Synthesis and characterization of new 3,3`-bipyrazole-4,4`-dicarboxylic acid derivatives and some of their palladium(II) complexes as pre-catalyst for Suzuki coupling reaction in water European Journal of Chemistry 10 (4) (2019) 367-375 European Journal of Chemistry View Journal Online View Article Online Synthesis and characterization of new 3,3`-bipyrazole-4,4`-dicarboxylic acid derivatives and some of their palladium(II) complexes as pre-catalyst for Suzuki coupling reaction in water Othman Abduallah Al-Fulaij , Abdel-Zaher Abdelaziz Elassar * and Kamal Mohamed Dawood Chemistry Department, Faculty of Science, Kuwait University, Safat-13060, Kuwait alfulaijothman@gmail.com (O.A.A.), aelassar@yahoo.com (A.A.E.), dr_dawood@yahoo.com (K.M.D.) * Corresponding author at: Chemistry Department, Faculty of Science, Kuwait University, Safat-13060, Kuwait. Tel: +965.24983680 Fax: +965 24816482 e-mail: aelassar@yahoo.com (A. A. Elassar). 10.5155/eurjchem.10.4.367-375.1915 Received: 07 July 2019 Received in revised form: 20 October 2019 Accepted: 27 October 2019 Published online: 31 December 2019 Printed: 31 December 2019 The 1,3-dipolar cycloaddition reaction of bis-hydrazonyl chlorides with methyl propiolate afforded dimethyl 1,1′-aryl-3,3`-bipyrazole-4,4`-dicarboxylates (5a,b). Heating the later compound 5a with a mixture of HCl/AcOH gave 3,3`-bipyrazole-5,5`-dicarboxylic acid derivative 6. Treatment of the hydrazonoyl chloride (1a) and 3,3`-bipyrazole-5,5`- dicarboxylic acid (6) with palladium(II) chloride gave the corresponding Pd-complexes 7 and 8, respectively. The catalytic activity of the prepared Pd-complexes was examined in the Suzuki cross-coupling reaction of phenylboronic acid with activated and deactivated aryl(hetaryl) bromides. The catalyst system provides very good to excellent yields, 85-94%. The structures of the obtained products were established from their elemental analysis, spectral data, XPS, EDX, and single crystal X-ray crystallography. Crystal data for C10H7N2O2 (6): triclinic, space group P-1 (no. 2), a = 3.9956(10) Å, b = 9.8917(18) Å, c = 10.810(3) Å, α = 94.167(15)°, β = 94.979(19)°, γ = 98.953(15)°, V = 418.83(16) Å3, Z = 2, T = 296.(2) K, μ(Cu Kα) = 0.887 mm-1, Dcalc = 1.484 g/cm3, 5469 reflections measured (11.72° ≤ 2Θ ≤ 133.24°), 1420 unique (Rint = 0.0633, Rsigma = 7.24%) which were used in all calculations. The final R1 was 0.1055 (>2sigma(I)) and wR2 was 0.3620 (all data). Bipyrazoles C-C coupling Heterocycles Pd-complexes X-ray single crystal Bis-hydrazonoyl chlorides Cite this: Eur. J. Chem. 2019, 10(4), 367-375 Journal website: www.eurjchem.com 1. Introduction Pyrazoles, as a class of multi-donor nitrogen ligands with changing coordination patterns, has played important roles in organometallic, inorganic and materials chemistry and were also used to establish pyrazolyl-bridged multi-metal and metal-metal bonding coordination systems [1,2]. Chemistry of the coordination of pyrazole and its derivatives have received special attention because of its structural diversity, such as metal-based polymers, [3,4]. Furthermore, pyrazole-based palladium(II) complexes were reported as examples for interesting coordination chemistry [5-7]. Pyrazolyl palladium complexes proved to be efficient catalysts for cross-coupling reactions [8,9]. Besides, pyrazoline ligands coordinated to palladium(II) were also assigned as very efficient DNA intercalator and artificial metallonuclease [10]. Bipyrazoles were found to be potential bioactive com- pounds [11], where they were reported to have antitumor [12], anti-inflammatory [13], antimicrobial [14] and cytotoxic [15] activities and scavengers for free radicals [16]. Further, pyrazole scaffold is a component of some commercial drugs in the market such as celecoxib and rimonabant [17,18]. 1,3-Dipolar cycloaddition was reported as one of the most valuable synthetic routes for the construction of pyrazole heterocycles [19,20]. In continuation of our research work about bis-hydrazonoyl chlorides [21-24], we report herein the hitherto unreported regioselective double 1,3-dipolar cyclo- addition of the bis-hydrazonoyl chlorides (1a,b) with methyl propiolate followed by acid hydrolysis of one of the products and its reaction with palladium(II) chloride and with urea. The regioselectivity of the obtained structures was confirmed from the single crystal X-ray analysis. Applications of the palla- dium(II) complex in Suzuki cross-coupling was also examined. 