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[ CAS No. 21487-45-6 ] {[proInfo.proName]}

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Chemical Structure| 21487-45-6
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Product Details of [ 21487-45-6 ]

CAS No. :21487-45-6 MDL No. :MFCD00525714
Formula : C16H12N2O Boiling Point : -
Linear Structure Formula :- InChI Key :LZGBMIZREYTWRI-UHFFFAOYSA-N
M.W :248.28 Pubchem ID :555820
Synonyms :

Calculated chemistry of [ 21487-45-6 ]

Physicochemical Properties

Num. heavy atoms : 19
Num. arom. heavy atoms : 17
Fraction Csp3 : 0.0
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 74.39
TPSA : 34.89 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.67 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.47
Log Po/w (XLOGP3) : 3.02
Log Po/w (WLOGP) : 3.35
Log Po/w (MLOGP) : 2.46
Log Po/w (SILICOS-IT) : 3.21
Consensus Log Po/w : 2.9

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.75
Solubility : 0.0446 mg/ml ; 0.000179 mol/l
Class : Soluble
Log S (Ali) : -3.42
Solubility : 0.0949 mg/ml ; 0.000382 mol/l
Class : Soluble
Log S (SILICOS-IT) : -5.4
Solubility : 0.000993 mg/ml ; 0.000004 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.28

Safety of [ 21487-45-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338+P310-P332+P313-P362-P403+P233-P405-P501 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 21487-45-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 21487-45-6 ]

[ 21487-45-6 ] Synthesis Path-Downstream   1~80

  • 1
  • [ 141-97-9 ]
  • [ 21487-45-6 ]
  • [ 112758-38-0 ]
YieldReaction ConditionsOperation in experiment
96% With ammonium acetate at 20℃; for 0.133333h;
89% With bismuth tungstate; ammonium acetate In water at 20℃;
85% With 1-methyl-2-oxopyrrolidinium hydrogen sulfate; ammonium acetate In ethanol at 20℃; for 5h; Sealed tube; Green chemistry; 3.2. General Procedure for the Synthesis of DHPs 4a-j General procedure: A 25 mL sealed tube was filled with a mixture of 3-aryl-1-phenyl-1H-pyrazole-4-carboxaldehydes 1 (1 mmol), ethylacetoacetate 2 (0.130 g, 2 mmol), NH4OAc 3 (0.085 g, 1.2mmol) and 100 mg of ionic liquid [HNMP][HSO4] in 10 mLof ethanol. Then the sealed tube was capped and the reactionmixture was stirred at room temperature using a magneticstirrer for appropriate time. The progress of the reaction wasmonitored by TLC. Once the reaction was completed, thecontent was poured over crushed ice, and the solid DHP derivativethus obtained was separated by filtration. The productwas dried and in some cases, the impure product wasrecrystallized from DMF-H2O.
84% With ammonium acetate In ethanol at 20℃; for 7h; (2) General procedure for the synthesis of 1,4-dihydropyridine derivatives(4a-j). General procedure: In a single neck 100 mL, round bottom flask 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde 1 (1 mmol), ethyl acetoacetate 2 (2 mmol), ammonium acetate3 (1.5 mmol), and 150 mg of pumice-based sulfonic acid was taken in 15 mL ofethyl alcohol. The resulting reaction mixture was stirred at room temperature forappropriate time (Scheme 2). The progress of the transformation was monitoredby TLC. Once the reaction was completed, the content was mixed with dichloromethane,and catalyst was separated by decantation. After the separation ofcatalyst, the dichloromethane was concentrated on rotary evaporator which gavesolid 1,4-dihydropyridine derivatives. The obtained product was dried and purifiedby recrystallization from n-hexane-ethyl acetate. The recovered catalyst waswashed with dichloromethane and dried to reuse for the next cycle.
73% With aminosulfonic acid; ammonium acetate In ethanol for 5h; Reflux;
37% With ammonia In methanol Reflux;
27% With ammonium hydroxide In ethanol for 4h; Heating;
With ammonium acetate In ethanol at 90℃; for 3h;
With ammonium acetate In ethanol for 1h; Reflux; 3.2. Synthesis of Substituted 1,4-dihydropyridines (1,4-DHPs): A general procedure General procedure: A mixture of aldehyde (1 mol), ethylacetoacetate (2 mol)and ammonium acetate (2 mol) was dissolved in ethanol(30ml) in a 250 ml RB flask. This reaction mixture was refluxed for about 60 min on waterbath. Progress of the reactionwas monitored by TLC. After the completion of reaction,the reaction mixture was cooled to room temperature toobtain solid dihydropyridine derivative which was filtered andfurther purified by recrystallization from aqueous ethanol.
With ammonium acetate In ethanol Reflux; Synthesis of substituted 1,4-dihydropyridines (1,4-DHPs): a general procedure General procedure: A mixture of aldehyde (1 mmol), ethyl acetoacetate (2 mmol) and ammonium acetate (2 mmol) was dissolved in ethanol (30 ml) in a 250-ml round bottom flask. This reaction mixture was refluxed for about 6-8 h as reported in the literature (Kumar et al. 2017c). Progress of the reaction was monitored by TLC. After the completion of reaction, the reaction mixture was cooled to room temperature and the solid thus obtained was filtered and purified further to obtain dihydropyridine derivatives (1) in good to excellent yield.

