.), 2955 (C–H Str.), 3152 (C–H Str.), 3446 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.35 (s, 3H, –CH₃), 7.59–7.93 (m, 9H, –CH_aro), 9.88 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 12.1, 113.8, 119.5, 124.3, 126.8, 128.5, 129.6, 136.8, 142.5, 147.1, 150.3, 162.2. MS (ESI, 70 eV): m/z 324.2 [M+H]⁺. Anal. Calcd. for C₁₆H₁₃N₅O₃: C, 59.44; H, 4.05; N, 21.66%. Found: C, 59.40; H, 4.09; N, 21.61%.

3.2.3

3.2.3 Reduction of monophenylic pyrazole or pyrazolone derivatives (6m–6t)

Reduction of nitro compounds (5m–5t) was carried out by the method reported in the literature (Ahluwalia and Aggarwal, 2004). Accordingly, it (0.0101 mol) was dissolved in 30 mL water and heated to boiling. To this solution, sodium polysulphide solution (0.0048 mol) in 20 mL of water was added dropwise over a period of 30 min. and the resulting mixture was boiled gently for 30 min in an open glass vessel. After completion of the reaction, the mass was poured to crushed ice, filtered and washed with cold water. Obtained solid was dissolved in 10% HCl solution, filtered and reprecipitated from 20% ammonia solution. The solid product (6m–6t) thus obtained was collected, washed with water and dried.

3.2.3.1

3.2.3.1 3-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)aniline (6m)

Yield: 2.99 g (68%). Decomposition temperature 218 °C. IR (KBr) ν max/cm^–1: 1471 (C⚌N Str.), 1748 (C⚌O Str.), 2958 (C–H Str.), 3167 (C–H Str.), 3430 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 3.25 (s, 6H, –CH₃), 6.42 (s, 2H, –NH₂), 7.22–7.39 (m, 4H, –CH_aro), 9.71 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.6, 101.8, 104, 105.9, 129.6, 137.4, 144.3, 148.4, 157.7. MS (ESI, 70 eV): m/z 216.2 [M+H]⁺. Anal. Calcd. for C₁₁H₁₃N₅: C, 61.38; H, 6.09; N, 32.54%. Found: C, 61.35; H, 6.10; N, 32.49%.

3.2.3.2

3.2.3.2 3-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)aniline (6n)

Yield: 2.01 g (67%). Decomposition temperature 235 °C. IR (KBr) ν max/cm^–1: 1460 (C⚌N Str.), 1720 (C⚌O Str.), 2919 (C–H Str.), 3145 (C–H Str.), 3418 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.22 (s, 3H, –CH₃), 2.58 (s, 3H, –CH₃), 6.39 (s, 2H, –NH₂), 6.97–7.28 (m, 9H, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.1, 13.1, 107.8, 114.7, 115.6, 119.3, 125.4, 126.9, 129.5, 130.3, 131.7, 138.2, 140.5, 149.1, 151.4. MS (ESI, 70 eV): m/z 292.4 [M+H]⁺. Anal. Calcd. for C₁₇H₁₇N₅: C, 70.08; H, 5.88; N, 24.04%. Found: C, 69.83; H, 5.55; N, 23.84%.

3.2.3.3

3.2.3.3 4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)aniline (6o)

Yield: 3.09 g (70%). Decomposition temperature 196 °C. IR (KBr) ν max/cm^–1: 1499 (C⚌N Str.), 1754 (C⚌O Str.), 2938 (C–H Str.), 3111 (C–H Str.), 3480 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 3.27 (s, 6H, –CH₃), 6.36 (s, 2H, –NH₂), 7.02–7.08 (m, 4H, –CH_aro), 9.82 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.7, 116.4, 119.7, 133.4, 136.7, 138.5, 158.7. MS (ESI, 70 eV): m/z 216.1 [M+H]⁺. Anal. Calcd. for C₁₁H₁₃N₅: C, 61.38; H, 6.09; N, 32.54%. Found: C, 61.40; H, 6.13; N, 32.50%.

3.2.3.4

3.2.3.4 4-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)aniline (6p)

Yield: 1.89 g (63%). Decomposition temperature 201 °C; IR (KBr) ν max/cm^–1: 1461 (C⚌N Str.), 1761 (C⚌O Str.), 2939 (C–H Str.), 3159 (C–H Str.), 3415 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.24 (s, 3H, –CH₃), 2.61 (s, 3H, –CH₃), 6.41 (s, 2H, –NH₂), 7.16 (d, J = 7.8 Hz, 2H, –CH_aro), 7.45 (d, J = 7.8 Hz, 2H, –CH_aro), 7.56–7.63 (m, 5H, –CH_aro). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.3, 13.2, 107.6, 114.1, 121.9, 125.4, 126.8, 130.5, 131.7, 138.1, 140.4, 149.6, 151.3. MS (ESI, 70 eV): m/z 292.2 [M+H]⁺. Anal. Calcd. for C₁₇H₁₇N₅: C, 70.08; H, 5.88; N, 24.04%. Found: C, 69.95; H, 5.58; N, 23.90%.

3.2.3.5

3.2.3.5 4-(2-(3-Aminophenyl)hydrazono)-3-methyl-1H-pyrazol-5(4H)-one (6q)

Yield: 2.88 g (49%). Decomposition temperature 230 °C. IR (KBr) ν max/cm^–1: 1451 (C⚌N Str.), 1791 (C⚌O Str.), 2952 (C–H Str.), 3144 (C–H Str.), 3465 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.27 (s, 3H, –CH₃), 6.12 (s, 2H, –NH₂), 6.96–7.12 (m, 4H, –CH_aro), 9.94 (s, 1H, –NH), 11.69 (br. s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 12.4, 101.5, 103.3, 106.2, 127.7, 131.5, 142.7, 147.5, 149.4, 160.5; MS (ESI, 70 eV): m/z 218.1 [M+H]⁺. Anal. Calcd. for C₁₀H₁₁N₅O: C, 55.29; H, 5.10; N, 32.24%. Found: C, 55.31; H, 5.13; N, 32.25%.

