73 American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) ISSN (Print) 2313-4410, ISSN (Online) 2313-4402 © Global Society of Scientific Research and Researchers http://asrjetsjournal.org/ Synthesis of Diaznylpyrazol Derivatives Sali Abdelala, Abdullah Gheathb, Naowara Alarafic*, Ghazala Hasimd a,b,c Chemistry Department, Faculty of Science, Benghazi University, Benghazi, Libya dChemistry Department, Faculty of Science, Omar Almukhtar University, Al-Bayda, Libya aEmail: sasoahmad5@gmail.com aEmail: a_gheath@yahoo.com aEmail: Nourapro@gmail.com bEmail: G_hasim@yahoo.com Abstract In our present study 4-methylaniline (1) has been reacted with acetyl acetone(2) in presence of sodium nitrite and sodium acetate yielded 3-(2-(p-tolyl) hydrazono) pentane-2,4-dione (3) which react with hydrazine hydrate to give 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) and react with 2-chloro-N(substituted phenyl) acetamide(5a-5g) to give (6a-6g). All the synthesized compounds were characterized on the basis of melting point, TLC and NMR spectra. Keywords: 4-substituted aniline; sodium nitrite; sodium acetate; hydrazine hydrate; phenyl hydrazine; 2-chloro- N (substituted phenyl) acetamide; 2-chloro-N(substituted phenyl) acetamide. 1. Introduction The condensation of symmetrical or unsymmetrical 1,3-diketones with hydrazine or aryl hydrazines in the presence of catalyst generally produced a mixture of two regioisomers where the reactions of 1,3-diketones compounds (8) with aryl hydrazines afforded pyrazole derivatives (9) and (10) [1]. Alkynes react with diazo compounds (12) to afford pyrazoles via [3+2]-cycloaddition for the preparation of 3,5-disubstituted pyrazoles(13) [2] . Another strategy for the synthesis of pyrazoles is the cyclo condensation of an appropriate hydrazine with a carbonyl compound having two electrophilic carbons at the 1 and 3 locations. Importantly, hydrazines behave like a bidentate nucleophile and react with these α,β-unsaturated aldehydes or ketones(14) [3]. ------------------------------------------------------------------------ * Corresponding author. http://asrjetsjournal.org/ American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 74 Pyrazoles were also synthesized by the reaction between N-tosyl-N-propargylhydrazine(17) and aryliodides(18) or vinyltriflates in the presence of palladium catalyst [4]. 2-Chloro-N-Alkyl or Arylacetamide was synthesized from Chloroacetylchloride with various amines. The prepared compounds were screened for their anti- inflammatory activity by carrageenan induced paw odema method in rats [5-9]. R1 R3 OO R2 ArNHNH2 N N R1R2 R3 Ar N N Ar R1R2 R3 + (8) (9) (10) R1 O H 1.TsNHNH2 2. NaOH R1H N N HR2 50oC N N R1 R2 H (11) (12) (13) R1 O Bt R2 N N R1Bt R2 Ar N N R1 R2 Ar NaOEt EtOH , reflux ArNHNH2 EtOH , reflux (14) (15) (16) N Ts NH2 N N Ar Ts N N Ar H Detosylation1.Pd(OAc)2(PPh3)4 ,Et3N 2.PdCl2 ,reflux (17) (19) (20) I (18) Figure 3 2. Materials and Methods All chemicals were purchased from Sigma-Aldrich (St. Louis, Mo, USA). All melting points (mps) were determined by SMP3 stuart scientific melting point