Reference: [1]Ashok; Shravant; Sarasija [Indian Journal of Heterocyclic Chemistry, 2012, vol. 21, # 3, p. 233 - 236]
[2]Paplal, Banoth; Nagaraju; Veerabhadraiah, Palakollu; Sujatha, Kodam; Kanvah, Sriram; Vijaya Kumar; Kashinath, Dhurke [RSC Advances, 2014, vol. 4, # 97, p. 54168 - 54174]
[3]Shirole, Gopinath D.; Mokal, Ramesh A.; Shelke, Sharad N. [Letters in Organic Chemistry, 2017, vol. 14, # 8, p. 548 - 556]
[4]Tambe, Adinath; Sadaphal, Gayatri; Dhawale, Ravindra; Shirole, Gopinath [Research on Chemical Intermediates, 2022, vol. 48, # 3, p. 1273 - 1286]
[5]Location in patent: experimental part Li, Jianping; Qiu, Jikuan; Li, Huijuan; Zhang, Guisheng [Chinese Journal of Chemistry, 2011, vol. 29, # 3, p. 511 - 514]
[6]Location in patent: experimental part Trivedi, Amit; Dodiya, Dipti; Dholariya, Bipin; Kataria, Vipul; Bhuva, Vimal; Shah, Viresh [Chemical Biology and Drug Design, 2011, vol. 78, # 5, p. 881 - 886]
[7]Chekavichus, B. S.; Odynets, A. G.; Sausin', A. E.; Berzinya, D. A.; Zolotoyabko, R. M.; et al. [Pharmaceutical Chemistry Journal, 1987, vol. 21, # 8, p. 581 - 587][Khimiko-Farmatsevticheskii Zhurnal, 1987, vol. 21, # 8, p. 959 - 965]
[8]Location in patent: experimental part Kumar, Parvin; Kumar, Ashwani; Hussain, Khalid [Ultrasonics Sonochemistry, 2012, vol. 19, # 4, p. 729 - 735]
[9]Khanna, Radhika; Dalal, Aarti; Kadyan, Kulbir; Kumar, Ramesh; Kumar, Parvin; Kamboj, Ramesh C. [Letters in Organic Chemistry, 2018, vol. 15, # 8, p. 673 - 677]
[10]Kumar, Parvin; Kadyan, Kulbir; Duhan, Meenakshi; Sindhu, Jayant; Hussain, Khalid; Lal, Sohan [Chemical Papers, 2019, vol. 73, # 5, p. 1153 - 1162]
  • 2
  • N-(1-phenylethylidene)phenylhydrazine [ No CAS ]
  • [ 33513-42-7 ]
  • [ 21487-45-6 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.25h; Stage #2: N-(1-phenylethylidene)phenylhydrazine In N,N-dimethyl-formamide at 75℃; for 5h; regioselective reaction; 4.1.2 General procedure of synthesis of compounds (7a-c) General procedure: A chilled solution of dimethyl formamide (2.58g, 2.73mL, 0.03mol) and POCl3 (5.40g, 3.28mL, 0.03mol) were added dropwise on each other and stirred for 15min at 0°C. A solution of 2-phenyl-1-(1-substitutedphenylethylidene)hydrazines (3a-c) (0.01mol) in DMF (3mL) was added dropwise to the reaction mixture and heated at 75°C for 5h. The reaction mixture was cooled and a solution of 10% sodium carbonate (2mL) was added. The obtained precipitate was filtered, washed with water (15mL), dried and crystallized from ethanol. 4.1.2.1 1,3-Dipheneyl-1H-pyrazole-4-carbaldehyde (7a) [60] (White crystals, C16H12N2O (248), Yield: 95%, m.p. 138-140°C.
92% Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: N-(1-phenylethylidene)phenylhydrazine In N,N-dimethyl-formamide at 0 - 60℃; for 4h; 2.2. Preparation of 1,3-diphenyl-1H-pyrazole-4-carboxaldehyde: Phosphoryl chloride (1.03 mL, 11.4 mmol, 1.2 equiv) was added to N, N-dimethylformamide (0.84 mL, 11.4 mmol, 1.2 equiv) at 0 °C and the mixture stirred at the same temperature for 1 h. The mixture was then slowly added to a solution of acetophenone phenylhydrazone (2 g, 9.5 mmol, 1 equiv) in DMF (5 mL) and the reaction mixture was allowed to stir for 10 min at the same temperature and then heated to 60 °C for 4 h. The reaction was monitored by TLC (30% EtOAc/Hexane; Rf is about 0.4 for the product). The reaction mixture was cooled to room temperature and basified with cold and saturated aqueous sodium hydroxide solution (PH = 8.0) when the off-white-colored solid precipitated out. The precipitate was filtered, washed with cold water (2*20 mL) to obtain the crude product as an off white solid (2.17 g, 92% yield)
90% Stage #1: N,N-dimethyl-formamide With 1,3,5-trichloro-2,4,6-triazine at 25℃; Stage #2: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide at 20℃; 1 EXAMPLE 1 1,3-Diphenyl-4-formylpyrazole (2) 2,4,6-Trichloro[1,3,5]triazine (1.83 g, 10.0 mmol) is added to DMF (2 mL), and maintained at 25° C. After the formation of a white solid, the reaction is monitored (TLC) until complete disappearance of the triazine. 1-Phenyl-2-(1-phenylethylidene)-hydrazine (1.0 g, 5.0 mmol) in DMF (15 mL) is added. After the addition, the mixture is then stirred at room temperature and monitored for completion (TLC) after which a 15% solution of Na2CO3 (20 mL) is added. The organic phase is extracted twice with 15 mL of diethyl ether. The organic layer is then dried (Na2SO4) and the solvent is removed in vacuo to afford the desired product. Yields of approximately 1.12 g (90%) of this product can be expected when the reaction is conducted on this scale. Mp 145° C.
89% With trichlorophosphate at 70 - 80℃; for 1h;
89% With trichlorophosphate for 1h; Cooling; Reflux; Synthesis of 3-(Substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde General procedure: A mixture of substituted acetophenone 1a-i (0.01 M), phenylhydrazine (0.01 M), one drop of conc. HCl and ethanolas a solvent was taken in a 100 mL conical flask and subjected to microwave irradiation for 1-2 min at 450 Wat an interval of 5 s each. The resulting solid products 2a-i were dried, dissolved in excess of DMF, and 0.015 M POCl3 was added dropwise under cold conditions. The reaction mixture is allowed to attain room temperature and refluxed at about 80 °C for 1 h conventionally, allowed to cool and then hydrolyzed by water to yield a white solid. The solid was washed with ample water to remove excess HCl, then filtered, dried and recrystallised using ethanol. Recrystallisation proceeded from a saturated solution in a mixture of ethanol and chloroform in a dark chamber at low temperature. 1,3-Diphenyl-1H-pyrazole-4-carbaldehde(3a) Off white needle like crystals, yield 89%, Melting point 135 °C. IR(υmax/cm-1): 3121 (Ar-CH), 2828 (C-H in CHO), 1677(C=O), 1519 (C=N), 1443 (C=C). 1H NMR (500 MHz,CDCl3,δ/ppm): 9.96 (s, 1H, -CHO); 8.46 (s, 1H, Pyrazole-CH); 7.68-7.72 (t, 4H, Ar-H); 7.55-7.57 (d, 2H, Ar-H);7.43-7.46 (t, 2H, Ar-H); 7.32-7.35 (t, 1H, Ar-H).
87% With trichlorophosphate at 0 - 60℃;
85% With 1,3,5-trichloro-2,4,6-triazine at 20℃; for 2h; Inert atmosphere;
84% Stage #1: N,N-dimethyl-formamide With trichlorophosphate for 0.333333h; Cooling with ice; Stage #2: N-(1-phenylethylidene)phenylhydrazine In N,N-dimethyl-formamide at 80℃; Cooling with ice; 2.2-7 2-7. Synthesis of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (4a) POCl3(8.31 g, 54.2 mmol) was added dropwise to anhydrous N,N-dimethylformamide (DMF, 3.95 g, 54.2 mmol), cooled in an ice bucket, and stirred for 20 minutes.Compound 3a (3.80 g, 18.1 mmol) dissolved in DMF (5 mL) was added and the reaction mixture was stirred for 30 min at room temperature, then heated to 80° C. overnight.The reaction mixture was poured into ice and basified in ice-cold saturated K2CO3solution.The obtained precipitate was filtered and recrystallized from EtOH to obtain compound 4a as a white solid (3.80 g, 84 %).
80% With trichlorophosphate Reflux;
80% at 70 - 80℃; for 7h; Cooling with ice;
79% With trichlorophosphate In N,N-dimethyl-formamide Reflux;
76% With trichlorophosphate at 50 - 60℃;
75% Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: N-(1-phenylethylidene)phenylhydrazine Heating;
75% With trichlorophosphate at 0℃; Reflux;
71.3% With trichlorophosphate
54% With trichlorophosphate at 20℃; for 18h; Inert atmosphere; Cooling with ice;
With trichlorophosphate at 50 - 60℃;
With trichlorophosphate at 50 - 60℃;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.5h; Stage #2: N-(1-phenylethylidene)phenylhydrazine
With trichlorophosphate Inert atmosphere;
With trichlorophosphate
With trichlorophosphate at 0 - 80℃; for 5h; 1. Synthesis of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde: All the pyrazolyl aldehydes needed for preparation of pyrazolyl 1,4-DHPs were prepared by using reported procedure and purified through recrystalization.1 DMF (3 equiv) and POCl3 (3 equiv) were previous separately cooled at 0 °C before being stirred at such temperature. A solution of 1-phenyl-2-(1-phenylethylidene) hydrazine (1 equiv) in DMF (3 mL) was added drop wise to the reaction mixture which was, then, warmed to room temperature and heated at 70-80 °C for 5 h. After cooling at room temperature, the mixture was basified with a cool saturated K2CO3 solution. The precipitate was filtered, strongly washed with water and crystallized from ethanol, yields desired pyrazolyl aldehydes.
With trichlorophosphate at 90℃; for 4h;
With trichlorophosphate at 50 - 60℃;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 0.5h; Stage #2: N-(1-phenylethylidene)phenylhydrazine In N,N-dimethyl-formamide at 50℃; for 3h;
With trichlorophosphate at 0 - 90℃; for 2h; 1.3.1. 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (11a) Acetophenone 9a (10 gm, 83.2 mmol,) was dissolved in AcOH (20 mL) and then phenylhydrazine (9.8 mL, 99.8 mmol,) was added slowly at 25 oC. After stirring for 15 min at this temperature, an orange-yellow colored solid was precipitated. Filtration of this product through a Buchner funnel and washing with water followed by drying under vacuum provided sufficiently pure (by TLC) hydrazone 10a which was immediately used in the next step. The obtained filtercake 10a was dissolved in DMF (100 mL) and then POCl3 (26 mL, 0.28 mol) was added slowly dropwise at 0 0C. After complete addition of POCl3, the reaction mixture was stirred at 90 0C for 2 h and then poured onto crushed ice. 10% aqueous NaOH solution was used to neutralize the solution. The product was extracted with DCM (3×200 mL) and the organic layer was washed with water (10 mL x 5) to remove excess DMF. The DCM layer was dried over anhydrous Na2SO4 and evaporated. To the crude product was added hexane (50 mL) to get a slurry which was stirred for 30 min and then filtered and dried under vacuum to give pure compound 11a as a white solid, 87% yield. mp 144-146 0C; IR (KBr): 1672, 1599, 1525, 1450, 1367, 1226, 752, 686 cm-1. 1H NMR (CDCl3, 400 MHz): δ 10.16 (s, 1H), 8.55 (s, 1H), 7.82 (t, J = 8.4 Hz, 4H), 7.48-7.54 (m, 5H), 7.40 (t, J = 7.2 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δ 185.2, 154.8, 139.0, 131.3, 130.9, 129.7, 129.3, 128.9, 128.7, 128.0, 122.5, 119.7. LCMS (EI): m/z 250.0 (M++1).
With trichlorophosphate at 70℃; Cooling with ice;
With trichlorophosphate at 50 - 60℃; for 6h; Cooling; General Procedure for the Preparation of 1, 3-diphenyl-1H-pyrazole-4-carboxylic acids (6-10) General procedure: The starting material substituted 1, 3-diphenyl-1H-pyrazole-4-carboxylic acid(6-10) was synthesized as following: para-substituted acetophenone(1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25mmol) couple with sodium acetate (40mmol in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene)hydrazine, which was then added to a cold solution of DMF (10 mL), then POCl3 (8 mL) was added and the resulting mixture was stirred at 50-60 °C for 6 h. The mixture was poured into ice-cold water. A saturated solution of sodium hydroxide was added to neutralize the mixture, the solid precipitate was filtered, washed with water, dried and recrystallized from ethanol. The isolated aldehydes were dissolved in acetone and sodium chlorite (20mmol) and sulfamic acid(25mmol) were added to give the desired oxidation products 6a-10e.
With trichlorophosphate at 50 - 60℃;
Stage #1: N-(1-phenylethylidene)phenylhydrazine With trichlorophosphate Stage #2: N,N-dimethyl-formamide at 60 - 70℃;
With trichlorophosphate at 0 - 85℃; for 6h;
With trichlorophosphate at 70 - 80℃;
With trichlorophosphate at 90℃; for 4h;
With trichlorophosphate at 80℃; for 5h;
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate Stage #2: With sodium hydrogencarbonate In water
With trichlorophosphate at 60 - 70℃; for 6h; Reflux;
With trichlorophosphate at 60 - 70℃; for 12h;
With trichlorophosphate at 50 - 60℃; for 5h; General method for the preparation of target compounds 6-10 General procedure: The starting material substituted 1,3-diphenyl-1H-pyrazole-4-carboxylic thioanhydride derivatives (6-10) was synthesized as following: para-substituted acetophenone (1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25 mmol) couple with sodium acetate (40 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethyli-dene) hydrazine, which was then dissolved in a cold mixed solution of DMF (20 mL) and POCl3 (16 mL), stirred at 50-60 °C for 5 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium hydroxide was added to neutralize the mixture, then the obtained solid precipitate were oxidized to the corresponding carboxylic acids by treatment with potassium permanganate (10mmol), stirred at 70-80°C for 3h while the transformation of acids into the appropriate acid chlorides was accomplished with thionyl chloride in refluxing toluene for 3h. A solution of substituted acid chlorides (4mmol) in anhydrous acetone (10mL) and 3% TBAB in acetone was added drop wise to a suspension of ammonium thiocyanate in acetone (10mL) and the reaction mixture was refluxed for 1h to give the desired compounds 6-10.
5.58 g With trichlorophosphate at 80℃; for 2h;
With trichlorophosphate at 60 - 70℃;
With potassium carbonate; trichlorophosphate at 0 - 80℃; for 6h;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 1.5h; Stage #2: N-(1-phenylethylidene)phenylhydrazine at 0 - 20℃; for 6h; Reflux; Synthesis of 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde (6) General procedure: To an ice cold dimethylformamide (10 ml), POCl3 (0.03 mol) was added dropwise with continuous stirring over a period of 30 min. Stirring was continued for further 60 min, keeping the reaction temp at 0 °C. Acetophenone phenylhydrazone derivative 5 (0.01 mol) was then added, the reaction mixture was allowed to attain room temperature and stirred for further 4 h. The mixture was then refluxed for 2 h, allowed to cool and poured onto ice. A saturated solution of sodium bicarbonate was added to neutralize the mixture. The solid product obtained was filtered, washed with water followed by hexane (2-3 times) and recrystallized from methanol. The completion of reaction was monitored by TLC using n-hexane:ethyl acetate (9:1) as a mobile phase.
With trichlorophosphate In ethanol at 50 - 60℃; for 6h;
With trichlorophosphate at 50 - 60℃; for 6h;
With trichlorophosphate at 50 - 60℃;
With trichlorophosphate
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: N-(1-phenylethylidene)phenylhydrazine at 0 - 80℃; for 5h; General Procedure for the Synthesis of Pyrazoles (4-6) General procedure: A mixture of 35.3 mmol of Dimethylformamide and 35.3mmol of POCl3 were separated earlier cooled at 0 °C before being stirred at such temperature. The Hydrazones (1-3) (11.76 mmol) was added to the reaction mixture which was, then, warmed at r.t. and heated at 70-80 °C for 5 h. After cooling at r.t., the mixture was then poured in crushed ice to yield precipitates (4-6), filtered and purified recrystallization using ethanol [27].
With trichlorophosphate at 50 - 60℃; 4.1.1. General procedure for the synthesis of 1, 3 diphenyl pyrazolecarboxaldehydes (4a-d) General procedure: The 1,3-diphenyl-1H-pyrazole-4-carboxaldehydes intermediates (4a-d) were synthesized based on a literature method as follows: para-substituted acetophenones (1a-d, 20 mmol) interact with phenylhydrazine (2, 25 mmol) in anhydrous ethanol to form acetophenone phenylhydrazones (3a-d),which were added to a cold solution of DMF (25 mL) and POCl3 (5 mL) and stirred at 50-60 ° for 6 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium bicarbonate was added to neutralize the mixture,extracted with ethyl acetate and then concentrated in vacuo. The resulting residue was purified by column chromatography to afford pure 1,3-diphenyl-1H-pyrazole-4-carbaldehydes (4a-d) in good yields. The spectroscopic data of the obtained aldehyde compound swas in agreement with the reported data [16,47].
With trichlorophosphate at 0 - 20℃;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; for 0.333333h; Stage #2: N-(1-phenylethylidene)phenylhydrazine In N,N-dimethyl-formamide at 90℃; for 3h; Stage #3: With potassium carbonate In water; N,N-dimethyl-formamide Synthesis General procedure: POCl3 (30 mmol) was added dropwise at 0 °C to 5 ml of dry DMF. The mixture was allowed to stand for 20 min at 0 °C, after which 10 mmol of arylhydrazone in 5 mL of dry DMF was added and uniform gas evolution was observed. The mixture was stirred for 3 h at 90 °C, cooled down and treated with 30% aqueous K2CO3 until the effervescence stopped. Then the reaction mixture was extracted with CH2Cl2 (3 * 10 mL) and the combined extracts were dried with anhydrous Na2SO4, filtered and evaporated under reduced pressure to obtain the corresponding compounds 1a-c which were isolated as white (1a, 1c) or pallid orange solids (1b) recrystallized from diethyl ether.
With trichlorophosphate at 50 - 60℃; for 5h;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; Stage #2: N-(1-phenylethylidene)phenylhydrazine at 70 - 80℃;
With trichlorophosphate at 50 - 60℃;
With trichlorophosphate at 0 - 80℃; for 6.5h;
With trichlorophosphate at 50 - 60℃; for 5h; General method for the preparation of target compounds 3a-3e General procedure: The starting material 1,3-diphenyl-1H-pyrazole-4-carbaldehyde(3ae3e) were synthesized as following: para-substituted acetophenone(1ae1e) (20 mmol) interact with phenylhydrazine hydrochloride(25 mmol) couple with sodium acetate (40 mmol) inanhydrous ethanol to form 1-phenyl-2-(1- phenylethylidene) hydrazine(2ae2e), whichwas then dissolved in a cold mixed solutionof DMF (20 mL) and POCl3 (16 mL), stirred at 50e60 C for 5 h. Theresulting mixture was poured into ice-cold water, a saturated solutionof sodium hydroxide was added to neutralize the mixture,and the solid precipitatewas filtered, washed with water, dried andrecrystallized from ethanol to give the compounds 3ae3e
With trichlorophosphate In N,N-dimethyl-formamide
With trichlorophosphate at 0 - 5℃; for 0.5h;
With trichlorophosphate at 50 - 60℃; for 5h;
With trichlorophosphate at 50 - 60℃;
With trichlorophosphate at 70℃; for 5h;
With trichlorophosphate at 50 - 60℃; for 5h; General procedure: The 1,3-diphenyl-1H-pyrazole-4-carboxylic acids (4a-d) were synthesized based on a literature method as following: para-substituted acetophenones (1a-d, 20mmol) interact with phenyl hydrazine (2, 25mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene) hydrazine, which was added to a cold solution of DMF (25mL) and POCl3 (5mL), stirred at 50-60°C for 5h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium bi carbonate was added to neutralize the mixture, the obtained solid (1, 3-diphenyl-1H-pyrazole-4-carbaldehyde) precipitate was filtered, then after reaction with NaClO2 and sulphamic acid in acetone to gave carboxylic acid derivatives (5a-d).
With trichlorophosphate at 20℃; for 8h;
With trichlorophosphate at 50 - 60℃; for 5h; General method for the preparation of target compounds 6-10 General procedure: The starting material substituted 1,3-diphenyl-1H-pyrazole-4-carbonyl chloride derivatives (6-10) was synthesized as following: para-substituted acetophenone (1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25 mmol) couple with sodium acetate (40 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene) hydrazine, which was then dissolved in a cold mixed solution of DMF (20 mL) and POCl3 (16 mL), stirred at 50-60 °C for 5 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium hydroxide was added to neutralize the mixture, then the obtained solid precipitate was oxidized to the corresponding carboxylic acids by treatment with potassium permanganate (10 mmol), stirred at 70-80 °C for 3 h while the transformation of acids into the appropriate acid chlorides was accomplished with thionyl chloride in refluxing for 3 h, and then thionyl chloride was removed under reduced pressure to give the desired compounds 6-10.
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 80℃; Stage #2: With water; sodium hydrogencarbonate
With trichlorophosphate at 60 - 70℃; Cooling with ice; Synthesis of 1, 3-diphenyl-1H-pyrazole-4-carbaldehyde (Scheme-1) [16] General procedure: Substituted phenyl hydrazones were prepared by heating substituted acetophenones with different hydrazines in methanol under reflux for 1-2 h. To a mixture of DMF (0.1 mol) and phosphorous oxychloride (0.02 mol), an ice-cold solution of phenyl hydrozone (0.01 mol) was added drop wise with stirring under cold condition. After the addition, the reaction mixture was refluxed at 60-70°C for 4-5 h. Solution was cooled and poured into crushed ice and neutralized with NaHCO3solution. The solid obtained was filtered under suction and recrystalized from methanol.
With trichlorophosphate at 80 - 85℃; for 5h; Preparation of the Intermediates 3-(4-Substituented Phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde Derivatives (3a-e) General procedure: The intermediates 3-(4-substituented phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (3a-e) were synthesized as following: para-substituted acetophenone (1a-e) (20 mmol) interacted with phenylhydrazine hydrochloride (20 mmol) couple with sodium acetate (40 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene) hydrazine (2a-e), which was then dissolved in a cold mixed solution of DMF (20 mL) and POCl3(16 mL), stirred at 80-85°C for 5 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium hydroxide was added to neutralize the mixture, and the solid precipitate was filtered, washed with water, dried and recrystallized from ethanol to give the compounds 3a-e.
With trichlorophosphate at 80 - 85℃; for 5h; Synthesis of 1-(4-substituented phenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde 2a-2d General procedure: Para-substituted acetophenone(20 mmol) interact with phenylhydrazine hydrochloride(20 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene)hydrazine, which was then dissolved in a cold mixedsolution of DMF (20 mL) and POCl3 (16 mL), stirred at 80-85 8C for5 h. The resulting mixture was poured into ice-cold water, asaturated solution of sodium hydroxide was added to neutralizethe mixture, and the solid precipitate was filtered, washed withwater, dried and recrystallized from ethanol.
With trichlorophosphate at 0 - 90℃; for 1h; General procedure for preparation of 1,3-diarylpyrazole aldehydes (3) General procedure: Hydrazone 2 (1.2 mmol) was dissolved in dimethylformamide (DMF) (15 ml) and then POC13 (7.2 mmol) was added slowly drop wise at 0 °C. After a complete addition of POC13, the reaction mixture was heated at 90 °C for 1 h. Then it was poured onto crushed ice and neutralized with 10% aq. NaOH solution. The product was extracted with methylene dichloride (3 × 30 ml) and the organic layer was washed (5-6 times) with water, dried over anhydrous Na2SO4 and evaporated. Finally, the crude material was purified by column chromatography using petroleum ether and ethyl acetate (9:1) as eluent to obtain title compound 3.
With trichlorophosphate at 70 - 75℃;
With trichlorophosphate at 80℃;
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 80℃; Stage #2: With water; sodium hydrogencarbonate
With trichlorophosphate Heating;
With trichlorophosphate at 10 - 90℃; for 8.5h; General procedure for synthesis of 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (4a-f) General procedure: Various required 3-(substituted aryl)-1-phenyl-1H-pyrazole-4-carbaldehydes (4a-f) were prepared according to literature method. In brief, required intermediate phenyl hydrazones (3a-f) were synthesized by refluxing equimolar mixture of phenylhydrazine (1) with various aromatic acetophenones (2a-f) in ethanol using few drops of glacial acetic acid. Further, to an ice cold solution of DMF (0.1 mol), was added phosphorus oxychloride (0.012 mol) drop-wise and the temperature was maintained below 10 °C. To the mixture, an ice-cold solution of phenyl hydrazone (0.01 mol) was added in lots wise with stirring under ice cold condition. After the completion of addition, the reaction mixture was stirred for 30 minutes and then refluxed at 80 - 90 °C for 8 h. Solution was cooled and poured into crushed ice with stirring and neutralized with aq. NaHCO3 solution. The solid product obtained was filtered under suction, dried and recrystallized from methanol.
With trichlorophosphate at 70 - 80℃; for 1h;
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0℃; Stage #2: N-(1-phenylethylidene)phenylhydrazine at 85℃; for 6h;
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 80℃; Stage #2: With sodium hydrogencarbonate In water
With trichlorophosphate at 90℃; for 2h;
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 80℃; Stage #2: With sodium hydrogencarbonate In water
With trichlorophosphate at 50 - 60℃; for 5 - 6h;
With trichlorophosphate Heating;
With trichlorophosphate at 0 - 70℃; for 3h;
With trichlorophosphate at 0 - 20℃; for 12h;
With trichlorophosphate at 0 - 70℃; for 6.5h; General Synthetic Procedure for the Key Intermediates 3, 7 and 10 General procedure: Dimethylformamide (2.58 g, 35.3 mmol) and POCl3 (5.4 g, 35.3 mmol) were previous separately cooled at 0°C before being stirred at such temperature. A solution of 2, 6 or 9 (3 g, 11.76 mmol) in DMF (3 mL) was added dropwise to the reaction mixture which was, then, warmed at r.t. and heated at 70°C for 6 h. After cooling at r.t., the mixture was basified with a cool saturated K2CO3 solution. The precipitate was filtered, strongly washed with water and crystallized from ethanol.
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 0 - 5℃; for 0.5h; Stage #2: N,N-dimethyl-formamide at 50℃;
With trichlorophosphate at 80℃;
With trichlorophosphate at 0 - 65℃; for 5.5h; Synthesis of 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (7a-f) General procedure: The solution of substituted acetophenone (0.042 mol) in ethanol (10 mL) was added to an ethanolic solution of phenylhydrazine (0.050 mol in10 mL ethanol) at room temperature. One drop of conc. H2SO4 was added and the mixture was stirred, refluxed for 55 min. The excess solvent was distilled off and the reaction mixture was cooled to 20-25 °C. The crude solid thus obtained was filtered, dried and recrystallized from ethanol. To the cold solution of DMF (15 mL) and acetophenone phenylhydrazone (0.024 mol), Vilsmeir-Haack reagent prepared from dimethylformamide (0.071 mol) and POCl3 (0.071 mol) was added in small lots within 30 min at 0-5 °C. The reaction mixture was stirred at 60-65 °C for 5 h and finally poured into ice-cold water. The precipitates obtained on neutralization with sodium bicarbonate were filtered, washed with water and recrystallized from ethanol (Scheme-II).
With trichlorophosphate
With trichlorophosphate at 80℃; for 4h; Cooling with ice; 1.2 2) using DMF as a solvent,Slowly add phosphorus oxychloride under ice bath.Stir for 1hAfter joining the last stepThe compound was heated at 80 ° C for 4 h.After the reaction,Quench the system with water,Add 1M sodium hydroxide solution to adjust pH=8,FilterAldehyde 1,3-diphenylpyrazole-4 formaldehyde
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 0 - 70℃; for 3h; Stage #2: With sodium hydroxide In water 4.3. General procedure for the synthesis of phenyl-3-aryl-1H-pyrazole-4-carbaldehydes (4a-g) General procedure: Synthesis of phenyl-3-aryl-1H-pyrazole-4-carbaldehydes (4a-g) reported in our previous work [29]. To a stirred solution of phenyl hydrazine1 (12 mmol, 1.29 g or 1.18 mL) in absolute ethanol (20 mL) was added acetophenone 2 (10 mmol) and glacial acetic acid (0.3 mL). The reaction mixture was kept on stirring at 70 °C. After completion of the reaction (as monitored by TLC), the excess solvent was evaporated to yield crude solid, which was filtered, washed with cold ethanol, dried and recrystallized from ethanol to yield the corresponding hydrazone(3).The appropriate acetophenone phenyl hydrazone (1.0 mmol) was added to a cold solution of dimethylformamide (DMF) (4 mL) and phosphorus oxychloride (0.5 g, 3.0 mmol) and the resulting mixture heated at 70 °C for 3 h. The mixture was cooled to room temperature and poured onto crushed ice, neutralized with an aqueous solution of sodium hydroxide (for compounds 4a, 4e and 4f) or sodium hydrogencarbonate (for compounds 4b-d and 4g). The precipitated solid was filtered and purified by flash column chromatography (20% EtOAc in nhexane)in case of compounds 4a, 4e and 4f, while recrystallized from ethanol to afford the rest of pyrazole-4-carbaldehydes (4b-d and 4g).
Stage #1: N,N-dimethyl-formamide With trichlorophosphate In methanol at 0 - 5℃; for 0.25h; Reflux; Stage #2: N-(1-phenylethylidene)phenylhydrazine In methanol at 5 - 80℃; for 5h; 3.1.1 General procedure to synthesize 1,3-Diphenyl-1H-pyrazole-4-carbaldehyde (1a-c) General procedure: Dimethyl formamide (DMF) and phosphorus oxychloride (POCl3) were separately cooled down to a temperature of 0°C. To previously cooled DMF (0.075mol) at 0-5°C, POCl3 was added drop-wise through dropping funnel. The resulting solution was stirred for 15min. A solution of hydrazone (prepared by refluxing desired acetophenone in methanol in the presence of catalytic amount of glacial acetic acid), made using minimum quantity of DMF was added to the mixture in drop-wise manner. The resulting mixture was warmed to room temperature and subsequently heated to a temperature of 75-80°C for a period of 5 hrs. Completion of the reaction was judged using TLC. Following completion, reaction mixture was cooled to room temperature and basified using a saturated solution of NaHCO3. Precipitate obtained on basification was filtered, washed and dried [16,17].
With trichlorophosphate at 60℃; for 6h;
With trichlorophosphate In N,N-dimethyl-formamide at 50 - 60℃; for 5h; 4.1. General procedure for the synthesis of 1,3-diphenyl-1Hpyrazole-4-carboxylic acids (5a-d) General procedure: 10 mmol) and phenyl hydrazine (2, 12.5 mmol) were added toanhydrous ethanol and heated to form the substituted acetophenonephenylhydrazone (3a-d). The solid was filtered off, dried, andadded to a cold solution of POCl3 (3 mL) in DMF (15 mL). Themixture was stirred at 50-60° C for 5 h to give the pyrazole carbaldehyde derivatives (4a-d). The reaction mixture was pouredinto ice-cold water and saturated solution of NaHCO3 was addedslowly to neutralize the reaction mixture. The precipitated solid(4a-d) was collected by filtration and dried. The aldehyde (4a-d,10 mmol) was dissolved in 15mL of acetone, sodium chlorite(NaClO2, 11 mmol) and sulfamic acid (NH2HSO3, 11 mmol) wasadded and the reactionwas stirred for 5 h at 40-50 °C. Acetonewasremoved by evaporation; the residue was dissolved in ethylacetateand the solution washed with water. The organic layer was separated,dried (Na2SO4) and the solvent removed by evaporation togive the pyrazole carboxylic acid derivative (5a-d) in good yields(85-90%).
With trichlorophosphate Synthesis of pyrazole-4-carbaldehydes (7a-g) General procedure: 3-(4-substituted-phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde wasprepared by the reaction of acetophenone and its derivatives withphenyl hydrazine in presence of ethanol as a solvent and acetic acid ascatalyst, then the resulted hydrazone derivative was treated with theVilsmeier-Haack reagent (DMF-POCl3) leading to the corresponding 4-carboxaldehyde functionalized pyrazole ring (7a-g). The progress of thereaction was ascertained by TLC using ethyl acetate: hexane (70:30) asthe mobile phase. Yield: 80%; IR (KBr, cm-1): 3060.82 (aromaticCeH), 1600.98 and 1450.37 (aromatic C]C), 697.81 (aromatic C]C-Hbending), 1656.63 (C]O).
Stage #1: N,N-dimethyl-formamide With trichlorophosphate Stage #2: N-(1-phenylethylidene)phenylhydrazine at 0 - 65℃; for 5.5h; Synthesis of 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes(4a-k) General procedure: To the cold solution of dimethyl formamide (15 mL) and acetophenone phenylhydrazone (0.024 mol), Vilsmeir-Haack reagent prepared from dimethylformamide (0.071 mol) and POCl3 (0.071 mol) was added in small lots within 30 min at 0-5 °C. The reaction mixture was stirred at 60-65 °C for 5 h and finally poured into ice-cold water. The precipitates thus obtained on neutralization with sodium bicarbonate were filtered, washed with water and recrystallized from ethanol
With trichlorophosphate at 0 - 60℃; for 3.16667h; Synthesis of 4-formyl pyrazoles (3) (Vilsmeier-Haack reaction): General procedure: To an ice-cold solution of 2a (0.74g, 5.0mmol) or 2b (1.05g, 5.0mmol) in N,N-dimethylformamide (DMF, 20mL), cold phosphoryl chloride (POCl3, 3equiv.) was added dropwise, and the mixture was first stirred at 0°C for 10min and then was heated to 60°C and kept at this temperature for 3h. The progress of the reaction was monitored by TLC (EtOAc/hexane=20:80). After cooling, the mixture was poured into ice-cold water (100mL), neutralized with NaOH aqueous solution, and the precipitate was filtered in vacuo, washed with water and crystallized from EtOH.
With trichlorophosphate for 5h; Reflux; 4.3. Method for the synthesis of compound 4 General procedure: The compound 3 (0.001 mol) was added to the cold solution of dimethyl formamide. Then phosphorous oxychloride (0.004 mol) was added dropwise with stirring and set for reflux for about 5 hrs. Afterwards, it was poured into cold water and neutralized with sodium bicarbonate. Then the formed precipitate was filtered and dried.
Stage #1: N,N-dimethyl-formamide With trichlorophosphate for 1h; Cooling with ice; Stage #2: N-(1-phenylethylidene)phenylhydrazine at 20℃; for 0.5h; Stage #3: at 80℃; for 4h; General procedure: To the solutionof ethanol (40 mL) was added substituted ketones (6a,10 mmol) and phenylhydrazines (15a, 10 mmol) and CH3COOH(11 mmol) were sequentially added. The solutionwas heated underreflux for 6e8 h, monitoring the progress of the reaction by TLC.After the reaction was completed, solvents were removed under vacuum and the residue was diluted with water (25 mL) andfiltered. The filter cakewas washed repeatedly with a small amountof ethyl acetate, the remaining solid compound 16 was used in thenext step without further purification. The mixture of DMF (3 mL)and phosphorus oxychloride (1 mL) was stirred for 1 h under icebath, to get Vilsmeier-Haack Reagent. Then adding the compound16 (5 mmol) to the solution, stirring at rt for 30 min, then transferringto 80 C for 4 h. After the reaction was over, the resultingmixturewas slowly poured into ice-cold water, a saturated solutionof sodium bicarbonate was added to neutralize the mixture, obtainedsolid 17 precipitatewas filtered. To a stirred suspension of 17(5 mmol) in 10 mL of Dioxane/water (4:1), were added of KOH(6 mmol) and potassium permanganate (6 mmol). The mixturewasstirred at room temperature for 3 h. Then slowly adding Hydrogenperoxide, filter out the MnO2 in the system. The dioxane in thefiltrate were removed under reduced pressure and added water(10 mL), the solution was acidified to pH 1e2 with concentratedHCl, and the resulting precipitate was filtered to get compounds18a. Compounds 18b-r were prepared through similar procedure asused for the synthesis of compound 18a and some of them requirecolumn chromatography to purify.
With trichlorophosphate at 70℃; for 2h; 4.2.8. Synthesis of OX13Step-1: To the stirred solution of phenyl hydrazine, 32 (1.0 eq) inethanol (10 mL) was added acetophenone, 31 (1.0 eq) followed byaddition of sodium acetate (3.0 eq) and the reaction mixture was refluxedfor 2 h. The reaction mixture was cooled and concentrated tohalf of its volume. The obtained solid precipitate was filtered and washedwith cold diethyl ether and dried under vacuo to afford lightyellow solid hydrazone 33.Step-2: POCl3 (4.0 eq) was added to an ice-cold DMF (10 mL), andthe mixture was stirred for 30 min. A solution of compound 33 (1.0 eq)in DMF (10 mL) was added, and the reaction was stirred at 70 °C for 2 h.The cooled reaction mixture was poured over crushed ice and neutralizedby adding solid NaHCO3.The compound was extracted withethyl acetate, and the combined organic layers were washed with brine,dried over anhydrous Na2SO4, filtered and concentrated under vacuo.The crude product was purified by column chromatography eluted withethyl acetate:hexane (3:7) to yield light brown solid 34.Step 3: In a round-bottomed flask, malonic acid (2.0 eq) was treatedwith compound 34 (1.0 eq) in a mixture of pyridine:piperidine (10:1)(10 mL). The reaction mixture was stirred at 115 °C for 4 h. Aftercompletion of the reaction, the reaction mixture was diluted with icecoldwater and acidified by adding 2 N HCl solution. The solid precipitatewas collected by filtration and dried under vacuo to afford offwhitesolid compound 35. To the stirred solution of carboxylic acid (3 and 4) (1.0 eq) in DCM(10 mL/ mmol) was added carbonyldiimidazole (CDI) (1.1 eq) and thereaction mixture was stirred for 30 min. N-hydroxybenzamidine, 2(1.0 eq) was added to this mixture and was stirred at room temperaturefor 6 h. After completion, the reaction mixture was diluted with DCM,washed with water and brine, dried over anhyd. Na2SO4, filtered andconcentrated under vacuo. The crude product was dissolved in tolueneand refluxed for 16 h. After completion of the reaction (monitored byTLC), the reaction mixture was cooled, and the solvent was removedunder vacuo. The product was purified by column chromatographyeluted with ethyl acetate:hexane (2:8) to yield the pure product.
Stage #1: N-(1-phenylethylidene)phenylhydrazine; N,N-dimethyl-formamide With trichlorophosphate at 70℃; for 3h; Stage #2: With water; sodium hydroxide General procedure: The appropriate 1-phenyl-2-(1-(substituted phenyl)ethylidene)hydrazine (3a-e) (1.0mmol) was added to a cold solution of dimethylformamide (4mL) and phosphorus oxychloride (0.5g, 3.0mmol); and the resulting mixture heated at 70°C for 3h. After cooling to room temperature, the reaction mixture was poured onto crushed ice and neutralized with an aqueous solution of sodium bicarbonate. The precipitated solid was filtered and purified through recrystallisation from ethanol
With trichlorophosphate at 0 - 20℃; for 12h;