3.2.3.6

3.2.3.6 4-(2-(3-Aminophenyl)hydrazono)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6r)

Yield: 2.13 g (66%). Decomposition temperature 211 °C. IR (KBr) ν max/cm^–1: 1444 (C⚌N Str.), 1754 (C⚌O Str.), 2938 (C–H Str.), 3121 (C–H Str.), 3439 (N–H Str.). ¹H NMR (400 MHz, DMSO–d₆): δ 2.26 (s, 3H, –CH₃), 6.33 (s, 2H, –NH₂), 7.03–7.48 (m, 9H, –CH_aro), 10.02 (s, 1H,–NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.6, 101.6, 102.7, 106.6, 119.4, 127.7, 128.6, 131.2, 139.4, 144.1, 146.3, 149.4, 161.2. MS (ESI, 70 eV): m/z 294.1 [M+H]⁺. Anal. Calcd. for C₁₆H₁₅N₅O: C, 65.52; H, 5.15; N, 23.88%. Found: C, 65.49; H, 5.18; N, 23.82%.

3.2.3.7

3.2.3.7 4-(2-(4-Aminophenyl)hydrazono)-3-methyl-1H-pyrazol-5(4H)-one (6s)

Yield: 2.67 g (61%). Decomposition temperature 227 °C. IR (KBr) ν max/cm^–1: 1480 (C⚌N Str.), 1728 (C⚌O Str.), 2920 (C–H Str.), 3137 (C–H Str.), 3465 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.20 (s, 3H, –CH₃), 6.18 (s, 2H, –NH₂), 7.02–7.14 (m, 4H, –CH_aro), 9.86 (s, 1H, –NH), 11.77 (br. s, 1H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.3, 116.4, 118.1, 129.4, 133.7, 137.1, 147.6, 161.9. MS (ESI, 70 eV): m/z 218.3 [M+H]⁺. Anal. Calcd. for C₁₀H₁₁N₅O: C, 55.29; H, 5.10; N, 32.24%. Found: C, 55.33; H, 5.16; N, 32.21%.

3.2.3.8

3.2.3.8 4-(2-(4-Aminophenyl)hydrazono)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6t)

Yield: 1.49 g (56%). Decomposition temperature 227 °C. IR (KBr) ν max/cm^–1: 1477 (C⚌N Str.), 1744 (C⚌O Str.), 2936 (C–H Str.), 3182 (C–H Str.), 3459 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.35 (s, 3H, –CH₃), 6.37 (s, 2H, –NH₂), 7.12–7.53 (m, 9H, –CH_aro), 10.11 (s, 1H,–NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.6, 115.8, 117.1, 119.6, 125.8, 128.3, 133.6, 137.3, 139.3, 150, 162. MS (ESI, 70 eV): m/z 294.2 [M+H]⁺. Anal. Calcd. for C₁₆H₁₅N₅O: C, 65.52; H, 5.15; N, 23.88%. Found: C, 65.56; H, 5.18; N, 23.92%.

3.2.4

3.2.4 Hydrazono derivatives of monophenylic pyrazole or pyrazolone derivatives (7m–7t)

According to the method available in the literature (Furniss et al., 2004; Saleh et al., 2003), the solution of 6m–6t (0.0092 mol) was prepared in conc. sulphuric acid (0.0334 mol) and NaNO₂ (0.0102 mol) in 10 mL water, and was kept in ice bath for 10 min. separately below 5 °C. After that, NaNO₂ solution was added dropwise to the acidic solution of 6m–6t for a period of 20 min. with constant stirring, by maintaining the same temperature. The diazonium salt of 6m–6t generated was immediately led to couple with the acetyl acetone (2a) (0.0102 mol) or methyl acetoacetate (2b) (0.0102 mol) in methanol. Solution of 2a or 2b was added dropwise to the diazonium salt solution for 20 min. with continuous stirring below 5 °C. After the completion of the addition with stirring, the reaction mass was allowed to reach room temperature. The product (7m–7t) obtained was washed with water, dried and recrystallized using acetone.

3.2.4.1

3.2.4.1 3-(2-(3-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)hydrazono)pentane-2,4-dione (7m)

Yield: 3.68 g (81%). Decomposition temperature 267 °C. IR (KBr) ν max/cm^–1: 1465 (C⚌N Str.), 1632 (C⚌O stretching of ester group), 2920 (C–H Str.), 3021 (C–H Str.), 3324 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.53 (s, 6H, –CH₃), 2.96 (s, 6H, –CH₃), 6.73–6.92 (m, 4H, –CH_aro), 9.78 (s, 1H, –NH), 10.54 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.7, 26.1, 103.6, 104.9, 129.2, 132.4, 137.7, 144.1, 161.2, 196.4. MS (ESI, 70 eV): m/z 327. 2 [M+H]⁺. Anal. Calcd. for C₁₆H₁₈N₆O₂: C, 58.88; H, 5.56; N, 25.75%. Found: C, 58.87; H, 5.51; N, 25.80%.

3.2.4.2

3.2.4.2 3-(2-(3-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)hydrazono)pentane-2,4-dione (7n)

Yield: 3.15 g (76%). Decomposition temperature 254 °C. IR (KBr) ν max/cm^–1: 1459 (C⚌N Str.), 1648 (C⚌O stretching of ester group), 2898 (C–H Str.), 3041 (C–H Str.), 3369 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.21 (s, 3H, –CH₃), 2.36 (s, 6H, –CH₃), 2.68 (s, 3H, –CH₃), 6.94–7.41 (m, 9H, –CH_aro), 10.56 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.1, 12.9, 27.3, 108.2, 114.4, 115.2, 119.7, 125.5, 126.9, 129.8, 130.6, 130.9, 133.5, 138.4, 140.2, 143.8, 151.1, 198.2. MS (ESI, 70 eV): m/z 403.1 [M+H]⁺. Anal. Calcd. for C₂₂H₂₂N₆O₂:C, 65.66; H, 5.81; N, 20.88%. Found: C, 65.40; H, 6.06; N, 20.72%.