2. Experimental 2.1. Instrumentations Melting points were measured on a Gallenkamp melting point apparatus. IR spectra were recorded using KBr disks using a Perkin-Elmer System 2000 FT-IR spectrophotometer. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded at 25 °C using DMSO-d6 as a solvent with TMS as internal standard on a Bruker DPX 400 or 600 super- conducting NMR spectrometer. Chemical shifts are reported in ppm. ABSTRACT RESEARCH ARTICLE KEYWORDS European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2019 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.10.4.367-375.1915 http://dx.doi.org/10.5155/eurjchem.10.4.367-375.1915 https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.367-375.1915&domain=pdf&date_stamp=2019-12-31 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.10.4.367-375.1915 mailto:alfulaijothman@gmail.com mailto:aelassar@yahoo.com mailto:dr_dawood@yahoo.com mailto:aelassar@yahoo.com http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.10.4.367-375.1915&domain=pdf&date_stamp=2019-12-31� 368 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 Scheme 1. Synthesis of 1,1`-diphenyl-3,3`-bipyrazole derivatives 5 and 6. Low-resolution electron impact mass spectra [MS(EI)] and high-resolution electron impact mass spectra [HRMS (EI)] were performed on high resolution GC-MS (DFS) thermo spectrometers at 70.1 eV using magnetic sector mass analyzer. The crystal structures were determined by a Rigaku R-AXIS RAPID diffractometer and Bruker X8 Prospector and the single crystal X-ray diffraction data collections were made by using Mo-Kα radiation. The data were collected at room tempe- rature. The structure was solved by direct methods and was expanded using Fourier techniques. The non-hydrogen atoms were refined anisotropically. The structure was solved and refined using the Bruker SHELXTL Software Package (Structure solution program-SHELXS-97 and Refinement program-SHELXL-97) [25]. Data were corrected for the absorption effects using the multi-scan method (SADABS). Scanning Electron Microscopy (SEM) and Energy Dispersive X- ray analysis (EDX) were examined at room temperature (25 °C) in a model JSM 6300 JEOL scanning electron microscope (Akishima, Japan) at 20 kV. X-ray Photoelectron Spectroscopy (XPS) was conducted using a Thermo Scientific ESCALAB- 250Xi spectrometer. The bis-hydrazonoyl chlorides (1a,b) was prepared following the literature procedure (Scheme 1) [26]. 2.2. Synthesis of 1,1'-diaryl-3,3'-bipyrazole derivatives (5a,b) To a solution of the appropriate bis-hydrazonoyl chloride 1a or 1b (10 mmol) in dry benzene (30 mL), methyl propiolate 3 (20 mmol) was added, followed by dropwise addition of triethylamine (0.2 mL). The reaction mixture was refluxed for 4 h then left to cool to room temperature. The solvent was evaporated under reduced pressure then the residue was treated with few drops of methanol. The precipitated product was filtered off, washed with methanol, dried and finally recrystallized from DMF to afford the corresponding 3,3'- bipyrazole derivatives 5a,b (Scheme 1). Dimethyl 1,1'-diphenyl-3,3'-bipyrazole-4,4'-dicarboxylate (5a): Color: Beige. Yield: 70%. M.p.: 260-262 °C. FT-IR (KBr, ν, cm−1): 3084 (CH), 2989 (CH), 1733 (C=O). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.53 (s, 2H, pyrazole-H), 7.52-7.34 (m, 10H, Ar-H), 3.45 (s, 6H, 2CH3). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 160.1 (2C, C=O), 144.9 (2C, pyrazole-C), 129.02 (2C, pyrazole-C), 116.6 (2C, pyrazole-C), 140.1 (2C, Ar-C), 128.9 (4C, Ar-C), 126.0 (2C, Ar-C), 121.1 (4C, Ar-C), 52.1 (2C, OCH3). HRMS (EI, m/z) calcd. for C22H18N4O4: 402.10 (M+); found: 402.13. Anal. calcd. for C22H18N4O4: C, 65.66; H, 4.51; N, 13.92. Found: C, 65.67; H, 4.32; N, 13.97%. Dimethyl 1,1'-di(4-chlorophenyl)-3,3'-bipyrazole-4,4'-dicar boxylate (5b): Color: Yellow. Yield: 60%. M.p.: 232-233 °C. IR (KBr, ν, cm−1): 3076 (CH), 2988 (CH), 1736 (C=O). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.56 (s, 2H, pyrazole-H), 7.64, 7.62 (d, 2H, Ar-H, J = 8 Hz); 7.40, 7.38 (d, 2H, Ar-H, J = 8 Hz), 7.60, 7.58 (d, 2H, Ar-H, J = 8 Hz), 7.33 (d, 2H, Ar-H, J = 8 Hz), 3.76 (s, 6H, 2OCH3). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 160.2 (2C, C=O), 147.4 (2C, pyrazole-C), 129.2 (2C, pyrazole- C), 117.5 (2C, pyrazole-C), 139.6 (2C, Ar-C), 129.2 (2C, Ar-C), 126.0 (4C, Ar-C), 120.9 (4C, Ar-C), 54.3 (2C, OCH3). HRMS (EI, m/z) calcd. for C22H16Cl2N4O4: 470.05 (M+); found: 470.10. Anal. calcd. for C22H16Cl2N4O4: C, 56.07; H, 3.42; N, 11.89. Found: C, 56.16; H, 3.34; N, 11.91%. 2.3. 1,1'-Diphenyl-3,3'-bipyrazole-4,4'-dicarboxylic acid (6) A solution of compound 5a (1 mmol) in a mixture of glacial acetic acid (15 mL), hydrochloric acid (5 mL) and water (5 mL), was refluxed for 5 h during which compound 5a was dissolved and a solid product was precipitated. The mixture was left to cool to room temperature and the precipitate was collected by filtration and recrystallized from acetonitrile : methanol (2:1, v:v) to give 3,3'-bipyrazole-4,4'-dicarboxylic acid (6) as pale gray crystals (2.32 g, 62%) (Scheme 1). M.p.: 208-210 °C. Color: Pale grey. Yield: 62%. IR (KBr, ν, cm−1): 3427 (OH, acid), 3064 (CH), 2981 (CH), 1702 (C=O, acid). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.49-7.37 (m, 10H, Ar-H), 7.53 (s, 2H, pyrazole-H), 13.45 (br. s, 2H, CO2H). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 158.2 (2C, C=O), 144.6 (2C, pyrazole- C), 128.6 (2C, pyrazole-C), 109.8 (2C, pyrazole-C), 140.0 (2C, Ar-C), 134.4 (4C, Ar-C), 128.5 (4C, Ar-C), 125.8 (2C, Ar-C). HRMS (EI, m/z) calcd. for C20H14N4O4: 374.1015 (M+); found: 374.1014. Anal. calcd. for C20H14N4O4: C, 64.17; H, 3.77; N, 14.97. Found: C, 64.54; H, 3.73: N, 14.75%. Crystal Data: Crystal dimensions 0.060 × 0.080 × 0.200 mm, triclinic, a = 3.9956(10) Å, b = 9.8917(18) Å, c = 10.810(3) Å, V = 418.83 (16) Å3, α = 94.167(15)°, β = 94.979(19)°, γ = 98.953(15)°, θmax 66.62° (0.84 Å resolution), Space Group P-1, Z = 2, Dcalc = 1.484 g/cm3, F000 = 194, R1 = 10.55%, wR2 = 36.20%. 2.4. Synthesis of bis-hydrazonoyl chloride-PdCl2 complex (7) A solution of compound 1a (0.307 g, 1 mmol) in DMF (25 mL) was added to a hot solution of palladium(II) chloride (0.177 g, 1 mmol) in methanol (30 mL). The reaction mixture was refluxed for 3 h, then left to cool to room temperature. The formed solid product was collected by filtration, washed with DMF then water and ethanol to give the Pd-complex 7 as pale gray solid (0.305 g, 63%) (Scheme 2). Color: Pale gray. Yield: 63%. M.p.: 280-281 °C. IR (KBr, ν, cm−1): 3321 (NH), 3238 (NH), 3053 (CH), 1639 (C=N). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 369 Scheme 2. Complexation of bis-hydrazonoyl chloride 1a and bipyrazole-dicarboxylic acid 6 with PdCl2. 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.08-6.38 (m, 10H, Ar-H), 7.96 (br. s, 1H, NH), 10.66 (br. s, 1H, NH). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 156.2 (2C, C=N), 144.3 (2C, Ar-C), 130.2 (4C, Ar-C), 120.0 (2C, Ar-C), 118.23 (4C, Ar-C). MS (EI), m/z (%)): 484.50 (M+, 73%), 271.0 (32%), 237.1 (44%), 214.0 (63%), 122.0 (23%). UV/Vis (CHCl3, λmax, nm, (ε)): 239.55, 292.0, 326.17. Anal. calcd. for C14H12Cl4N4Pd: C, 34.71; H, 2.50; N, 11.56. Found: C, 34.54; H, 2.73; N, 11.43%. EDX Anal. for Pd: calcd.: 21.96%, found 21.70%. 2.5. Synthesis of 1,1'-diphenyl-3,3'-bipyrazole-4,4'-dicar boxylic acid-palladium(II) chloride complex (8) A solution of palladium(II) chloride (0.354 g, 2 mmol) in methanol (25 mL) was added to a solution of compound 6 (0.374 g, 1 mmol) in methanol (25 mL). The reaction mixture was refluxed for 5h, then left to cool to room temperature. The precipitated solid product was collected by filtration and recrystallized from DMF/acetonitrile (1:1) to yield the Pd- complex 8 as green solid (0.67 g) (Scheme 2). Color: Green. Yield: 92%. M.p.: 264-266 °C. IR (KBr, ν, cm−1): 3435 (OH), 3062 (CH), 1725 (C=O), 1703 (C=O). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.07 (s, 2H, pyrazole-H), 7.53-7.19 (m, 10H, Ar-H), 13.48 (br. s, 2H, CO2H). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 159.7 (2C, C=O, CO2H), 158.2 (2C, C=N, pyrazole-C), 144.6 (2C, Ar-C), 140.0 (4C, Ar-C), 134.4 (2C, pyrazole-C), 128.6 (2C, Ar-C), 125.8 (4C, Ar-C), 109.8 (2C, pyrazole-C). UV/Vis (CHCl3, λmax, nm, (ε)): 266. Anal. calcd. for C20H14Cl4N4O4Pd2 : C, 32.95; H, 1.94; N, 7.69. Found: C, 32.75; H, 2.03; N, 6.87%. EDX Anal. for Pd: calcd. 29.20%, found. 29.6%. 2.6. Synthesis of poly-N-bis(3,3`-bi-pyrazolylcarbonyl)urea derivative (10) To a solution of compound 6 (0.374 g, 1 mmol) in DMF (25 mL), urea (0.060 g, 2 mmol) were added. The reaction mixture was refluxed for 5 h then left to cool to room temperature. The precipitated product was collected by filtration and recrystallized from DMF/acetonitrile (1:1) to give the poly- bis(3,3`-bi-pyrazolylcarbonyl)urea derivative 10 as yellow powder (0.35 g) (Scheme 3). Colour: Yellow powder. M.p.: > 300 oC. IR (KBr, ν, cm−1): 3208 (NH), 3122 (NH), 3069 (CH), 1726 (C=O), 1660 (C=O). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 12.47 (br. s, 2H, NH), 7.99-7.39 (m, 10H, Ar-H), 7.59 (s, 2H, pyrazole-CH). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 163.3 (1C, C=O), 159.6 (2C, C=O), 146.0 (2C, pyrazole-C), 138.8 (2C, Ar-C), 131.7 (4C, Ar-C), 129.8 (2C, pyrazole-C), 127.2 (2C, Ar- C), 118.9 (4C, Ar-C), 117.1 (2C, pyrazole-C). Anal. calcd. for repeating unit C21H14N6O3: C, 63.31; H, 3.54; N, 21.10. Found: C, 63.51; H, 3.72; N, 21.21%. 2.7. Suzuki-Miyaura cross-coupling of aryl(hetaryl) bromides with phenylboronic acid in water A mixture of the appropriate aryl(hetaryl) bromides 12-17 (1 mmol), phenylboronic acid 11 (146 mg, 1.2 mmol), tetrabutylammonium bromide (TBAB) (194 mg, 0.6 mmol), palladium complex 7 (7 mg, 1 mol%) and KOH (112 mg, 2 mmol) in distilled water (3 mL) was thermally heated with stirring at 100 °C under open air for the appropriate reaction time (monitored by TLC), as listed in Table 4. After the reaction was complete, the product was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over anhydrous MgSO4 then filtered and the solvent was evaporated under reduced pressure. The residue was then subjected to separation via flash column chromatography with hexane: ethyl acetate (10:1, v:v) as an eluent to give the corresponding pure cross-coupled products 18-23. All experiments were done in triplicate. 4-Acetylbiphenyl (18): M.p.: 117-119 °C (Lit. M.p.: 118-120 °C [27]). 1,1'-Biphenyl-4-carbonitrile (19): M.p.: 85-86 °C (Lit. M.p.: 86-87 °C [28]). 3-Nitrobiphenyl (20): M.p.: 56-58 °C (Lit. M.p.: 57-59 °C [29]). 4-Phenylphenol (21): M.p.: 144-145 °C (Lit. M.p.: 146-147 °C [29]). N-Acetyl-4-aminobiphenyl (22): M.p.: 152-154 °C (Lit. M.p.: 150-153 °C [29]). 4, 6-Dimethyl-2-oxo-5-phenyl-1, 2-dihydropyridine-3-carbo nitrile (23): Color: Brown crystals. Yield: 88%. M.p.: 230-231 °C. IR (KBr, ν, cm−1): 3434 (NH), 2218 (C≡N), 1658 (C=O). 1H NMR (400 MHz, DMSO-d6, δ, ppm): 7.77-7.31 (m, 5H, Ar-H); 6.15 (br. s, 1H, NH, D2O-exchangeable), 2.49 (s, 3H, CH3), 2.21 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 160.93 (1C, C=O), 158.41 (1C, pyridine-C), 151.37 (1C, Ar-C), 134.01 (2C, Ar-C), 129.87 (2C, Ar-C), 127.26 (1C, Ar-C), 115.90 (1C, pyridine-C), 107.39 (1C, pyridine-C), 100.45 (1C, pyridine-C), 99.07 (1C, CN), 18.85 (1C, CH3), 13.44 (1C, CH3). 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 370 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 Scheme 3. Synthesis of poly-bis(3,3`-bi-pyrazolylcarbonyl)urea derivative 10. Figure 1. ORTEP plot of the X-ray crystallographic data of compound 6. HRMS (EI, m/z) calcd. for C14H12N2O (M+): 224.09496; found: 224.09487. Anal. calcd. for C14H12N2O: C, 74.98; H, 5.39; N, 12.49. Found: C, 75.01; H, 5.33; N, 12.63%. 