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[88]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN109970654, 2019, A Location in patent: Paragraph 0079; 0083
[89]Andleeb, Hina; Hameed, Shahid; Ejaz, Syeda Abida; Khan, Imtiaz; Zaib, Sumera; Lecka, Joanna; Sévigny, Jean; Iqbal, Jamshed [Bioorganic Chemistry, 2019, vol. 88]
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[99]Abida Ejaz, Syeda; Andleeb, Hina; Farman, Muhammad; Hameed, Shahid; Hussain, Muzammal; Iqbal, Jamshed; Sevigny, Jean; Yasinzai, Masoom; Zhang, Jiancun [Bioorganic Chemistry, 2020, vol. 101]
[100]Subhashini; Kumar, Kolluri Prashanth; Kumar, Edigi Praveen; Shravani, Putta; Singh, Surya Sathyanarayana; Vani, Tamalapakula; Vijjulatha, Manga [Molecular Diversity, 2021, vol. 25, # 4, p. 2017 - 2033]
  • 3
  • [ 98-86-2 ]
  • [ 21487-45-6 ]
  • [ 144118-63-8 ]
YieldReaction ConditionsOperation in experiment
85% With potassium hydroxide In methanol; water at 5 - 35℃;
78% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1. Synthesis of Pyrazolyl Chalcone Derivatives (1) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as:3.1.1. 1-Phenyl-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1a): M.P. 132-133 [26], Yield: 78%;
77% With potassium hydroxide In ethanol; water Reflux; 3.2 General procedure for synthesis ofchalcones 3a-3d General procedure: A mixture of carbaldehyde 2a, 2b, or 2e (5 mmol) and acetophenonederivative (5 mmol) was dissolved in ethanol(15 mL), and then aqueous potassium hydroxide (20%,1.0 mL) was added. The reaction mixture was heated underreflux for 3-5 h. It was kept to attain ambient temperature,and the separated solid was filtered, washed with water,dried, and recrystallized from a mixture of chloroform andethanol.3.2.1 3-(1,3-Diphenyl-1H-pyrazol-4-yl)-1-phenylprop-2-en-1-one (3a)Yellow crystals, yield 77% (1.349 g), m. p. 140-141°C.- IR (KBr): ν = 1659 (C=O), 1592 (C=N), 1533 (C=C) cm-1.- 1H NMR (500 MHz, CDCl3): δ = 8.36 (s, 1 H, 5-H of pyrazolering), 7.95 (d, J = 8 Hz, 2 H, Ar-H), 7.88 (d, J = 16 Hz,1 H, CH = CHCO), 7.79 (d, J = 8 Hz, 2 H, Ar-H), 7.70-7.72(m, 2 H, Ar-H), 7.34-7.58 (m, 12 H, Ar-H and CH=CHCO).- C24H18N2O (350.41): calcd. C 82.26, H 5.18, N 7.99; found C82.33, H, 5.09, N 8.04.
70% With sodium hydroxide In ethanol at 25℃; for 3h;
60% With sodium hydroxide In ethanol at 0 - 20℃; 2.2. General Procedure for the Synthesis of 1,3-Diarylprop-2-en-1-one Derivatives 3a-m General procedure: Aqueous sodium hydroxide (12 mmol) was added to a mixture of appropriate ketone (10 mmol) and 1, 3-disubstituted-1H-pyrazole-4-carbaldehyde (10 mmol) in ethanol at 0 C. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and upon completion, the reaction mixture was poured into iced water. The pH of the mixture was adjusted to 6 using a 0.01 N HCl solution. The precipitates were filtered and recrystallized from ethanol to obtain the compounds 3a-m in 40-93% yield.
With barium(II) hydroxide at 20℃;
With sodium hydroxide In ethanol
With sodium hydroxide In methanol Reflux;
With sodium hydroxide In methanol
With sodium hydroxide In ethanol at 0 - 20℃;

Reference: [1]Location in patent: experimental part Brahmbhatt; Kaneria, Ankit R.; Patel, Anil K.; Patel, Niraj H. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 7, p. 971 - 977]
[2]Ranjan, Pooja; Arora, Loveena; Prakash, Richa; Aneja, Deepak K.; Prakash, Om [Letters in Organic Chemistry, 2017, vol. 14, # 4, p. 236 - 242]
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[9]Akhtar, Wasim; Marella, Akranth; Alam, Mohammad Mumtaz; Khan, Mohemmed F.; Akhtar, Mymoona; Anwer, Tariq; Khan, Farah; Naematullah, Md.; Azam, Faizul; Rizvi, Moshahid A.; Shaquiquzzaman, Mohammad [Archiv der Pharmazie, 2021, vol. 354, # 1]
[10]Kolla, Sai Teja; Somanaboina, Ramya; Bhimapaka, China Raju [Synthetic Communications, 2021, vol. 51, # 9, p. 1425 - 1432]
  • 4
  • [ 122-00-9 ]
  • [ 21487-45-6 ]
  • [ 144118-64-9 ]
YieldReaction ConditionsOperation in experiment
89% With potassium hydroxide In methanol; water at 5 - 35℃;
78% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1.5. 1-(4-Methylphenyl)-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1e) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as
63% With sodium hydroxide In ethanol at 25℃; for 3h;
With sodium hydroxide In methanol Reflux;
With sodium hydroxide In methanol

  • 5
  • [ 79-19-6 ]
  • [ 21487-45-6 ]
  • [ 221619-42-7 ]
YieldReaction ConditionsOperation in experiment
98% at 20℃; for 1h; ball-milling;
92% In ethanol for 1h; Reflux; Molecular sieve; Synthesis of 1-((3-(4-phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thiosemicarbazide(3a): A mixture of 3-(4-phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1a) (10 mmol) and thiosemicarbazide (2) (10 mmol) was refluxed in ethanol in the presence of activated molecular sieves of size 4A° (10 g). After 1 h of reflux the reaction mixture was filtered to remove molecular sieves. Ethanol was removed under vacuum. The residual mass was poured on crushed ice. The solid obtained was filtered and washed with water. The crude solid was purified by crystallization. Similarly the other compounds, (3b-g) of the series were prepared. The melting points and the yields of the derivatives are recorded in Table 1 1-((3-(4-phenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thiosemicarbazide (3a). IR (KBr, m cm1): 3410, 3100, 1597, 1590, 1334 and 1250. 1H NMR (200 MHz, DMSO-d6, d ppm): 7.55 (s, 1H, ACHNA), 8.01 (s,1H, pyrazoline-H), 8.29-8.77 (m, 10H, Ar-H), 9.10 (s, 1H, NH) 9.36 (s, 1H, NH,tautomeric) and 11.73 (s, 1H, SH, enolic). MS (ESI+, m/z): 322 (M+).
84% In ethanol for 3h; Heating;
80% With sodium acetate In ethanol Inert atmosphere;
79.6% With acetic acid In methanol for 10h; Reflux;
With sodium acetate In ethanol for 2h; Reflux;
With sodium acetate In ethanol for 5h; Reflux;
With acetic acid In ethanol
With acetic acid In ethanol at 80℃; for 0.0833333h; Microwave irradiation; Synthesis of Me-pyrTSC and Ph-pyrTSC: General procedure: To a solution of 3a (186mg, 1.0mmol) or 3b (248mg, 1.0mmol) in EtOH (5mL), a catalytic amount of glacial AcOH (0.1mL) and thiosemicarbazide (109mg, 1.2equiv.) were added, and the reaction mixture was irradiated with microwave (MW) (80°C) for 5min (alternatively 2h under reflux is sufficient). The completion of the reaction was determined by TLC (EtOAc/hexane=40:60). The crude product was poured into ice cold water. The solid thus obtained was filtered in vacuo, washed with ice-cold water and purified by column chromatography (silica gel, EtOAc/hexane=30:70 to EtOAc using gradient elution).
With acetic acid In ethanol for 2h; Reflux;

Reference: [1]Location in patent: experimental part Bondock, Samir; El-Azap, Hossam; Kandeel, Ez-Eldin M.; Metwally, Mohamed A. [Monatshefte fur Chemie, 2008, vol. 139, # 11, p. 1329 - 1335]
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  • 6
  • [ 89-25-8 ]
  • [ 21487-45-6 ]
  • 4-((1,3-dipheny-1H-pyrazole-4-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With glycine In dimethyl sulfoxide at 20℃; for 12h; Green chemistry; General procedure for the synthesis of products 3a-r General procedure: To a mixture of an aldehyde 1a-f (2.0 mmol) and an active methylene 2a-d (2.0 mmol) dissolved in 5 mL of DMSO, 0.022 g of glycine (0.40 mmol, 20 mol%, 0.20 equiv) was added. The stirring was continued at room temperature for 3-15 h and then the reaction was quenched with ice water to obtain neat precipitates of pyrazole acryloyl compound 3a-r, which were further purified by recrystallization with ethanol.
74% With piperidine In methanol for 12h; Reflux; 2.3.6. 4-((1,3-Dipheny-1H-pyrazole-4-yl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (3e) 1,3-Dipheny-1H-pyrazole-3-carbaldehyde (248 mg, 1 mmol, 1equiv) and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (174 mg,1 mmol, 1 equiv) were dissolved in dry methanol (15 mL). 0.1 mL of piperidine were added, and the solution was refluxed for 12 h. After completion of the reaction, the reaction mixture cooled to room temperature, the orange solid was filtered, washed with methanol and dried. The dye obtained was purified by column chromatography using silica gel 100-200 mesh and toluene as eluent system. Colour: Orange solid, Yield: 300 mg, 74%, M. P.: 239-240 °C. FT-IR (KBr, cm-1): 1666 (amide stretching). 1H NMR (500 MHz, CDCl3, Me4Si) δ 2.26 (s, 3H, CH3), 7.20 (t,J 6.9 Hz, 1H, ArH), 7.38 (t, J 7.4 Hz, 1H, ArH), 7.41-7.47 (m, 2H, ArH), 7.48 (s, 1H, ArH), 7.49-7.60 (m, 5H, ArH), 7.69 (d, J 6.6 Hz,2H, ArH), 7.93 (dd, J 8.5, 0.9 Hz, 2H, ArH),7.97 (dd, J 8.6, 1.0 Hz,2H, ArH), 10.27 (s, 1H, NeCH). 13C NMR (126 MHz, CDCl3, Me4Si) δ 13.0, 115.9, 119.3, 119.9,123.8, 124.9, 127.8, 128.8, 128.9, 129.1(2), 129.3, 129.4, 129.5, 131.4,134.2, 135.4, 138.5, 139.1, 150.4, 157.2, 162.7. MS (m/z): 405.5 (M+H).Anal. Calcd. for C26H20N4O: C, 77.21; H, 4.98; N, 13.85. Found: C,77.23; H, 4.99; N, 13.90.HRMS m/z [M+H]+ Calcd for C26H20N4O: 405.1715. Found: 405.1653.
70% With triethylamine In ethanol for 0.25h; Heating;
With aminosulfonic acid In neat (no solvent) at 20℃; for 0.166667h; Green chemistry; 4.2 Synthesis of 4-((1, 3-diphenyl-1H-pyrazol-4-yl) methylene)-1-phenyl pyrazolin-5(4H)-one 6(a-n) General procedure: Stepwise synthesis: A mixture of appropriate 1,3-diphenylpyrazolin-5-(4H)-4-carbaldehyde 4(a-h) (5mmol), pyrazolones 9(a, b) (5mmol) and sulfamic acid (20 mol%) was thoroughly grind with pestle in an open mortar at room temperature. Reaction progress was monitored by TLC. Upon completion of the reaction, isolation and purification of the crude products 6(a-n) was carried out by using above methodology. All the synthesized products are stable, coloured solids and authenticity of these compounds was established based on their melting points and spectral analysis (IR, 1H NMR and LC-MS). Spectral data for compound 6(a-n): (Z)-3-Methyl-1-phenyl-4-(1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)methylene-1H-pyrazol-5(4H)-one (6a): IR (KBr, cm-1): 3125.7, 2982, 1675; 1H NMR (400MHz, DMSO-d6/TMS): δ 2.42 (s, 3H, -CH3), 7.38-7.99 (m, 15H, aromatic protons and 1H olefinic proton), 10.88 (s, 1H pyrazole ring proton); LC-MS: m/z 405 (Q+1).

  • 7
  • [ 563-41-7 ]
  • [ 21487-45-6 ]
  • 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With phosphoric acid In ethanol for 0.75h; Reflux;
69% With sodium acetate In ethanol for 2h; Reflux;
67% With sodium acetate In ethanol Inert atmosphere;
65% With sodium acetate In ethanol for 2h; Heating;
With sodium acetate In ethanol at 80℃; for 0.0833333h; Microwave irradiation; Procedure for the synthesis of Ph-pyrSC: General procedure: To a solution of 2b (248mg, 1.0mmol) in EtOH (5mL), semicarbazide hydrochloride (134mg, 1.2equiv.) and sodium acetate (NaOAc) (98mg, 1.2equiv.) were added, and the reaction mixture was irradiated with MW (80°C) for 5min (alternatively 2h under reflux is sufficient). The completion of the reaction was determined by TLC (EtOAc/hexane=40:60). The crude product was poured into ice-cold water. The solid thus obtained was filtered in vacuo, washed with ice-cold water and purified by column chromatography (silica gel, EtOAc).

  • 8
  • [ 21487-45-6 ]
  • [ 109-77-3 ]
  • [ 221619-37-0 ]
YieldReaction ConditionsOperation in experiment
96% In water at 20℃; for 0.0833333h; Green chemistry; General procedure for the synthesis of pyrazole decorated nitriles and acrylates General procedure: When equimolar quantity of 3-(4-bromophenyl)-1-phenylpyrazolecarbaldehyde (1.0 mmol) and malononitrile (1.0 mmol) were stirred in polyethylene glycol (PEG-400) / water (3:1) mixture at ambient temperature for a couple of minutes, a solid was obtained. Water was then added, filtered and dried under vacuum to give 2-[(3-(4-bromophenyl)-1-phenylpyrazolyl)methylene]malononitrile (1a). Recrystallization from ethanol-DMF mixture afforded the analytically pure target molecule. Similar experimental procedure was adopted for the synthesis of 2-[(1,3-diaryl-4-pyrazolyl)methylene]malononitriles 1b-1j, arylidenemalononitriles 2a-2f and ethyl 3-(1,3-diaryl-4-pyrazolyl)-2-cyanoacrylates 3a-3e from their corresponding aldehydes. In the synthesis of 1b-1j and 2a-2f, the reactions were completed in 5 minutes while the reactions were ended in 4 hours in the synthesis of 3a-3e.
91% In propylene glycol; water at 20℃; for 0.133333h; Green chemistry; Typical experimental procedurefor the synthesis of nitriles / acrylates / acrylamides General procedure: When3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) andmalononitrile (1.0 mmol) were stirred in a mixture of propan-1,2-diol and water(4 mL and 2.5 mL, respectively) for 8minutes, a light yellow solid was obtained which was filtered and dried.Recrystallization from ethanol-DMF mixture afforded the pure 2-[(3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene]malononitrile.Similar procedure was adopted for the synthesis of homo/heteroaryl basedacrylates and acrylamides from their corresponding aldehydes and ethyl2-cyanoacetate and 2-cyanoacetamide, respectively in 2 - 6 hours.
85% With piperidine In ethanol for 2h; Reflux;
83% With piperidine In ethanol for 4h; Heating;
83% With piperidine In ethanol for 2h; Reflux;
81% With piperidine In ethanol for 0.0833333h; Heating;
81% With piperidine In methanol at 20℃; for 2h; Inert atmosphere; 2.3.2. 2-[(1,3-Diphenyl-1H-pyrazol-4-yl)methylene]malononitrile (3a) Under nitrogen atmosphere, 1,3-dipheny-1H-pyrazole-3-carbaldehyde (248 mg, 1 mmol, 1 equiv) and malononitrile (66 mg, 1 mmol, 1 equiv) were dissolved in dry methanol (15 mL). 0.1 mL of piperidine was added, and the solution was stirred at RT for 2 h. After completion of the reaction, the off white coloured solid was filtered, washed with methanol, and dried. The dye obtained was purified by column chromatography using silica gel 100-200 mesh and toluene as eluent system. Colour: Off -white solid, Yield: 240 mg, 81%, M. P.: 160-162 °C [51]. FT-IR (KBr, cm-1): 2224 (CN stretching). 1H NMR (400 MHz, CDCl3, Me4Si) δ 7.455 (d, J = 7.6 Hz, 1H, ArH), 7.524-7.564 (m, 7H, ArH), 7.803 (s, 1H, NeCH), 7.811-7.834 (m, 2H,ArH), 9.064 (s, 1H, C]CH). 13C NMR (126 MHz, CDCl3, Me4Si) δ 78.5, 113.8, 113.9, 114.9,120.1, 128.7, 129.2 (2), 129.3, 129.8 (2), 130.1, 138.5, 151.1, 156.4. MS (m/z): 297.2 (M+H). Anal. Calcd. for C19H12N4: C, 77.01; H, 4.08; N, 18.91. Found: C,77.23; H, 4.01; N, 18.82. HRMS m/z [M+H]+ Calcd for C19H12N4: 297.1140. Found: 297.1099.
80% With thiourea for 0.0333333h; Microwave irradiation; neat (no solvent);
In water at 50℃; for 0.5h; General procedure for the One-pot synthesis of thiolanes General procedure: A mixture of aldehyde (1 Equiv) and malononitrile/barbituric acid (1 Equiv) in water (2 mL; total reaction concentration 0.086 M) was heated at 50°C for 30 min. After the formation of intermediate (olefin), 1,4-dithiane-2,5-diol (0.75 Equiv) was added at same temperature and heating continued until the completion of the reaction (monitored by TLC). Then the reaction mixture was extracted EtOAc (20x2 mL). The combined organic layers were dried using sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by column chromatography. Purification using petroleum ether-EtOAc gave the desired product.
With piperidine In ethanol at 20℃; for 1h; Reaction of 1 with malononitrile Malononitrile (10 mmol) and a few drops of piperidine were added to a stirred solution of 1 (10 mmol) in ethanol (40 mL). The reaction mixture was stirred for 1 h. The yellow precipitate obtained was filtered off, washed with ethanol and recrystallised from ethanol-dioxane to give compound 9.2-[(1,3-Diphenyl-1H-pyrazol-4-yl)methylene]malononitrile (9): Yellow crystals; m.p. 180 -182 °C (lit. 16 158-160 °C).
With piperidine In ethanol for 10h; Reflux;
With piperidine In ethanol at 20℃;

Reference: [1]Jayalakshmi, Lakshmi Narayanan; Stalindurai, Kesavan; Karuppasamy, Ayyanar; Sivaramakarthikeyan, Ramar; Devadoss, Vellasamy; Ramalingan, Chennan [Synlett, 2015, vol. 26, # 13, p. 1857 - 1861]
[2]Jayalakshmi, Lakshmi Narayanan; Karuppasamy, Ayyanar; Stalindurai, Kesavan; Sivaramakarthikeyan, Ramar; Devadoss, Vellasamy; Ramalingan, Chennan [Tetrahedron Letters, 2015, vol. 56, # 28, p. 4207 - 4210]
[3]Amer, Atef M.; Ramses, Neveen; Mahgoub, Sebaey [Egyptian Journal of Chemistry, 2018, vol. 61, # Conference Issue, p. 51 - 65]
[4]Aly, El-Saied A.; El-Borai, Mohamed A.; Barren, Mohamed A. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 6, p. 1355 - 1359]
[5]Ali, Tarik E. [Heteroatom Chemistry, 2013, vol. 24, # 5, p. 426 - 436]
[6]El-Emary; Bakhite [Pharmazie, 1999, vol. 54, # 2, p. 106 - 111]
[7]Lanke, Sandip K.; Sekar, Nagaiyan [Dyes and Pigments, 2016, vol. 126, p. 62 - 75]
[8]Location in patent: experimental part Li, Jian-Ping; Qiu, Ji-Kuan; Li, Hui-Juan; Zhang, Gui-Sheng [Journal of the Chinese Chemical Society, 2011, vol. 58, # 2, p. 268 - 271]
[9]Nagaraju, Sakkani; Sathish, Kota; Paplal, Banoth; Kashinath, Dhurke [Tetrahedron Letters, 2017, vol. 58, # 29, p. 2865 - 2871]
[10]Atta-Allah, Saad R.; Abou-Elmagd, Wael S. I.; Kandeel, Kamal A. A.; Hemdan, Magdy M.; Haneen, David S. A.; Youssef, Ahmed S. A. [Journal of Chemical Research, 2017, vol. 41, # 11, p. 617 - 623]
[11]Nossier, Eman S.; Abd El-Karim, Somaia S.; Khalifa, Nagy M.; El-Sayed, Ali S.; Hassan, Emad S.I.; El-Hallouty, Salwa M. [Molecules, 2018, vol. 23, # 12]
[12]Kaddah, Mohamed M; Fahmi, Abdelgawad A.; Kamel, Mustafa M.; Ramadan, Sayed K.; Rizk, Sameh A. [Synthetic Communications, 2021, vol. 51, # 12, p. 1798 - 1813] Ramadan, Sayed K.; Rizk, Sameh A. [Journal of the Iranian Chemical Society, 2022, vol. 19, # 1, p. 187 - 201]
  • 9
  • [ 21487-45-6 ]
  • [ 77169-12-1 ]
YieldReaction ConditionsOperation in experiment
95% With bis(acetylacetonate)oxovanadium; dihydrogen peroxide In water; acetonitrile at 70℃; for 8h; Green chemistry;
94% With pyridine; potassium permanganate In water at 20 - 22℃;
88% With potassium permanganate; water; potassium hydroxide In 1,4-dioxane at 20℃; 2.2-15 2-15.Synthesis of 1,3-diphenyl-1H-pyrazole-4-carboxylic acid (5a) A stirred solution of compound 4a (3.58 g, 14.4 mmol) in dioxane (20 mL) and water (5 ml) were added to KOH (1.21 g, 21.6 mmol) dissolved in 3 mL of water, and further KMnO4( 3.42 g, 21.6 mmol) was added.The reaction mixture was stirred at room temperature and monitored by TLC.Excess KMnO4was decomposed withdiluted H2O2(1 mL in 5 mL water).The reaction mixture was filtered through a pad of celite, and the filtrate was concentrated under reduced pressure.The residue was acidified with 10% HCl solution.The precipitate was filtered, washed with water and recrystallized from EtOH to give compound 5a as a white solid (3.36 g, 88%).
85% With potassium permanganate; <i>tert</i>-butyl alcohol In water at 75℃; for 3h;
With trichloroisocyanuric acid; sodium hydrogencarbonate; sodium bromide In acetone at 20℃;
With pyridine; potassium permanganate In water at 22 - 24℃; for 2h; To a suspension of l,3-diphenyl-lH-pyrazole-4-carbaldehyde (1.2g, 4.8mmol) in 5ml of 50% aqueous pyridine at stirring and cooling with tap water was added by small portion of potassium permanganate (0.76g, 4.8mmols) within 1 hour. The reaction temperature was maintained between 22-24°C during the addition. Keep stirring for 1 hour, and then the precipitate was filtered off, washed with 5% of sodium hydroxide. The filtrate was added 10% hydrochloric acid (40ml). The EPO product was filtered off, dried in vacuo to givel .3g of crude product as a dark brown solid, which was used for next step without further purification.
With sodium chlorite; aminosulfonic acid In acetone at 40 - 50℃; for 5h; General Procedure for the Preparation of 1, 3-diphenyl-1H-pyrazole-4-carboxylic acids (6-10) General procedure: The starting material substituted 1, 3-diphenyl-1H-pyrazole-4-carboxylic acid(6-10) was synthesized as following: para-substituted acetophenone(1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25mmol) couple with sodium acetate (40mmol in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene)hydrazine, which was then added to a cold solution of DMF (10 mL), then POCl3 (8 mL) was added and the resulting mixture was stirred at 50-60 °C for 6 h. The mixture was poured into ice-cold water. A saturated solution of sodium hydroxide was added to neutralize the mixture, the solid precipitate was filtered, washed with water, dried and recrystallized from ethanol. The isolated aldehydes were dissolved in acetone and sodium chlorite (20mmol) and sulfamic acid(25mmol) were added to give the desired oxidation products 6a-10e.
With potassium permanganate at 70 - 80℃; for 3h; General method for the preparation of target compounds 6-10 General procedure: The starting material substituted 1,3-diphenyl-1H-pyrazole-4-carboxylic thioanhydride derivatives (6-10) was synthesized as following: para-substituted acetophenone (1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25 mmol) couple with sodium acetate (40 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethyli-dene) hydrazine, which was then dissolved in a cold mixed solution of DMF (20 mL) and POCl3 (16 mL), stirred at 50-60 °C for 5 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium hydroxide was added to neutralize the mixture, then the obtained solid precipitate were oxidized to the corresponding carboxylic acids by treatment with potassium permanganate (10mmol), stirred at 70-80°C for 3h while the transformation of acids into the appropriate acid chlorides was accomplished with thionyl chloride in refluxing toluene for 3h. A solution of substituted acid chlorides (4mmol) in anhydrous acetone (10mL) and 3% TBAB in acetone was added drop wise to a suspension of ammonium thiocyanate in acetone (10mL) and the reaction mixture was refluxed for 1h to give the desired compounds 6-10.
With potassium permanganate; water; potassium hydroxide In 1,4-dioxane at 20℃;
With sodium chlorite; aminosulfonic acid In acetone at 0 - 20℃; for 4h;
With sodium chlorite; aminosulfonic acid In acetone at 40 - 50℃; for 5h; 4.1 General procedure for the synthesis of 1,3-diphenyl-1H-pyrazole-4-carboxylic acids (5a-d) General procedure: The 1,3-diphenyl-1H-pyrazole-4-carboxylic acids (4a-d) were synthesized based on a literature method as following: para-substituted acetophenones (1a-d, 20mmol) interact with phenyl hydrazine (2, 25mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene) hydrazine, which was added to a cold solution of DMF (25mL) and POCl3 (5mL), stirred at 50-60°C for 5h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium bi carbonate was added to neutralize the mixture, the obtained solid (1, 3-diphenyl-1H-pyrazole-4-carbaldehyde) precipitate was filtered, then after reaction with NaClO2 and sulphamic acid in acetone to gave carboxylic acid derivatives (5a-d).
With potassium permanganate at 70 - 80℃; for 3h; General method for the preparation of target compounds 6-10 General procedure: The starting material substituted 1,3-diphenyl-1H-pyrazole-4-carbonyl chloride derivatives (6-10) was synthesized as following: para-substituted acetophenone (1-5) (20 mmol) interact with phenylhydrazine hydrochloride (25 mmol) couple with sodium acetate (40 mmol) in anhydrous ethanol to form 1-phenyl-2-(1-phenylethylidene) hydrazine, which was then dissolved in a cold mixed solution of DMF (20 mL) and POCl3 (16 mL), stirred at 50-60 °C for 5 h. The resulting mixture was poured into ice-cold water, a saturated solution of sodium hydroxide was added to neutralize the mixture, then the obtained solid precipitate was oxidized to the corresponding carboxylic acids by treatment with potassium permanganate (10 mmol), stirred at 70-80 °C for 3 h while the transformation of acids into the appropriate acid chlorides was accomplished with thionyl chloride in refluxing for 3 h, and then thionyl chloride was removed under reduced pressure to give the desired compounds 6-10.
With potassium permanganate In water; <i>tert</i>-butyl alcohol at 75℃; for 0.75h;
With pyridine; potassium permanganate
With potassium permanganate; sodium hydroxide In 1,4-dioxane; water at 20℃; for 2h; 1.3 3) using dioxane/water (4:1) as solvent,1 eq aldehyde compound 1,3-diphenylpyrazole-4 formaldehyde,1.2 eq of sodium hydroxide and 1.2 eq of potassium permanganate, reacted at room temperature for 2 h. After complete conversion, slowly add hydrogen peroxide to filter out solid impurities in the system.Vacuum removal of dioxane,After adding water, adjust the pH to 1 with 1M HCl.Precipitating a white solid,Filtration to give carboxylic acid compounds1,3-diphenylpyrazole-4carboxylic acid.
With sodium chlorite; aminosulfonic acid In acetone at 40 - 50℃; for 5h; 4.1. General procedure for the synthesis of 1,3-diphenyl-1Hpyrazole-4-carboxylic acids (5a-d) General procedure: 10 mmol) and phenyl hydrazine (2, 12.5 mmol) were added toanhydrous ethanol and heated to form the substituted acetophenonephenylhydrazone (3a-d). The solid was filtered off, dried, andadded to a cold solution of POCl3 (3 mL) in DMF (15 mL). Themixture was stirred at 50-60° C for 5 h to give the pyrazole carbaldehyde derivatives (4a-d). The reaction mixture was pouredinto ice-cold water and saturated solution of NaHCO3 was addedslowly to neutralize the reaction mixture. The precipitated solid(4a-d) was collected by filtration and dried. The aldehyde (4a-d,10 mmol) was dissolved in 15mL of acetone, sodium chlorite(NaClO2, 11 mmol) and sulfamic acid (NH2HSO3, 11 mmol) wasadded and the reactionwas stirred for 5 h at 40-50 °C. Acetonewasremoved by evaporation; the residue was dissolved in ethylacetateand the solution washed with water. The organic layer was separated,dried (Na2SO4) and the solvent removed by evaporation togive the pyrazole carboxylic acid derivative (5a-d) in good yields(85-90%).
With potassium permanganate; potassium hydroxide In 1,4-dioxane; water at 20℃; for 3h; General procedure: To the solutionof ethanol (40 mL) was added substituted ketones (6a,10 mmol) and phenylhydrazines (15a, 10 mmol) and CH3COOH(11 mmol) were sequentially added. The solutionwas heated underreflux for 6e8 h, monitoring the progress of the reaction by TLC.After the reaction was completed, solvents were removed under vacuum and the residue was diluted with water (25 mL) andfiltered. The filter cakewas washed repeatedly with a small amountof ethyl acetate, the remaining solid compound 16 was used in thenext step without further purification. The mixture of DMF (3 mL)and phosphorus oxychloride (1 mL) was stirred for 1 h under icebath, to get Vilsmeier-Haack Reagent. Then adding the compound16 (5 mmol) to the solution, stirring at rt for 30 min, then transferringto 80 C for 4 h. After the reaction was over, the resultingmixturewas slowly poured into ice-cold water, a saturated solutionof sodium bicarbonate was added to neutralize the mixture, obtainedsolid 17 precipitatewas filtered. To a stirred suspension of 17(5 mmol) in 10 mL of Dioxane/water (4:1), were added of KOH(6 mmol) and potassium permanganate (6 mmol). The mixturewasstirred at room temperature for 3 h. Then slowly adding Hydrogenperoxide, filter out the MnO2 in the system. The dioxane in thefiltrate were removed under reduced pressure and added water(10 mL), the solution was acidified to pH 1e2 with concentratedHCl, and the resulting precipitate was filtered to get compounds18a. Compounds 18b-r were prepared through similar procedure asused for the synthesis of compound 18a and some of them requirecolumn chromatography to purify.
With potassium permanganate; potassium hydroxide In water
With pyridine; potassium permanganate In water at 20℃; 2.3. Preparation of the aryl-1-phenylpyrazole-4-carboxylic acid (3a-3g): General procedure: Aldehyde (1 mmol) was dissolved in 50 mL (pyridine: water =1:1) and KMnO4 (1 mmol) was added. The reaction was stirred overnight at room temperature. The completion of reaction was monitored by TLC using 30% EtOAc/hexane (Rf is about 0.2 for the product). Upon completion, ice cold water was added to the reaction mixture followed by the addition of aq. NaOH to effect precipitation. The mixture was filtered and the filtrate was acidified with conc. HCl which resulted in the precipitation. The solid was filtered and recrystallized in hexane to yield the carboxylic acid.

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[2]Bratenko; Chornous; Vovk [Russian Journal of Organic Chemistry, 2001, vol. 37, # 4, p. 552 - 555]
[3]Current Patent Assignee: CHONNAM NATIONAL UNIVERSITY - KR2021/109861, 2021, A Location in patent: Paragraph 0095-0099; 0150-0151
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[5]De Luca, Lidia; Giacomelli, Giampaolo; Masala, Simonetta; Porcheddu, Andrea [Synlett, 2004, # 13, p. 2299 - 2302]
[6]Current Patent Assignee: BAUSCH HEALTH COMPANIES INC - WO2006/33995, 2006, A2 Location in patent: Page/Page column 25-26
[7]Li, Xi; Lu, Xiang; Xing, Man; Yang, Xian-Hui; Zhao, Ting-Ting; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 11, p. 3589 - 3593]
[8]Sun, Jian; Lv, Xian-Hai; Qiu, Han-Yue; Wang, Yan-Ting; Du, Qian-Ru; Li, Dong-Dong; Yang, Yong-Hua; Zhu, Hai-Liang [European Journal of Medicinal Chemistry, 2013, vol. 68, p. 1 - 9]
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[11]Ganga Reddy; Srinivasa Reddy; Lakshma Nayak; Prasad, Budaganaboyina; Reddy, Adiyala Praveen; Ravikumar; Taj, Shaik; Kamal, Ahmed [European Journal of Medicinal Chemistry, 2016, vol. 122, p. 164 - 177]
[12]Lv, Xian-Hai; Ren, Zi-Li; Zhou, Ben-Guo; Li, Qing-Shan; Chu, Ming-Jie; Liu, Dao-Hong; Mo, Kai; Zhang, Li-Song; Yao, Xiao-Kang; Cao, Hai-Qun [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 19, p. 4652 - 4659]
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[15]Current Patent Assignee: ZHENGZHOU UNIVERSITY - CN109970654, 2019, A Location in patent: Paragraph 0079; 0084
[16]Reddy, Velma Ganga; Reddy, T. Srinivasa; Jadala, Chetna; Reddy, M. Soumya; Sultana, Faria; Akunuri, Ravikumar; Bhargava, Suresh K.; Wlodkowic, Donald; Srihari; Kamal, Ahmed [European Journal of Medicinal Chemistry, 2019, vol. 182]
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  • 10
  • [ 21487-45-6 ]
  • [ 40278-32-8 ]
YieldReaction ConditionsOperation in experiment
99% With sodium tetrahydroborate In methanol at 20℃; for 0.5h;
91% With sodium tetrahydroborate In ethanol for 1h;
52% With sodium tetrahydroborate
52% With sodium tetrahydroborate In ethanol; dichloromethane at 0 - 25℃; for 1h; 1 Typical procedure for synthesis of compounds 3-aryl-4-hydroxymethyl-1H-1-phenylpyrazoles (3a-c). 4.2.1.1. 4-Hydroxymethyl-1H-1,3-diphenylpyrazole (3a). General procedure: The reduction reactions of 3-aryl-4-formyl-1H-1-phenylpyrazoles (1a-c) (1 mmol) were conducted in anhydrous EtOH and CH2Cl2 (for better solubilization), at 0 °C, where small portions of sodium borohydride (1.2 mmol) were added to the solution. After the addition, the reaction mixture was stirred at 25 °C for 1 h. Then the solvents were evaporated under reduced pressure. The residue was dissolved in 20 mL H2O/CH2Cl2 (1:1), stirred for 1 h and extracted with CH2Cl2 (3 x 10 mL). The combined extracts were dried with anhydrous Na2SO4, filtered and evaporated under reduced pressure to obtain the corresponding compounds 3a-c which were isolated as white (3a, 3c) or orange solids (3b) recrystallized from diethyl ether. Only compound 3a is already described and its analytical data were also compared with the available literature [38]. 4.2.1.1. 4-Hydroxymethyl-1H-1,3-diphenylpyrazole (3a). White solid, yield 52%, mp 73-75 °C. 1H NMR (400.13 MHz, DMSO-d6): δ 8.50 (s, 1H), 7.90 (d, 4H), 7.53-7.46 (m, 4H), 5.18 (s, 1H), 4.59 (s, 2H). 13C NMR (100.61 MHz, DMSO-d6): δ 151.8, 140.0; 133.5; 138.7; 130.0; 129.0; 128.3, 127.8, 126.5, 118.5, 129.1, 122.5, 54.6. HRMS Calcd. for C16H14N2O: 251.1179. Found: 251.1151.
With sodium tetrahydroborate In dichloromethane for 8h; Reflux;
With sodium tetrahydroborate In ethanol at 0℃; for 1h;
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h; 2 4.1.3. General procedure for the synthesis of (1,3-diphenyl-1H-pyrazol-4-yl)-methanols (5a-h) General procedure: Sodium borohydride (1.2 mmol) was added to a stirred solutionof pyrazole aldehyde 4a (1.0 mmol) in methanol at 0 C. The reactionmixture was stirred for 1 h at room temperature. After completionof the reaction (TLC), the solvent was removed underreduced pressure; cold water was added and extracted with ethylacetate (2 10 mL). The organic layer was washed with brine,dried over Na2SO4 and solvent was removed under reduced pressureprovided (1,3-diphenyl-1H-pyrazol-4-yl)methanol 5a. The1H-pyrazolylmethanols 5b-h were prepared from the correspondingpyrazole aldehydes 4b-h under similar conditions.
With sodium tetrahydroborate In ethanol at 20℃; for 1h;
With sodium tetrahydroborate; ethanol at 0℃; for 2h;

Reference: [1]Radulović, Niko S.; Nikolić, Milica G.; Mladenović, Marko Z.; Ranđelović, Pavle; Stojanović, Nikola M.; Stojanović-Radić, Zorica; Jovanović, Ljiljana [Applied Organometallic Chemistry, 2022, vol. 36, # 2]
[2]Bratenko; Chornous; Vovk [Russian Journal of Organic Chemistry, 2002, vol. 38, # 3, p. 411 - 414]
[3]Bonacorso, Helio G.; Pittaluga, Everton P.; Porte, Liliane M. F.; Libero, Francieli M.; Junges, Andrizia F.; Zanatta, Nilo; Martins, Marcos A. P. [Synlett, 2015, vol. 26, # 14, p. 2009 - 2013]
[4]Bonacorso, Helio G.; Pittaluga, Everton P.; Porte, Liliane M.F.; Junges, Andrizia F.; Libero, Francieli M.; Zanatta, Nilo; Martins, Marcos A.P. [Journal of Fluorine Chemistry, 2015, vol. 176, # 1, p. 44 - 50]
[5]Zhang, Wei-Ming; Xing, Man; Zhao, Ting-Ting; Ren, Yu-Jia; Yang, Xian-Hui; Yang, Yu-Shun; Lv, Peng-Cheng; Zhu, Hai-Liang [RSC Advances, 2014, vol. 4, # 70, p. 37197 - 37207]
[6]Qin, Ya-Juan; Xing, Man; Zhang, Ya-Liang; Makawana, Jigar A.; Jiang, Ai-Qin; Zhu, Hai-Liang [RSC Advances, 2014, vol. 4, # 95, p. 52702 - 52711]
[7]Dayakar, Cherupally; Kumar, Buddana Sudheer; Sneha, Galande; Sagarika, Gudem; Meghana, Koneru; Ramakrishna, Sistla; Prakasham, Reddy Shetty; China Raju, Bhimapaka [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5678 - 5691]
[8]Taban, Ismail M.; Elshihawy, Hosam E. A. E.; Torun, Beyza; Zucchini, Benedetta; Williamson, Clare J.; Altuwairigi, Dania; Ngu, Adeline S. T.; McLean, Kirsty J.; Levy, Colin W.; Sood, Sakshi; Marino, Leonardo B.; Munro, Andrew W.; De Carvalho, Luiz Pedro S.; Simons, Claire [Journal of Medicinal Chemistry, 2017, vol. 60, # 24, p. 10257 - 10267]
[9]Andersen, Thomas L.; Donslund, Aske S.; Neumann, Karoline T.; Skrydstrup, Troels [Angewandte Chemie - International Edition, 2018, vol. 57, # 3, p. 800 - 804][Angew. Chem., 2018, vol. 57, # 3, p. 800 - 804,5]
  • 11
  • [ 141-97-9 ]
  • [ 17356-08-0 ]
  • [ 21487-45-6 ]
  • ethyl1,2,3,4-tetrahydro-6-methyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)-2-thioxopyrimidine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With zinc(II) chloride at 20℃; Milling; Green chemistry; Synthesis of ethyl 4-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates: General procedure General procedure: A mixture of 3-aryl-1-phenyl-1H-pyrazole-4-carboxaldehyde (0.006 mol), ethyl acetoacetate (0.006 mmol), urea/thiourea (0.006 mol) and catalytic amountof ZnCl2 was ground for 10-15 min at room temp. The progress of the reaction was checked by TLC. At the end of the reaction ice cold water was added to it and the precipitate obtained was filtered and purified by column chromatography using EtOAc; pet ether (1:9) as an eluent and recrystallized from chloroform.
70% With toluene-4-sulfonic acid In ethanol for 7h; Reflux; 1.4.1. 1,2,3,4-tetrahydro-6-methyl-2-oxo-N-phenyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)pyrimidine-5-carboxamide (13c) General procedure: A round bottom flask containing a mixture of acetoacetanilide 8a (0.29 g, 1.6 mmol), 1,3-diaryl-1H-pyrazole-4-carbaldehyde 11a (0.40 g, 1.6 mmol), urea 12a (0.15 g, 2.4 mmol) and p-toluenesulfonic acid (0.12 g, 0.6 mmol) in ethanol (16 mL) was refluxed at for a period of 7 h. After completion of reaction (by TLC using EtOAc:hexane (3:2), In many cases after cooling to 25 oC obtained a solid compound which was filtered and washed with cold ethanol (3 mL) followed by washing with Et2O (5 mL) provided pure product.), ethanol was removed under vacuum and triturated with CH2Cl2/Et2O (1:1) to give a solid. The solid was taken into cold methanol (1 mL) to get slurry and filtered at cold condition followed by washing with ether (5 mL) provided the pure product 13c as a white solid, 59% yield.
62% With hydrogenchloride In ethanol Heating;
55% With iron(III) chloride In ethanol for 3h; Heating;

  • 12
  • [ 141-97-9 ]
  • [ 57-13-6 ]
  • [ 21487-45-6 ]
  • ethyl 4-(1,3-diphenyl-1H-pyrazol-4-yl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate n [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With zinc(II) chloride at 20℃; Milling; Green chemistry; Synthesis of ethyl 4-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates: General procedure General procedure: A mixture of 3-aryl-1-phenyl-1H-pyrazole-4-carboxaldehyde (0.006 mol), ethyl acetoacetate (0.006 mmol), urea/thiourea (0.006 mol) and catalytic amountof ZnCl2 was ground for 10-15 min at room temp. The progress of the reaction was checked by TLC. At the end of the reaction ice cold water was added to it and the precipitate obtained was filtered and purified by column chromatography using EtOAc; pet ether (1:9) as an eluent and recrystallized from chloroform. 5a: Yield: 96%, m.p. (°C) : 205 (Lit. m.p. 205-20716), IR (KBr): 3351, 1692, 1642 cm-1; 1H NMR: (300 MHz, CDCl3): δ 1.12 (t, 3H, CH3), 2.37 (s, 3H, CH3), 4.08 (q, 2H, OCH2), 5.57 (s, 1H, C4-H), 7.28-7.70 (m, 10H, ArH), 7.81 (s, 2H, 2xNH), 8.09 (s, 1H, pyrazole proton). 13C NMR (75 MHz, CDCl3): δ 165.4, 153.01, 151.16, 146.34, 140.12, 133.39, 131.12, 129.66, 129.36, 129.06, 128.73, 126.58, 126.29, 119.90, 101.39, 60.05, 46.96, 18.34, 14.17. LCMS [M+H]+ m/z 403 (100%). [Found: C, 68.66, H, 5.52, N, 13.93 C23H22N4O3 requires C, 68.64, H, 5.51, N, 13.92%].
67% In methanol for 7h; Heating;
62% With toluene-4-sulfonic acid In ethanol for 7h; Reflux; 1.4.1. 1,2,3,4-tetrahydro-6-methyl-2-oxo-N-phenyl-4-(1,3-diphenyl-1H-pyrazol-4-yl)pyrimidine-5-carboxamide (13c) General procedure: A round bottom flask containing a mixture of acetoacetanilide 8a (0.29 g, 1.6 mmol), 1,3-diaryl-1H-pyrazole-4-carbaldehyde 11a (0.40 g, 1.6 mmol), urea 12a (0.15 g, 2.4 mmol) and p-toluenesulfonic acid (0.12 g, 0.6 mmol) in ethanol (16 mL) was refluxed at for a period of 7 h. After completion of reaction (by TLC using EtOAc:hexane (3:2), In many cases after cooling to 25 oC obtained a solid compound which was filtered and washed with cold ethanol (3 mL) followed by washing with Et2O (5 mL) provided pure product.), ethanol was removed under vacuum and triturated with CH2Cl2/Et2O (1:1) to give a solid. The solid was taken into cold methanol (1 mL) to get slurry and filtered at cold condition followed by washing with ether (5 mL) provided the pure product 13c as a white solid, 59% yield.
52% With iron(III) chloride In ethanol for 3h; Heating;

  • 13
  • [ 3984-34-7 ]
  • [ 21487-45-6 ]
  • 5-(4-chloro-phenyl)-3-(1,3-diphenyl-1<i>H</i>-pyrazol-4-ylmethylene)-3<i>H</i>-furan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: 4-(4-chlorophenyl)-4-oxobutanoic acid With <(chlorosulfinyloxy)methylene>dimethylammonium chloride In dichloromethane at 0℃; for 0.25h; Stage #2: 1,3-diphenyl-4-formylpyrazole With triethylamine In dichloromethane at 20℃; for 5h;
  • 14
  • [ 21487-45-6 ]
  • [ 3153-44-4 ]
  • 3-(1,3-diphenyl-1<i>H</i>-pyrazol-4-ylmethylene)-5-(4-methoxy-phenyl)-3<i>H</i>-furan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% Stage #1: 4-(4-methoxy-phenyl)-4-oxo-butyric acid With <(chlorosulfinyloxy)methylene>dimethylammonium chloride In dichloromethane at 0℃; for 0.25h; Stage #2: 1,3-diphenyl-4-formylpyrazole With triethylamine In dichloromethane at 20℃; for 5h;
  • 15
  • [ 10075-50-0 ]
  • [ 21487-45-6 ]
  • 5-bromo-3-[(5-bromo-1H-indol-3-yl) (1,3-diphenyl-1H-pyrazol-4-yl) methyl]-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With copper(II) ferrite In water at 100℃; for 1h; Green chemistry; General experimental procedure for synthesis of pyrazolyl methylene bis indoles General procedure: 1, 3-diphenyl-1H-pyrazole-4-carbaldehyde (1 mmol), indole (2 mmol), 15 mol% CuFeNPS and water as solvent were taken in a 100 ml round bottam flask. The reaction mixture was stirred for 60 min at 100°C. The progress of the reaction was monitored by TLC. After the completion of the reaction, the catalyst was separated by using external magnet and reaction mixture was cooled, filterd. The obtained solid product is washed with ethyl acetate before drying over Na2SO4. After removal of the excess solvent over rotavapour, the desired pyrazolyl methylene bis indoles were obtained in excellent yields. The residual solvents were seperated under vaccum and the products were purified by column chromatography. The identity and purity of the products were confirmed by 1H, 13C NMR, and mass spectra.
89% With phospho-tungstic acid; phosphotungstic acid In acetonitrile at 20℃; for 0.416667h;
79% With lewis acidic amorphous mesoporous silicate containing Zr In acetonitrile at 80℃; Synthesis of pyrazolylbisindole (PBI) derivatives General procedure: The synthesis of PBI derivatives were carried out in a 25 mL round bottom (RB) flask fitted with a magnetic stirrer set up. The reactant mixtures of indole (2 mmol), pyrazole aldehyde (1 mmol), and acetonitrile solvent (5 mL, dried over 4Å molecular sieves) were added to the 50 mg of ZrTUD-1 catalyst and kept at 80 °C temperature, under magnetic stirring (∼800 rpm). The reaction progress was monitored by using thin layer chromatography (TLC) with detection by iodine chamber. After completion of reaction, the reaction mixture was separated from the catalyst by filtration. The pure product was isolated using column chromatography method (20 % ethylacetate-80 % petroleum ether mixture). 1H NMR and 13C NMR spectra of the isolated products were obtained on a Bruker Avance-400 spectrometer. FTIR spectra were measured on a Bruker (Tensor) spectrometer with a resolution of 4 cm-1. The mass (MS) spectra of representative compounds were recorded on a Q-TOF-Mass spectrometer. Elemental analyses were carried out using a Perkin-Elmer 2400 Series CHNS-O Analyzer. The product characterizations of pyrazolylbisindoles derivatives listed in Table 1 are given in the Supplementary material.
  • 16
  • [ 6146-52-7 ]
  • [ 21487-45-6 ]
  • 5-nitro-3-[(5-nitro-1H-indol-3-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methyl]-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With phospho-tungstic acid; phosphotungstic acid In acetonitrile at 20℃; for 0.5h;
77% With lewis acidic amorphous mesoporous silicate containing Zr In acetonitrile at 80℃; Synthesis of pyrazolylbisindole (PBI) derivatives General procedure: The synthesis of PBI derivatives were carried out in a 25 mL round bottom (RB) flask fitted with a magnetic stirrer set up. The reactant mixtures of indole (2 mmol), pyrazole aldehyde (1 mmol), and acetonitrile solvent (5 mL, dried over 4Å molecular sieves) were added to the 50 mg of ZrTUD-1 catalyst and kept at 80 °C temperature, under magnetic stirring (∼800 rpm). The reaction progress was monitored by using thin layer chromatography (TLC) with detection by iodine chamber. After completion of reaction, the reaction mixture was separated from the catalyst by filtration. The pure product was isolated using column chromatography method (20 % ethylacetate-80 % petroleum ether mixture). 1H NMR and 13C NMR spectra of the isolated products were obtained on a Bruker Avance-400 spectrometer. FTIR spectra were measured on a Bruker (Tensor) spectrometer with a resolution of 4 cm-1. The mass (MS) spectra of representative compounds were recorded on a Q-TOF-Mass spectrometer. Elemental analyses were carried out using a Perkin-Elmer 2400 Series CHNS-O Analyzer. The product characterizations of pyrazolylbisindoles derivatives listed in Table 1 are given in the Supplementary material.
  • 17
  • [ 2033-24-1 ]
  • [ 21487-45-6 ]
  • [ 108446-77-1 ]
YieldReaction ConditionsOperation in experiment
76% With triethylamine-formic acid at 95 - 100℃; for 2h;
  • 18
  • [ 21487-45-6 ]
  • [ 108446-77-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 78 percent / pyridine; piperidine / 4 h / Heating 2: 64 percent / NaOH; hydrazine hydrate / Renay nickel / ethanol / Heating
Multi-step reaction with 2 steps 1: 93.8 percent / piperidine / pyridine / 95 - 100 °C 2: 88.2 percent / H2 / PtO2 / tetrahydrofuran / 7 h / Ambient temperature
Multi-step reaction with 3 steps 1: piperidine / pyridine / 95 - 100 °C 2: pyridine / 0.5 h / 100 °C 3: 88.2 percent / H2 / PtO2 / tetrahydrofuran / 7 h / Ambient temperature
Multi-step reaction with 4 steps 1: 94.7 percent / piperidine 2: 75 percent / NaOH / methanol; H2O / 2 h / Heating 3: pyridine / 0.5 h / 100 °C 4: 88.2 percent / H2 / PtO2 / tetrahydrofuran / 7 h / Ambient temperature
Multi-step reaction with 2 steps 1: pyridine; piperidine / Reflux 2: hydrazine hydrate; copper(II) sulfate; dihydrogen peroxide / water / 0.67 h / 20 °C / Cooling with ice

  • 19
  • [ 21487-45-6 ]
  • [ 55432-05-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 91 percent / sodium tetrahydridoborate / ethanol / 1 h 2: 87 percent / thionyl chloride / benzene / 2 h / Heating
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / ethanol / 1 h / 20 °C 2: thionyl chloride / toluene / 2 h / 115 °C
  • 21
  • [ 21487-45-6 ]
  • 1,2-bis[(1,3-diphenyl-1H-pyrazol-4-yl)methylene]hydrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 85 percent / N2H4*H2O / ethanol / 2 h / Heating 2: 90 percent / HOAc / ethanol / 0.08 h / Heating
With hydrazine hydrate In ethanol at 20℃; for 3h; General procedure: Hydrazine monohydrate (10 mmol) was added to a solution of 2 (10 mmol) in ethanol (40 mL). The reaction mixture was stirred at room temperature for 3 h. The solid obtained was filtered off and washed with cold ethanol and then recrystallised from ethanol to give compound 4.
Multi-step reaction with 2 steps 1: ethanol / 4 h / Reflux 2: hydrazine hydrate / ethanol / 3 h / 20 °C
Multi-step reaction with 2 steps 1: ethanol / 4 h / Reflux 2: hydrazine hydrate / ethanol; 1,4-dioxane / 5 h / Reflux
Multi-step reaction with 2 steps 1: piperidine / ethanol / 1 h / 20 °C 2: hydrazine hydrate / ethanol / 3 h / 20 °C
Multi-step reaction with 3 steps 1: ethanol / 4 h / Reflux 2: piperidine / ethanol 3: hydrazine hydrate / ethanol; 1,4-dioxane / 5 h / Reflux
Multi-step reaction with 2 steps 1: acetic acid / ethanol 2: ethanol / 6 h / Reflux
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate

  • 22
  • [ 22722-98-1 ]
  • [ 21487-45-6 ]
  • [ 40278-32-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water; benzene; (a) 1,3-Diphenylpyrazole-4-carboxaldehyde (16.0 g.) was dissolved in benzene (100 ml.) and a 70% benzene solution of sodium dihydrobis(2-methoxyethoxy)aluminate (14.0 ml.) was added dropwise at room temperature. The solution was heated under reflux for 2 hours and then water and an excess of 2N hydrochloric acid added at room temperature. The benzene layer was separated, washed with water, dried (MgSO4) and evaporated to give a white solid which after recrystallisation from aqueous ethanol gave 10 g. of 1,3-diphenyl-4-hydroxymethylpyrazole, m.p. 98-100 C. (Found: C, 76.8; H, 5.7; N, 11.2. C16 H14 N2 O requires C, 76.8; H, b 5.7; N, 11.2%).
  • 23
  • [ 645-35-2 ]
  • [ 21487-45-6 ]
  • [ 1206607-08-0 ]
  • 24
  • [ 403-42-9 ]
  • [ 21487-45-6 ]
  • [ 1228954-07-1 ]
YieldReaction ConditionsOperation in experiment
80% With sodium hydroxide In ethanol; water at 0 - 20℃; GENERAL PROCEDURE The starting material 1,3-disubstituted-1H-pyrazole-4-carbaldehydes were prepared according to the literatureprocedure[29]. To a mixture of an appropriateacetophenone (1, 10 mmol) and 1,3-disubstituted-1H-pyrazole-4-carbaldehyde (2,10 mmol) in ethanol wasadded aqueous sodium hydroxide (12 mmol ) at 0 °C. Theresulting reaction mixture was allowed to stir for 6-8 h atroom temperature. The reaction was monitored by TLCand on its completion, the reaction mixture was pouredinto ice-cold water. Then pH of the mixture adjusted to 6using 0.01N HCl solution. Thus, obtained product wasfiltered and recrystallized from ethanol to give the pure 3a. Rest compounds were synthesized according to thisprocedure to obtain compounds 3b-k in good to excellentyield.
64% With sodium hydroxide Reflux;
Stage #1: 1-(4-fluorophenyl)ethanone With sodium hydroxide In methanol for 0.166667h; Cooling; Stage #2: 1,3-diphenyl-4-formylpyrazole In tetrahydrofuran; methanol at 0 - 20℃; for 7h;
  • 25
  • [ 98-86-2 ]
  • [ 21487-45-6 ]
  • [ 905441-76-1 ]
YieldReaction ConditionsOperation in experiment
82% With potassium hydroxide In ethanol at 20℃;
76% With sodium hydroxide In ethanol; water at 0 - 20℃; GENERAL PROCEDURE The starting material 1,3-disubstituted-1H-pyrazole-4-carbaldehydes were prepared according to the literatureprocedure[29]. To a mixture of an appropriateacetophenone (1, 10 mmol) and 1,3-disubstituted-1H-pyrazole-4-carbaldehyde (2,10 mmol) in ethanol wasadded aqueous sodium hydroxide (12 mmol ) at 0 °C. Theresulting reaction mixture was allowed to stir for 6-8 h atroom temperature. The reaction was monitored by TLCand on its completion, the reaction mixture was pouredinto ice-cold water. Then pH of the mixture adjusted to 6using 0.01N HCl solution. Thus, obtained product wasfiltered and recrystallized from ethanol to give the pure 3a. Rest compounds were synthesized according to thisprocedure to obtain compounds 3b-k in good to excellentyield.
Stage #1: acetophenone With sodium hydroxide In methanol for 0.166667h; Cooling; Stage #2: 1,3-diphenyl-4-formylpyrazole In tetrahydrofuran; methanol at 0 - 20℃; for 7h;
  • 26
  • [ 1187-84-4 ]
  • [ 21487-45-6 ]
  • N-[(1,3-diphenylpyrazol-4-yl)methyl]-S-methyl-L-cysteine [ No CAS ]
  • 27
  • [ 99-90-1 ]
  • [ 21487-45-6 ]
  • [ 371917-93-0 ]
YieldReaction ConditionsOperation in experiment
92% With potassium hydroxide In methanol; water at 5 - 35℃;
82% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1.3. 1-(4-Bromophenyl)-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1c) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as
  • 28
  • [ 21487-45-6 ]
  • [ 100-06-1 ]
  • [ 313361-38-5 ]
YieldReaction ConditionsOperation in experiment
78% With potassium hydroxide In methanol; water at 5 - 35℃;
78% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1.4. 1-(4-Methoxyphenyl)-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1d) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as
With sodium hydroxide In methanol Reflux;
With sodium hydroxide In methanol

  • 29
  • [ 21487-45-6 ]
  • anti-1,3-diphenyl-1H-pyrazole-4-carbaldehyde oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With hydroxylamine hydrochloride; sodium acetate In ethanol for 5h; Reflux; 3.4 General procedure for synthesis ofpyrazole-4-carbaldehyde oximes 5a-5e General procedure: To a solution of 2a-2e (1.0 mmol) in ethanol (20 mL),hydroxylamine hydrochloride (0.069 g, 1.0 mmol) andanhydrous sodium acetate (0.082 g, 1.0 mmol) were added.The mixture was heated under reflux for 5 h; the reactionprogress was monitored by TLC using chloroform-ethanol(9:1). The product that separated out on cooling was filteredand recrystallized from ethanol.3.4.1 Anti-1,3-diphenyl-1H-pyrazole-4-carbaldehydeoxime (5a) [27]Colorless crystals, yield 88% (0.231 g), m. p. 155-157°C.- IR (KBr): ν = 3265 (OH), 1597 (C=N), 1534 (C=C) cm-1.- 1H NMR (500 MHz, [D6]DMSO): δ = 8.97 (s, 1 H, CH=N),7.79 (d, J = 8 Hz, 2 H, Ar-H), 7.68 (d, J = 8 Hz, 2 H, Ar-H),7.58 (s, 1 H, 5-H of pyrazole ring), 7.43-7.51 (m, 5 H, Ar-H),7.31-7.35 (m, 1 H, Ar-H), 6.38 (broad s, D2O-exchangeable,1 H, OH). 13C NMR (125 MHz, [D6]DMSO): δ = 111.96, 119.59,127.52, 129.18, 129.35, 130.17, 131.89, 132.46, 137.37 (Ar-C, C-4and C-5 of pyrazole ring), 139.64 (CH=N), 152.53 (C-3 ofpyrazole ring). - C16H13N3O (263.29): calcd. C 72.99, H 4.98,N 15.96; found C 73.05, H 5.01, N 15.92.
83% With hydroxylamine hydrochloride; sodium acetate In ethanol for 4h; Reflux;
  • 30
  • [ 21487-45-6 ]
  • [ 109-77-3 ]
  • [ 191089-78-8 ]
  • [ 1276542-86-9 ]
YieldReaction ConditionsOperation in experiment
76% With piperidine In acetonitrile Reflux;
  • 31
  • [ 105-56-6 ]
  • [ 21487-45-6 ]
  • [ 302938-30-3 ]
YieldReaction ConditionsOperation in experiment
95% In water at 20℃; for 4h; Green chemistry; General procedure for the synthesis of pyrazole decorated nitriles and acrylates General procedure: When equimolar quantity of 3-(4-bromophenyl)-1-phenylpyrazolecarbaldehyde (1.0 mmol) and malononitrile (1.0 mmol) were stirred in polyethylene glycol (PEG-400) / water (3:1) mixture at ambient temperature for a couple of minutes, a solid was obtained. Water was then added, filtered and dried under vacuum to give 2-[(3-(4-bromophenyl)-1-phenylpyrazolyl)methylene]malononitrile (1a). Recrystallization from ethanol-DMF mixture afforded the analytically pure target molecule. Similar experimental procedure was adopted for the synthesis of 2-[(1,3-diaryl-4-pyrazolyl)methylene]malononitriles 1b-1j, arylidenemalononitriles 2a-2f and ethyl 3-(1,3-diaryl-4-pyrazolyl)-2-cyanoacrylates 3a-3e from their corresponding aldehydes. In the synthesis of 1b-1j and 2a-2f, the reactions were completed in 5 minutes while the reactions were ended in 4 hours in the synthesis of 3a-3e.
89% With sodium ethanolate at 20℃; for 0.0833333h; 4.2 Typical Procedure for the Synthesis of Aryl/Heteroaryl/Aliphatic Acrylates and Nitriles(1-29) General procedure: In a mortar, respective aldehydes (1.0 mmol), respectivecompounds with active methylene moiety (ethyl cyanoacetate/malononitrile) (1.1 mmol), and solid sodium ethoxide(15 mol%) have been taken and ground well using a pestlefor 2-5 min at ambient temperature. Distilled water hasthen been added to the reaction mixture and the solid thusobtained after stirring has been filtered, washed well withwater and dried in vacuum. Recrystallization from aqueousethanol afforded the analytically pure target molecules,aryl/heteroaryl/aliphatic acrylates and nitriles. Most of the synthesized compounds are reported onesand their physical and spectroscopic data are compared with the literature/authentic samples. Physical and spectroscopicdata for the compounds, ethyl 3(1,3-diphenyl-1H-pyrazol-4-yl)-2-cyanoacrylate (11), ethyl 3-[1-phenyl-3-(4-methylphenyl)-1H-pyrazol-4-yl]-2-cyanoacrylate(12), ethyl 3-[3-(4-bromophenyl)-1-phenyl-1 H-pyrazol-4-yl]-2-cyanoacrylate (13), 2-[(3-(2-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene]malononitrile ( 27) and 2-[(3-(4-methoxyphenyl)-1-phenyl-1 H-pyrazol-4-yl)methylene]malononitrile (28) are furnished below. 4.2.1 Ethyl 3-(1,3-diphenyl-1H-pyrazol-4-yl)-2-cyanoacrylate (11) Dirty-white solid; m.p. 133-135 °C; 1H NMR (300 MHz;CDCl3) δ 9.15 (s, 1H), 8.32 (s, 1H), 7.84 (d, J = 8.0 Hz,2H), 7.61 (d, J = 6.4 Hz, 2H), 7.56-7.50 (m, 5H), 7.42 (t,J = 7.2 Hz, 1H), 4.36-4.33 (m, 2H), 1.37 (t, J = 7.2 Hz,3H); 13C NMR (75 MHz; CDCl3) δ 162.7, 156.4, 146.3,138.8, 130.8, 129.7, 129.4, 129.3, 129.2, 129.0, 128.5,119.9, 116.7, 114.9, 99.8, 62.4, 14.2; GC/MS (m/z) 343(M+); Anal. Calcd for C21H17N3O2: C, 73.45; H, 4.99; N,12.24, Found: C, 73.50; H, 4.89; N, 12.27.
83% for 2h; Heating; Green chemistry; 3.7 General procedure for synthesis ofKnoevenagel condensation products10a-10d General procedure: In a dry test tube, carbaldehyde 2a, 2b, 2d, or 2e (5 mmol)was added to ethyl 2-cyanoacetate (0.53 mL, 5 mmol), andthe mixture was heated over a boiling water bath for 2 h.The separated product was collected by filtration, washedwith water, and dried. It was recrystallized from a mixtureof chloroform and ethanol.3.7.1 Ethyl 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)propenoate (10a)Colorless crystals, yield 83% (1.425 g), m. p. 118-120°C.- IR (KBr): ν = 2218 (C ≡ N), 1722 (C=O), 1591 (C=N), 1528(C=C) cm-1. - 1H NMR (500 MHz, CDCl3): δ = 9.14 (s, 1 H,5-H of pyrazole ring), 8.31 (s, 1 H, CH=C), 7.83-7.84 (m, 2 H,Ar-H), 7.61-7.63 (m, 2 H, Ar-H), 7.49-7.54 (m, 5 H, Ar-H), 7.39(t, J = 8 Hz, 2 H, Ar-H), 4.34 (q, J = 7 Hz, 2 H, CH2-CH3), 1.38(t, J = 7 Hz, 3 H, CH2-CH3). - C21H17N3O2 (343.38): calcd. C73.45, H 4.99, N 12.24; found C 73.44, H 5.03, N 12.23.
78% With piperidine In methanol at 20℃; for 2h; Inert atmosphere; 2.3.3. Ethyl 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylate (3b) Under nitrogen atmosphere, 1,3-dipheny-1H-pyrazole-3-carbaldehyde (248 mg, 1 mmol, 1 equiv) and ethyl-2-cyanoacetate (113 mg, 1 mmol, 1 equiv) were dissolved in dry methanol (15 mL). 0.1mL of piperidine was added, and the solution was stirred at RT for 2 h. After completion of the reaction, the white solid was filtered, washed with methanol and dried. The dye obtained was purified by column chromatography using silica gel 100-200 mesh and toluene as eluent. Colour: White crystal, Yield: 268 mg, 78%, M. P.: 136-138 °C [51]. FT-IR (KBr, cm-1): 2218 (CN stretching), 1726 (ester C]Ostretching), 1581 (Ar). 1H NMR (400 MHz, CDCl3) δ 1.382 (t, J 7.2 Hz, 3H, CH3), 4.327-4.380 (m, 2H, CH2), 7.412 (t, J 7.2 Hz, 1H, ArH), 7.501-7.558(m, 5H, ArH), 7.621 (d, J 6.4 Hz, 2H, ArH), 7.837 (d, J 8.0 Hz, 2H,ArH), 8.313 (s, 1H, NeCH), 9.145 (s, 1H,C]CH). 13C NMR (126 MHz, CDCl3, Me4Si) δ 14.2, 62.4, 99.8, 114.9, 116.7, 119.9, 128.5, 129.01, 129.2, 129.3, 129.4, 129.7, 130.8, 138.8, 146.3,156.4, 162.7. MS (m/z): 344.4 (MH). Anal. Calcd. for C21H17N3O2: C,73.45; H, 4.99; N, 12.24. Found: C,73.49; H, 4.82; N, 12.28. HRMS m/z [MH] Calcd for C21H17N3O2: 344.1399. Found: 344.1340.
78% With piperidine In ethanol for 3h; Reflux;
75% With thiourea for 0.0666667h; Microwave irradiation; neat (no solvent);
With piperidine In ethanol at 20℃;

  • 32
  • [ 15108-18-6 ]
  • [ 21487-45-6 ]
  • [ 882223-28-1 ]
YieldReaction ConditionsOperation in experiment
70% With acetic acid; In ethanol; for 5h;Reflux; General procedure: A mixture of 1,3-dipheny l - 1H- py r a z o l -4-carboxaldehyde (1) (0.74 g, 3 mmol), the correspondinghydrazine (2a,b, 6a,b and 10a,b) (3 mmol), and 2-3 dropsglacial acetic acid in ethanol (20 mL) was reuxed on awater bath for about 5 h. The solvent was removed and theresidue was recrystallized from the suitable solvent. 2-(2-((1,3-Diphenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-1H-benzimidazole (3a)Yield: 70% (ethanol, brown powder); mp 196-197 C;IR (KBr) nu/ cm-1 3414, 3118, 3017, 1637; 1H NMR(90 MHz, DMSO-d6) delta 6.40 (s, 1H, CH=N), 7.00-8.00(m, 14H, Ar-H), 8.20 (s, 1H, NH, D2O exchanged), 8.35(s, 1H, pyrazole-H), 9.50 (s, 1H, benzimidazole-NH,D2O exchanged). Anal. calcd. for C23H18N6 (378.43):C, 73.00; H, 4.79; N, 22.21. Found: C, 72.91; H, 4.70;N, 22.13.
  • 33
  • [ 1008-79-3 ]
  • [ 21487-45-6 ]
  • 34
  • [ 5718-83-2 ]
  • [ 21487-45-6 ]
  • [ 1204732-26-2 ]
YieldReaction ConditionsOperation in experiment
92% In N,N-dimethyl-formamide at 100℃; for 0.0833333h; Microwave irradiation;
83% With piperidine; acetic acid In ethanol at 40 - 50℃; for 4h; 5.3.5. (Z)-2-(5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid (10) General procedure: To a solution of 1,3-diaryl-4-formylpyrazoles 4 (1.0 mmol) and rhodanine analogs 5 (1.0 mmol) in absolute ethanol (8.0 mL) was added drops of acetic acid and piperidine. The reaction mixture was stirred at 40-50 °C, until the completion of the reaction as evidenced by TLC. After the solution was cooled, the resulting reaction mixture was ltered off and crude product was purified by 95% ethanol to afford pure products 6-29. The yield, melting point and spectral data of each compound are given below.
  • 35
  • [ 1385690-74-3 ]
  • [ 21487-45-6 ]
  • [ 1385690-91-4 ]
YieldReaction ConditionsOperation in experiment
87% With sodium hydroxide In ethanol at 20℃; General Procedure for the synthesis of chalcones (17a-l and 18a-l) General procedure: To the mixture of 1-[4-(benzyloxy)-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl] ethanone (14) or 1-[4-(benzyloxy)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl] ethanone (16) (1 mmol) and aldehyde (1 mmol) in ethanol (5 ml), sodium hydroxide solution (20%, 5 ml) was added and stirred overnight. After completion of the reaction, the reaction mixture was poured into crushed ice, stirred and acidified with 1M HCl. The solid obtained was filtered, washed with water, dried and then purified by column chromatography.
  • 36
  • [ 1385690-78-7 ]
  • [ 21487-45-6 ]
  • [ 1385691-12-2 ]
YieldReaction ConditionsOperation in experiment
89% With sodium hydroxide In ethanol at 20℃; General Procedure for the synthesis of chalcones (17a-l and 18a-l) General procedure: To the mixture of 1-[4-(benzyloxy)-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl] ethanone (14) or 1-[4-(benzyloxy)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl] ethanone (16) (1 mmol) and aldehyde (1 mmol) in ethanol (5 ml), sodium hydroxide solution (20%, 5 ml) was added and stirred overnight. After completion of the reaction, the reaction mixture was poured into crushed ice, stirred and acidified with 1M HCl. The solid obtained was filtered, washed with water, dried and then purified by column chromatography.
  • 37
  • [ 56278-50-3 ]
  • [ 21487-45-6 ]
  • [ 302939-19-1 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine In ethanol Reflux;
84% With piperidine In methanol at 20℃; for 2h; Inert atmosphere; 2.3.5. 2-(Benzo[d]thiazol-2-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylonitrile (3d) Under nitrogen atmosphere, 1,3-dipheny-1H-pyrazole-3-carbaldehyde (248 mg, 1 mmol, 1 equiv) and 2-benzo[d]thiazol-2-yl)acetonitrile (174 mg, 1 mmol, 1 equiv) were dissolved in dry methanol (15 mL). 0.1 mL of piperidine were added, and the solution was stirred at RT for 2 h. After completion of the reaction, the greenish yellow solid was filtered, washed with methanol and dried. The dye obtained was purified by column chromatography using silica gel 100-200 mesh and toluene as eluent system. Colour: Greenish yellow solid, Yield: 350 mg, 84%, M. P.: 222-224 °C. FT-IR (KBr, cm-1): 2224 (CN stretching). 1H NMR (500 MHz, CDCl3, Me4Si) δ 7.40 (t, J 7 Hz, 2H, ArH), 7.50-7.57 (m, 6H, ArH), 7.70 (d, J 6.5 Hz, 2H, ArH), 7.86 (d, J 8 Hz,3H, ArH), 8.05 (d, J 8 Hz, 1H, ArH), 8.19 (s, 1H, NeCH), 9.14 (s, 1H,C]CH). 13C NMR (126 MHz, CDCl3, Me4Si) δ 103.4, 115.6, 117.2, 119.9,121.5, 123.5, 125.8, 126.8, 127.9, 128.3, 129.3, 129.2(2), 129.7, 131.3,134.7, 138.1, 139.1, 153.7, 155.7, 162.5.MS (m/z): 405.4 (M+H). Anal. Calcd. for C25H16N4S: C, 74.23; H, 3.99; N, 13.85; S, 7.93.Found: C, 74.29; H, 3.93; N, 13.82; S, 7.89. HRMS m/z [M+H]+ Calcd for C25H16N4S: 405.1174. Found: 405.1124.
  • 38
  • [ 2033-24-1 ]
  • [ 21487-45-6 ]
  • [ 191089-78-8 ]
  • [ 1329116-46-2 ]
YieldReaction ConditionsOperation in experiment
71% With piperidine In acetonitrile for 6h; Reflux;
  • 39
  • [ 2295-31-0 ]
  • [ 21487-45-6 ]
  • [ 1346173-80-5 ]
YieldReaction ConditionsOperation in experiment
90% With piperidine In ethanol Reflux;
74% With piperidine; acetic acid In ethanol at 80 - 90℃; General procedure for synthesis of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl) methylene)thiazolidine-2,4-diones (10a-f) General procedure: To a mixture of 1,3-thiazolidine-2,4-dione (7) (0.4g, 2mmol) and 3-(substituted phenyl)-1-phenyl-1H-pyrazole-4-carbaldehydes (4a-f) (0.5 g, 2 mmol) in ethanol (20 mL), few drops of piperidine and glacial acetic acid was added and the reaction mixture was refluxed. A solid was separated out of the reaction mixture within 15-20 min and the refluxing was continued for 4-5 h to complete the reaction. The reaction mixture was cooled to room temperature, filtered, and recrystallized from ethanol to give pure compounds (10a-f). (Z)-5-((1,3-Diphenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-dione (10a) Yellow solid, yield: 74%; m.p.: 261-263C; IR (KBr) vmaxcm-1: 3406 (N-H stretching); 3096 (aromatic C-H stretching); 1738 and 1684 (C=O), 1603 (C=N), 1539 (C=C); 1H NMR (300MHz, DMSO- d6): δ (ppm) 12.34 (bs, IH, N-H); 8.64 (s, 1H, C5-H of pyrazole); 7.99-7.96 (d, J = 8.1 Hz, 2H, ArH), 7.64-7.43 (m, 9H, Ar-H & -CH=C-); 13C NMR (75 MHz, DMSO- d6):δ (ppm) 167.09 (C2=O), 166.41 (C4=O), 153.11 (-C=N-), 139.69 (=CH-), 133.58, 130.38, 130.14, 129.54, 129.08, 128.54, 127.88, 126.97, 119.56, 118.65, 117.19. MS (ESI) m/z(%): 348.1 [M + H]+; Anal. Calcd. For C19H13N3O2S: C-65.69, H-3.77, N-12.10; Found: C-65.61, H-3.69, N-12.04%.
With piperidine; acetic acid In toluene at 110 - 115℃; for 8h;
  • 40
  • [ 934367-84-7 ]
  • [ 21487-45-6 ]
  • [ 1416218-95-5 ]
YieldReaction ConditionsOperation in experiment
79% With piperidine; acetic acid In ethanol at 40 - 50℃; 5 (R,Z)-2-(5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)-3-phenylpropanoic acid (7) General procedure: To a solution of compound 1 (1.0 mmol) and compound 2 (1.0 mmol) in absolute ethanol (8.0 ml) was added drops of glacial acetic acid and piperidine. The reaction mixture was stirred at 40-50 °C for 2-4 h, until the completion of the reaction as evidenced by TLC. The resulting reaction mixture was concentrated to dryness, purified by silica gel column chromatography (dichloromethane/methanol, 40:1) to afford pure products 3-17.
  • 41
  • [ 1074-41-5 ]
  • [ 504-02-9 ]
  • [ 21487-45-6 ]
  • [ 1415662-81-5 ]
  • 42
  • [ 403-42-9 ]
  • [ 21487-45-6 ]
  • [ 372107-05-6 ]
YieldReaction ConditionsOperation in experiment
78% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1.6. 1-(4-Fluorophenyl)-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1f) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as
67% With sodium hydroxide In ethanol at 0 - 20℃; 2.2. General Procedure for the Synthesis of 1,3-Diarylprop-2-en-1-one Derivatives 3a-m General procedure: Aqueous sodium hydroxide (12 mmol) was added to a mixture of appropriate ketone (10 mmol) and 1, 3-disubstituted-1H-pyrazole-4-carbaldehyde (10 mmol) in ethanol at 0 C. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and upon completion, the reaction mixture was poured into iced water. The pH of the mixture was adjusted to 6 using a 0.01 N HCl solution. The precipitates were filtered and recrystallized from ethanol to obtain the compounds 3a-m in 40-93% yield.
67% With water; sodium hydroxide In ethanol at 0 - 20℃; Synthesis of 1-(Thien-2-yl)-3-(3-methyl-1-phenyl-1Hpyrazole-4-yl)prop-2-en-1-one (3a) General procedure: To a mixture of 2-acetylthiophene (1 mL, 0.0092 mol) and 3-methyl-1-phenyl-1H-pyrazole-4-yl (1.72 g, 0.0092 mol) in ethanol was added aqueous sodium hydroxide (0.44 g, 0.011 mol) at 0 oC. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and on completion, reaction mixture was poured into ice coldwater. Then pH of the mixture adjusted to 6 using 0.01 N HCl solution. The obtained precipitates were filtered, dried and recrystallized from ethanol to get the compound 3a. Remaining compounds (3b-j) were prepared according to this procedure.
With sodium hydroxide at 40 - 50℃; for 1h;
With sodium hydroxide In methanol

  • 43
  • [ 21487-45-6 ]
  • [ 17647-21-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium hydroxide / ethanol / 2 h / Reflux 2: acetic anhydride / 1 h / 150 °C / Reflux
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium hydroxide / ethanol / 2 h / Reflux 2: acetic anhydride / 1 h / 140 - 150 °C
Multi-step reaction with 2 steps 1: potassium hydroxide / methanol / 12 h 2: hydroxylamine hydrochloride; sodium acetate / acetic acid / 6 h / Reflux
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride / ethanol / 6 h / Reflux 2: Vilsmeier reagent / N,N-dimethyl-formamide / 0.03 h / 40 °C / Microwave irradiation
With phosphoric acid; hydroxylamine hydrochloride In formic acid at 5 - 100℃; 2.3 General procedure for the preparationof nitrile derivatives (D1-10) General procedure: A mixture of pyrazole-4-carbaldehyde (1 mmol), formicacid (2.5 mL) was cooled to 5-10 C andhydroxylamine hydrochloride (1 mmol) was added.After 1 min, orthophosphoric acid (1 mol%) wasadded to the reaction mixture and heat about 100 Ctill the completion of the reaction, monitored by TLCin DCM: Methanol (9:1) as a mobile phase. The reaction mixture was cooled and poured in 10 mLice-cold water and the precipitated solid was recrystallizedwith ethanol to get pure nitrile. The productswere analyzed by IR, 1H, 13C NMR and Mass spectraltechniques.

  • 44
  • [ 134-81-6 ]
  • [ 21487-45-6 ]
  • 4-(4,5-diphenyl-1H-imidazole-2-yl)-1,3-diphenyl-1H-pyrazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With ammonium acetate In ethanol at 50℃; for 0.5h; General procedure: A mixture of benzil or 9,10-phenanthrenequinone (1mmol), corresponding aldehyde (1mmol), ammonium acetate (4mmol) and a catalytic amount of supported ionic liquid-like phase (SILLP) (0.1g) in ethanol (3mL) was stirred in an oil bath at 50°C or under ultrasonic irradiations (40kHz, 50°C) for a specified period of time. The progress of the reaction was monitored by TLC analysis (petroleum ether/ethyl acetate, 2/1). After the completion of the reaction, the crude product from the reaction mixture was dissolved in ethanol and the catalyst was separated by filtration. The filtrate was evaporated under reduced pressure to remove ethanol. The solid was then recrystallized from methanol to obtain the pure product. The data of some new compounds are listed below:
86% With ammonium acetate; 1-butyl-3-methyl-1H-imidazolium tetrafluoroborate for 0.116667h; Microwave irradiation; General Procedure for the Synthesis of 2,4,5-Trisubstituted Imidazole Derivatives 4a-i Under MW Irradiation General procedure: A 10 mL round bottom flask was charged with 3-aryl-1-phenyl-1H-pyrazole-4-carboxaldehyde 1 (1 mmol), benzil 2(1 mmol), ammonium acetate 3 (2 mmol) and catalyticamount of [BMIM] [BF4] (15 mmol %), and placed underMW irradiation at 240 watts for 7-9 min. The course of thereaction was monitored by thin layer chromatography. Aftercompletion of the reaction, the mixture was poured overcrushed ice, the solid imidazole thus obtained was separatedby filtration, dried well, and recrystallized by ethanol
78% With ammonium acetate; glacial acetic acid Reflux; 4-(4,5-Diphenyl-1H-imidazole-2-yl)-1,3-diphenyl)-1H-pyrazole General procedure: 1H-Pyrazole-4-carbaldehyde (2a-f) (1 mmol), benzil (3) (1 mmol) and ammonium acetate (10 mmol) were dissolved in glacial acetic acid and heated under reflux for 10-14 h on water bath using a water condenser. Progress of the reaction was monitored by TLC. After completion of the reaction as indicated by TLC, the reaction mass was poured over crushed ice with constant stirring. A bright yellow to offwhite product was formed and washed with water several times, isolated by filtration on vacuum, dried over silica in a vacuum desiccator and recrystallized from ethanol to yield compounds (4a-f, Scheme-II).
76% With ammonium acetate; glacial acetic acid for 4h; Reflux;

  • 45
  • [ 84-11-7 ]
  • [ 21487-45-6 ]
  • 2-(1,3-diphenyl-1H-pyrazol-4-yl)-1H-phenanthro[9,10-d]imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With ammonium acetate In ethanol at 50℃; for 0.333333h; General procedure: A mixture of benzil or 9,10-phenanthrenequinone (1mmol), corresponding aldehyde (1mmol), ammonium acetate (4mmol) and a catalytic amount of supported ionic liquid-like phase (SILLP) (0.1g) in ethanol (3mL) was stirred in an oil bath at 50°C or under ultrasonic irradiations (40kHz, 50°C) for a specified period of time. The progress of the reaction was monitored by TLC analysis (petroleum ether/ethyl acetate, 2/1). After the completion of the reaction, the crude product from the reaction mixture was dissolved in ethanol and the catalyst was separated by filtration. The filtrate was evaporated under reduced pressure to remove ethanol. The solid was then recrystallized from methanol to obtain the pure product. The data of some new compounds are listed below:
92% With ammonium cerium (IV) nitrate; ammonium acetate In water; acetonitrile for 12h; Reflux;
With ammonium acetate; acetic acid at 150℃; Microwave irradiation; Sealed tube; Inert atmosphere; 3.2.5. General Procedure for the Synthesis of Compound 7a-g General procedure: 35 mL microwave vial was charged with 1,2-diketone (0.5-5 mmol), substituted pyrazole aldehyde (1.2 eq.), ammonium acetate (10 eq.) and glacial acetic acid (6.410 mL).The mixture was heated at 150 °C for 15-30 min under microwave irradiation (300 W). Following reaction completionby TLC, the mixture was cooled to room temperature and added slowly to ammonium hydroxide (35%; 30 mL). The resulting precipitate was collected by filtration and purified by flash column chromatography, recrystallization or trituration from DCM-MeOH (1:1) or EtOH or Hexane-DCM (1:2) to give the product.
  • 46
  • [ 1994-13-4 ]
  • [ 6642-31-5 ]
  • [ 21487-45-6 ]
  • [ 1537195-77-9 ]
YieldReaction ConditionsOperation in experiment
84% In acetic acid; at 120℃; for 1h; General procedure: A mixture of hydroxy coumarin (3a/3b/3c/3d) (1 mmol), aldehyde (4) (1 mmol), 6-amino uracil (1) (1 mmol) and Acetic acid (5 ml) in 25 ml round bottom flask was refluxed in a pre heated oil bath for 1 h. The reaction mixture was evaporated, residual mixture taken into ethyl acetate followed by washed with NaHCO3 solution, with water and brine respectively and dried with Na2SO4. The organic phase was evaporated by rotary evaporator under reduced pressure to give the crude product. The crude product was purified by column chromatography over silica gel to furnish the pure product 4.
  • 47
  • [ 140675-42-9 ]
  • [ 21487-45-6 ]
  • [ 1333240-81-5 ]
  • 48
  • [ 140675-42-9 ]
  • [ 21487-45-6 ]
  • [ 1333240-91-7 ]
  • 50
  • [ 99-91-2 ]
  • [ 21487-45-6 ]
  • [ 312601-53-9 ]
YieldReaction ConditionsOperation in experiment
76% With potassium hydroxide In tetrahydrofuran; methanol at 20℃; for 6h; Cooling with ice; 3.1.2. 1-(4-Chlorophenyl)-3-[1,3-diphenyl-4-pyrazolyl]prop-2-en-1-one (1b) General procedure: To a cold solution of acetophenones (50 mmol) in methanol(30 ml) containing potassium hydroxide (50 mmol) wasadded a solution of pyrazole-4-carboxaldehyde (50 mmol) intetrahydrofuran (10 ml). The solution was allowed to stir inice bath for 4 h and then at room temperature for another 2 h.It was then poured onto ice-cold water (200 ml). The resulting solution was neutralized with dil. hydrochloric acid. Thesolid obtained was filtered, dried and recrystallized withethanol-chloroform. Detailed spectroscopic data of the unknowncompounds are given below as
73% With sodium hydroxide In ethanol at 0 - 20℃; 2.2. General Procedure for the Synthesis of 1,3-Diarylprop-2-en-1-one Derivatives 3a-m General procedure: Aqueous sodium hydroxide (12 mmol) was added to a mixture of appropriate ketone (10 mmol) and 1, 3-disubstituted-1H-pyrazole-4-carbaldehyde (10 mmol) in ethanol at 0 C. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and upon completion, the reaction mixture was poured into iced water. The pH of the mixture was adjusted to 6 using a 0.01 N HCl solution. The precipitates were filtered and recrystallized from ethanol to obtain the compounds 3a-m in 40-93% yield.
With sodium hydroxide In methanol Reflux;
With sodium hydroxide In methanol

  • 51
  • [ 1193-79-9 ]
  • [ 21487-45-6 ]
  • [ 1570069-63-4 ]
YieldReaction ConditionsOperation in experiment
79% With sodium hydroxide; In ethanol; at 0 - 20℃; General procedure: Aqueous sodium hydroxide (12 mmol) was added to a mixture of appropriate ketone (10 mmol) and 1, 3-disubstituted-1H-pyrazole-4-carbaldehyde (10 mmol) in ethanol at 0 C. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and upon completion, the reaction mixture was poured into iced water. The pH of the mixture was adjusted to 6 using a 0.01 N HCl solution. The precipitates were filtered and recrystallized from ethanol to obtain the compounds 3a-m in 40-93% yield.
79% With water; sodium hydroxide; In ethanol; at 0 - 20℃; General procedure: To a mixture of 2-acetylthiophene (1 mL, 0.0092 mol) and 3-methyl-1-phenyl-1H-pyrazole-4-yl (1.72 g, 0.0092 mol) in ethanol was added aqueous sodium hydroxide (0.44 g, 0.011 mol) at 0 oC. The resulting reaction mixture was allowed to stir for 6-8 h at room temperature. The reaction was monitored by TLC and on completion, reaction mixture was poured into ice coldwater. Then pH of the mixture adjusted to 6 using 0.01 N HCl solution. The obtained precipitates were filtered, dried and recrystallized from ethanol to get the compound 3a. Remaining compounds (3b-j) were prepared according to this procedure.
  • 52
  • [ 2033-24-1 ]
  • [ 1074-41-5 ]
  • [ 21487-45-6 ]
  • [ 1569612-87-8 ]
YieldReaction ConditionsOperation in experiment
81% With 1,2-dimethyl-1H-imidazol-3-ium-3-butanesulfonic acid hydrogensulfate; at 80℃; for 0.1h;Green chemistry; General procedure: A mixture of equimolar amounts of <strong>[1074-41-5]6-amino-2-(methylthio)pyrimidin-4(3H)-one</strong> (1) (1 mmol), ethylcyanoacetateor meldrum?s acid (2 or 5) (1 mmol) and aldehyde(3 or 6) (1 mmol) was added to a vial containinga magnetic stirring bar and [DMBSI]HSO4 (0.18 mmol,0.06g) and heated at 80 C in an oil bath. Stirring at 80C was continued until disappearance of the startingmaterials. At this stage, due to the poor solubility in theionic liquid, the product appears as a precipitate. Thereaction mixture was cooled and washed with water toextract the ionic liquid. The solid obtained was recrystallizedfrom ethanol to furnish the desired pure product.The ionic liquid was recovered from the aqueous extractsby evaporation under reduced pressure, and reusedin the next run.
  • 53
  • [ 118-48-9 ]
  • [ 62-53-3 ]
  • [ 21487-45-6 ]
  • [ 1611458-01-5 ]
YieldReaction ConditionsOperation in experiment
91% With γ-Fe2O3-HAp-SO3H nanocatalyst In ethanol; water at 60℃; for 0.916667h; Sonication; 3.4. General Procedure for the Synthesis of Products (a-j) General procedure: The mixture of one-pot three component of isatoic anhydride (1 mmol), amines (1.2 mmol) or ammonium salts (ammonium acetate: 1.2 mmol, ammonium carbonate: 0.6mmol), pyrazole carbaldehyde (1 mmol) and nanocatalyst(10 mg) in H2O: EtOH (3:1) was poured into a 25 ml roundbottomedflask and positioned in the ultrasonic and irradiatedat 60°C. The progress of the reaction was checked by TLC.The solid catalyst was separated by an external magnet. Theprecipitation of the reaction was filtered off, washed withwater and ethanol and recrystallized from ethanol to givepure products (Scheme 1) (Table 3) [8, 12, 19].
80% With <i>L</i>-proline In methanol for 1.58333h; Reflux; General procedure for the synthesis of compounds 5a-h and 6a-h General procedure: Synthesis of the titled compounds 5a-h was carried out using 1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 1 (0.002 mol), isatioc anhydride 2 (0.002 mol), aromatic amines 3a-h (0.002 mol) and l-proline 4 (5 mol%) in 10mL of MeOH in a 25mL round bottom flask attached with a reflux condenser. Reaction mixture was refluxed for 1-2.5h and the precipitates were filtered and recrystallized from MeOH. Compounds 5a-h were oxidized using 5% KMnO4 in acetone for 8h at room temperature and the product was extracted with chloroform. Excess of chloroform was removed in vacuo and the crystals of product 6a-h were separated.
  • 54
  • [ 118-48-9 ]
  • [ 106-49-0 ]
  • [ 21487-45-6 ]
  • [ 1611458-04-8 ]
YieldReaction ConditionsOperation in experiment
93% With γ-Fe2O3-HAp-SO3H nanocatalyst In ethanol; water at 60℃; for 1h; Sonication; 3.4. General Procedure for the Synthesis of Products (a-j) General procedure: The mixture of one-pot three component of isatoic anhydride (1 mmol), amines (1.2 mmol) or ammonium salts (ammonium acetate: 1.2 mmol, ammonium carbonate: 0.6mmol), pyrazole carbaldehyde (1 mmol) and nanocatalyst(10 mg) in H2O: EtOH (3:1) was poured into a 25 ml roundbottomedflask and positioned in the ultrasonic and irradiatedat 60°C. The progress of the reaction was checked by TLC.The solid catalyst was separated by an external magnet. Theprecipitation of the reaction was filtered off, washed withwater and ethanol and recrystallized from ethanol to givepure products (Scheme 1) (Table 3) [8, 12, 19].
83% With <i>L</i>-proline In methanol for 1.75h; Reflux; General procedure for the synthesis of compounds 5a-h and 6a-h General procedure: Synthesis of the titled compounds 5a-h was carried out using 1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 1 (0.002 mol), isatioc anhydride 2 (0.002 mol), aromatic amines 3a-h (0.002 mol) and l-proline 4 (5 mol%) in 10mL of MeOH in a 25mL round bottom flask attached with a reflux condenser. Reaction mixture was refluxed for 1-2.5h and the precipitates were filtered and recrystallized from MeOH. Compounds 5a-h were oxidized using 5% KMnO4 in acetone for 8h at room temperature and the product was extracted with chloroform. Excess of chloroform was removed in vacuo and the crystals of product 6a-h were separated.
  • 55
  • [ 118-48-9 ]
  • [ 106-47-8 ]
  • [ 21487-45-6 ]
  • [ 474378-40-0 ]
YieldReaction ConditionsOperation in experiment
88% With γ-Fe2O3-HAp-SO3H nanocatalyst In ethanol; water at 60℃; for 1.33333h; Sonication; 3.4. General Procedure for the Synthesis of Products (a-j) General procedure: The mixture of one-pot three component of isatoic anhydride (1 mmol), amines (1.2 mmol) or ammonium salts (ammonium acetate: 1.2 mmol, ammonium carbonate: 0.6mmol), pyrazole carbaldehyde (1 mmol) and nanocatalyst(10 mg) in H2O: EtOH (3:1) was poured into a 25 ml roundbottomedflask and positioned in the ultrasonic and irradiatedat 60°C. The progress of the reaction was checked by TLC.The solid catalyst was separated by an external magnet. Theprecipitation of the reaction was filtered off, washed withwater and ethanol and recrystallized from ethanol to givepure products (Scheme 1) (Table 3) [8, 12, 19].
79% With <i>L</i>-proline In methanol for 2.33333h; Reflux; General procedure for the synthesis of compounds 5a-h and 6a-h General procedure: Synthesis of the titled compounds 5a-h was carried out using 1-phenyl-3-aryl-1H-pyrazole-4-carbaldehyde 1 (0.002 mol), isatioc anhydride 2 (0.002 mol), aromatic amines 3a-h (0.002 mol) and l-proline 4 (5 mol%) in 10mL of MeOH in a 25mL round bottom flask attached with a reflux condenser. Reaction mixture was refluxed for 1-2.5h and the precipitates were filtered and recrystallized from MeOH. Compounds 5a-h were oxidized using 5% KMnO4 in acetone for 8h at room temperature and the product was extracted with chloroform. Excess of chloroform was removed in vacuo and the crystals of product 6a-h were separated.
  • 56
  • [ 54-85-3 ]
  • [ 21487-45-6 ]
  • [ 351988-48-2 ]
YieldReaction ConditionsOperation in experiment
92% With sulfuric acid In ethanol; dichloromethane Reflux; Synthesis of Isonicotinoyl hydrazones (3a-g) General procedure: General procedure A solution of an appropriate4-formylpyrazole derivative (2, 0.01 mol) in dichloromethanewas added to an ethanolic solution of isoniazid(1, 0.01 mol). One drop of concentrated sulfuric acid wasadded to the reaction mass and refluxed it for 40-45 mintill completion of reaction. The reaction was monitored bythin-layer chromatography. The excess of solvent wasevaporated and then cooled to room temperature. The obtainedproduct was filtered, washed with alcohol, and recrystallizedfrom ethanol. Noted m.p. and submitted toanalysis. N-Isonicotinoyl-N0-(10,30-diphenyl-40-pyrazolylmethylidene)hydrazine(3a) Yield 92 %; mp 195-197 °C; Rf = 0.09[ethylacetate: hexane (1:1)]; IR (KBr) νmax: 3427 (N-Hstr.), 1668 (C=O str.) cm-1; 1H NMR (DMSO-d6,400 MHz,): δ = 11.97 (1H, s, H-N, D2O exchangeable),9.05 (1H, s, H-5'), 8.79 (2H, d, J = 3.6 Hz, H-2, H-6), 8.59(1H, s, H-6'), 8.04 (2H, d, J = 7.6 Hz, H-2'', H-6''), 7.83(2H, d, J = 3.2 Hz, H-3, H-5), 7.75 (2H, d, J = 6.8 Hz, H-2''', H-6'''), 7.39-7.55 (6H, m, H-3'', H-4'', H-5'' & H-3''',H-4''', H-5'''); 13C NMR (DMSO-d6, 100 MHz,):δ = 161.1 (C, C-7), 152.1 (C, C-3'), 150.3 (CH, C-2, C-6),142.2 (CH, C-6'), 140.5 (C, C-1''), 139.0 (C, C-4), 131.9(C, C-1'''), 129.6 (CH, C-3''', C-5'''), 128.8 (CH, C-3'',C-5''), 128.7 (C, C-4'''), 128.4 (CH, C-2''', C-6'''), 127.2(CH, C-5'), 127.0 (CH, C-4''), 121.5 (CH, C-3, C-5), 118.8(CH, C-2'', C-6''), 116.6 (C, C-4'); MS (ESI) m/z: 368.14(M + 1)+; Anal. Calcd. for C22H17N5O: C, 71.91; H, 4.63;N, 19.07. Found: C, 71.89; H, 4.62; N, 19.05.
With acetic acid In ethanol for 4h; Reflux; Synthesis of 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde-acylhydrazones (7a-n, 8a-g) General procedure: To an ethanolic solution of acid hydrazide or isoniazid (0.01 mol), aldehyde (0.01 mol) was added and the solution was refluxed in the presence of few drops of acetic acid for 4 h. The progress of reaction was monitored by TLC using n-hexane:ethyl acetate (4:6) as a mobile phase. After completion of reaction, solvent was evaporated under vacuum to half of its volume, cooled to room temperature and poured onto ice cold water. The precipitated product thus obtained was filtered, washed with water, dried, and recrystallized from ethanol.
With acetic acid In ethanol Reflux;
  • 57
  • [ 30991-42-5 ]
  • [ 21487-45-6 ]
  • [ 1552291-96-9 ]
  • 58
  • [ 61832-41-5 ]
  • [ 21487-45-6 ]
  • [ 1620024-53-4 ]
YieldReaction ConditionsOperation in experiment
80% With toluene-4-sulfonic acid In water at 20℃; for 0.25h; Green chemistry; 4.1.1. General procedure for the synthesis of multi-substituted 1,4-DHPs (6a-u) General procedure: A mixture of solution containing aldehyde (1.0 equiv), NMSM (2.0equiv) and PTSA (0.1 equiv) in water (3 mL) was stirred at room temperaturefor about 15 min. The solid formation observed. The TLC withmobile phase of hexane: EtOAc mixture has been used to monitor thecompletion of the reaction. The resulted solid was cooled to 0-5 C andfiltered under vaccum. The crude products were recrystallized fromdichloromethane and hexane mixture (9:1) to obtain analytically pureproducts (6a-u). The spectral characterisation data and spectra areincluded in the supporting information.
78% With 2-aminopyridine In ethanol at 80℃; for 12h;
  • 59
  • 1-(6,8-dibromo-2-methylquinolin-3-yl)ethanone [ No CAS ]
  • [ 21487-45-6 ]
  • 1-(6,8-dibromo-2-methylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 60
  • [ 14428-41-2 ]
  • [ 21487-45-6 ]
  • 1-(2,4-dimethylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 61
  • [ 13337-57-0 ]
  • [ 21487-45-6 ]
  • 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-(2-methyl-4-phenylquinolin-3-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 62
  • [ 22609-02-5 ]
  • [ 21487-45-6 ]
  • 1-(6-chloro-2-methyl-4-phenylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 63
  • [ 312750-41-7 ]
  • [ 21487-45-6 ]
  • 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-(2-methyl-6-nitro-4-phenylquinolin-3-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 64
  • [ 21487-45-6 ]
  • 1-[6-chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl]ethan-1-one [ No CAS ]
  • 1-(6-chloro-4-(2-chlorophenyl)-2-methylquinolin-3-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium hydroxide In ethanol at 20℃; for 0.25h; Sonication; General procedure for the synthesis of 3a-f and 4a-r General procedure: By ultrasonic method (US) In a 50 mL Erlenmeyer flask, substituted 2-methyl-3-acetylquinoline(1.0 mmol) and 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde or substituted 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1.0 mmol) were mixed in ethanol (20 mL) and 0.75 mmol of KOH was added. The ultrasound probe was immersed directly in the reaction mixture. The ultrasound generator emits the sound vibration into the reaction mixture for the period of 15min. Sonication was achieved at frequencies of 22 kHz (amplitudeof 50%). The reaction mixture was maintained at room temperature by addition or removal of water from ultrasonic bath.Sonication was continued until the starting material had disappeared as indicated by TLC. On completion of the reaction, the reaction mixture was neutralized by dilute acetic acid, the resultant solid was filtered, dried and purified by recrystallisation. The purity of the products was checked by TLC using mixture of ethylacetate and hexane as mobile phase and also by 1H NMR spectroscopy.
  • 65
  • [(2S,3R)-3-(4-Nitro-phenyl)-aziridin-2-yl]-phenyl-methanone [ No CAS ]
  • [ 21487-45-6 ]
  • 2-(1,3-diphenyl-1H-pyrazol-4-yl)-6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0]hex-3-ene [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With ammonium acetate In ethanol at 20℃; General procedure for the synthesis of target compounds 9a-k General procedure: To a magnetically stirred solution of 1 mmol of trans-ketoaziridine4 and 1 mmol of 1-phenyl-3-arylpyrazole-4-carbaldehyde8 in 7 mL of absolute ethanol was added NH4OAc (0.78 g,10 mmol) at room temperature. The reaction mixture was stirredfor specified time. The solvent from the mixture was evaporatedunder reduced pressure to leave a residue that was washed withabsolute ethanol, dried under vacuum, and the resulting solidwas recovered, purified by silica gel column chromatography usingethyl acetate: hexane (1:3, v/v) as the eluent, and recrystallizedfrom absolute ethanol (10 mL) to afford the target compounds9a-k. Spectral data are listed below.
  • 66
  • (3-(3-nitrophenyl)aziridin-2-yl)(phenyl)methanone [ No CAS ]
  • [ 21487-45-6 ]
  • 2-(1,3-diphenyl-1H-pyrazol-4-yl)-6-(3-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0]hex-3-ene [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% With ammonium acetate In ethanol at 20℃; 2-(1,3-Diphenyl-1H-pyrazol-4-yl)-6-(3-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0]hex-3-ene (9b) 2-(1,3-Diphenyl-1H-pyrazol-4-yl)-6-(3-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0]hex-3-ene (9b) Yield: 85%; m.p. 176-178 °C; as a colorless solid; IR (KBr, cm-1): 3061, 1598, 1529, 1500, 1450, 1350, 1213, 1046, 958, 907, 875, 771, 691; (closed-form, 72%): 1H NMR (500 MHz, CDCl3): δ 2.74 (s, 1H, H-6), 3.75 (s, 1H, H-5), 6.87 (s, 1H, H-2), 7.32 (d, J = 1H, 1H), 7.40-7.62 (m, 9H), 7.79-7.83 (m, 2H), 7.97 (s, 1H, H-pyrazole), 8.02-8.13 (m, 5H), 8.19 (d, J = 7.3 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 42.0 (C-6), 58.0 (C-5), 90.3 (C-2), 119.0, 119.2, 122.0, 122.7, 129.0, 127.3, 128.0, 128.5-129.8 (8 C Ar), 132.0, 132.3, 133.1, 140.2, 148.7, 151.2, 171.4 (C-4); after irradiation with UV light converted to deep orange (open-form, 28%): 1H NMR (500 MHz, CDCl3): δ 2.88 (s, 1H, H-6'), 3.85 (s, 1H, H-5'), 6.41 (d, J = 2.28 Hz, 1H, H-2'), 7.32 (t, J = 6.25 Hz, 1H), 7.40-7.62 (m, 9H), 7.79-7.83 (m, 2H), 7.97 (s, 1H, H-pyrazole'), 8.02-8.13 (m, 4H), 8.19 (d, J = 7.34 Hz, 2H), 8.28 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 48.5 (C-6'), 57.0 (C-5'), 92.3 (C-2'), 119.2, 119.7, 122.0, 122.7, 129.0, 127.3, 128.0, 128.5-129.8 (8 C-Ar), 132.0, 132.3, 133.2, 140.2, 148.7, 151.2, 171.4 (C-4'); UV/Vis (EtOH) λmax/nm: 255 before irradiation and 260, 370 nm after irradiation; UV/Vis (DCM) λmax/nm: 260 before irradiation and 265, 375 nm after irradiation.
  • 67
  • 3-(4-methoxyphenyl)aziridin-2-yl-4-nitrophenylmethanone [ No CAS ]
  • [ 21487-45-6 ]
  • 2-[3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]-6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0]hex-3-ene [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With ammonium acetate In ethanol at 20℃; 2-[3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]-6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0] hex-3-ene (9c) 2-[3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]-6-(4-nitrophenyl)-4-phenyl-1,3-diazabicyclo[3.1.0] hex-3-ene (9c) Yield: 89%; m.p. 173-174 °C; as a beige solid; IR (KBr, cm-1): 3062, 1597, 1576, 1548, 1511, 1500, 1449, 1437, 1341, 1298, 1252, 1072, 974, 860, 771, 705, 695; (closed-form, 47%): 1H NMR (500 MHz, CDCl3): δ 2.72 (s, 1H, H-6), 3.74 (dd, J = 1.3, 1.8 Hz, 1H, H-5), 3.90 (s, 3H, OCH3), 6.82 (s, 1H, H-2), 7.03 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 7.2 Hz, 2H), 7.45-7.49 (m, 2H), 7.54-7.62 (m, 4H), 7.77-7.79 (m, 2H), 7.92 (s, 1H, H-pyrazole), 8.01-8.04 (m, 2H), 8.11-8.13 (m, 4H). 13C NMR (125 MHz, CDCl3) δ 48.5 (C-6), 58.3 (C-5), 55.7 (OCH3), 90.4 (C-2), 114.3, 119.1, 119.6, 123.9, 126.7, 128.9-130.3 (8 CAr), 132.3, 160.1, 171.2 (C-4); after irradiation with UV light converted to green (open-form, 53%): 2.86 (1H, H-6'), 3.82 (t, J = 2.4 Hz, 1H, H-5'), 3.86 (s, 3H, OCH3'), 6.37 (d, J = 2.8 Hz, 1H, H-2'), 6.98 (d, J = 8.7 Hz, 2H), 7.30 (m, 2H), 7.45-7.49 (m, 2H) 7.54-7.62 (m, 4H), 7.77-7.79 (m, 2H), 7.96 (s, 1H, H-pyrazole), 8.01-8.04 (m, 4H), 8.26 (d, J = 8.7 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 42.3 (C-6'), 54.9 (OCH3), 57.0 (C-5'), 90.4 (C-2'), 114.3, 118.6, 119.6, 124.1, 126.2, 128.9-130.3 (8 C-Ar), 132.4, 160.1, 171.2 (C-4'); UV/Vis (EtOH) λmax/nm: 280 before irradiation and 275, 415 nm after irradiation; UV/Vis (DCM) λmax/nm: 275 before irradiation and 275, 420 nm after irradiation.
  • 68
  • [ 23906-13-0 ]
  • [ 21487-45-6 ]
  • 2-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-1-(4,6-dimethylpyrimidin-2-yl)hydrazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% In ethanol;Reflux; General procedure: To the ethanolic solution of <strong>[23906-13-0]1-<strong>[23906-13-0](4,6-dimethylpyrimidin-2-yl)hydrazine</strong></strong> (1, 0.01 mol) was added appropriate 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde derivative (2,0.01 mol), and the solution was refluxed for 4-5 min. The solvent was evaporated in vacuo to half its volume and cooled to room temperature. The solid obtained was filtered and re-crystallized with ethanol to get the target compound 3.
  • 69
  • [ 1646-26-0 ]
  • [ 21487-45-6 ]
  • (E)-1-(benzofuran-2-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With bleaching earth clay pH 12.5 at 60 - 70℃; for 3h; Green chemistry; General procedure for synthesis of α,β-unsaturated ketones (chalcones) 3a-j General procedure: A mixture of 2-acetylbenzofuran (1 mmol), heteroaldehydes (2a-j) (1 mmol), and a catalytic amount of bleaching earth (10 wt.%, pH 12.5) was taken in polyethylene glycol-400 (PEG-400, 20 mL). The reaction mixture was stirred for the time shown in Table 1 at 60-70 °C. Reaction progress was monitored by thin-layer chromatography from time to time. After reaction completion, the result was filtered to separate the solid catalyst powder. The filtrate was then poured into a beaker containing water (100 mL) with stirring. The obtained solid product was filtered, washed using water (2 x 20 mL). It was then dried and recrystallized from appropriate solvent. The residual bleaching earth was recovered, dried, and furtherused for three more times.
  • 70
  • [ 95-54-5 ]
  • [ 21487-45-6 ]
  • 2-(1,3-diphenyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With anhydrous zinc chloride In acetonitrile for 5h; Reflux; Synthesis of 2-(1,3-diaryl-1H-pyrazol-4-yl)-1H-benzimidazoles 3a-h (General method). General procedure: 1,2-Diaminobenzene(1) (0.108 g, 1.00 mmol), an appropriate pyrazole aldehyde2a-h (1.00 mmol), and ZnCl2 (6.82 mg, 5 mol %) wereplaced into a 50-ml round-bottomed flask, and acetonitrile(15 ml) was added. The contents were refluxed for about5 h. The reaction progress was monitored by TLC on silicagel (hexane-AcOEt, 2:1). After completion of the reaction,as indicated by TLC, the reaction mixture was poured intoice water, the precipitate was filtered off and dried undervacuum.2-(1,3-Diphenyl-1H-pyrazol-4-yl)-1H-benzimidazole (3a).Yield 91%, mp 200-202°C (mp 200°C). 23 IR spectrum,ν, cm-1: 3356 (N-H), 2910 (C-H). 1H NMR spectrum,δ, ppm: 5.23 (1H, br. s, NH); 7.15-7.18 (2H, m, H Ar);7.32-7.50 (10H, m, H Ar); 7.64-7.67 (2H, m, H Ar); 9.08(1H, s, H-5 pyrazole). 13C NMR spectrum, δ, ppm: 148.8(C Ar); 146.0 (C Ar); 143.2 (C Ar); 135.3 (C Ar); 134.2(C Ar); 132.5 (CH Ar); 129.9 (2CH Ar); 129.8 (2CH Ar);128.1 (CH Ar); 127.6 (2CH Ar); 127.0 (CH Ar); 122.9(2CH Ar); 119.7 (2CH Ar); 115.0 (2CH Ar); 109.1 (C-4pyrazole). Mass spectrum, m/z: 337 [M+H]+. Found, %:C 78.35; H 4.61; N 16.45. C22H16N4. Calculated, %: C 78.55;H 4.79; N 16.66.
84% With potassium peroxomonosulfate In lithium hydroxide monohydrate; N,N-dimethyl-formamide Reflux; 7 General procedure for synthesis of 2-(1,3-diaryl-1Hpyrazol-4-yl)-1H-benzo[d]imidazoles (2 and 3) General procedure: To a solution of 4-formylpyrazole 1027, 1132,33 (1 mmol) andortho-phenylenediamine 12 (1.2 mmol) in 10 ml of dimethylformamide was added oxone (1 mmol) and 1 mL of water. The reaction mixture was refluxed for 1-2 h when color of reactionchanged from greenish to reddish brown. The course of reactionwas monitored by thin layer chromatography. Reaction mixturewas poured in water whereupon a brown solid precipitated out.The solid so precipitated out was filtered, washed with hot waterand dried to afford the target compound in good yield
77% With disodium metabisulfite In ethanol; lithium hydroxide monohydrate Reflux; 1 4.1.2. General procedure for the synthesis of 2-(1,3-diphenyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole derivatives (6-45) General procedure: A solution of Na2S2O5 (40 mmol) in H2O (1.6 mL) was added to a mixture of appropriate 1,3 diphenyl carboxaldehydes (10 mmol) and different substituted o-phenylenediamines (10 mmol) in ethanol. After completion of the reaction, the resulting mixture was stirred at reflux for 4 h,the mixture diluted with 50 mL of H2O and then extracted with ethyl acetate (2 x 40 mL). The combined extracts were washed with brine, dried over Na2SO4, and evaporated in vacuo. The crude product was purified by column chromatography using EtOAc/hexane as the eluent to produce pure 2-(1,3-diphenyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole derivatives ingood yields. 4.1.2.1 2-(1,3-diphenyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazole (6) White solid, yield 77%, Mp: 178-182 °C.; 1H NMR (300 MHz, CDCl3+DMSO-d6) δ 8.60 (s, 1H), 7.82-7.73 (m, 4H), 7.55 (dd, J = 6.0, 3.1 Hz, 2H), 7.45 (t, J = 7.8 Hz, 2H), 7.39-7.27 (m, 4H), 7.20 (dd, J = 6.0, 3.2 Hz, 2H). 13C NMR (75 MHz, CDCl3+DMSO-d6) δ 150.2, 145.2, 138.7, 138.3, 131.8, 128.8, 128.7, 127.8, 127.7, 126.3, 121.5, 118.2, 114.3, 112.3. MS (ESI): m/z 337 [M+H]+. HRMS (ESI) calcd for C22H16N4 [M+H]+ 337.14477; found: 337.14257.
With ferric(III) chloride In acetonitrile at 80℃; for 4h;

  • 71
  • 1-(6-((3-(trifluoromethyl)phenyl)diazenyl)benzofuran-2-yl)ethanone [ No CAS ]
  • [ 21487-45-6 ]
  • 3-(1,3-diphenyl-1H-pyrazol-4-yl)-1-(6-((3-(trifluoromethyl)phenyl)diazenyl)benzofuran-2-yl)prop-2-en-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With sodium hydroxide In ethanol; water at 20℃; for 2h; 5.3 General method for the preparation of chalcone derivatives 3 and 4a,b General procedure: 2-Acetylbenzofuran 2 (3.32 g, 0.01 mol) and the selected aldehydes (0.01 mol) were taken in ethanol (25 mL) and cooled. Ten percent aqueous sodium hydroxide solution (2.5 mL) was added to the above solution with constant stirring, until the turbidity appears. The reaction mixture was further stirred for 2 h and left overnight. The mixture was carefully acidified using dilute hydrochloric acid to obtain deep colored (yellow-orange) solid. The product obtained was filtered, washed with water and recrystallized from ethanol.
  • 72
  • [ 2687-43-6 ]
  • [ 21487-45-6 ]
  • (E)-1,3-diphenyl-1H-pyrazole-4-carbaldehyde O-benzyl oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With sodium acetate In ethanol at 30℃; for 3h; (E)-1,3-diphenyl-1H-pyrazole-4-carbaldehyde O-benzyloxime (4a) General procedure: To a solution of 3ae3e (1 mmol) in anhydrous ethanol (10 mL),corresponding O-benzylhydroxylamine hydrochloride (1 mmol)and NaOAc (1.2 mmol) were added and the resulting solution wasstirred at the room temperate for 3 h. The mixture was concentratedand taken in ethyl acetate (20 mL), washed with water(20 mL), saturated sodium chloride solution (20 mL) and dried oversodium sulfate. The resulting solution was concentrated and thepurification of the residue by recrystallization from ethanol yieldedthe desired compounds 4a-4t
  • 73
  • [ 21487-45-6 ]
  • O-(2-chlorobenzyl)hydroxylamine hydrochloride [ No CAS ]
  • (E)-1,3-diphenyl-1H-pyrazole-4-carbaldehyde O-(2-chlorobenzyl) oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With sodium acetate In ethanol at 30℃; for 3h; (E)-1,3-diphenyl-1H-pyrazole-4-carbaldehyde O-(2-chlorobenzyl) oxime (4c) General procedure: To a solution of 3ae3e (1 mmol) in anhydrous ethanol (10 mL),corresponding O-benzylhydroxylamine hydrochloride (1 mmol)and NaOAc (1.2 mmol) were added and the resulting solution wasstirred at the room temperate for 3 h. The mixture was concentratedand taken in ethyl acetate (20 mL), washed with water(20 mL), saturated sodium chloride solution (20 mL) and dried oversodium sulfate. The resulting solution was concentrated and thepurification of the residue by recrystallization from ethanol yieldedthe desired compounds 4a-4t
  • 74
  • [ 51572-93-1 ]
  • [ 21487-45-6 ]
  • (E)-1,3-diphenyl-1H-pyrazole-4-carbaldehyde O-(2,4-dichlorobenzyl) oxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With sodium acetate; In ethanol; at 30℃; for 3h; General procedure: To a solution of 3ae3e (1 mmol) in anhydrous ethanol (10 mL),corresponding O-benzylhydroxylamine hydrochloride (1 mmol)and NaOAc (1.2 mmol) were added and the resulting solution wasstirred at the room temperate for 3 h. The mixture was concentratedand taken in ethyl acetate (20 mL), washed with water(20 mL), saturated sodium chloride solution (20 mL) and dried oversodium sulfate. The resulting solution was concentrated and thepurification of the residue by recrystallization from ethanol yieldedthe desired compounds 4a-4t
  • 75
  • [ 2555-37-5 ]
  • [ 21487-45-6 ]
  • C27H18N2O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With piperidine In methanol at 20℃; for 6h; Inert atmosphere; 2.3.7. 3-(3-(1, 3-Diphenyl-1-H-pyrazol-4-yl)-4-hydroxy-2Hchromen-2-one (3f) Under nitrogen atmosphere, 1,3-dipheny-1H-pyrazole-3-carbaldehyde (248 mg, 1 mmol. 1 equiv) and 3-acetyl-4-hydroxy-2H-chromen-2-one (204 mg, 1 mmol, 1 equiv) were dissolved in dry methanol (25 mL). 0.1 mL of piperidine was added and the solution was stirred at RT for 6 h. After completion of the reaction, the yellow solid was filtered, washed with methanol and dried. The dye obtained was purified by column chromatography using silica gel 100-200 mesh and toluene as eluent. Colour: Yellow solid, Yield: 320 mg, 73%, M. P.: 237-238 °C. FT-IR (KBr, cm-1): 3654 (O-H stretching), 2224 (CN stretching),1710 (lactone C]O stretching). 1H NMR (500 MHz, CDCl3, Me4Si) δ 7.41-7.28 (m, 3H, ArH), 7.57-7.44 (m, 5H, ArH), 7.69-7.65 (t, 1H, ArH), 7.71 (d, J 7.0 Hz,2H, ArH),7.84 (d, J 7.7 Hz, 2H, ArH), 8.09 (dd, J 7.9, 1.4 Hz, 1H,ArH), 8.16 (d, J 15.5 Hz, 1H, C]CH), 8.29 (d, J 15.5 Hz, 1H, HC]C), 8.54 (s, 1H, NeCH). 13C NMR (126 MHz, CDCl3, Me4Si) δ 100.4, 116.8, 116.9, 118.6,119.6, 121.5, 124.3, 125.8, 127.5, 127.6, 128.8, 128.9(2), 129.9, 131.9,135.8, 138.3, 139.3, 154.6(2), 181.6, 191.6. MS (m/z): 435.4 (M+H). Anal. Calcd. for C27H18N2O4: C, 74.64; H, 4.18; N, 6.45. Found: C,74.61; H, 4.11; N, 6.49.HRMS m/z [M+H]+ Calcd for C27H18N2O4: 435.1345. Found: 435.1285.
  • 76
  • [ 326916-95-4 ]
  • [ 21487-45-6 ]
  • (E)-N′-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carbohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With acetic acid In methanol at 20℃; General procedure for the synthesis of hydrazones (5a-h) General procedure: To a stirred solution of carbohydrazide 1 (1 mmol) in methanol, was added an equimolar amount of the appropriate 1,3-diphenyl-1H-pyrazole-4-carbaldehydederivatives (4a-h) with a few drops of acetic acid. The reaction mixture was stirred at room temperature, until TLC indicated the end of reaction (15-30 min). After completion of the reaction, the reaction mixture was poured on crushed ice. The resulting crude product was purified by column chromatography on silica gel by EtOAc:petroleum ether (8:2) as an eluent to afford the pure title compounds 5a-h.
65% With acetic acid In methanol at 20℃;
  • 77
  • [ 344-95-6 ]
  • [ 21487-45-6 ]
  • N'-[(1,3-diphenyl-1H-pyrazol-4-yl)methylene]-2-(trifluoromethyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With potassium hydroxide; In ethanol; at 20℃; for 3.0h; General procedure: To a mixture of 2-(trifluoromethyl) (1 mmol) and aromatic aldehyde (1 mmol) in ethanol (5 mL), was added (4 mmol) of 50 % of potassium hydroxide. Stirred the reaction mass for 2-3 h reaction was monitored by TLC. After completion of the reaction the ethanol was distilled off from the reaction mass, the solid mass poured in to cold water (25 mL) filtered off the product then washed with cold water and the compounds were confirmed by their spectral data.
  • 78
  • [ 28144-70-9 ]
  • [ 21487-45-6 ]
  • 2-(1,3-diphenyl-1H-pyrazole-4-yl)-2,3-dihydroquinazolin-4 (1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With thionyl chloride In ethanol at 20℃; for 0.583333h;
93% With MMT-K10 In ethanol at 90℃; for 0.5h; 3.3. General Procedure of Synthesis of 2-(3(substitutedphenyl)-1-phenyl-1H-pyrazole-4-yl)-2, 3-dihydroquinazoline-4 (1H)-one 3(a-c) General procedure: The mixture of anthranilamide 2 (1 mmol), pyrazolecarbaldehydes 1(a-d) (1 mmol), in EtOH (10 ml) as a solvent,and MMT-K10 (5% w/w) [17, 28] as a catalyst, wasstirred in a round-bottom flask with an oil bath of 90°C forabout 30 minutes. The mixture, then, was monitored by TLC(Ethyl acetate/n-Hexane 1:1 ratio), and cooled down to roomtemperature, diluted with EtOH (96%) and filtered. The filteredmaterial was saved and concentrated for the separationof catalyst. Finally, the pure product was obtained from recrystallizationin hot ethanol 96% (Scheme 2) (Table 1) [7,16, 37-40].
  • 79
  • [ 141-82-2 ]
  • [ 21487-45-6 ]
  • [ 108446-65-7 ]
YieldReaction ConditionsOperation in experiment
93% With glycine In dimethyl sulfoxide at 20℃; for 3h; Green chemistry; General procedure for the synthesis of products 3a-r General procedure: To a mixture of an aldehyde 1a-f (2.0 mmol) and an active methylene 2a-d (2.0 mmol) dissolved in 5 mL of DMSO, 0.022 g of glycine (0.40 mmol, 20 mol%, 0.20 equiv) was added. The stirring was continued at room temperature for 3-15 h and then the reaction was quenched with ice water to obtain neat precipitates of pyrazole acryloyl compound 3a-r, which were further purified by recrystallization with ethanol.
  • 80
  • [ 21487-45-6 ]
  • [ 105-34-0 ]
  • (E)-methyl 2-cyano-3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With glycine In dimethyl sulfoxide at 20℃; for 5.5h; Green chemistry; General procedure for the synthesis of products 3a-r General procedure: To a mixture of an aldehyde 1a-f (2.0 mmol) and an active methylene 2a-d (2.0 mmol) dissolved in 5 mL of DMSO, 0.022 g of glycine (0.40 mmol, 20 mol%, 0.20 equiv) was added. The stirring was continued at room temperature for 3-15 h and then the reaction was quenched with ice water to obtain neat precipitates of pyrazole acryloyl compound 3a-r, which were further purified by recrystallization with ethanol.
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