Short communication
Reactions of 1,3-Diphenyl-2-pyrazolin-5-one and 4-Amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one. Synthesis of Some New Pyrazoles and Pyrazolones
Souad El-Metwally1 and Ali Kh. Khalil*'2
1 Higher Technological Institute, 10th of Ramadan City, Egypt.
2 Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, Cairo, Egypt
* Corresponding author: E-mail: khalilali123@yahoo.com Tel: +20101648960, Fax: +20224831836
Received: 23-04-2010
Abstract
1,3-Diphenyl-2-pyrazolin-5-one 1 was converted to 5-azido-4-formylpyrazolone 3 which is used as the key starting compounds of some new pyrazole derivatives 4-9. Also, 4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one 10 is coupled with some diazonium salts to give coloured products 11, and reacted with isocyanates and isothiocyanates to give pyrazolylurea and thiourea derivatives which are then reacted with organohalogen compounds under PTC conditions to give 13,14 while with some active methylene compounds yielded 15 via Michael 1,4-addition reaction.
Keywords: Azidoformylpyrazole, pyrazolotriazine, pyrazolopyridinone, antipyrene, pyrazolyl phenyl thiourea, hexa-hydropyrrolo [3,2-c] pyrazoles.
1. Introduction
Pyrazoles and pyrazolones are very important class of heterocycles due to their biological and pharmacological activities,1'2 which exhibit an anti-inflammatory3 her-bicidal,4 fungicidal,5 bactericidal,5 plant growth regulating properties,4 antipyretic6 and protein kinase inhibitors.7 Also, they are used as key starting material for the synthesis of commercial aryl/heteroarylpyrazolone dyes.811 Some arylidenepyrazolones are used as anti-fungal agents1215 or antidepressant agents,16 while others are used as photographic dyes or as intermediates in pharmaceuti-cals17-20 and antioxidants.21
The approach reported here deals with the synthesis of some new pyrazoles and pyrazolones starting from 2-pyrazolin-5-one 1 and aminopyrazolone 10 as key starting compounds. The new products might possess novel biological activity and may be used as commercial dyes.
2. Results and Discussion
2-Pyrazolin-5-one 1 has been synthesized by treating a mixture of ethyl benzoylacetate and phenylhydrazi-
ne in boiling acetic acid as reported.22 Vilsmeier-Haack formylation of pyrazolone 1 by DMF/POCl3 yielded pyra-zole-4-carbaldehyde 2 as reported in the literature,23,24 which was treated with sodium azide in DMSO to give azidoformylpyrazole 3.25 (Scheme 1)
Scheme 1
Treatment of azidoformylpyrazole 3 with 4-chloro-aniline and 4-hydroxyaniline afforded the corresponding Schiff's bases 4a and 4b, respectively. Azidoformyl-pyrazole 3 also reacted with hydrazine hydrate to give pyrazolo[3,4-d][1,2,3]triazine 5.26 (Scheme 2)
Reduction of azidoformylpyrazole 3 by hydrogen sulphide in methanol gave aminoformylpyrazole 6 (Scheme 2),27 which was fused with ethyl acetoacetate
Scheme 2
at 150 °C to give pyrazolo[3,4-£]pyridinone 7, which exists in keto-enol forms and was crystallized from ethanol/DMF as yellow crystals, m.p. 108-110 °C. (Scheme 3)
Diazotization of aminopyrazole 6 which was coupled in pyridine with 3-phenyl-2-pyrazolin-5-one, 1,3-di-phenyl-2-pyrazolin-5-one and 2-naphthol gave the corresponding coloured azo-dyes 8a,b and 9, respectively.
rated cyclic ketone. Treatment of a solution of aminopyra-zolone 10 with sodium nitrite and conc. HCl at low temperature gives the corresponding diazonium salt which is coupled in water (in the presence of AlCl3 as catalyst)28'29 with 3-phenyl-1#-pyrazol-2-en-5-one, 3-(3-pyridyl)-1#-pyrazol-2-en-3-one and 1,3-diphenyl-2-pyrazolin-5-one to give the corresponding azo-dyes 11a-c in good yields as orange to red crystals. (Scheme 5).
Scheme 3
Scheme 4
On the other hand, the aminopyrazolone 10 can also be used as a key starting material in this approach, as it might behave as an aromatic amine and as an a,B-unsatu-
It is reported that treatment of aminopyrazolone 10 with ethyl isothiocyanate, phenylisothiocyanate or phenyl isocyanate in boiling benzene gives the corresponding
Scheme 5
Scheme 6
well known thiourea or urea derivatives 12a-c, possessing ethyl or phenyl substituent,30-34 respectively. (Scheme 6)
Treatment of the thiourea 12b with 1,3-dibromo-propane under phase-transfer catalysis condition using tetrabutylammonium bromide (TBAB) as catalyst in benzene/anhydrous K2CO3 as liquid/solid phases gives thiox-otetrahydropyrimidine 13, while under the same PTC-con-dition, ethyl bromoacetate reacts with ureas 14a-c with
ring closure to give imidazolidinediones 14a-c. (Scheme 7) On the other hand, base-catalyzed cycloaddition of some active methylene compounds such as ethyl acetoac-etate, diethyl malonate, ethyl cyanoacetate or malononi-trile on pyrazolylphenylthiourea 12b proceeds via Michael addition to cyclic a,P-unsaturated ketone followed with ring closure with subsequent elimination of phenyl isothio-cyanate to give pyrrolo[3,2-c]pyrazoles 15a-d. (Scheme 8)
X = S X = S x = o
Scheme 7
14
a)	R = Et,
b)	R = Ph,
c)	R = Ph,
COOEt
H s
Me N—^ W N-Ph
I
Ph 12b
MeCOCH,CO,Et / TEA
Boiling Ethanol
CH2(C(XEt), CH2CN(CO,Et),
CH2(CN)2 / TEA, Ethanol
Scheme 8
15b) X = OH, Y = C02Et 15c) X = NH2, Y = C02Et 15d) X = NH2, Y=CN
3. Conclusion
Compounds 3 and 10 are used as key starting materials for the synthesis of a set of annulated heterocyclic products containing pyrazole moiety. The new synthesized azo-dyes have been prepared in aqueous medium as environmental friendly solvent. It is expected that these new products might have biological and pharmacological activities.
4. Experimental
Melting points reported are uncorrected. IR spectra were recorded on Perkin Elmer's Spectrum RXIFT-IR spectrophotometer (v in cm-1), 1H NMR spectra were recorded in CDCl3 on Bruker Avance DPX400,13C NMR spectra were recorded on Varian Gemini 300 MHz spectrometers using TMS as internal standard (chemical shifts in a values in ppm). Mass spectra were measured on GC-MS QP1000 EX Shimadzu. Elemental analyses were preformed by Perkin-Elmer 2400, Series II micro-analyzer. Light petroleum (b.p. 60-80 °C) used was as supplied. 4-Amino-2,3-dimethyl-1-phenyl-1 #-pyrazol-3-en-5-one (10) is an Aldrich product and was used without any further purification.
General procedure for preparation of 4 and 5. A solution of 3 (1.45 g, 0.005 mol) and 4-chloroaniline or 4-hy-doxyaniline or hydrazine hydrate (0.005 mol) in benzene (50 mL) was refluxed for 4 h. After evaporation the solid residue was crystallized from light petroleum to give 4a (65% yield) and 4b (68% yield) as white crystals or 5 (56% yield) as yellow crystals.
N-[(5-Azido-1,3-diphenyl-1H-pyrazol-4-yl)methylide-ne]-4-chloroaniline (4a). mp 175-176 °C. IR (KBr, vmax/cm-1) 1573 (C=C, C=N), 3061, 3187 (Ar-H). 1H NMR 6 6.01 (s, 1H, CH=), 6.94-8.07 (m, 14H, Ar-H). 13C
NMR 6 108.2, 123.5, 124.5, 128.8, 130.4, 133.6, 135.3, 140.3, 144.7, 152.4, 162.3. Anal. Calcd. for C22H15ClN6 (398.1): C, 66.25; H, 3.79; N, 21.07%. Found: C, (56.38; H, 3.64; N, 20.93%.
N-[(5-Azido-1,3-diphenyl-1H-pyrazol-4-yl)methylene] -4-hydroxyaniline (4b). mp 160-162 °C. IR (KBr, vmax/cm-1) 1598 (C=C, C=N), 3059, 3134 (Ar-H), 3428 (OH). 1H NMR 6 5.98 (s, 1H, CH=), 6.62-7.99 (m, 15H, Ar-H, OH). 13C NMR 6 107.5, 118.8, 125.4, 127.8, 130.3,
134.7,	139.7, 141.7, 142.3, 151.4, 158.7, 161.2. Anal. Calcd. for C22H16N6O (380.1): C, 69.46; H, 4.24; N, 22.09%. Found: C, 69.37; H, 4.13; N, 21.88%.
5,7-Diphenyl-7H-pyrazolo[3,4-d][1,2,3]triazine (5). mp
132 °C. IR (KBr, vmax/cm-1) 1597 (C=C, C=N), 3054, 3132 (Ar-H). 1H NMR 6 7.30-8.41 (m, 11H, Ar-H). 13C NMR 6 107.2, 120.4, 127.2, 127.9, 130.2, 133.6, 140.2, 146.3. Anal. Calcd. for C16H11N5 (273.1): C, 70.32; H, 4.06; N, 25.63%. Found: C, 70.45; H, 3.97; N, 25.51%.
5-Acetyl-1,3-diphenyl-1H-pyrazolo-[3,4-#]pyridine-6(7H)-one (7). A mixture of 6 (1.3 g, 0.005 mol), ethyl acetoacetate (0.006 mol) and few drops of piperidine was heated at 150 C for 4 h. The solid product was crystallized from ethanol to give pyrazolopyridinone 7 (64% yield) as yellow crystals. mp 112-114 °C. IR (KBr, vmax/cm-1) 1591 (C=C, C=N), 1667 (C=O acetyl), 3326 (OH). 1H NMR 6 2.13 (s, 3H, CH3), 7.22-7.67 (m, 11H, Ar-H), 9.61 (s, 1H, OH). 13C NMR 6 30.3, 98.7, 124.2, 126.6, 128.3, 129.0,
134.8,	138.5, 149.7, 162.3, 198.5. Anal. Calcd. for C20H15N3O2 (329.4): C, 72.94; H, 4.59; N, 12.76%. Found: C, 72.63; H, 4.47; N, 12.50%.
Diazoformylpyrazole Derivatives 8 and 9. A solution of sodium nitrite (1.0 g, 0.014 mol) in water (10 mL) was added to a mixture of 6 (1.3 g, 0.005 mol) and conc. HCl (1.0 mL) at 0 C with stirring. The mixture was added to a
cold alkaline solution of 3-phenyl-2-pyrazolin-5-one, 1,3-diphenyl-2-pyrazolin-5-one or 2-naphthol (0.005 mol) in NaOH (5 mL, 10% aqueous alcoholic solution). The precipitated coloured products were filtered, washed with water (3 x 10 mL), dried and crystallized from ethanol/ DMF mixture to give 8a (58% yield) as orange red crystals, 8b (65% yield) as deep red crystals, and 9 (78% yield) as red crystals.
5-[(5-Oxo-1,3-diphenyl-4,5-dihydro-1_ff-pyrazol-4-yl) diazenyl]-1,3-diphenyl-1_ff-pyrazole-4-carbaldelhyde
(8a). mp 237-239 °C. IR (KBr, vmax/cm-1) 1603 (C=C, C=N), 1650, 2523 (CHO), 2836 (AUph-CH), 3187 (Ar-H), 3376 (OH, or NH). 1H NMR 5 2.42 (s, 1H, CH), 7.08-8.07 (m, 16H, Ar-H, OH), 9.75 (s, 1H, CH=O). 13C NMR 5 72.7, 108.4, 125.4, 128.2, 129.9, 130.5, 132.3,
133.7,	135.9, 141.5, 151.3, 157.4, 174.6, 190.3. Anal. Calcd. for C25H18N6O2 (434.2): C, 69.11; H, 4.18; N, 19.34%. Found: C, 69.03; H, 4.09; N, 19.21%.
5-[(5-Oxo-1,3-diphenyl-4,5-dihydro-1_ff-pyrazol-4-yl) diazenyl]-1,3-diphenyl-1_ff-pyrazole-4-carbaldehyde
(8b). mp 208-210 °C. IR (KBr, vmax/cm-1) 1605 (C=C, C=N), 1658, 2493 (CHO), 3706 (Ar-H), 3341 (NH2 or OH). 1H NMR 5 7.19-8.13 (m, 21H, Ar-H, OH enolic), 9.72 (s, 1H, CH=O). 13C NMR 5 68.4, 108.2, 124.3,
126.8,	129.5, 131.6, 133.9, 139.4, 151.2, 156.7, 169.5,
192.2.	Anal. Calcd. for C31H22N6O2 (510.2): C, 72.93; H, 4.34; N, 16.46%. Found: C, 73.07; H, 4.29; N, 16.28%.
5-[(2-Hydroxylnaphthalen-1-yl)diazenyl]-1,3-diphen-yl-1#-pyrazole-4-carbaldehyde (9). mp 222-224 °C. IR (KBr, vmax/cm-1) 1602 (C=C, C=N), 1653, 2437 (CHO), 3098-3113» (Ar-H), 3420 (OH). 1H NMR 5 7.03-8.17 (m, 16H, Ar-H), 9.77 (s, 1H, CH=O), 10.97 (s, 1H, OH). 13C NMR 5 108.5, 124.7, 125.3, 126.8, 128.2, 129.4, 130.4,
132.3,	133.7, 144.3, 161.6, 190.3. Anal. Calcd. for C26H18N4O2 (418.1): C, 74.63; H, 4.34; N, 13.39%. Found: C, 74.50; H, 4.27; N, 13.12%.
Coupling of diazonium salt of aminopyrazolone 10 A
solution of 10 (2.03 g, 0.01 mol) in concentrated hydrochloric acid (2 mL), diluted by water (20 mL) was cooled at 0-5 C in an ice-bath. An aqueous cold solution of sodium nitrite (0.69 g, 0.01 mol in 1.0 mL H2O) at 0 °C was added to the prepared aminopyrazolone hydrochlo-ride to give the desired diazonium chloride solution. The latter solution was added drop-wise with stirring for 30 min in an ice-bath to a cold suspension of pyrazolones (0.01 mol) in water (50 mL) containing AlCl3 (3.0 g). The pH of the reaction mixture was adjusted to 8-8.5 by adding drop-wise sodium hydroxide solution (10%). The coloured precipitated azo-dye was filtered, washed with water (3 x 20 mL), dried and crystallized from benze-ne/ethanol mixture to give 11a (66% yield) as red crystals, while 11b (61% yield) crystallized from ethanol/DMF
mixture as orange crystals and 11c (66% yield) from benzene as red crystals.
4-[(5-Hydroxy-3-phenyl-1_ff-pyrazol-4-yl)diazenyl]-1,5-dimethyl-2-phenyl-1,2-dihydro-3ff-pyrazol-3-one (11a). mp 234 °C. IR (KBr, vmax/cm-1) 1594 (C=C, C=N), 1671 (C=O), 2807-2886 (Alipli-CH), 3088-3106 (Ar-H), 3465, 3537 (NH, OH). 1H NMR 5 2.60 (s, 3H, C-CH3), 3.16 (s, 3H, N-CH3), 7.2-8.18 (m, 10H, Ar-H), 10.03 (s, 1H, OH), 11.43 (s, 1H, NH). 13C NMR 5 13.5, 34.2, 97.3, 106.7, 123.3, 124.7, 128.7, 129.2, 136.5, 153.7, 164.4. Anal. Calcd. for C^H^N^ (374.2): C, 64.16; H, 4.85; N, 22.45%. Found: C, 64.03; H, 4.80; N, 22.27%.
4-{[5-Hydroxy-3-(3-pyridyl)-1_ff-pyrazol-4-yl]dia-zenyl}-1,5-dimethyl-2-phenyl-1,2-dihydro-3_ff-pyra-zol-3-one (11b). mp 251-253 °C. IR (KBr, vmax/cm-1) 1574 (C=C, C=N), 1685, 1716 (C=O), 2895 (Alipjhi CH), 3010 (Ar-CH), 3416-3438 (OH, NH). 1H NMR 5 2.48 (s, 3H, C-CH3), 3.31 (s, 3H, N-CH3), 7.08-9.32 (m, 9H, Ar-H), 10.332 (s, 1H, OH), 11.34 (s, 1H, NH). 13C NMR 5 14.7, 35.3, 106.5, 123.5, 124.3, 125.7, 134.4, 135.9, 138.4, 151.2, 156.8, 161.7, 162.7. Anal. Calcd. for C19H17N7O2 (375.4): C, 60.78; H, 4.57; N, 26.13%. Found: C, (50.83; H, 4.50; N. 25.88%.
4-[(5-Hydroxy-1,3-diphenyl-1_ff-pyrazol-4-yl)diazen-yl]-1,5-dimethyl-2-phenyl-1,2-dihydro-3_ff-pyrazol-3-
one (11c). mp 230-231 °C. IR (KBr, vmax/cm-1) 1583 (C=C, C=N), 1698, 1712 (C=O), 2904 (Aliph-CH), 3107 (Ar-CH), 3483-3497 (OH, NH). 1H NMR 5 2.60 (s, 3H, C-CH3), 3.16 (s, 3H, N-CH3), 7.26-8.20 (m, 15H, Ar-H), 12.03 (s, 1H, OH). 13C NMR 5 14.7, 35.2, 98.9, 106.6, 123.2, 124.4, 125.2, 134.7, 135.7, 138.3, 151.8, 156.4, 161.7, 162.7. Anal. Calcd. for C^H^N^ (450.5): C, 69.32; H, 4.92; N, 18.65%. Found: C, 6911; H, 4.82; N, 18.50%.
Synthesis of pyrazolylurea and thiourea 12a-c:32-34 A solution of 10 (0.005 mol) in benzene (28 mL) and phenylisocyanate or ethyl, or phenyl isothiocyonate (0.005 mol) was refluxed for 3 h. The solid products which are separated after concentration and cooling was filtered and crystallized from benzene/ethanol mixture to give the corresponding ureas 12a-c as white crystals.32-34
PTC-alkylation of pyrazolylphenylthiourea 12b. Formation of 13 and 14. A solution of 1,3-dibromopropane or ethyl bromoacetate (0.006 mol) in THF (20 mL) was added to a stirred solution of 12 (1.7 g, 0.005 mol) and anhydrous potassium carbonate (2.7 g, 0.02 mol) in tetrahy-drofuran (THF, 50 mL). The reaction mixture was kept at room temperature with stirring for 48 h. K2CO3 was removed by filtration and the solution was evaporated. The solid residue was triturated with light petroleum, filtered and crystallized from light petroleum to give 13 (71%
yield) as yellow crystals or 14a (43% yield) as white crystals, whereas 14b (58% yield) crystallized from benzene as white crystals, while 14c (41% yield) crystallized from ethanol as white crystals.
1,5-Dimethyl-2-phenyl-4-(3-phenyl-2-thioxotetrahy-dropyrimidin-1(2_ff)-yl)-1,2-dihydro-3ff-pyrazol-3-one (13). mp 173-175 °C. IR (KBr, vmax/cm-1) 1574 (C=C), 1422 (C=S), 1669 (C=O), 2830-29210 (Aliph-CH), 3080 (Ar-H). 1H NMR 5 1.83 (m, 2H, CH2), 2.28 (s, 3H, C-CH3), 3.23 (s, 3H, N-CH3), 4.14 (m, 2H, CH2), 4.82 (m, 2H, CH2), 6.73-7.48 (m, 10H, Ar-H). 13C NMR 5 13.8, 20.3, 35.1, 55.5, 57.2, 117.3, 123.4, 124.7, 128.3, 129.5, 131.9, 133.6, 134.5, 141.0, 161.3, 178.2. Anal. Calcd. for C21H22N4OS (378.2): C, 66.64; H, 5.86; N, 14.80%. Found: C, 66.42; H, 5.77; N, 14.63%.
4-(3-Ethyl-4-oxo-2-thioxoimidazolidin-1-y1)-1,5-di-methy1-2-pheny1-1,2-dihydro-3_ff-pyrazo1-3-one (14a). mp 182-183 °C. IR (KBr, vmax/cm-1) 1603 (C=C), 1661 (C=O), 1708 (C=O), 2870 (Aliph-CH), 3050 (Ar-OH). 1H NMR 5 1.27 (m, 3H, CH3), 2.19 (s, 3H, N-CH3), 3.04 (s, 3H, N-CH3), 3.83 (m, 23H, CH2), 3.91 (m, 2H3 , CH2), 7.26-7.45 (m, 5H, Ar-H). 13C NMR 5 13.4, 15.1, 39.7, 45.2, 58.3, 124.3, 125.7, 130.8, 135.6, 156.3, 162.8, 174.2. Anal. Calcd. for C16H18N4O2S (330.1): C, 58.16; H, 5.49; N, 16.96%. Found: C, 58.27; H, 5.36; N, 16.80%.
1,5-Dimethy1-4-(4-oxo-3-phenyl-2-thioxoimidazoli-din-1-y1)-2-pheny1-1,2-dihydro-3_ff-pyrazo1-3-one (14b). mp 235 °C. IR (KBr, vmax/cm-1) 1593 (C=C), 1658, 1687 (C=O), 2803 (Aliph-CH), 2978-3093 (Ar-CH). 1H NMR 5 2.32 (s, 3H, C-CH3), 3.27 (s, 3H, N-CH3), 3.934.10 (m, 2H, CH2), 6.97-7.53 (m, 10H, Ar-H). 13C NMR 5 15.3, 35.6, 58.4, 118.0, 123.7, 124.2, 128.7, 129.2, 134.6,
142.8,	162.5, 175.6, 176.4. MS (m/z): 378 (100%), 379 (32%), 380 (7.3%). Anal. Calcd. for C20H18N4O2S (378.12): C, 63.47; H, 4.79; N, 14.80%. Found: C, 63.63; H, 4.66; N, 14.68%.
1-(1,5-Dimethy1-3-oxo-2-pheny1-2,3-dilydro-1_ff-py-razol-4-yl)-3-phenylimidazolidine-2,4-dione (14c). mp
132-134 °C. IR (KBr, vmax/cm-1) 1603 (C=C), 1648, 1690 (C=O), 2853 (Aliph-CH), 2946 (Ar-CH). 1H NMR 5 2.33 (s, 3H, C-CH3) 3.19 (s, 3H, N-CH3), 4.61 (m, 2H, CH2), 7.27-7.53 (m, 10H, Ar-H). 13C NMR 5 13.2, 35.3, 49.7, 124.2, 125.5, 129.5, 130.4, 135.5, 137.1, 138.7, 154.6,
157.9,	162.3, 173.7. Anal. Calcd. for C20H18N4O3 (362.1): C, 66.29; H, 5.01; N, 15.46%. Found: C, 66.43; H, 4.87; N, 15.23%.
Base-catalyzed cycloaddition of active methylene compounds to pyrazolylphenylthiourea (3b). Formation of Cyclic Michael Adduct 15a-d. A solution of 3b (1.7 g, 0.05 mol), ethyl acetoacetate, diethyl malonate, ethyl cyanoacetate or malononitrile (0.06 mol) and few drops of
triethylamine in ethanol (30 mL) was refluxed for 4 h. The solvent was evaporated and the residue was triturated with light petroleum, dried and crystallized from light petroleum to give 15a (48% yield) as white crystals and 15b (53% yield) crystallized from benzene/light petroleum as white crystals, whereas 14c,d (57%, 47% yield, respectively) crystallized from benzene as white crystals.
Ethyl 1,5,6a-trimethy1-3-oxo-2-phenyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,2-c]pyrazole-6-carboxylate (15a).
mp 170-171 °C. IR (KBr, vmax/cm-1) 1585 (C=C, C=N), 1673, 1725 (C=O), 2833 (/Aliph-CH), 2994-3017 (Ar-CH), 3320 (br, NH). 1H NMR 5 1.30 (m, 3H, CH3), 1.47 (s, 3H, CH3), 2.19 (s, 3H, C-CH3), 3.08 (s, 3H, N-CH3), 3.78 (d, 1H, CH), 4.44 (q, 2H, CH2), 7.22-7.45 (m, 5H, Ar-H), 8.78 (s, 1H, NH). 13C NMR 5 15.2, 20.6, 42.7,
53.6,	58.2, 63.5, 113.3, 128.7, 129.2, 133.4, 158.9, 169.1,
170.6.	MS (m/z): 315 (100%), 316 (23.5%). Anal. Calcd. for C17H21N3O3 (315.16): C, 64.74; H, 6.71; N, 13.32%. Found: C, 64.85; H, 6.57; N, 13.22%.
Ethyl 1,6a-Dimethy1-3,5-dioxo-2-phenyloctahydropy-rrolo[3,2-c]pyrazole-6-carb-oxylate (15b). mp 168-170 °C. IR (KBr, vmax/cm-1) 1605 (C=C, C=N), 1665, 1730 (C=O), 2808 (Aliph-CH), 3107 (Ar-CH), 3380 (br, CH or MH ). 1H NMR 5 1.37 (m, 3H, CH3), 2.23 (s, 3H, C-CH3), 3.11 (s, 1H, CH), 3.22 (s, 3H, N-CH3), 4.54 (m, 2H, CH2), 7.28-7.51 (m, 5H, Ar-H), 8.32 (br s, 1H, OH or NH), 5.67 (br s, 1H, OH). 13C NMR 5 15.3, 24.6, 38.8, 42.7, 58.3,
63.7,	128.4, 129.2, 133.9, 136.3, 157.1, 170.4, 170.9. MS (m/z): 317 (100%), 318 (28.4%). Anal. Calcd. for C16H19N3O4 (317.14): C, 60.56; H, 6.03; N, 13.24%. Found: C, 60.68; H, 5.79; N, 13.12%.
Ethyl 5-Amino-1,6a-dimethy1-3-oxo-2-pheny1-1,2,3, 3a,6,6a-hexahydropyrrolo[3,2-c]pyrazole-6-carboxy-late (15c). mp 158-160 °C. IR (KBr, vmax/cm-1) 1585 (C=C, C=N), 1648, 1723 (C=O), 2905 (Aliph-CH), 2990-3108 (Ar-CH), 3435 (NH2). 1H NMR 5 1.38 (m, 3H, CH3), 1.93 (s, 1H, CH), 2.31 (s, 3H, C-CH3), 3.07 (s, 1H, CH), 3.21 (s, 3H, CH3), 4.53 (m, 2H, CH2), 7.29-7.50 (m, 5H, Ar-H), 9.07 (br s, 2H, NH2). 13C NMR 5 15.7, 25.2, 39.4, 42.3, 58.3, 64.4, 128.7, 129.3, 133.5, 156.1, 166.7, 171.3, 171.7. Anal. Calcd. for C16H20N4O3 (316.15): C, 60.75; H, 6.37; N, 17.71%. Found: C, 60.56; H, 6.23; N, 17.83%.
5-Amino-1,6a-dimethy1-3-oxo-2-phenyl-1,2,3,3a,6,6a-hexahydropyrrolo[3,2-c]pyrazole-6-carbonitrile (15d).
mp 190 °C. IR (KBr, vmax/cm-1) 1603 (C=C, C=N), 1665 (C=O), 2227 (CN), 2875-2904 (Aliph-CH), 2998-3107 (Ar-CH), 3433 (NH2). 1H NMR 5 2.29 (s, 3H, C-CH3), 2.54 (s, 1H, CH), 2.13 (s, 1H, CH), 3.17 (s, 3H, N-CH3), 4.53 (br s, 2H, NH2), 7.29-7.49 (m, 5H, Ar-H). 13C NMR 5 25.4, 39.7, 40.9, 43.2, 63.2, 118.1, 128.7, 129.3, 133.6,
135.7,	167.2, 171.4. Anal. Calcd. for C14H15N5O (269.13):
C, 62.44; H, 5.61; N, 26.01%. Found: C, 62.73; H, 5.50; N, 25.87%.
5. Acknowledgments
The authors express their appreciation and gratitude to the authorities of the Central Labs of Chemistry Department, Faculty of Science, University of King Abdulaziz, Jeddah, Saudi Arabia for measurements of elemental analysis and spectral data.
6. References
1.	S. Scheibye, A. A. El-Barbary, S. O. Lawesson, H. Fritz, G. Rihs, Tetrahedron 1982, 38, 3753-3760.
2.	A. Weissberger, R. H. Wiley, P. Wiley, "The Chemistry of Heterocyclic Compounds: Pyrazolinones, pyrazolidones and derivatives" John Wiley & Sons, New York (1964).
3.	S. P. Hiremath, K. Rudresh, A. R. Saundan, Indian J. Chem. 2002, 41B, 394-399.
4.	S. Joerg, G. Reinhold, S. Otto, S. H. Joachim, S. Robert, L. Klaus, Patent Ger. Offen 04 Feb. 1988; DE 3, 625, 686 (C1 C07D 231/ 22) [Chem. Abstr. 1988,108, 167465].
5.	D. R. Gupta, R. K. Arora, Acta Chim. Hung. 1985, 118, 79-83.
6.	F. R. Souza, V. T. Souaza, V. Ratzlaff, L. P. Borges, M. R. Olivera, H. G. Bonacorso, N. Zanatta, M. A. Martina, C. F. Mello, Eur. J. Pharmacology 2002, 451, 141-147.
7.	R. Tripathy, A. Ghose, J. Singh, E. R. Bacon, T. S. Angeles, S. X. Yang, M. S. Albom, L. D. Aimone, J. L. Herman, J. P. Mallamo, Bioorg. Med. Chem. Lett. 2007, 17, 1793-1798.
8.	F. Karci, N. Ertan, Dyes Pigm. 2002, 55, 99-108.
9.	Y. W. Ho, Dyes Pigm. 2005, 64, 223-230.
10.	A. Kh. Khalil, M. A. Hassan, M. M. Mohamed, A. M. El-Sayed, Dyes Pigm. 2005, 66, 241-245.
11.	N. Ertan, Dyes Pigm. 1999, 44, 41-48.
12.	K. G. Ojha, N. Jaisinghani, H. Tahiliani, J. Indian Chem. Soc. 2002, 79, 191-192.
13.	L. Pezdirc, D. Bevk, S. Pirc, J. Svete, Acta Chim. Slov. 2009, 56, 545-558.
14.	M. A. H. A. G. Awas, Acta Chim. Slov. 2008, 55, 492-501.
15.	W. W. Wardakhan, N. A. Louca, M. M. Kamel, Acta Chim. Slov. 2007, 54, 229-241.
16.	R. B. Pathak, S. C. Bahel, J. Indian Chem. Soc. 1980, 57, 1108-11.
17.	J. M. Panchal, K. R. Desai, Asian J. Chem. 2000, 12, 609-611.
18.	E. Palaska, D. Erol, R. Demirdamar, Eur. J. Med. Chem. 1996, 31, 43-47.
19.	A. A. Wasfy, A. El-Shenawy, S. A. Nassar, Heterocycl. Commun. 2001, 7, 493-500.
20.	H. Li-Jiau, K. Sheng-Chu, L. Hantch, Taiwan Yao Hsuch Tsa Chih 1979, 31, 47-56 [Chem. Abstr. 1980, 93, 71631].
21.	Y. Yamamoto, T. Kuwahara, K. Watanabe, Redox Report 1996, 2, 333-338.
22.	A. Sammour, A. Abd El-Raouf, M. El-Kasaby, M. A. Hassan, Egypt. J. Chem. 1972, 15, 429-432.
23.	A. Babaqi, A. El-Shekeil, M. Hassan S. Shiba, Heterocycles 1988, 27, 2119-2123.
24.	A. Babaqi, A. El-Shekeil, M. Hassan S. Shiba, Heterocycles 1988, 27, 2577-2582.
25.	H. Park, J. Lee, Y. Kim, K. Lee, K. Kee-In, Bull. Korean Chem. Soc. 2005, 26, 668-670.
26.	R. Justoni, R. Fusco, Gazz. Chim. Ital. 1938, 68, 59-76.
27.	V. K. Ahluwalia, B. A. Goyal, Synth. Commun. 1996, 26, 1341-1348.
28.	S. A. Basaif, M. A. Hassan, A. A. Gobouri, Dyes Pigm. 2007, 72, 387-392.
29.	S. A. Basaif, M. A. Hassan, A. A. Gobouri, Indian J. Chem. 2006, 45B, 1431-1438.
30.	N. Mishriky, F. M. Asaad, Y. A. Ibrahim, A. S. Girgis, Pharmazie 1996, 51, 544-548.
31.	J. H. Eussen, J. L. Thus, K. Wellinga, B. Stork, Pestic. Sci. 1990, 29, 101-108.
32.	S. Cunha, S. M. Oliveira, M. T. Rodrigues, R. M. Bastos, J. Ferrari, J. C. M. De Oliveira, L. Kato, H. B. Napolitano, I. Vencato, C. Lariucci, J. Mol. Struct. 2005, 752, 32-39.
33.	A. H. Moustafa, H. A. Saad, J. Chem. Res. 2005, 5, 328-331.
34.	R. W. Buerli, H. Xu, X. Zou, K. Muller, J. Golden, M. Frohn, M. Adlam, M. H. Plant, M. Wong, M. McElvain, K. Regal, V. N. Viswanadhan, P. Tagari, R. Hungate, Bioorg. Med. Chem. Lett. 2006, 16, 3713-3718.
Povzetek
1,3-Difenil-2-pirazolin-5-on 1 smo pretvorili v 5-azido-4-formilpirazolon 3, ki smo ga uporabili kot ključno izhodno spojino za pripravo nekaterih novih pirazolskih derivatov 4-9. 4-Amino-2-fenil-1,5-dimetil-1^-pirazol-3(2fl)-on 10 smo pripojili z nekaterimi diazonijevimi solmi in dobili obarvane produkte 11; reagirali z izocianati in izotiocianati do derivatov pirazolilsečnin in tiosečnine, ki smo jih nato reagirali z organohalogeni pod PTC pogoji do spojin 13,14; z nekaterimi spojinami, ki vsebujejo aktivne metilenske skupine, smo z Michaelovo 1,4-adicijo pripravili produkte 15.