3. Results and discussion 3.1. Synthesis of the bipyrazole-dicarboxylic acid derivatives (5 and 6) The bis-hydrazonoyl chlorides 1a,b were prepared following our previously reported procedure [26]. Then, the reaction of bis-hydrazonoyl chloride 1a with methyl propiolate 3, in 1:2 molar ratio, was conducted in benzene at reflux temperature in the presence of triethylamine to afford only one product as checked by TLC. The obtained pure product was correctly analyzed for C22H18N4O4 based on its mass spectrum and elemental analyses. Structure of the obtained reaction product can be either dimethyl 1,1′-diphenyl-3,3`- bipyrazole-5,5`-dicarboxylate (4a) or its regioisomer dimethyl 1,1′-diphenyl-3,3`-bipyrazole-4,4`-dicarboxylate (5a) (Scheme 1). Spectroscopic analyses were fully compatible with structure 5a. For example, the isolated product revealed a singlet signal at δH 7.54 ppm in its 1H NMR spectrum due to the pyrazole-5-CH proton (structure 5a) and not the pyrazole-4- CH proton (structure 4a) (where pyrazole-4-CH proton appears at a lower chemical shift) [24]. Moreover, 13C NMR spectrum exhibited a peak at δC 168.1 (C=O), 144.9, 128.8, 116.6 (pyrazole-carbons), 138.8, 130.3, 124.9, 121.2 (aromatic-carbons), 50.4 ppm (CH3). In a similar manner, reaction of bis-hydrazonoyl chloride (1b) with methyl propiolate 3 under similar reaction condition yielded dimethyl 1,1′-di(4-chlorophenyl)-3,3`-bipyrazole-5,5`-dicarboxylate (5b) (Scheme 1). Structure of compound 5b was confirmed from its elemental and spectral analyses. Heating of dimethyl 1,1′-diphenyl-3,3`-bipyrazole-4,4`- dicarboxylate (5a) with a mixture of hydrochloric acid : acetic acid (1:3, v:v) led to the formation of a product that was determined as 3,3`-bipyrazole-5,5`-dicarboxylic acid (6). The structure of the product 6 was confirmed from all possible spectral analyses (IR, MS, 1H- and 13C-NMR) as well as its single crystal X-ray analysis as depicted in Figure 1 and Tables 1-3 (CCDC 1548525). 3.2. Synthesis of the palladium(II) complexes (7 and 8) The complexation behaviour of the bis-hydrazonoyl chloride 1a as a ligand (L) towards PdCl2 was investigated. Thus, the addition of a hot solution of compound 1a in DMF to the PdCl2 solution in methanol at adjusted pH = 5.76 led to the formation of complex 7 of type LPdCl2 (Scheme 2). Structure of the complex 7 was established based on its elemental analyses and spectral data. Besides, the experi-mental UV-visible absorption spectrum of the ligand 1a exhibited two bands centred at 267.72 and 283.00 nm, while that of the Pd-complex 7 exhibited three peaks in the ultraviolet region at 239.55, 292.00 and 326.17 nm. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 371 Table 1. Crystal data and details of the structure refinement for compound 6. Empirical formula C10H7N2O2 Formula weight 187.18 Temperature (K) 296.(2) Crystal system Triclinic Space group P-1 a (Å) 3.9956(10) b (Å) 9.8917(18) c (Å) 10.810(3) α (°) 94.167(15) β (°) 94.979(19) γ (°) 98.953(15) Volume (Å3) 418.83(16) Z 2 ρcalc (g/cm3) 1.484 Μ (mm-1) 0.887 F(000) 194.0 Crystal size (mm3) 0.200 × 0.080 × 0.060 Radiation Cu Kα radiation (λ = 1.54178 Å) 2Θ range for data collection (°) 11.72 to 133.24 Index ranges -4 ≤ h ≤ 4, -11 ≤ k ≤ 11, -10 ≤ l ≤ 12 Reflections collected 5469 Independent reflections 1420 [Rint = 0.0633] Data/restraints/parameters 1420/0/130 Goodness-of-fit on F2 1.422 Final R indexes [I≥2σ (I)] R1 = 0.1055, wR2 = 0.3206 Final R indexes [all data] R1 = 0.1314, wR2 = 0.3620 Largest diff. peak/hole (e Å-3) 0.43/-0.33 Absorption correction Multi-scan Max. and min. transmission 0.9487 and 0.8425 Structure solution technique direct methods Structure solution program SHELXS-97 (Sheldrick, 2008) Refinement method Full-matrix least-squares on F2 Refinement program SHELXL-97 (Sheldrick, 2008) Table 2. Bond lengths (Å) for compound 6. Atom-Atom Bond length Atom-Atom Bond length N2-C5 1.334(6) C5-C5#1 1.465(9) O2-C10 1.217(6) C9-C10 1.466(8) O3-H7 1.09(8) N2-N1 1.356(5) N1-C4 1.433(6) O3-C10 1.326(6) C1-C2 1.362(9) N1-C8 1.344(7) C2-C3 1.386(8) C1-C6 1.359(8) C3-C4 1.378(7) C5-C9 1.427(6) C4-C7 1.377(8) C6-C7 1.386(7) #1 Symmetry code: -x+1, -y+1, -z+1. Table 3. Bond angles (°) for compound 6. Atom-Atom-Atom Bond angle Atom-Atom-Atom Bond angle C5-N2-N1 106.0(4) C10-O3-H7 110.0(4) C8-N1-N2 111.1(4) C8-N1-C4 128.5(4) N2-N1-C4 120.4(4) C6-C1-C2 120.5(5) C1-C2-C3 120.8(5) C4-C3-C2 118.2(5) C7-C4-C3 121.4(5) C7-C4-N1 119.6(4) C3-C4-N1 119.0(5) N2-C5-C9 110.5(4) N2-C5-C5#1 117.3(5) C9-C5-C5#1 132.2(6) C1-C6-C7 120.4(5) C4-C7-C6 118.7(5) N1-C8-C9 108.5(4) C8-C9-C5 103.9(4) C8-C9-C10 