3.2.4.3

3.2.4.3 3-(2-(4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)hydrazono)pentane-2,4-dione (7o)

Yield: 3.54 g (78%). Decomposition temperature 263 °C. IR (KBr) ν max/cm^–1: 1470 (C⚌N Str.), 1668 (C⚌O stretching of ester group), 2867 (C–H Str.), 3033 (C–H Str.), 3228 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.58 (s, 6H, –CH₃), 3.02 (s, 6H, –CH₃), 6.84–7.08 (m, 4H, –CH_aro), 9.81 (s, 1H, –NH), 10.65 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 18.2, 27.2, 121.1, 131.7, 133.5, 137.5, 159.2, 196.3. MS (ESI, 70 eV): m/z 327.4 [M+H]⁺. Anal. Calcd. for C₁₆H₁₈N₆O₂: C, 58.88; H, 5.56; N, 25.75%. Found: C, 58.91; H, 5.60; N, 25.70%.

3.2.4.4

3.2.4.4 3-(2-(4-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)hydrazono)pentane-2,4-dione (7p)

Yield: 2.90 g (71%). Decomposition temperature 207 °C. IR (KBr) ν max/cm^–1: 1472 (C⚌N Str.), 1595 (C⚌O stretching of ester group), 2872 (C–H Str.), 3062 (C–H Str.) 3340 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.27 (s, 3H, –CH₃), 2.37 (s, 6H, –CH₃), 2.70 (s, 3H, –CH₃), 7.08 (d, J = 7.6 Hz, 2H, –CH_aro), 7.38 (d, J = 7.6 Hz, 2H, –CH_aro), 7.48–7.60 (m, 5H, –CH_aro), 10.68 (s, 1H,–NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.2, 13.1, 27.5, 108.4, 113.3, 121.9, 125.6, 126.7, 129.8, 131.6, 133.7, 138.1, 140.5, 143.8, 151.3, 198.4. MS (ESI, 70 eV): m/z 403.2 [M+H]⁺. Anal. Calcd. for C₂₂H₂₂N₆O₂: C, 65.66; H, 5.51; N, 20.88.Found: C, 65.37; H, 5.22; N, 20.70%.

3.2.4.5

3.2.4.5 Methyl 2-(2-(3-(2-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7q)

Yield: 3.72 g (82%). Decomposition temperature 288 °C. IR (KBr) ν max/cm^–1: 1467 (C⚌N Str.), 1698 (C⚌O stretching of ester group), 2942 (C–H Str.), 3057 (C–H Str.), 3343 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.37 (s, 3H, –CH₃), 2.48 (s, 3H, –CH₃), 4.09 (s, 3H, –CH₃), 6.87–7.04 (m, 4H, –CH_aro), 9.63 (s, 1H, –NH), 9.82 (s, 1H, –NH), 11.74 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.1, 27.3, 50.5, 101.5, 104.4, 127, 129.7, 134.6, 144.5, 148.9, 160.7, 165, 195.7. MS (ESI, 70 eV): m/z 345.2 [M+H]⁺. Anal. Calcd. for C₁₅H₁₆N₆O₄: C, 52.32; H, 4.68; N, 24.41%. Found: C, 52.29; H, 4.62; N, 24.37%.

3.2.4.6

3.2.4.6 Methyl-2-(2-(3-(2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7r)

Yield: 2.98 g (72%). Decomposition temperature 259 °C. IR (KBr) ν max/cm^–1: 1476 (C⚌N Str.), 1652 (C⚌O stretching of ester group), 2933 (C–H Str.), 3028 (C–H Str.), 3372 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.40 (s, 3H, –CH₃), 2.57 (s, 3H, –CH₃), 4.18 (s, 3H, –CH₃), 6.98–7.44 (m, 9H, –CH_aro), 9.85 (s, 1H, –NH), 10.12 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.2, 27.6, 50.9, 102.2, 104.5, 119.8, 127.2, 128.8, 129.4, 131.7, 134.6, 141.1, 144.7, 147.6, 158.3, 161.9, 196.2. MS (ESI, 70 eV): m/z 421.3 [M+H]⁺. Anal. Calcd. for C₂₁H₂₀N₆O₄: C, 59.99; H, 4.79; N, 19.99%. Found: C, 59.94; H, 4.75; N, 20.06%.

3.2.4.7

3.2.4.7 Methyl-2-(2-(4-(2-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7s)

Yield: 3.27 g (69%). Decomposition temperature 192 °C. IR (KBr) ν max/cm^–1: 1453 (C⚌N Str.), 1621 (C⚌O stretching of ester group), 2886 (C–H Str.), 3064 (C–H Str.), 3311 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.41 (s, 3H, –CH₃), 2.53 (s, 3H, –CH₃), 4.11 (s, 3H, –CH₃), 6.93–6.96 (m, 4H, –CH_aro), 9.68 (s, 1H, –NH), 10.04 (s, 1H, –NH), 11.78 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 12.0, 27.4, 52.6, 119.5, 127.6, 132.3, 134.1, 147.4, 160.8, 164.1, 196.8. MS (ESI, 70 eV): m/z 345.3 [M+H]⁺. Anal. Calcd. for C₁₅H₁₆N₆O₄: C, 52.32; H, 4.68; N, 24.41%. Found: C, 52.27; H, 4.70; N, 24.39%.

3.2.4.8

3.2.4.8 Methyl-2-(2-(4-((E)-2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7t)

Yield: 3.20 g (77%). Decomposition temperature 284 °C. IR (KBr) ν max/cm^–1: 1461 (C⚌N Str.), 1576 (C⚌O stretching of ester group), 2949 (C–H Str.), 3071 (C–H Str.), 3354 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.43 (s, 3H, –CH₃), 2.58 (s, 3H, –CH₃), 4.20 (s, 3H, –CH₃), 6.90–7.38 (m, 9H, –CH_aro), 9.91 (s, 1H, –NH), 10.14 (s, 1H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.4, 25.9, 52.3, 117.3, 121.3, 127.2, 129.4, 131.9, 134.6, 139.7, 149.1, 158.3, 164.5, 195.9. MS (ESI, 70 eV): m/z 421.1 [M+H]⁺. Anal. Calcd. for C₂₁H₂₀N₆O₄: C, 59.99; H, 4.79; N, 19.99%. Found: C, 60.01; H, 4.81; N, 20.03%.

3.2.5

3.2.5 Monophenylic bispyrazole or bispyrazolone derivatives (4m–4t)

Compounds 7m–7t were cyclized to produce 4m–4t by following the method reported in the literature (Saleh et al., 2003). Accordingly, compounds 7m–7t (0.0045 mol) were dissolved in 20 mL of ethanol and hydrazine hydrate (0.0051 mol) in 15 mL of ethanol or phenyl hydrazine (0.0051 mol) in 20 mL CH₃COOH and were mixed in a 50 mL round bottomed flask with stirring for 5 min.. Further, it was refluxed for 3.5 h or 6 h respectively. After refluxing, it was allowed to cool to room temperature. The orange yellow product obtained was filtered and recrystallized using acetone.

3.2.5.1

3.2.5.1 1,3-Bis(2-(3,5-dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)benzene (4m)

Yield: 0.72 g (48%). Decomposition temperature 197 °C. IR (KBr) ν max/cm^–1: 1601 (C⚌N Str.), 3108 (C–H Str.), 3389 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.66 (s, 12H, –CH₃), 8.13–8.18 (m, 4H, –CH_aro), 9.97 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 19.6, 102.4, 104.5, 130.8, 135.9, 143.5, 157.8. MS (ESI, 70 eV): m/z 323.1 [M+H]⁺. Anal. Calcd. for C₁₆H₁₈N₈: C, 59.61; H, 5.63; N, 34.76%. Found: C, 59.44; H, 5.41; N, 34.59%.

3.2.5.2

3.2.5.2 1,3-Bis((3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)benzene (4n)

Yield: 0.72 g (48%). Decomposition temperature 197 °C. IR (KBr) ν max/cm^–1: 1577 (C⚌N Str.), 2893 (C–H Str.), 3155 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.24 (s, 6H, –CH₃), 2.69 (s, 6H, –CH₃), 7.31–7.65 (m, 14H, –CH_aro) ¹³C NMR (100 MHz, DMSO-d₆): δ 11.1, 13.0, 108.1, 125.5, 126.9, 128.2, 129.4, 130.1, 130.7, 131.2, 138.0, 140.3, 151.4. MS (ESI, 70 eV): m/z 475.3 [M+H]⁺. Anal. Calcd. for C₂₈H₂₆N₈: C, 70.87; H, 5.52; N, 23.61%. Found: C, 70.64; H, 5.36; N, 23.44%.

3.2.5.3

3.2.5.3 1,4-Bis(2-(3,5-dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)benzene (4o)

Yield: 0.69 g (46%). Decomposition temperature 209 °C. IR (KBr) ν max/cm^–1: 1498 (C⚌N Str.), 3143 (C–H Str.), 3408 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.69 (s, 12H, –CH₃), 2.83–2.87 (m, 4H, –CH_ali), 9.96 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 19.2, 121.2, 133.6, 136.5, 158.8. MS (ESI, 70 eV): m/z 323.2 [M+H]⁺. Anal. Calcd. for C₁₆H₁₈N₈: C, 59.61; H, 5.63; N, 34.76%. Found: C, 59.39; H, 5.87; N, 34.51%.

3.2.5.4

3.2.5.4 1,4-Bis((3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)benzene (4p)

Yield: 0.63 g (42%). Decomposition temperature 235 °C. IR (KBr) ν max/cm^–1: 1508 (C⚌N Str.), 2963 (C–H Str.), 3129 (C–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.29 (s, 6H, –CH₃), 2.70 (s, 6H, –CH₃), 7.04 (d, J = 8 Hz, 2H, –CH_aro), 7.27 (d, J = 8 Hz, 2H, –CH_aro), 7.43–7.56 (m, 10H, –CH_aro). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.2, 13.4, 108.3, 125.7, 125.9, 126.6, 127.1, 129.8, 138.2, 140.5, 151.6. MS (ESI, 70 eV): m/z 475.3 [M+H]⁺. Anal. Calcd. for C₂₈H₂₆N₈: C, 70.87; H, 5.52; N, 23.61.Found: C, 70.65; H, 5.77; N, 23.64%.

3.2.5.5

3.2.5.5 4,4′-(2,2′-(1,3-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4q)

Yield: 0.705 g (47%). Decomposition temperature 222 °C. IR (KBr) ν max/cm^–1: 1601 (C⚌N Str.), 1758 (C⚌O Str.), 2865 (C–H Str.), 3145 (C–H_aro), 3389 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.39 (s, 6H, –CH₃), 7.2–7.9 (m, 4H, –CH_aro), 9.52 (s, 2H, –NH), 13.32 (br. s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.3, 102.7, 103.9, 128.7, 130.3, 143.8, 148.2, 161.8. 11.5, 101.8, 104.3, 128.4, 133.3, 144.2, 149.1, 161.7. MS (ESI, 70 eV): m/z 327.2 [M+H]⁺. Anal. Calcd. for C₁₄H₁₄N₈O₂: C, 51.53; H, 4.32; N, 34.34%. Found: C, 51.38; H, 4.63; N, 34.12%.

3.2.5.6

3.2.5.6 4,4′-(2,2′-(1,3-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4r)

Yield: 0.66 g (44%). Decomposition temperature 218 °C. IR (KBr) ν max/cm^–1: 1591 (C⚌N Str.), 1719 (C⚌O Str.), 2897 (C–H Str.), 3167 (C–H Str.), 3375 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.40 (s, 6H, –CH₃), 7.19–8.01 (m, 14H, –CH_aro), 9.63 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.6, 101.4, 103.6, 117.3, 127.3, 128.6, 129.1, 130.3, 140.3, 143.6, 147.5, 162.1. MS (ESI, 70 eV): m/z 479.1 [M+H]⁺. Anal. Calcd. for C₂₆H₂₂N₈O₂: C, 65.26; H, 4.63; N, 23.42%. Found: C, 65.43; H, 4.39; N, 23.53%.

3.2.5.7

3.2.5.7 4,4′-(2,2′-(1,4-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4s)

Yield: 0.735 g (49%). Decomposition temperature 230 °C. IR (KBr) ν max/cm^–1: 1485 (C⚌N Str.), 1735 (C⚌O Str.), 2911 (C–H Str.), 3143 (C–H Str.), 3415 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.38 (s, 6H, –CH₃), 7.53 (s, 4H, –CH), 9.49 (s, 2H, –NH), 12.97 (br. s, 2H, –NH). ¹³C NMR (100 MHz, DMSO-d₆): δ 11.8, 116.3, 122.2, 126.6, 127.9, 130.1, 135.2, 141.1, 150.2, 163.5. MS (ESI, 70 eV): m/z 327.1 [M+H]⁺. Anal. Calcd. for C₁₄H₁₄N₈O₂: C, 51.53; H, 4.32; N, 34.34%. Found: C, 51.22; H, 4.57; N, 34.19%.

3.2.5.8

3.2.5.8 4,4′-(2,2′-(1,4-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4t)

Yield: 0.585 g (39%). Decomposition temperature 202 °C. IR (KBr) ν max/cm^–1: 1508 (C⚌N Str.), 1778 (C⚌O Str.), 2987 (C–H Str.), 3135 (C–H Str.), 3427 (N–H Str.). ¹H NMR (400 MHz, DMSO-d₆): δ 2.39 (s, 6H, –CH₃), 7.21–7.91 (m, 14H, –CH_aro), 9.54 (s, 2H, –NH). ¹³C NMR (100 MHz, DMSO–d₆): δ 11.4, 117.5, 121.4, 127.5, 128.7, 128.9, 132.2, 143.3, 147.2, 161.5. MS (ESI, 70 eV): m/z 479.3 [M+H]⁺. Anal. Calcd. for C₂₆H₂₂N₈O₂:%: C, 65.26; H, 4.63; N, 23.4%. Found: C, 65.22; H, 4.59; N, 23.37%.

3.3

3.3 General synthetic method for pyrazole and pyrazolone ring formation via microwave irradiation

A 10 mL microwave round bottom flask equipped with a standard condenser was filled with 1 mmol of hyrazono compound (3m, 3n, 3q, 3r and 7m–7t) and 1.2 mmol of hydrazine hydrate or phenyl hydrazine in 3 mL ethanol or acetic acid respectively. Thereafter, the mixture was irradiated by microwave for the specific time and temperature as indicated in Table 1. The solid product obtained was filtered, dried and recrystallized using acetone.

3.4

3.4 Antimicrobial study for the synthesized compounds (4a–4t)

The antimicrobial activities were determined using the agar–cup method (Sujatha, 1975; Cruickshank et al., 1975) by measuring the zone of inhibition in mm. All newly synthesized compounds 4a–4t were screened in vitro for their antibacterial activity against Gram positive species (B. sublitis) and Gram negative species (E. coli), while antifungal activity was tested against As. niger and As. flavus at a concentration of 200 μg/mL. Benzylpenicillin was used as a standard drug for antibacterial screening, while Imidil was used as a standard drug for antifungal screening and solvent DMSO was used as a control. Each experiment was made in triplicate and the average reading was taken. The results are summarized in Table 2.

4 Conclusion

In summary, the present study reports a series of new heterocyclic compounds that have bispyrazole and bispyrazolone scaffold in their basic structure acquiring pharmacological activity. The compounds 4g and 4h have shown good microbial activity among all the tested compounds.

Acknowledgement

Authors gratefully acknowledge the Director, ARIBAS and Charuter Vidya Mandal for providing all the necessary research facilities.

References

Ahluwalia V.K., Aggarwal R., . Comprehensive Practical Organic Chemistry–Quantitative Chemistry, 1st ed. Hyderguda, Hydrabad, India: Universities Press (India) Pvt. Ltd.; 2004.
Alvarez H.M., Barbosa D.P., Fricks A.T., Aranda D.A.G., Valdés R.H., Antunes O.A.C., . Org. Proc. Res. Dev.. 2006;10:941.
Badawey E.S.A.M., El–Ashmawey I.M., . Eur. J. Med. Chem.. 1998;33:349.
Batten S.R., Robson R., . Angrew. Chem. Int. Ed.. 1998;37:1460.
Bose A.K., Manhas M.S., Ghosh M., Shah M., Raju V.S., Bari S.S., Newaz S.N., Banik B.K., Chaudhary A.G., Barakat K.J., . J. Org. Chem.. 1991;56:6968.
Cruickshank R., Duguid J.P., Marmion B.P., Swain R.H.A., . Medical Microbiology – The practice of medical microbiology. vol 2 (12th ed.). Edinburgh, London: Churchill Livingstone; 1975.
Deb M.L., Majumder S., Bhuyan P.J., . Synlett. 2009;12:1982.
Dos Santos A.A., Wendler E.P., Marques F.A., Simonelli F., . Lett. Org. Chem.. 2004;1:47.
Elmorsi M.A., Hassanein A.M., . Corros. Sci.. 1999;41:2337.
Foulds G., . Coord. Chem. Rev.. 1998;169:3.
Furniss B.S., Hannaford A.J., Smith P.W.G., Tatchell A.R., . Vogel’s textbook of practical organic Chemistry, 5th ed. Delhi, India: Pearson Education (Singapore) Pvt. Ltd.; 2004.
Gedye R., Smith F., Westaway K., Ali H., Baldisera L., Laberge L., Rousell J., . Tetrahedron Lett.. 1986;27:279.
Geronikaki A., Babaev E., Dearden J., Dehaen W., Filimonov D., Galaeva I., Krajneva V., Lagunin A., Macaev F., Molodavkin G., Poroikov V., Pogrebnoi S., Saloutin V., Stepanchikova A., Stingaci E., Tkach N., Vlad L., Voronina T., . Bioorg. Med. Chem.. 2004;12:6559.
Gürsoy A., Demirayak S., Çapan G., Erol K., Vural K., . Eur. J. Med. Chem.. 2000;35:359.
Haddad N., Salvagno A., Busacca C., . Tetrahedron Lett.. 2004;45:5935.
Ito T., Goto C., . Noguchi. K.. 2001;443:41.
[Google Scholar]
Jagani C.L., Sojitra N.A., Vanparia S.F., Patel T.S., Dixit R.B., Dixit B.C., . J. Saudi Chem. Soc. 2011
[CrossRef]
Jones G.B., Chapman B.J., . J. Org. Chem.. 1993;58:5558.
Kees K.L., Fitzgerald J.J., Steiner K.E. Jr., Mattes J.F., Mihan B., Tosi T., Mondoro D., McCaleb M.L., . J. Med. Chem.. 1996;39:3920.
Kepe V., Požgan F., Golobič A., Polanc S., Kočevar M., . J. Chem. Soc., Perkin Trans.. 1998;1:2813.
Laurent R., Laporterie A., Dubac J., Berlan J., . Organometallics. 1994;13:2493.
Liu G., Liu L., Jia D., Yu K., . J. Chem. Crystallogr.. 2004;34:835.
Mabkhoot Y.N., . Molecules. 2009;14:1904.
Majumder S., Gipson K.R., Staples R.J., Odom A.L., . Adv. Synth. Catal.. 2009;351:2013.
Marquez H., Loupy A., Calderon O., Pérez E.R., . Tetrahedron. 2006;62:2616.
Niknam K., Saberi D., Sadegheyan M., Deris A., . Tetrahedron Lett.. 2010;51:692.
Pavia D.L., Lampman G.M., Kriz G.S., Vyvyan J.A., . Introduction to spectroscopy (4th ed.). California: Brookes Cole publishers; 2008.
Rama Rao A.V., Gurjar M.K., Kaiwar V., . Tetrahedron Asymm.. 1992;3:859.
Saleh M.A., Abdel–Megeed M.F., Abdo M.A., Shokr A.M., . Molecules. 2003;8:363.
Sharma L.K., Kyung B.K., Elliott G.I., . Green Chem.. 2011;13:1546.
Srikrishna A., Nagaraju S., . J. Chem. Soc. Perkin Trans.. 1992;1:311.
Tanitame A., Oyamada Y., Ofuji K., Fujimoto M., Iwai N., Hiyama Y., Suzuki K., Ito H., Terauchi H., Kawasaki M., Nagai K., Wachi M., Yamagishi J., . J. Med. Chem.. 2004;47:3693.
Tewari A.K., Srivastava P., Singh V.P., Singh A., Goel R.K., Mohan C.G., . Chem. Pharm. Bull.. 2010;58:634.
Uzoukwu B.A., Gloe K., Duddeck H., . Synth. React. Inorg. Met–Org. Nano–Met. Chem.. 1998;28:819.
Veettil S.P., Haridas K.R., . Mol. Bank 2009:M624.
Yang L., Jin W., Lin J., . Polyhedron. 2000;19:93.
Yu H.M., Chen S.T., Wang K.T., . J. Org. Chem.. 1992;57:4781.
Yulin J., Yuncheng Y., . Synth. Commun.. 1994;24:1045.
Zhang C.Y., Liu X.H., Wang B.L., Wang S.H., Li Z.M., . Chem. Biol. Drug Des.. 2010;75:489.
Zheng L.W., Li Y., Ge D., Zhao B.X., Liu Y.R., Lv H.S., Ding J., Miao J.Y., . Bioorg. Med. Chem. Lett.. 2010;20:4766.
Zheng L.W., Wu L.L., Zhao B.X., Dong W.L., Miao J.Y., . Bioorg. Med. Chem.. 2009;17:1957.

Introduction

Results and discussion

Chemistry
Antibacterial and antifungal activity

Experimental

Experimental procedure for the synthesis of entitled compounds (4a–4l)
Experimental procedure for the synthesis of entitled compounds (4m–4t)
General synthetic method for pyrazole and pyrazolone ring formation via microwave irradiation
Antimicrobial study for the synthesized compounds (4a–4t)

Conclusion

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[1] Ahluwalia V.K., Aggarwal R., . Comprehensive Practical Organic Chemistry–Quantitative Chemistry, 1st ed. Hyderguda, Hydrabad, India: Universities Press (India) Pvt. Ltd.; 2004.

[2] Alvarez H.M., Barbosa D.P., Fricks A.T., Aranda D.A.G., Valdés R.H., Antunes O.A.C., . Org. Proc. Res. Dev.. 2006;10:941.

[3] Badawey E.S.A.M., El–Ashmawey I.M., . Eur. J. Med. Chem.. 1998;33:349.

[4] Batten S.R., Robson R., . Angrew. Chem. Int. Ed.. 1998;37:1460.

[5] Bose A.K., Manhas M.S., Ghosh M., Shah M., Raju V.S., Bari S.S., Newaz S.N., Banik B.K., Chaudhary A.G., Barakat K.J., . J. Org. Chem.. 1991;56:6968.

[6] Cruickshank R., Duguid J.P., Marmion B.P., Swain R.H.A., . Medical Microbiology – The practice of medical microbiology. vol 2 (12th ed.). Edinburgh, London: Churchill Livingstone; 1975.

[7] Deb M.L., Majumder S., Bhuyan P.J., . Synlett. 2009;12:1982.

[8] Dos Santos A.A., Wendler E.P., Marques F.A., Simonelli F., . Lett. Org. Chem.. 2004;1:47.

[9] Elmorsi M.A., Hassanein A.M., . Corros. Sci.. 1999;41:2337.

[10] Foulds G., . Coord. Chem. Rev.. 1998;169:3.

[11] Furniss B.S., Hannaford A.J., Smith P.W.G., Tatchell A.R., . Vogel’s textbook of practical organic Chemistry, 5th ed. Delhi, India: Pearson Education (Singapore) Pvt. Ltd.; 2004.

[12] Gedye R., Smith F., Westaway K., Ali H., Baldisera L., Laberge L., Rousell J., . Tetrahedron Lett.. 1986;27:279.

[13] Geronikaki A., Babaev E., Dearden J., Dehaen W., Filimonov D., Galaeva I., Krajneva V., Lagunin A., Macaev F., Molodavkin G., Poroikov V., Pogrebnoi S., Saloutin V., Stepanchikova A., Stingaci E., Tkach N., Vlad L., Voronina T., . Bioorg. Med. Chem.. 2004;12:6559.

[14] Gürsoy A., Demirayak S., Çapan G., Erol K., Vural K., . Eur. J. Med. Chem.. 2000;35:359.

[15] Haddad N., Salvagno A., Busacca C., . Tetrahedron Lett.. 2004;45:5935.

[16] Ito T., Goto C., . Noguchi. K.. 2001;443:41.
[Google Scholar]

[17] Jagani C.L., Sojitra N.A., Vanparia S.F., Patel T.S., Dixit R.B., Dixit B.C., . J. Saudi Chem. Soc. 2011
[CrossRef]

[18] Jones G.B., Chapman B.J., . J. Org. Chem.. 1993;58:5558.

[19] Kees K.L., Fitzgerald J.J., Steiner K.E. Jr., Mattes J.F., Mihan B., Tosi T., Mondoro D., McCaleb M.L., . J. Med. Chem.. 1996;39:3920.

[20] Kepe V., Požgan F., Golobič A., Polanc S., Kočevar M., . J. Chem. Soc., Perkin Trans.. 1998;1:2813.

[21] Laurent R., Laporterie A., Dubac J., Berlan J., . Organometallics. 1994;13:2493.

[22] Liu G., Liu L., Jia D., Yu K., . J. Chem. Crystallogr.. 2004;34:835.

[23] Mabkhoot Y.N., . Molecules. 2009;14:1904.

[24] Majumder S., Gipson K.R., Staples R.J., Odom A.L., . Adv. Synth. Catal.. 2009;351:2013.

[25] Marquez H., Loupy A., Calderon O., Pérez E.R., . Tetrahedron. 2006;62:2616.

[26] Niknam K., Saberi D., Sadegheyan M., Deris A., . Tetrahedron Lett.. 2010;51:692.

[27] Pavia D.L., Lampman G.M., Kriz G.S., Vyvyan J.A., . Introduction to spectroscopy (4th ed.). California: Brookes Cole publishers; 2008.

[28] Rama Rao A.V., Gurjar M.K., Kaiwar V., . Tetrahedron Asymm.. 1992;3:859.

[29] Saleh M.A., Abdel–Megeed M.F., Abdo M.A., Shokr A.M., . Molecules. 2003;8:363.

[30] Sharma L.K., Kyung B.K., Elliott G.I., . Green Chem.. 2011;13:1546.

[31] Srikrishna A., Nagaraju S., . J. Chem. Soc. Perkin Trans.. 1992;1:311.

[32] Tanitame A., Oyamada Y., Ofuji K., Fujimoto M., Iwai N., Hiyama Y., Suzuki K., Ito H., Terauchi H., Kawasaki M., Nagai K., Wachi M., Yamagishi J., . J. Med. Chem.. 2004;47:3693.

[33] Tewari A.K., Srivastava P., Singh V.P., Singh A., Goel R.K., Mohan C.G., . Chem. Pharm. Bull.. 2010;58:634.

[34] Uzoukwu B.A., Gloe K., Duddeck H., . Synth. React. Inorg. Met–Org. Nano–Met. Chem.. 1998;28:819.

[35] Veettil S.P., Haridas K.R., . Mol. Bank 2009:M624.

[36] Yang L., Jin W., Lin J., . Polyhedron. 2000;19:93.

[37] Yu H.M., Chen S.T., Wang K.T., . J. Org. Chem.. 1992;57:4781.

[38] Yulin J., Yuncheng Y., . Synth. Commun.. 1994;24:1045.

[39] Zhang C.Y., Liu X.H., Wang B.L., Wang S.H., Li Z.M., . Chem. Biol. Drug Des.. 2010;75:489.

[40] Zheng L.W., Li Y., Ge D., Zhao B.X., Liu Y.R., Lv H.S., Ding J., Miao J.Y., . Bioorg. Med. Chem. Lett.. 2010;20:4766.

[41] Zheng L.W., Wu L.L., Zhao B.X., Dong W.L., Miao J.Y., . Bioorg. Med. Chem.. 2009;17:1957.

Synthesis and antimicrobial activities of new mono and bisphenyl linked bispyrazole and bispyrazolone derivatives

Abstract

Keywords

Bispyrazole

Bispyrazolone

Antimicrobial activities

Microwave

1 Introduction

2 Results and discussion

2.1 Chemistry

2.2 Antibacterial and antifungal activity

2.2.1 Structural activity relationship (SAR)

3 Experimental

3.1 Experimental procedure for the synthesis of entitled compounds (4a–4l)

3.1.1 General procedure for the synthesis of diphenylic bishydrazono compounds (3a–3f)

3.1.2 General procedure for the synthesis of diphenylic bispyrazole or bispyrazolone compounds (4a–4l)

3.1.2.1 4,4′–(2,2′–(4,4′–Sulphonylbis(4,1–phenylene))bis(hydrazin–2–yl–1–ylidene))bis(3,5–dimethyl–4H–pyrazole) (4a)

3.1.2.2 4,4′-Sulphonylbis(4,1–phenylene)bis(diazene–2,1–diyl)bis(3,5–dimethyl–1–phenyl–1H–pyrazole) (4b)

3.1.2.3 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2-yl-1-lidene))bis(3,5-dimethyl-4H-pyrazole) (4c)

3.1.2.4 4,4′-Oxybis(4,1-phenylene)bis(diazene-2,1-diyl)bis(3,5-dimethyl-1-phenyl-1H-pyrazole) (4d)

3.1.2.5 bis(4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)methane (4e)

3.1.2.6 bis(4-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)methane (4f)

3.1.2.7 4,4′-(2,2′-(4,4′-Sulphonylbis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4g)

3.1.2.8 4,4′-(2,2′-(4,4′-Sulphonylbis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4h)

3.1.2.9 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2–yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4i)

3.1.2.10 4,4′-(2,2′-(4,4′-Oxybis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4j)

3.1.2.11 4,4′-(2,2′-(4,4′-Methylenebis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4k)

3.1.2.12 4,4′-(2,2′-(4,4′-Methylenebis(4,1-phenylene))bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4l)

3.2 Experimental procedure for the synthesis of entitled compounds (4m–4t)

3.2.1 Monophenylic hydrazono derivatives (3m, 3n, 3q, 3r)

3.2.2 Monophenylic pyrazole or pyrazolone derivatives (5m–5t)

3.2.2.1 3,5-Dimethyl-4-(2-(3-nitrophenyl)hydrazono)-4H-pyrazole (5m)

3.2.2.2 3,5-Dimethyl-4-((3-nitrophenyl)diazenyl)-1-phenyl-1H-pyrazole (5n)

3.2.2.3 3,5-Dimethyl-4-(2-(4-nitrophenyl)hydrazono)-4H-pyrazole (5o)

3.2.2.4 3,5-Dimethyl-4-((4-nitrophenyl)diazenyl)-1-phenyl-1H-pyrazole (5p)

3.2.2.5 3-Methyl-4-(20(3-nitrophenyl)hydrazono)-1H-pyrazol-5(4H)-one (5q)

3.2.2.6 3-Methyl-4-(2-(3-nitrophenyl)hydrazono)-1-phenyl-1H-pyrazol-5(4H)-one (5r)

3.2.2.7 3-Methyl-4-(2-(4-nitrophenyl)hydrazono)-1H-pyrazol-5(4H)-one (5s)

3.2.2.8 3-Methyl-4-(2-(4-nitrophenyl)hydrazono)-1-phenyl-1H-pyrazol-5(4H)-one (5t)

3.2.3 Reduction of monophenylic pyrazole or pyrazolone derivatives (6m–6t)

3.2.3.1 3-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)aniline (6m)

3.2.3.2 3-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)aniline (6n)

3.2.3.3 4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)aniline (6o)

3.2.3.4 4-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)aniline (6p)

3.2.3.5 4-(2-(3-Aminophenyl)hydrazono)-3-methyl-1H-pyrazol-5(4H)-one (6q)

3.2.3.6 4-(2-(3-Aminophenyl)hydrazono)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6r)

3.2.3.7 4-(2-(4-Aminophenyl)hydrazono)-3-methyl-1H-pyrazol-5(4H)-one (6s)

3.2.3.8 4-(2-(4-Aminophenyl)hydrazono)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6t)

3.2.4 Hydrazono derivatives of monophenylic pyrazole or pyrazolone derivatives (7m–7t)

3.2.4.1 3-(2-(3-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)hydrazono)pentane-2,4-dione (7m)

3.2.4.2 3-(2-(3-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)hydrazono)pentane-2,4-dione (7n)

3.2.4.3 3-(2-(4-(2-(3,5-Dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)phenyl)hydrazono)pentane-2,4-dione (7o)

3.2.4.4 3-(2-(4-((3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)phenyl)hydrazono)pentane-2,4-dione (7p)

3.2.4.5 Methyl 2-(2-(3-(2-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7q)

3.2.4.6 Methyl-2-(2-(3-(2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7r)

3.2.4.7 Methyl-2-(2-(4-(2-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7s)

3.2.4.8 Methyl-2-(2-(4-((E)-2-(3-methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-ylidene)hydrazinyl)phenyl)hydrazono)-3-oxobutanoate (7t)

3.2.5 Monophenylic bispyrazole or bispyrazolone derivatives (4m–4t)

3.2.5.1 1,3-Bis(2-(3,5-dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)benzene (4m)

3.2.5.2 1,3-Bis((3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)benzene (4n)

3.2.5.3 1,4-Bis(2-(3,5-dimethyl-4H-pyrazol-4-ylidene)hydrazinyl)benzene (4o)

3.2.5.4 1,4-Bis((3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)diazenyl)benzene (4p)

3.2.5.5 4,4′-(2,2′-(1,3-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4q)

3.2.5.6 4,4′-(2,2′-(1,3-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4r)

3.2.5.7 4,4′-(2,2′-(1,4-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1H-pyrazol-5(4H)-one) (4s)

3.2.5.8 4,4′-(2,2′-(1,4-Phenylene)bis(hydrazin-2-yl-1-ylidene))bis(3-methyl-1-phenyl-1H-pyrazol-5(4H)-one) (4t)

3.3 General synthetic method for pyrazole and pyrazolone ring formation via microwave irradiation

3.4 Antimicrobial study for the synthesized compounds (4a–4t)

4 Conclusion

Acknowledgement

References

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