apparatus (stuart, Staffordshire, UK) and are uncorrected. All the reactions were monitored by thin-layer chromatography (TLC) using silica gel 60 F254 TLC plates (Merck KGaA, Darmstadt, Germany). Spectroscopic data were recorded with the following instruments: NMR, H1-NMR all the accurate analyzes of NMR were conducted in Micro-Analytical Unit at Research Center of the Faculty of Science, University of Alexandria, Proton magnetic resonance spectra were measured in (CDCl3) solution, on Bruker 500 MHz with chemical shift (δ) expressed in ppm down field from tetramethylsilane as an internal stander (δ MS=0). The multiplicity of the signal is as follow: s (Singlet), d (Doublet), t(Triplet), q(Quartet), m(Multiplet). C13-NMR were measured on Bruker 400MHz with internal reference TMS δ=0, were measured by DEPT spectroscopy (Brucker Company, Elk GroveVillage, USA). 2.1 Synthesis of products 2.1.1 Synthesis of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole(4) American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 75 4-methylaniline(1) (0.01 mole) was dissolved in a mixture of concentrated HCl (8 mL) with water (6 mL) then cooled to 0 oC on ice bath. A cold aqueous solution of sodium nitrite (0.02 mole) was added. The cold diazonium salt solution was filtered into a cooled solution of acetyl acetone(2) in presence of sodium nitrite (0.01 mole) and sodium acetate (0.05 mole) in ethanol (20 mL). the solution was stirred for 2 hours. Resulting solid was filtered, dried and purified by recrystallization using ethanol to afford compound(3) [10]. A mixture of 3-(2-(p-tolyl)hydrazono)pentane-2,4-dione (3) (0.01 mole) and hydrazine hydrate (0.1mole) in glacial acetic acid (15 mL) is refluxed for 4-5 hours. The resulting mixture was concentrated and allowed to cool. The resulting solid was filtered, washed, dried & recrystallized from ethanol to afford compound (4). H3C N N NH N CH3 H3C (4) Yield:65% mp: 129-1300C 2.1.2 Synthesis of 2-Chloro-N-phenylacetamide derivatives (5a-5g) In 250 ml round-bottomed flask aniline derivatives (0.1 mole) in 120 ml of ethanol were stirred for 2-3hours then chloroacetyl chloride (0.1 mole) was added drop wise to the above mixture then stirred for 1-2 hours. The stirred mixture was then refluxed for 2-2.5 hours and poured into ice cold water. The solid obtained was filtered and recrystallized from ethanol. The percentage yield of the products was 82-85%. Table (1) shows the melting points for the prepared compounds (5a-5g). HN O Cl R Table 1: The melting points for the prepared compounds (5a-5g) Compound R M.P. (°C) 5a H 138 5b p-Cl 175 5c o-Cl 79 5d m-OCH3 94 5e p-COOCH3 141-142 5f p-COOC2H5 117 5g p-COOC3H7 109 American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 76 2-Chloro-N-phenylacetamide (5a) H1-NMR:δ =4.18 (2H, s, CH2); 8.25 (H, s, exchangeable, NH); 7.15 &7.17&7.18(H ,t, H-Ar); 7.34&7.35& .37(2H,t,H-Ar); 7.53& 7.55(2H,d,H-Ar). C13 NMR: δ: 42.97(1C), 120.24(2C), 125.37(1C), 129.24(2C), 136.74(1C), 163.92(1C). DEPT: δ: 42.98(1C), 120.24(2C), 125.37(1C), 129.24(2C). 2-Chloro-N-(4-chlorophenyl) acetamide (5b) H1 NMR: δ: 4.21(2H, s, CH2); 9.57(H, s, exchangeable, NH); 7.31& 7.33 (2H, d, H-Ar); 7.66& 7.68(2H,d,H- Ar). C13 NMR: δ: 43.20(1C), 121.19(2C), 128.46(2C), 128.78(1C), 164.65(1C), 164.72(1C). DEPT: δ: 43.24(1C), 121.08(2C), 128. 78(2C). 2-Chloro-N-(2-chlorophenyl)acetamide (5c) H1 NMR:δ:4.23(2H,s,CH2); 8.92(H,s exchangeable, NH); 7.08&&7.09& 7.09& 7.11(1H,t,H-Ar); 7.27& 7.28& 7.29& 7.31& 7.31(1H,t,H-Ar); 7.39 &7.39& 7.40& 7.40(1H,d,H-Ar); 8.35& 8.35& 8.36 &8.37(1H,d,H-Ar). C13 NMR: δ: 43.22(1C), 121.34(1C), 123.55(1C), 125.60(1C), 127.89(1C), 129.30(1C), 133.74(1C), 163.98(1C). DEPT: δ: 43.22(1C), 121.34(1C), 125.59(1C), 127.89(1C), 129.30(1C). 2-Chloro-N-(3-methoxyphenyl)acetamide(5d) H1 NMR: δ:3.80(3H,s,OCH3); 4.17(2H,s,CH2) 8.23(H,s exchangeable, NH); 6.71&6.72(1H,d,H-Ar); 7.01&7.03(1H,d,H-Ar);7.24(1H,s,H-Ar);7.25 7.26 7.27(1H,s,H-Ar). C13 NMR: δ: 42.99(1C), 55.45(1C), 105.95(1C), 111.10(1C), 112.32(1C), 129.93(1C), 137.94(1C), 160.30(1C), 163.90(1C). DEPT: δ: 43.00(1C), 55.46(2C), 105.95(1C), 111.10(1C), 112.31(1C), 129.94(1C). Methyl 4-(2-chloroacetamido)benzoate (5e) H1 NMR: δ:3.90(3H,s,OCH3); 4.19(2H,s,CH2) 8.40(H,s exchangeable, NH); 7.63& 7.65(2H,d,H-Ar); 8.02& 8.04(2H,d,H-Ar) . C13 NMR: δ: 42.96(1C), 52.23(1C), 119.26(2C), 126.68(1C), 130.98(2C), 140.86(1C), 164.11(1C), 166.52(1C) American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 77 DEPT: δ: 42.97(1C), 52.24(1C), 119.25(2C), 130.99(2C). Ethyl 4-(2-chloroacetamido)benzoate (5f) H1 NMR: δ:1.36& 1.38& 1.39(3H,t,OCH2CH3); 4.19(2H,s,CH2); 4.35& 3.45& 3.46& 3.47(2H,q,CH2); 8.41(H,s exchangeable, NH); 7.63& 7.64 (2H,d,H-Ar); 8.02& 8.04(2H,d,H-Ar). C13 NMR: δ: 14.42(1C), 42.97(1C), 61.12(1C), 119.22(2C), 127.05(1C), 130.92(2C), 140.76(1C), 164.11(1C), 166.04(1C) . DEPT: δ: 14.43(1C), 42.98(1C), 61.12(1C), 119.22(2C), 130.93(2C). Propyl 4-(2-chloroacetamido)benzoate (5g) H1 NMR: δ:1.00& 1.01& 1.03(3H,t,OCH2CH2CH3); 1.76& 1.77& 1.78& 1.80 &1.81 (2H,m,CH2) 4.19(2H,s, CH2); 4.24&&4.26& 4.27(2H,t, OCH2CH2 CH3) 8.40(H,s exchangeable, NH); 7.63& 7.65(2H,d,H-Ar); 8.02& 8.04(2H,d,H-Ar). C13 NMR: δ: 10.6(1C), 22.18(1C), 42.97(1C), 66.69(1C), 119.24(2C), 127.06(1C), 130.92(2C), 140.76(1C), 164.09(1C),166.10(1C). DEPT: δ: 10.61(1C), 22.19(1C); 42.98(1C); 66.12(1C), 119.24(2C), 130.93(2C). 2.1.2.Synthesis of N-(4-substitutedphenyl)-2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamide(6a- 6g) In 100 ml round-bottomed flask a mixture of 2-chloro-N-Alkyl/Arylacetamide derivatives (5a-5g) (0.02mole) in DMF was mixed with another mixture of 4-((4-methylphenyl)-diazenyl)-3,5-dimethyl-1H-pyrazole(4) (0.02mole) in DMF. Anhydrous Potassium Carbonate (0.02mole) was added to above reaction mixture then heated on water bath overnight. The desired product was isolated as precipitate after pouring the reaction mixture in an ice-cold water for 30 minute. Precipitate was filtered, washed with cold water then dried. Product was recrystallized using 95% methanol. Table(2) indicates the % yield and melting points for the compounds (6a-6g). CH3N NN N CH3 CH3H2 C H N O R American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 78 Table 1: The % yield and lting points for the compounds (6a-6g) Compound R M.P. (°C) Yield 6a H 219 98 6b p-Cl 221 91 6c o-Cl 189-190 98 6d m-OCH3 180-181 94 6e p-COOCH3 220-221 88 6f p-COOC2H5 201 92 6g p-COOC3H7 202-203 98 2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)-N-phenylacetamide(6a) CH3N NN N CH3 CH3H2 C H N O H1-NMR : δ = 2.41 (3H, s, CH3), 2.57(3H, s, CH3), 2.63(3H, s, CH3), 4.90 (2H, s, CH2) 7.08& 7.10 &7.11(2H, t, H-Ar), 7.25& 7.27& 7.30(1H, t, H-Ar), 7.26 &7.29 (1H, d, H-Ar), 7.46& 7.48 (2H, d, H-Ar), 7.96,7.71(2H, d, H-Ar) 8.62 (1H, s, exchangeable, NH). C13-NMR: δ = 9.97 (1C), 13.77 (1C), 21.51 (1C), 52.55 (1C), 120.16 (2C), 122.05(2C), 124.95 (1C), 129.09 (2C), 129.74 (2C), 135.27 (2C), 137.18 (1C), 140.69 (2C), 151.41 (1C), 164.8 (1C) . DEPT: δ = 9.98(1C), 13.72(1C), 21.53(1C), 52.51(1C), 120.15(2C), 122.07(2C), 124.93(1C), 129.08(2C), 129.75(2C). N-(4-chlorophenyl)-2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamide(6b) CH3N NN N CH3 CH3H2 C H N O Cl H1-NMR : δ = 2.42 (3H, s, CH3), 2.59 (3H, s, CH3), 2.65 (3H, s, CH3), 5.01 (2H, s, CH2), 7.21& 7.22 (2H, d, H- Ar),7.26& 7.28 (2H, d, H-Ar),7.45& 7.47(2H, d, H-Ar ), 7.70& 7.71(2H, d, H-Ar), 9.21(1H exchangeable, NH). C13-NMR: δ = 9.97 (1C), 13.96 (1C), 21.51 (1C), 52.46 (1C), 121.34 (2C), 122.03 (2C), 129.11 (2C), 129.75 (2C), 129.91 (1C), 135.34 (1C), 135.78 (1C), 140.63 (2C). 144.32 (1C), 151.43 (1C), 164.38 (1C). DEPT: δ = 9.98(1C), 13.59(1C), 21.55(1C), 52.32(1C), 121.28(2C), 122.12(2C), 129.07(2C), 129.78(2C). N-(2-chlorophenyl)-2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamide(6c) American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 79 CH3N NN N CH3 CH3H2 C H N O Cl H1-NMR : δ = 2.41 (3H, s, CH3), 2.57(3H, s, CH3), 2.63(3H, s, CH3), 4.89 (2H, s, CH2), 7.04& 7.05(1H, t, H- Ar), 7.25& 7.27 (2H, d, H-Ar), 7.31 &7.33 (1H, d, H-Ar), 7.70& 7.71 (2H, d, H-Ar), 8.35& 8.37(2H, d, H-Ar), 8.92 (1H, s, NH). C13-NMR: δ = 9.97 (1C), 14.02 (1C), 21.51 (1C), 52.72 (1C), 121.57 (1C), 122.01(2C), 125.29 (1C), 127.73 (1C), 129.28 (1C), 129.72 (2C), 134.22 (1C), 135.59 (1C), 140.06 (1C), 140.42 (1C), 144.79(1C), 151.48(1C), 164.99(1C) . DEPT: δ = 9.96(1C), 14.05(1C), 21.52(1C), 52.72(1C), 122.00(1C), 125.28(2C), 127.74(1C), 129.28(2C), 129.72(2C). 2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)-N-(3-methoxyphenyl)acetamide(6d) CH3N NN N CH3 CH3H2 C H N O OCH3 H1-NMR : δ = 2.41 (3H, s, CH3), 2.57(3H, s, CH3), 2.64(3H, s, CH3), 3.763(3H, s,OCH3), 4.91 (2H, s, CH2), 6.64& 6.65 (1H, d, H-Ar), 6.93& 6.95 (1H, d, H-Ar), 7.15 &7.17& 7.19 (1H, t, H-Ar), 7.23(1H, s, H-Ar), 7.25& 7.26 (2H, d, H-Ar), 7.69& 7.71(2H, d, H-Ar), 8.68 (1H, s, NH). C13-NMR: δ = 9.97 (1C), 13.81 (1C), 21.53 (1C), 52.57 (1C), 55.39(1C), 105.83 (1C), 110.75(2C), 112.32 (1C), 122.05 (2C), 129.75 (2C), 135.27 (1C), 138.34(1C), 140.65 (2C), 143.95 (1C), 151.41 (1C), 160.16(1C) 164.36(1C). DEPT: δ = 9.98(1C), 13.74(1C), 21.53(1C), 52.54(1C), 55.39(1C) 105.78(1C), 110.75(2C), 112.30(1C), 122.07(2C), 129.75(2C). methyl4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamido)benzoate(6e) CH3N NN N CH3 CH3H2 C H N O H3COOC H1-NMR : δ = 2.41 (3H, s, CH3), 2.61(3H, s, CH3), 2.65(3H, s, CH3), 3.85(3H, s,OCH3), 5.09 (2H, s, CH2), 7.26& 7.28 (2H, d, H-Ar), 7.58& 7.60 (2H, d, H-Ar), 7.69 &7.71 (2H, d, H-Ar), 7.91& 7.92(2H, d, H-Ar), 9.55 (1H, s, NH). American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 80 C13-NMR: δ = 9.97 (1C), 13.64 (1C), 21.53 (1C), 52.13(1C), 52.40(1C), 119.19 (2C), 122.10(2C), 126.17 (1C), 129.77 (2C), 130.82 (2C), 135.17 (1C), 140.90(2C), 141.39 (1C), 143.74 (1C), 151.33 (1C), 164.42(1C), 166.53(1C) . DEPT: δ = 9.98(1C), 13.75(1C), 21.54(1C), 52.14(1C), 52.42(1C) 119.20(2C), 122.09(2C), 129.76(2C), 130.83(2C). Ethyl 4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamido)benzoate(6f) CH3N NN N CH3 CH3H2 C H N O C2H5OOC H1-NMR : δ = 1.35 &1.36 & 1.38(3H, t, CH3), 2.41 (3H, s, CH3), 2.57(3H, s, CH3), 2.64(3H, s, CH3), 4.31& 4.32 & 4.34 & 4.35(2H, q,OCH2), 4.91 (2H, s, CH2), 7.25& 7.27 (2H, d, H-Ar), 7.55& 7.56 (2H, d, H-Ar), 7.69 &7.71 (2H, d, H-Ar), 7.95& 7.97(2H, d, H-Ar), 9.04 (1H, s, NH). C13-NMR: δ = 9.97 (1C), 13.64 (1C), 14.42(1C), 21.53 (1C), 52.46(1C), 61.00(1C), 119.17 (2C), 122.07(2C), 126.55 (1C), 129.75 (2C), 130.78 (2C), 135.27 (1C), 140.72(2C), 141.28 (1C), 144.02 (1C), 151.39(1C), 164.65(1C), 166.08(1C) . DEPT: δ = 9.98(1C), 13.86(1C), 21.53(1C), 52.47(1C), 61.00(1C) 119.17(2C), 122.06(2C), 129.75(2C), 130.79(2C). Propyl 4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamido)benzoate(6g) CH3N NN N CH3 CH3H2 C H N O C3H7OOC H1-NMR : δ = 0.99 &1.00 & 1.01(3H, t, CH3), 1.74& 1.75& 1.77& 1.78 (2H, m, CH2), 2.41(3H, s, CH3), 2.57(3H, s, CH3), 2.64(3H, s, CH3), 4.22& 4.23 & 4.25 (2H, t,OCH2), 4.91 (2H, s, CH2), 7.25& 7.26& (2H, d, H-Ar), 7.55& 7.57 (2H, d, H-Ar), 7.69 &7.71 (2H, d, H-Ar), 7.96& 7.98(2H, d, H-Ar), 9.01 (1H, s, NH). C13-NMR: δ = 9.97 (1C), 10.60(1C), 13.88 (1C), 21.51(1C), 22.18 (1C), 52.49(1C), 66.59(1C), 119.21 (2C), 122.05(2C), 126.61 (1C), 129.74 (2C), 130.80 (2C), 135.33 (1C), 140.63(2C), 141.24 (1C), 144.02 (1C), 151.41(1C), 164.65(1C), 166.08(1C) . DEPT: δ = 9.98(1C), 10.60(1C), 13.83(1C), 21.53(1C), 22.17(1C), 52.47(1C), 66.58(1C) 119.20(2C), 122.07(2C), 129.75(2C), 130.79(2C). American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 81 3. Discussion In this study 2-chloro-N-(substituted phenyl) acetamides (5a-5g) were synthesized by the method described in experimental section. Compounds (6a-6g) were prepared by reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H- pyrazole (4) with amide derivatives (5a-5g) as shown in Figure (1). The desired products obtained in good yield. Their formation was tested by TLC and The melting point which compared with the literature. CH3 NH2 H3C O O CH3 H3C N N O CH3 O CH3 NaNO2 , HCl, 0-5 0C CH3COONa/EtOH NH2NH2 .H2O, CH3COOH H3C N N NH N CH3 H3C CH3N NN N CH3 CH3H2 C H N O Cl CH3N NN N CH3 CH3H2 C H N O Cl CH3N NN N CH3 CH3H2 C H N O CH3N NN N CH3 CH3H2 C H N O OCH3 CH 3N NN N CH3 CH3H2 C H N O H3COOC CH 3N NN N CH3 CH3H2 C H N O C2H5OOC CH 3N NN N CH3 CH3H2 C H N O C3H7OOC N H O Cl N H O Cl Cl NH O Cl Cl N H O Cl COOCH3 NH O Cl C2H5OOC N H O Cl OCH3 NH O Cl C3H7OOC (1) (4) (5a) (5b) (5c) (5d) (5e) (5f) (5g) (3) (6a) (6b) (6c) (6d) (6e) (6f ) (6g) (2) Figure 1: Reaction Figure The Mechanism of this reaction (Figure 2) is SN2 reaction where the nucleophile (HN-) attacks the carbon atom which attached with the good leaving group, forming a C–N bond and followed by breaking the C–Cl bond. N H O Cl SN2 N N N N H NHO KCO3 N H O N N N N R (4) (5a-5g) (6a-6g) NH N N N R 5a R= C6H6 5b R=P-C6H5Cl 5c R=O-C6H5Cl 5d R=m-C6H5OCH3 5e R= P-C6H5COOCH3 5f R= P-C6H5COOC2H5 5g R= P-C6H5COOC3H7 6a R= C6H6 6b R=P-C6H5Cl 6c R=O-C6H5Cl 6d R=m-C6H5OCH3 6e R= P-C6H5COOCH3 6f R= P-C6H5COOC2H5 6g R= P-C6H5COOC3H7 Figure 2: Mechanism of the reaction American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 82 The structure obtained was confirmed by satisfactory spectroscopic analysis 1H-NMR spectra which showed ten different types of protons, the CH2 signal was deshielded and shifted from 4.18 ppm for compound (5a) to 4.90 ppm for compound (6a) and the -NH group of amide has been disappeared. a singlet signal at 8.62 ppm belong to NH was appear using D2O exchange. On the other hand, carbon magnetic resonance spectrum showed 14 signals at 120.16 (2C), 122.05(2C), 129.09 (2C), 129.74 (2C), 135.27 (2C), 140.69 (2C), and at 164.8 (1C) for carbonyl group .DEPT spectroscopy technique established existence of CH2 & CH3, as well as CH groups of benzene ring. The compound (6b) showed good solubility in chloroform. The nuclear magnetic resonance spectral data gave additional support for the composition of the compound. The observed changes are evidence of the reaction that occurred because the chemical shift of a compound is deeply depending on its electronic environment. The 1H-NMR spectrum of compound (6b) showed the appearance of a proton signal of CH2 at about 5.01ppm that differ from CH2 signal of compound (5b) which appear at 4.21 ppm due to the effect of pyrazole ring . Furthermore, the proton signal of NH appeared at 9.21 ppm which is lower than the value in compound (6b) which detected at about 9.57 ppm because of the deshielding by withdrawing groups in para position. Reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) with 2-chloro-N-(2-chlorophenyl) acetamide (5c) gave N-(2-chlorophenyl) -2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl) acetamide (6c). In this case the value of the chemical shifts for the CH2 group and NH decreased compared to the values of CH2 in compounds (6a) ,(6b) due to the presence of chlorine atom in the ortho position. Reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) with 2-chloro-N-(3-methoxyphenyl) acetamide (5d) afforded 2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)-N-(3-methoxyphenyl)acetamide (6d). This compound showed ten types of protons, singlet signal of OCH3 at about 3.76 ppm, in addition there were some differences in chemical shift of CH2 and NH group as a result of the presence of methoxy group in meta position. Reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) with methyl 4-(2-chloroacetamido) benzoate (5e) produced methyl 4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl) acetamido) benzoate (6e). 1H-NMR spectra show eleven different types of protons the most important signals between of them signal at about3.85 ppm belongs to OCH3 group as well as 13C-NMR shows beak for COOCH3 at 166.53 ppm. Reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) with ethyl4-(2-chloroacetamido) (5f) generated ethyl 4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamido)benzoate (6f). 1H-NMR spectra show twelve different types of protons, triplet signal of OCH2CH3 at 1.35, 1.36, 1.38 ppm and quartet signal of OCH2CH3 at 4.31, 4.32, 4.34, 4.35 ppm. On the other hand, 13C- NMR spectrums clarified a COOCH2CH3 signal at about 166.08 ppm. Reaction of 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) with propyl4-(2-chloroacetamido) benzoate (5g) resulted propyl 4-(2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamido)benzoate (6g). 1H- NMR American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 83 spectra show thirteen different types of protons triplet signal of OCH2CH2CH3 at 0.99 , 1.00 , 1.01 ppm , triplet signal of OCH2CH2CH3 at 4.22 , 4.23 , 4.25 ppm ,and sextet signal of OCH2CH2CH3 at 1.74 , 1.75 , 1.77 , 1.78 ppm. 13C-NMR analysis for the compound (6g) illustrated a beak at 166.13 ppm belongs to COOCH2CH2CH3. There is an increasing in NH chemical shifts of compound (6e),(6f), and (6g), due to the effect of ester group which located in para position. In comparison between two chemical shift values of CH2 group for compound (6a),(6b) found that increasing the chemical shift value from 4.9 ppm for compound (6a) to 5.9 ppm for compound (6e) due to the presence of ester group which was not noticed in the compound contained ester group with more carbon atoms (6f) and (6g) 4. Conclusion N-(4-substitutedphenyl)-2-(3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazol-1-yl)acetamide(6a-6g) was successfully synthesized with high percentage yield (88-98%) using with 2-chloro-N(substituted phenyl) acetamide (5a-5g) with 3,5-dimethyl-4-(p-tolyldiazenyl)-1H-pyrazole (4) which prepared by adding hydrazine hydrate in glacial acetic acid to 3-(2-(p-tolyl) hydrazono) pentane-2,4-dione (3). The 1H, 13C-NMR and dept analysis proved the proposed structure for the resulting compounds. Acknowledgements The researchers acknowledge the university of Benghazi for the direct contributions of the support staff from department of chemistry, Faculty of sciences, Benghazi university and university of Al Alexandria for assist in the NMR analysis. References [1] (a) L. Knorr (1883, July). "Ein wirkung von acettessiges ter auf phenyl hydrazine", Beriche Der Deutschen Chemischen Gesellschaft [on-line], 16 (2), pp. 2597-2599. Available: http://onlinelibrary.wiley.com/doi/10.1002/cber.188301602194/abstract;jsessionid=877B9714679A460 8CEC5F556DCB69FCF.f03t03 (b) L. Knorr (1884, July). "Ueber die constitution der chinizinderivate ", Beriche Der Deutschen Chemischen Gesellschaft [on-line], 17 (2), pp. 2032-2049. Available: http://onlinelibrary.wiley.com/doi/10.1002/cber.18840170298/full (c) T. L. Jacobs. “Pyrazoles and related compounds,” in Heterocyclic Compound, vol. 5. R. C. Elderfield, Ed. New York: John Willy & Sons, 1957, pp.45. (d) S. M. Sakya. "Knorr Pyrazole Synthesis", In Name Reactions in Heterocyclic Chemistry,. J. J. Li,. E. J.;Corey, Eds. Hoboken, New Jersey: John Willy & Sons, 2005, pp.292-300. http://onlinelibrary.wiley.com/doi/10.1002/cber.188301602194/abstract;jsessionid=877B9714679A4608CEC5F556DCB69FCF.f03t03 http://onlinelibrary.wiley.com/doi/10.1002/cber.188301602194/abstract;jsessionid=877B9714679A4608CEC5F556DCB69FCF.f03t03 American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) (2017) Volume 27, No 1, pp 73-84 84 [2] V. K. Aggarwal, J. De Vicente, R. V. Bonnert , (2003,May ). " A Novel One-Pot Method for the Preparation of Pyrazoles by 1,3-Dipolar Cycloadditions of Diazo Compounds Generated in Situ". The Journal of Organic Chemistry. 68 (13),pp. 5381-5383. [3] S. Fustero, A. Simon-Fuentes, J. F. Sanz-Cervera, (2009, July). "Recent advances in the synthesis of pyrazoles. A Review ", Organic Preparations and Procedures International, 41 (4), pp. 253-290. [4] S. Cacchi, G. Fabrizi, A. Carangio, (1997). "Functionalised pyrazoles through a facile one-pot procedure from N-tosyl-N-propargyl-hydrazine and aryl iodides or vinyl triflates", Synlett. 8, pp. 959- 961, (1997). [5] Vivek, K.K, International Conference on Bioencapsulation, Groningen, Netherlands, 17, 24-26, ( 2009). [6 ] T. Amita, M. Maridula, K. Sushil, (2011,November)."Synthesis, computional study and preliminary pharmacological evaluation of 2-[4-(2-chlorobenzyl/benzoyl) substituted piperazin-1-yl]-N- phenylacetamide: potential anti psychotics". International Journal of Research in Ayurveda and Pharmacy.6 (2), pp. 1822-1824. Available: http://www.ijrap.net/admin/php/uploads/727_pdf.pdf [7] S. Banerjee, S. Ganguly, K. K. Sen, K. Choowongkomon, S. Seetaha, (2013) "Synthesis, evaluation and binding mode analysis of some novel triazole derivatives as antimicrobials". Journal of Advanced Pharmacy Education & Research , 3, pp. 494-511. [8] L. Yurttas, Y. Ozkay,; F. Demirci, G. Goger, S.U. Yildirim, U. Abu mohsen, O. Ozturk, Z.A. Kaplancikli, (2014). "Synthesis, anti candidal activity, and cytotoxicity of some thiazole derivatives with dithiocarbamate side chain". Turkish Journal of Chemistry 38(5), p.p. 815- 824. [9] S.K. Mohanty, A. Khuntia, M.S. Harika, S.P. Sarangi, D.J. Susmitha, (2015, February)." Synthesis, characterization and antimicrobial activity of some oxazole and thiazole derivatives" International Journal of Pharmacy and Pharmaceutical Research, 2 (3), pp. 60-66. Available: http://ijppr.humanjournals.com/wp-content/uploads/2015/02/12.Sujit-Kumar-Mohanty-Anuradha- Khuntia-M.-Sai-Harika-Sarada-Prasad-Sarangi-D.-Jenny-Susmitha.pdf [10] N.R Thakare, A.K. Dhawas, P.S. Ganoskar, P.D. Kale (2012) ,"Synthesis, characterization of some new 3, 5-dimethyl azopyrazoles and its derivatives". Journal of Chemical and Pharmaceutical Research, 4(6), p.p, 3329-3332. Available: http://www.jocpr.com/articles/synthesis-characterization- of-some-new-3-5dimethyl-azopyrazoles-and-its-derivatives.pdf