120.7(4) C5-C9-C10 135.3(4) O2-C10-O3 119.6(5) O2-C10-C9 121.2(5) #1 Symmetry code: -x+1, -y+1, -z+1. On the other hand, all trials to chelate the bipyrazole- dicarboxylate ester derivative 5a with PdCl2 were failed. This may be interpreted in terms of the non-planarity of the bipyrazole ester derivative 5 due to the high steric hindrance of the ester groups and consequently, the nitrogen-dentates are not in the appropriate positions to interact with palladium ions. However, treatment of the bipyrazole-dicarboxylic acid derivative 6 with PdCl2 in DMF resulted in the formation of the bipyrazole-palladium(II) complex structure 8 (Scheme 2). 3.3. XPS and EDX measurements of palladium(II) complexes All attempts to get a single crystal of the obtained complex 7 and 8 were not successful. Therefore, X-ray Photoelectron Spectroscopy (XPS) technique was used to elucidate the chemical composition of the palladium complex 8. The XPS analysis (Figure 2) confirmed the presence of palladium, carbon, nitrogen and oxygen elements in the complex 8. In the XPS valence band spectra for the Pd, two pairs Pd 3d peaks were observed (Figure 2A). The binding energy values of 338.1, 343.3 and 345.1 eV were assigned to incarcerate Pd (II) [30,31]. The peak at 339.86 was assigned to Pd-O bond. N1s high-resolution spectra (Figure 2B) showed two peaks, the first peak falling at binding energy 399.9 eV was assigned to Pd-N bond [32,33] and the second one, falling at binding energy 406.7 eV attributed to oxidized N. O1s peak (Figure 2C) at binding energy 531.46 eV assigned to C−O and O-H bond. C1s high-resolution spectra for Pd-complex are reported in Figure 2D. They were assigned to C–C, and C=C (284.5 eV), C–O (285.82 eV) and C=O and may be for C-O-M (M metal ion) at binding energy 287.4 eV) groups. Moreover, the binding energies 198.23 and 199.82 eV were assigned for Cl 2p, 3/2 and Cl 2p, 1/2. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 372 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 Figure 2. XPS of Pd-complex 8, binding energy of C, N, O and Pd. N N NN Ph Ph C C Pd Cl Cl O O O O Pd Cl Cl N N NN Ph Ph C C Pd Cl Cl O O O O Pd Cl Cl H H N N NN Ph Ph C C Pd Cl Cl O O O O Pd Cl Cl H HH H Figure 3. H-bonding between compound 8 forms consecutive layers. Furthermore, the IR spectrum of compound 8 showed a shift in the carbonyl absorption, ∆νC=O = 23 cm-1, and hydroxyl absorption, ∆νOH = 10 cm-1 when compared with the IR of compound 6, this result is attributed to the hydrogen bonding between the carboxylic groups (Figure 3). Moreover, the microanalyses of palladium in compounds 7 and 8 were determined from the Energy Dispersive X-ray analysis (EDX), which is a technique of elemental analysis associated to electron microscopy based on the generation of characteristic X-rays that reveals the presence of elements present in the samples. The EDX analyses of compounds 7 and 8 exhibited the presence of Pd in 21.7 and 29.6% that were very closer to the calculated values 21.96 and 29.2%, respect- tively, as depicted in Figure 4. 3.4. Structure morphology In general, the change in the surface morphology is attributed to the introduction of metal ions into the matrix. The mode of chelation of the palladium ions within the consecutive layers of the bis-pyrazole-carboxylic acid 6 was examined by measuring the SEM of the Pd-complex 8 as outlined in Figure 5. The results of the SEM provided consecutive layers which is consistent with PdCl2-bipyrazole- PdCl2 layers. The morphology of the metal complex 8 is shown in Figure 5, with 10000 and 40000 magnifications. Heating of 3,3`-bipyrazole-5,5`-dicarboxylic acid 6 with double equivalents of urea led to the formation of the poly- bis(3,3`-bi-pyrazolylcarbonyl)urea derivative 10 (Scheme 3). The structure of the product 10 was formed through the intermediate 9 via loss of ammonia molecules in a step-type polymerization reaction. Comparing with its carboxylic acid precursor 6, the IR spectrum of the polyamide 10 showed new broad bands for the NH groups at 3208 and 3122 cm-1 in addition to, two carbonyl absorptions at 1726 and 1660 cm-1. Moreover, the structure of the polyamide 10 was investigated using SEM analysis. The results of SEM provided consecutive layers which is consistent with the postulated structure 10. The morphological structure of the polymeric product 10 is shown in Figure 6, with 10000 and 40000 magnifications. It was observed that the bipyrazole-based polyamide 10 has a high degree of crystallinity. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 373 Figure 4. EDX of compounds 7 and 8 (Spectrum 9 represent compound 7 and spectrum 15 represent compound 8). Figure 5. SEM micrograph of palladium complex 8. Figure 6. SEM micrograph of the polyamide product 10. 3.5. Catalytic activity of Pd-Complex in Suzuki cross- coupling reactions The palladium catalyzed Suzuki-Miyaura cross-coupling reaction represents one of the most widely and eco-friendly method for the construction of carbon-carbon bonds in organic molecules [34-36]. One of our goals in this work is to study the catalytic activity of the prepared Pd-complexes in Suzuki cross-coupling reaction. Thus, the catalytic activity of the Pd(II) complex 8 in the cross-coupling reaction between phenylboronic acid (11) and 4-bromoacetophenone (12) was examined and the results are shown in Table 4. The reaction was conducted in water (3 mL) at 100 °C using 1 mol% of the Pd(II) complex 8 with 1 mmol 4-bromoacetophenone (12), 1.2 mmol phenylboronic acid (11), 0.6 mmol TBAB and 2 mmoles of potassium hydroxide. TLC of the reaction mixture showed that 4-bromoacetophenone (12) was completely consumed after 45 min of heating and the product 4-acetylbiphenyl (18) was isolated in 90 % yield. Next, the utility of Pd-complex 8 in Suzuki-Miyaura cross-coupling reactions of further aryl and heteroaryl bromides under the above condition was also conducted. Thus, Suzuki coupling of the activated aryl bromides 13, 14, 15 and 16 with phenylboronic acid 11 resulted in the formation of the corresponding cross-coupled products 19, 20, 21 and 22, respectively in excellent isolated yields as shown in Table 4. Cross-coupling of the 5-bromo pyridine-3-carbonitrile derivative 17 [37] with phenylboronic acid 11 in water using Pd-complex 8 (1 mol%) afforded the 5- phenylpyridine-3-carbonitrile derivative 23, to the best of our knowledge, this is the first preparing by Suzuki-Miyaura cross- coupling reaction, (run 6, Table 4). The identities of the cross- coupled products were confirmed by HRMS, 1H and 13C NMR spectra. In similar manner, the catalytic activity of Pd-complex 7 was investigated (Table 5). Thus, Suzuki coupling of the activated aryl bromides 12-16 with phenylboronic acid 11 resulted in the formation of the corresponding cross-coupled products 18- 22 in excellent isolated yields as shown in Table 5. 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 374 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 Table 4. Suzuki coupling of aryl bromides with phenylboronic acid in water. 1 mol% Cat. 8 or 7, H2O TBAB, KOH, 100 oC 11 18-23 Ar(Het)-Br 12-17 B(OH)2 + Ar(Het) Run Ar (Het)-Br Product Time (min) Yield %a 1 Br O 12 O 18 45 90 2 NC Br 13 NC 19 45 91 3 BrO2N 14 O2N 20 45 92 4 HO Br 15 OH 21 60 91 5 H3COCHN Br 16 H3COCHN 22 60 85 6 N H CN Me Me O Br 17 N H CN Me Me O 23 45 88 a Reaction conditions: Bromide/boronic acid/KOH/TBAB/water: 1.0/1.2/2.0/0.6/3.0 mL at 100 °C temperature. All values refer to the isolated yields. Table 5. Suzuki coupling of aryl bromides with phenylboronic acid in water using Pd-complex 7 as a catalyst. Run Ar (Het)-Br Product Time (min) Yield (%) 1 12 18 45 91 2 13 19 45 90 3 14 20 45 94 4 15 21 60 90 5 16 22 60 85 6 17 23 45 91 Table 6. The comparison of the data obtained by Pd-complex 7 and 8 with that reported in literature. Compound Time (min) Yield (%) Comment or reference 18 1140 96 Reference 28 45 90 Catalyst used: compound 8 40 91 Catalyst used: compound 7 19 120 88 Reference 28 45 91 Catalyst used: compound 8 30 90 Catalyst used: compound 7 20 120 92 Reference 29 45 92 Catalyst used: compound 8 45 94 Catalyst used: compound 7 21 720 90 Reference 29 91 Catalyst used: compound 8 90 Catalyst used: compound 7 22 660 88 Reference 29 60 85 Catalyst used: compound 8 60 85 Catalyst used: compound 7 23 To the best of our knowledge, this is the first reporting for compound 23 for Suzuki coupling reaction 45 88 Catalyst used: compound 8 45 91 Catalyst used: compound 7 Cross-coupling of the 5-bromopyridine-3-carbonitrile derivative 17 [37] with phenylboronic acid 11 in water using Pd-complex 7 (1 mol%) afforded the 5-phenylpyridine-3- carbonitrile derivative 23 (run 6, Table 5). The identities of the cross-coupled products were confirmed by HRMS, 1H and 13C NMR spectra. The yield in case of compound 18, 20 and 23 showed an improvement from 1 to 3% as compared by Pd- complex 8. Comparison between literature data and data obtained upon using catalytic compounds 7 and 8 showed an observed 2019 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.10.4.367-375.1915 Al-Fulaij et al. / European Journal of Chemistry 10 (4) (2019) 367-375 375 improvement in the time of the reactions in addition to the yield % (cf. Table 6). 4. Conclusions The current work described an efficient one-pot region- selective double 1,3-dipolar cycloaddition of bis-hydrazonoyl chlorides with two equivalents of the electron deficient alkyne; methyl propiolate to give the corresponding bipyrazole esters which underwent acid hydrolysis to give the bipyrazole dicarboxylic acid. Palladium(II)-complexes of the bis- hydrazonoyl chloride and bipyrazole dicarboxylic acid were synthesized and both of them was found to be an efficient catalyst for Suzuki cross-coupling reaction. Acknowledgments The authors kindly acknowledge the financial support of this project by Kuwait University, Research Administration through research project grant SC 13/15. The analytical services provided by the ANALAB and SAF in the faculty of Science through the grant no. GS-01/01, GS 01/05 and GS 03/08 are also gratefully acknowledged. Supporting information CCDC-1548525 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/, or by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Funding This research work is funded by Kuwait University, research project grant SC-13/15. ORCID Othman Abduallah Al-Fulaij http://orcid.org/0000-0002-3013-6019 Abdel-Zaher Abdelaziz Elassar http://orcid.org/0000-0002-9754-4578 Kamal Mohamed Dawood http://orcid.org/0000-0002-1351-9886 References [1]. Ballhausen, C. J. Introduction to Ligand Field Theory, McGraw Hill, New York, 1962. [2]. Atwood, J. D.; Wovkulich, M. J.; Sonnenberger, D. C. Acc. Chem. Res. 1983, 16, 350-355. [3]. Cotton, F. A.; Lin, C.; Murillo, C. A. Acc. Chem. Res. 2001, 34, 759-771. [4]. Chifotides, H.; Dunbar, K. R. Acc. Chem. Res. 2005, 38, 146-156. [5]. Muhammad, S.; Hussain, S.; Chen, X.; Al-Sehemi, A. G.; Li, Z. J.; Lai, C. - H.; Iqbal, J. Inorg. Chim. Acta 2019, 494, 160-167. [6]. Fornies, J.; Martin, A.; Sicilia, V.; Martin, L. F. Chem. Eur. J. 2003, 9, 3427-3435. [7]. DeAngelis, A. J.; Peter, G. G.; Ruishan C.; Thomas J. C. J. Org. Chem. 2015, 80, 6794-6813. [8]. Ocansey, E.; Darkwa, J.; Makhubela, B. C. E. RSC Adv. 2018, 8, 13826- 13834 [9]. Li, K.; Mohlala, M. S.; Segapelo, T. V.; Shumbula, P. 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Introduction 2. Experimental 2.1. Instrumentations 2.2. Synthesis of 1,1'-diaryl-3,3'-bipyrazole derivatives (5a,b) 2.3. 1,1'-Diphenyl-3,3'-bipyrazole-4,4'-dicarboxylic acid (6) 2.4. Synthesis of bis-hydrazonoyl chloride-PdCl2 complex (7) 2.5. Synthesis of 1,1'-diphenyl-3,3'-bipyrazole-4,4'-dicar boxylic acid-palladium(II) chloride complex (8) 2.6. Synthesis of poly-N-bis(3,3`-bi-pyrazolylcarbonyl)urea derivative (10) 2.7. Suzuki-Miyaura cross-coupling of aryl(hetaryl) bromides with phenylboronic acid in water 3. Results and discussion 3.1. Synthesis of the bipyrazole-dicarboxylic acid derivatives (5 and 6) 3.2. Synthesis of the palladium(II) complexes (7 and 8) 3.3. XPS and EDX measurements of palladium(II) complexes 3.4. Structure morphology 3.5. Catalytic activity of Pd-Complex in Suzuki cross-coupling reactions 4. Conclusions Acknowledgments Supporting information Disclosure statement Funding ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField15: PrintField16: PrintField17: PrintField18: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: PrintField25: PrintField26: PrintField27: PrintField28: