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[ CAS No. 4664-55-5 ] {[proInfo.proName]}

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Chemical Structure| 4664-55-5
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Product Details of [ 4664-55-5 ]

CAS No. :4664-55-5 MDL No. :MFCD00297030
Formula : C8H10N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :XSONSBDQIFBIOY-UHFFFAOYSA-N
M.W : 166.18 Pubchem ID :101390
Synonyms :

Calculated chemistry of [ 4664-55-5 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 43.45
TPSA : 64.35 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.12 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.94
Log Po/w (XLOGP3) : 0.27
Log Po/w (WLOGP) : 0.06
Log Po/w (MLOGP) : 0.61
Log Po/w (SILICOS-IT) : 0.06
Consensus Log Po/w : 0.39

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.15
Solubility : 11.9 mg/ml ; 0.0714 mol/l
Class : Very soluble
Log S (Ali) : -1.18
Solubility : 10.9 mg/ml ; 0.0657 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.18
Solubility : 1.11 mg/ml ; 0.00667 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.6

Safety of [ 4664-55-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 4664-55-5 ]

* 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 [ 4664-55-5 ]

[ 4664-55-5 ] Synthesis Path-Downstream   1~93

  • 1
  • [ 120-57-0 ]
  • [ 4664-55-5 ]
  • (E)-N′-(benzo[d][1,3]dioxol-5-ylmethylene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 2
  • [ 2555-49-9 ]
  • [ 4664-55-5 ]
YieldReaction ConditionsOperation in experiment
98% With hydrazine hydrate In ethanol Reflux; 4.3.2. General procedure for the synthesis of hydrazides from corresponding esters (Procedure A) General procedure: Ester (1 eq) and N2H2.H2O (5 eq) were solubilized in EtOH (5 mL/mmol). The resulting mixture was refluxed 18-24 h. The reaction was monitored by TLC (CH2Cl2/MeOH, 95/5) and LCMS. Solvents were removed under reduced pressure and crude products were extracted with CH2Cl2 or ethyl acetate. The combined organics werewashed with saturated Na2CO3 aqueous solution, and dried (Na2SO4) and concentrated under reduced pressure to give the desired hydrazide.
90% With hydrazine hydrate In ethanol Reflux; 4.b B. Preparation of phenoxyacetohydrazide Take the steps pale yellow oily liquid in the reaction flask, ethanol 25mL, 80% hydrazine hydrate .99g (40mmol), an oil bath at reflux overnight. The reaction solution methanol was distilled off under reduced pressure, allowed to stand for cooling to room temperature, whereupon white crystals precipitated, washed by suction filtration to give about 2.30g of white crystalline product, yield of about 90% (to the phenol).
88% With hydrazine hydrate In ethanol at 85℃;
83% With hydrazine hydrate In ethanol for 5h; Reflux; Synthesis of Phenoxyacetohydrazide Derivatives (D1-7) General procedure: Compounds D1-7 were prepared by similar procedures. In atypical synthesis of D1, a mixture of phenoxyacetate(10 mmol, 1.80 g), hydrazine hydrate (80 %, 5 mL) and absoluteethanol (30 mL) was added to a 150 mL three-neckflask, then the reaction mixture was refluxed for 5 h. Themixture was cooled to room temperature. The crude productwas collected by filtration and washed several times with ethanol.After drying, white needle crystal was recrystallizedfrom ethanol and dried in vacuum
78% With hydrazine hydrate Reflux; Alcoholic solution;
70% With hydrazine hydrate In methanol at 20℃; for 1h; 4.1.2. Synthesis of 4-methoxy phenoxy acetohydrazide (3a) General procedure: To 2a (2 g, 9.5 mmol) in methanol (10 mL), 80% hydrazine hydrate (0.475 g, 9.5 mmol) was added in drops and stirred for 1 h at room temperature. A white solid separated, which on recrystallization with ethanol gave 3a (75%) as white needles.
With ethanol; hydrazine hydrate
With hydrazine hydrate
With hydrazine hydrate In ethanol for 3h; Heating;
With hydrazine hydrate
With hydrazine hydrate In ethanol for 14h; Heating;
With NH2-NH2.H2O
With hydrazine hydrate In ethanol
With hydrazine
With hydrazine In water
With hydrazine hydrate In ethanol for 24h; Reflux; General method for the synthesis of hydrazides General procedure: Substituted aromatic acid (0.01 mol) was dissolved in 20 ml absolute ethanol added 1 ml conc. H2SO4 and refluxed for 8 h. The two third volume of reaction mixture was removed under reduced pressure and then poured into crushed ice and neutralized with sodium bicarbonate to obtain esters. In the subsequent step equimolar quantity of substituted ester (0.005 mol) and hydrazine hydrate (0.25 ml, 0.005 mol) in ethanol was refluxed for 24 h with stirring. The two third volume of alcohol was removed under reduced pressure and the reaction mixture was poured into the crushed ice. The resultant precipitate was filtered, washed with water and dried. The solid was recrystallized from 25 ml of 90 % ethanol. The purity of the compounds was checked by TLC using toluene-ethyl acetate-formic acid (5:4:1) as mobile phase.
With hydrazine hydrate
With hydrazine hydrate Reflux;
With hydrazine hydrate
With hydrazine hydrate In ethanol for 3h; Reflux;
With hydrazine hydrate Reflux; 4.3. General procedure for the synthesis of acid hydrazides (9a-s) General procedure: The 0.015 mol of ethyl aromatic esters (8a-s) and 0.02 mol of hydrazine hydrate were dissolved in absolute ethanol or methanol (20 mL) to reflux the reaction mixture for 3-6 h for complete hydrazinolysis of ethyl aromatic esters. The product obtained was isolated after cooling as a white or yellow solid and recrystallized from ethanol or methanol.
With hydrazine hydrate In ethanol Reflux; Synthesis of Substituted Aryloxy hydrazide 5(a-g) General procedure: The substituted acid (0.1 mole) and ethanol (50 ml) were taken with a few drops of concentrated sulfuric acid and it was refluxed for 6 hours.The reaction mixture was concentrated bydistilling of the excess of ethanol under reduced pressure and treated with a saturated solution of sodium bicarbonate. The ester obtained used for the preparation of hydrazide directly. The ester(0.1 mole) was dissolved in appropriate quantity of ethanol and to this hydrazine hydrate (0.1 mole) was added. The reaction mixture was taken in a round bottomed flask and refluxed for a period of 12-18 hours. Excess of ethanol was distilled off under reduced pressure. It was then poured into ice cold water and the solid obtained was filtered. It was crystallized from ethanol.
With hydrazine hydrate Reflux;
With hydrazine In ethanol for 12h; Cooling with ice;
With hydrazine hydrate In ethanol at 85℃; for 6h;
With hydrazine hydrate In ethanol Reflux; General procedure for intermediates 14 General procedure: Intermediates 14 were prepared by following the knownprocedure [22, 29, 30]. The mixture of ethyl 2-chloroacetate(1 mmol), substituted phenols (1 mmol), and K2CO3(1.2 mmol) in acetonitrile was stirred in refluxing for 2 h(the course of the reactions was monitored by TLC), thenfiltered, and the mother liquid was evaporated in vacuo toafford corresponding substituted ethyl 2-phenoxyacetates,which were then reacted with hydrazine hydrate (80%) toyield substituted 2-phenoxyacetohydrazides 14 in>90%yield.
With hydrazine hydrate In ethanol at 20℃; for 1h; 5.2 The second step: to 2.00gAdd 1.39g to a 100mL single-mouth bottle of ethyl phenoxyacetateHydrazine hydrate and 15mL ethanol,React at room temperature,After a large amount of solids were produced (about 1 hour), the reaction was stopped.After suction filtration, the petroleum ether is washed several times to obtain a white solid to be dried, which is an intermediate.
With hydrazine hydrate In ethanol
With hydrazine hydrate In ethanol
With hydrazine In ethanol at 60℃; for 12h; Inert atmosphere; 2-(Benzo[d][1,3]dioxol-5-yloxy)acetohydrazide (7). General procedure: To a solution of 6 (1.58 g, 7.0 mmol) in EtOH (18 mL) was added hydrazine monohydrate (3.45 mL, 70.5 mmol). The reaction mixture was stirred for 12 h at 60 C, cooled down to room temperature, then EtOH was removed under reduced pressure. The crude compound was washed with n-hexane to obtain the desired product as white powder (86-99% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.28 (s,1H), 6.80 (d, J = 8.5 Hz, 1H), 6.66 (d, J = 2.5 Hz, 1H), 6.38 (dd, J = 8.5, 2.5 Hz, 1H), 5.96 (s, 2H), 4.39 (s, 2H), 4.31 (s, 2H). HRMS (ESI) m/z calculated for C9H10N2O4Na+ [M + Na]+: 233.0538. Found: 233.0517.
With hydrazine hydrate In acetonitrile Reflux;
With hydrazine In methanol for 3h; Reflux; 2.2.1 2-phenoxyacetohydrazide H1 To a solution of phenol (300mg, 3.19mmol) and K2CO3 (661mg, 4.78mmol) in CH3CN (10mL) was added ethyl bromoacetate (421μL, 3.83mmol) at 0 °C dropwise. The reaction mixture was stirred at 0 °C for 1h and then at r.t. overnight. The solution was filtered, and the filtrate was concentrated under vacuum. The crude product was purified by silica gel chromatography (hexane:EtOAc=15:1) to yield product E1 (495mg, 86%) as a white solid. Subsequently, all the white solid was dissolved in methanol (10mL), and hydrazine anhydrate (2.66mL, 27.5mmol) was added to this solution. The reaction mixture was refluxed for 3h, at which time the solvent was removed under vacuum. The crude product was purified by silica gel chromatography (DCM:MeOH=20:1) to yield product H1 (420mg, 92%) as a white solid. 1H NMR (400MHz, CDCl3) δ: 7.93 (s, 1H), 7.30 (dd, J=8.0Hz, 2H), 7.02 (t, J=8.0Hz, 1H), 6.89 (d, J=8.0Hz, 2H), 4.56 (s, 2H), 3.95 (s, 2H); 13C NMR (100MHz, CDCl3) δ: 168.6, 157.1, 129.8, 122.3, 114.5, 66.9.

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[2]Current Patent Assignee: CHINA MEDICAL UNIVERSITY (PRC) - CN105461705, 2016, A Location in patent: Paragraph 0119; 0122; 0123
[3]Wu, Yongqiang; Guo, Tiantong; Shu, Dehua; Zhang, Wu; Luan, Fangfei; Shi, Ling; Guo, Dongcai [Luminescence, 2018, vol. 33, # 5, p. 855 - 862]
[4]Yan, Dong; Li, Dong; Cheng, Guang; Yang, Zehui; Shi, Ling; Guo, Dongcai [Journal of Fluorescence, 2015, vol. 25, # 4, p. 849 - 859]
[5]Location in patent: experimental part Kaushik, Darpan; Khan, Suroor Ahmad; Chawla, Gita; Kumar, Suresh [European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 3943 - 3949] Location in patent: experimental part Kaushik, Darpan; Khan, Suroor Ahmad; Chawla, Gita [European Journal of Medicinal Chemistry, 2010, vol. 45, # 9, p. 3960 - 3969]
[6]Location in patent: experimental part Sathisha; Khanum, Shaukath A.; Chandra, J.N. Narendra Sharath; Ayisha; Balaji; Marathe, Gopal K.; Gopal, Shubha; Rangappa [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 1, p. 211 - 220]
[7]Baltazzi; Delavigne [Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1955, vol. 241, p. 633] Yale et al. [Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934] Mirek [Zeszyty Naukowe Uniwersytetu Jagiellonskiego., 1958, # 4, p. 163,166][Chem.Abstr., 1958, p. 19992]
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  • 3
  • [ 104-88-1 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-chlorobenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 4
  • [ 123-11-5 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-methoxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 5
  • [ 2058-72-2 ]
  • [ 4664-55-5 ]
  • 1-methyl-5-bromo-3-phenoxy acetyl hydrazono-2-indolinone [ No CAS ]
  • 6
  • [ 73568-25-9 ]
  • [ 4664-55-5 ]
  • [ 154255-38-6 ]
YieldReaction ConditionsOperation in experiment
87% With PEG (polyethylene glycol) 400 at 20℃; for 4.5h;
80% In ethanol for 3h; Heating;
70% In ethanol Reflux;
67% In ethanol for 5h; Reflux; Procedure for the synthesis of (2-chloroquinolin-3-yl)methylidene]-substituted benzohydrazide (11a-i) General procedure: A mixture of substituted hydrazide 8a-i (0.003 mol) and 2-chloroquinoline-3-carbaldehyde 2 (0.003 mol; 0.57 g) in ethanol was refluxed for 5 h. After completion of the reaction, the reaction mixture was concentrated, cooled and poured in ice-cold water; the precipitate so formed was filtered, dried and recrystallized to give the desired compound.

  • 7
  • [ 1147550-11-5 ]
  • [ 122-01-0 ]
  • [ 4664-55-5 ]
  • [ 123296-11-7 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: ammonium thiocyanate; 4-chloro-benzoyl chloride With PEG-400 In dichloromethane at 20℃; for 1h; Stage #2: phenoxyacetyl hydrazine at 20℃; for 0.5h;
  • 8
  • [ 1147550-11-5 ]
  • [ 100-07-2 ]
  • [ 4664-55-5 ]
  • 1-phenyloxyacetyl-4-(4-methoxyibenzoyl)-thiosemicarbazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: ammonium thiocyanate; 4-methoxy-benzoyl chloride With polyethylene glycol-400 In dichloromethane at 20℃; for 1h; Stage #2: phenoxyacetyl hydrazine In dichloromethane at 20℃; for 0.5h;
  • 9
  • [ 122-59-8 ]
  • [ 4664-55-5 ]
YieldReaction ConditionsOperation in experiment
91% With hydrazine monohydrate; N-(chloromethylene)-N-methylmethanaminium chloride; triethylamine In dichloromethane at 20℃; for 7h; General procedure for synthesis of acylhydrazines 2-5 General procedure: A solution of carboxylic acid (1.0 mmol), Vilsmeier reagent (1.0 mmol) and Et3N (3.0 mmol) in dry CH2Cl2 (10 mL) at room temperature was added to a solution of hydrazine hydrate (4.0 mmol) in dry CH2Cl2 (5 mL) and the mixture was stirred 7 h. The mixture was washed successively with saturated NaHCO3 (15 mL) andbrine (15 mL). The organic layer was dried (Na2SO4), filtered and the solvent was removed under reduced pressure to give the crude products. The crude residues were purified by crystallization from ethanol 95 %. Spectral data for 2-5 have been previously reported.
With hydrazine hydrate monohydrate In methanol for 25h; Heating;
With hydrazine hydrate monohydrate at 90℃; for 4h;
Multi-step reaction with 2 steps 1: H2SO4 / 3 h / Heating 2: hydrazine hydrate / ethanol / 14 h / Heating
Multi-step reaction with 2 steps 1: H2SO4 / 3 h 2: hydrazine hydrate / ethanol / 14 h / Heating
Multi-step reaction with 2 steps 1: H2SO4 2: NH2NH2*H2O
Multi-step reaction with 2 steps 1: p-toluenesulfonic acid / 5 h / Heating 2: hydrazine hydrate / ethanol / 3 h / Heating
Multi-step reaction with 2 steps 1: sulfuric acid / 8 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 24 h / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate monohydrate
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / 3 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 3 h / Reflux
Multi-step reaction with 2 steps 1: hydrogenchloride / Reflux 2: hydrazine hydrate monohydrate / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / Reflux
With sulfuric acid; hydrazine hydrate monohydrate In ethanol for 6h; Reflux; General procedure for the preparation of acid hydrazides(10a-i) General procedure: The appropriate aromatic acids 9a-i (0.01 mol) were dissolved in absolute ethanol (10 ml). Hydrazine hydrate (0.02 mol, 1 ml) and few drops of conc. sulphuric acid were added. The reaction mixture was refluxed for 6 h. The resulting solid obtained was filtered, dried and crystallized from methanol. The completion of reaction was monitored by thin-layer chromatography and infrared spectrophotometer (Jha et al., 2010). (10a: naphthoxy acetic acidhydrazide; 10b: phenylacetic acid hydrazide; 10c: p-nitrobenzoic acid hydrazide; 10d: o-chlorobenzoic acid hydrazide; 10e: p-chlorobenzoic acid hydrazide; 10f: nicotinic acid hydrazide; 10g: phenoxyacetic acid hydrazide; 10h: 3,5-dinitrobenzoic acid hydrazide; 10i: salicylic acid hydrazide.)
Multi-step reaction with 2 steps 1: acetyl chloride / 20 h / 80 °C 2: hydrazine hydrate monohydrate / ethanol / 6 h / 85 °C
With hydrazine monohydrate; Vilsmeier reagent; triethylamine In dichloromethane at 20℃;
With hydrazine hydrate monohydrate
Multi-step reaction with 2 steps 1: acetyl chloride / 24 h / 80 °C / Cooling with ice 2: hydrazine hydrate monohydrate / ethanol / 85 °C
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate monohydrate / ethanol
Multi-step reaction with 2 steps 1: sulfuric acid / 24 h / Heating 2: hydrazine / ethanol / 1 h / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 2 h / Reflux 2: hydrazine hydrate monohydrate / ethanol / 4 h / Reflux
With hydrazine monohydrate In ethanol

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[3]Li, Jian-Ping; Zheng, Peng-Zhi; Zhu, Jun-Ge; Liu, Rui-Jie; Qu, Gui-Rong [South African Journal of Chemistry, 2006, vol. 59, p. 90 - 92]
[4]Shahar Yar; Ahmad Siddiqui; Ashraf Ali [Journal of the Chinese Chemical Society, 2007, vol. 54, # 1, p. 5 - 8]
[5]Ali, Mohamed Ashraf; Shaharyar, Mohammad [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 12, p. 3314 - 3316]
[6]yar, Mohammad Shahar; Siddiqui, Anees Ahmad; Ali, Mohamed Ashraf [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 17, p. 4571 - 4574]
[7]Shi; Shi; Wang [Journal of Heterocyclic Chemistry, 2001, vol. 38, # 4, p. 929 - 932]
[8]Ahsan, Mohamed Jawed; Samy, Jeyabalan Govinda; Khalilullah, Habibullah; Nomani, Md. Shivli; Saraswat, Pankaj; Gaur, Ramakant; Singh, Abhimanyu [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250]
[9]Kaushik, Darpan; Kumar, Rajnish; Khan, Suroor Ahmed; Chawla, Gita [Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3646 - 3655]
[10]Polucci, Paolo; Magnaghi, Paola; Angiolini, Mauro; Asa, Daniela; Avanzi, Nilla; Badari, Alessandra; Bertrand, Jay; Casale, Elena; Cauteruccio, Silvia; Cirla, Alessandra; Cozzi, Liviana; Galvani, Arturo; Jackson, Peter K.; Liu, Yichin; Magnuson, Steven; Malgesini, Beatrice; Nuvoloni, Stefano; Orrenius, Christian; Sirtori, Federico Riccardi; Riceputi, Laura; Rizzi, Simona; Trucchi, Beatrice; O'Brien, Tom; Isacchi, Antonella; Donati, Daniele; D'Alessio, Roberto [Journal of Medicinal Chemistry, 2013, vol. 56, # 2, p. 437 - 450]
[11]More, Uttam A.; Joshi, Shrinivas D.; Aminabhavi, Tejraj M.; Gadad, Andanappa K.; Nadagouda, Mallikarjuna N.; Kulkarni, Venkatrao H. [European Journal of Medicinal Chemistry, 2014, vol. 71, p. 199 - 218]
[12]Kumar, P. Sudhir; Sahoo [Oriental Journal of Chemistry, 2014, vol. 30, # 1, p. 211 - 217]
[13]Salahuddin; Mazumder, Avijit; Shaharyar, Mohammad [Medicinal Chemistry Research, 2014, vol. 24, # 6, p. 2514 - 2528]
[14]Xiao, Haihua; Jiang, Xi; Li, Dong; Wu, Limin; Zhang, Wu; Guo, Dongcai [Luminescence, 2015, vol. 30, # 5, p. 677 - 685]
[15]Zarei, Maaroof [Tetrahedron, 2017, vol. 73, # 14, p. 1867 - 1872]
[16]Pachuta-Stec, Anna; Biernasiuk, Anna; Malm, Anna; Pitucha, Monika [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 5, p. 2867 - 2873]
[17]Wu, Yongqiang; Guo, Tiantong; Shu, Dehua; Zhang, Wu; Luan, Fangfei; Shi, Ling; Guo, Dongcai [Luminescence, 2018, vol. 33, # 5, p. 855 - 862]
[18]Tariq, Sana; Kamboj, Payal; Alam, Ozair; Amir, Mohd. [Bioorganic Chemistry, 2018, vol. 81, p. 630 - 641]
[19]Apaydın, Çağla Begüm; Cesur, Nesrin; Stevaert, Annelies; Naesens, Lieve; Cesur, Zafer [Archiv der Pharmazie, 2019, vol. 352, # 6]
[20]Tokalı, Feyzi Sinan; Taslimi, Parham; Demircioğlu, İbrahim Hakkı; Şendil, Kıvılcım; Tuzun, Burak; Gülçin, İlhami [Journal of the Iranian Chemical Society, 2022, vol. 19, # 2, p. 563 - 577]
[21]Agarwal, Deepak K.; Ahsan, Mohamed J.; Jadav, Surender S.; Khalilullah, Habibullah; Khan, Masood Alam; Khan, Riaz; Mohammed, Hamdoon A.; Mohammed, Salman A. A. [International Journal of Molecular Sciences, 2022, vol. 23, # 12]
  • 10
  • [ 57753-80-7 ]
  • [ 1147550-11-5 ]
  • [ 4664-55-5 ]
  • [ 364331-60-2 ]
  • 11
  • [ 333-20-0 ]
  • [ 4664-55-5 ]
  • [ 35687-21-9 ]
YieldReaction ConditionsOperation in experiment
61% With ethanol for 4h; Reflux; 4.1.3. Synthesis of 4-methoxy phenoxy acetyl-N-hydrazine carbothioamides (4a) General procedure: A mixture of potassium isothiocyanate (0.44 g, 3.28 mmol) and 3a (0.6 g, 3.18 mmol) in dry ethanol (20 ml) was refluxed with stirring for 4 h, the mixture was cooled, filtered, washed with ethanol, dried and recrystallized with ethanol to give 4a (60%) as colorless needles.
With hydrogenchloride for 4h; Heating;
  • 12
  • [ 2065-23-8 ]
  • [ 4664-55-5 ]
YieldReaction ConditionsOperation in experiment
99% With hydrazine hydrate In methanol for 0.0166667h; microwave irradiation;
95% With hydrazine hydrate In ethanol for 3h; Reflux; General procedure for the preparation of 2-phenoxyacetohydrazide (23) To an ethanolic solution of 22 (9.97 g; 0.06 mol; 1.0 eq.)was added slowly hydrazine hydrate 80% (aq.) (15 g;0.3 mol; 5.0 eq.) and the reaction mixture was stirred for 3 hunder reflux. The mixture was cooled, the precipitate wascollected by vacuum filtration, washed with cold ethanol,and dried under vacuum.2-phenoxyacetohydrazide (23). White crystal (EtOH);95% yield; m.p. 113.5-114.2 °C; IR (ATR. cm-1): νmax3400 (N-H2); 1598 (C = Oamide); 1496 (C = CAr); 1241 and1069 (C-Oether); 1H NMR (400 MHz. DMSO-d6): δ 4.33(N-H2); 4.47 (2H; s; H2); 6.94-6.97 (3H; m; H6; H7; H8);7.27-7.31 (2H; m; H5; H9); 9.33 (1H; s; N-H); 13C NMR(100 MHz. DMSO-d6): δ 66.0 (C2); 114.5 (C6; C8); 121.0(C7); 129.3 (C5; C9); 157.7 (C4); 166.5 (C1).
87% With hydrazine hydrate at 110 - 120℃;
67.5% With hydrazine hydrate In ethanol for 24h; Reflux; Syntheses of neutral guests Take guest AA0 as an example, in a 50 mL round-bottomed flask 1 (0.1 mmol), hydrazine hydrate (2.0 mmol) was refluxed in 25 mL CH3CH2OH for 24 h. The reaction mixture was then washed with water 3 times and recrystallised in methanol to afford AA0 (yield: 67.5%) of a white power product. AA0: white solid, yield: 67.5%, 1H NMR (400 MHz,CDCl3) δ 7.74 (s, 1H, C-NH), 7.33 (t, J = 8.0 Hz, 2 H, ArH),7.04 (t, J = 8.0 Hz, 2 H, ArH), 6.91 (t, J = 8.0 Hz, 1H, ArH),4.58 (s, 2 H, -CH2-), 3.91 (s, 2 H, -NH2). 13C NMR (101 MHz,CDCl3) δ 167.11, 158.23, 129.90, 121.53, 115.07, 66.60. MS(m/z): HRMS (ESI) Calcd. for C8H11N2O2+ ([Ma + H]+):167.0821, found: 167.0028.
With hydrazine hydrate In ethanol; N,N-dimethyl-formamide for 0.0166667h; microwave irradiation;
With hydrazine hydrate In ethanol for 6h; Reflux; 3.2.1. Synthesis of Substituted Phenoxyacetohydrazide (2) as Intermediate General procedure: To an oven-dried round bottomed flask with a stirring bar was added a solution of substituted phenol (0.01 mol, 1 eq.) and K2CO3 (1.2 eq.) in 50 mL of dry DMF. Excess ethyl chloroacetate dissolved in 10 mL of DMF was then slowly added through a dropping funnel to the above solution.The resulting mixture was stirred at 90 °C for 5-6 h. The reaction was quenched with saturated NaCl solution, then extracted with dichloromethane(DCM), washed with brine, dried over MgSO4 and then concentrated on a rotary evaporator affording methyl 2-phenoxyacetate 1 (80%-95% yield) which was used for the next step without further purification [17].This product 1 (0.009 mol, 1 eq.) wasdissolved in 30 mL of ethanol and then placed in a round-bottomed flask equipped with a stirring bar; 80% of hydrazine hydrate (0.018 mol, 2 eq.) was slowly added to this mixture at room temperature through a dropping funnel. The resulting solution was heated up to reflux temperature and stirring was continued under this condition for another 6 h. The reaction mixture was filtered through celite,the filtrate was washed with brine, dried over MgSO4, and then concentrated in vacuo. The crudephenoxyacetohydrazide 2 was used directly without further purification in the next step.
With hydrazine In ethanol for 1h; Reflux;
With hydrazine hydrate In ethanol for 4h; Reflux; General procedure for synthesis compounds 4a-e General procedure: Concentrated H2SO4 (1 mL) was added to the solution ofsuitable carboxylic acids (10 mmol) in methanol (20 mL) and refluxed for 2 h. The mixture was cooled to room temperature,and saturated NaHCO3solution (50 mL) was addedslowly. The aqueous layer was extracted with dichloromethane(3 × 15 mL). Organic layer was dried with sodium sulfateand the solvent was removed by evaporation under reducedpressure. The crude product was dissolved ethanol (20 ml)and hydrazinium hydroxide (5 ml, 80%) was added to thismixture. It was refluxed for 4 h and left in the freezer overnight.Formed crystals were filtered off, dried and recrystallizedfrom ethanol (Fig. 5).

  • 13
  • [ 1885-14-9 ]
  • [ 4664-55-5 ]
  • phenyl 2-(2-phenoxyacetyl)hydrazinecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With sodium hydrogencarbonate In dichloromethane at 20℃;
  • 14
  • [ 42082-29-1 ]
  • [ 1147550-11-5 ]
  • [ 4664-55-5 ]
  • 1-phenyloxyacetyl-4-(4-methoxyphenyloxyacetyl)-thiosemicarbazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% Stage #1: p-methoxyphenoxyacetyl chloride; ammonium thiocyanate With PEG 400 In dichloromethane at 20℃; for 1h; Stage #2: phenoxyacetyl hydrazine In dichloromethane for 0.5h;
  • 15
  • [ 28115-92-6 ]
  • [ 4664-55-5 ]
  • 1-phenyloxyacetyl-4-(4-nitrobenzoyl)-thiosemicarbazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% In acetone at 60℃; for 2h; 3.2. Synthesis of 1,4-Diacylthiosemicarbazide Substrates (1a-1s) General procedure: To a solution of acyl chloride (1.0 equiv.) in 20 mL dry acetone, potassium thiocyanate (1.1equiv.) was added at room temperature. The solution was stirred at room temperature for 0.5 h. Then,relevant acylhydrazine (1.05 equiv.) was added. The reaction was stirred at 60 °C for 2 h until thereaction was complete based on TLC (thin-layer chromatography) (DCM:MeOH = 15:1). Then, it wascooled to room temperature, and concentrated under reduced pressure. The resulting residue waswashed by water and recrystallized in MeOH to give the corresponding intermediate as a white solid.
In chloroform for 0.0666667h; 675 W microwave irradiation;
  • 17
  • [ 58490-93-0 ]
  • [ 4664-55-5 ]
  • 5-phenoxymethyl-4-(1,2,3,4-tetrahydro-naphthalen-1-yl)-2,4-dihydro-[1,2,4]triazole-3-thione [ No CAS ]
YieldReaction ConditionsOperation in experiment
16% Stage #1: 1-isothiocyanato-1,2,3,4-tetrahydronaphthalene; phenoxyacetyl hydrazine In isopropyl alcohol for 1 - 21h; Heating / reflux; Stage #2: With sodium hydroxide In water for 2 - 12h; Heating / reflux; 3 Example 35-Phenoxγmethyl-4-(L2.3.4-tetrahvdro-naphthalen-l-ylV2.4-dihvdro-rL2.41triazole-3- thioneThe title compound was obtained as white foam in 16% yield starting from phenoxyacetic o acid hydrazide (669 mg, 2.77 mmol) and 1, 2,3, 4-tetrahydronaphthalene-l -isothiocyanate (655 mg, 3.47 mmol) using general procedure A with the following modifications. After the first step, the reaction mixture was concentrated directly and not poured onto ice. The residue was purified by flash chromatography (gradient elution 0-5% MeOH in CH2Cl2). The final product did not crystallize and was therefore extracted with EtOAc and purified 5 by column chromatography (gradient elution 0-30% EtOAc in hexane).1H NMR (CDCl3) δ 7.28-7.17 (4H, m), 7.13 (IH, t, J=7.2 Hz), 7.07 (IH, br d, J=7.2 Hz), 6.98 (IH, t, J=7.2 Hz), 6.86 (IH, br d, J=7.6 Hz), 6.72 (IH, m), 6.29 (IH, br s), 4.72 (IH, br s), 4.28 (IH, br s), 2.75 (2H, m), 2.42 (IH, m), 2.33-2.17 (IH, m), 2.12-2.02 (IH, m), 1.91-1.78 (IH, m). EPO 13C NMR (CDCl3) δ 156.9, 138.8, 132.4, 129.64, 129.58, 128.0, 127.0, 126.7, 122.0, 114.5, 60.3, 56.1, 29.1, 28.9, 21.9. MS (ESI) m/z 338 (M+l).
  • 18
  • 3-isothiocyanatodihydrofuran-2(3H)-one [ No CAS ]
  • [ 4664-55-5 ]
  • 5-phenoxymethyl-4-(2-oxo-dihydrofuran-3-yl)-2,4-dihydro-[1,2,4]triazole-3-thione [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% Stage #1: 3-isothiocyanatodihydrofuran-2(3H)-one; phenoxyacetyl hydrazine In isopropyl alcohol for 1 - 21h; Heating / reflux; Stage #2: With sodium hydroxide In water for 2 - 12h; Heating / reflux; Stage #3: With acetic acid In water at 100℃; for 72h; 1 Example 15 -Phenoxymethyl-4-(dihvdrofuran-2-one-3 -ylV2,4-dihydro-r 1 ,2,4"]triazole-3 -thione The title compound was obtained as a white foam in 22% yield starting from s phenoxyacetic acid hydrazide (200 mg, 1.2 mmol) and 3-isothiocyanatodihydrofuran- 2(3H)-one (258 mg, 1.8 mmol) using general procedure A with the following modifications. After treatment with 2% NaOH the mixture was acidified with HO Ac, heated at 100 °C for three days, and then concentrated. The residue was dissolved in CH2Cl2 (10 mL) and DMF (2 mL), and EDC (230 mg, 1.2 mmol) was added. After 40 o minutes, water was added and the mixture was extracted with CHCl3. The organic phase was dried (Na2SO4), filtered, concentrated and purified by flash column chromatography (CHCl3MeOH, 50:1).1H NMR (DMSO-d6, 340K) δ 13.88 (IH, s), 7.33 (2H, t, J=7.6 Hz), 7.03 (3H, m), 5.68 (IH, t, J=8.2 Hz), 5.20 (2H5 m), 4.53 (IH, m), 4.42 (IH, m), 2.99 (IH, br s), 2.63 (IH, m). 5 13C NMR (DMSO-de, 340K) δ 170.6, 161.90, 156.7, 147.8, 129.2, 121.6, 114.8, 65.6, 60.0, 52.7, 24.9. MS (ESI) m/z 292 (M+l).
  • 19
  • [ 4619-20-9 ]
  • [ 4664-55-5 ]
  • [ 1160652-13-0 ]
  • 20
  • [(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]acetic acid [ No CAS ]
  • [ 4664-55-5 ]
  • [ 1350743-90-6 ]
YieldReaction ConditionsOperation in experiment
84% With trichlorophosphate Reflux; General method for the synthesis of 1,5-dimethyl-2-phenyl-4-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one analogues (4a-n) General procedure: [(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]acetic acid (1.01 g, 0.005 mol) (3) was refluxed with hydrazide (0.005 mol) in 5 ml phosphorus oxychloride for 18-20 h. After completion of reaction the mixture was poured into crushed ice followed by neutralization with aqueous sodium hydroxide solution furnished the 1,5-dimethyl-2-phenyl-4-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]amino}-1,2-dihydro-3H-pyrazol-3-one analogue, and recrystallized with which was filtered washed ethanol. The purity of the compounds was checked by TLC using chloroform-methanol (9:1) and toluene-ethyl acetate-formic acid (5:4:1) as mobile phase.
  • 21
  • [ 86-81-7 ]
  • [ 151096-09-2 ]
  • [ 4664-55-5 ]
  • 1-cyclopropyl-5-fluoro-7-methoxy-4-oxo-6-(1-((2-(2-phenoxyacetyl)hydrazinyl)(3,4,5-trimethoxyphenyl)methyl)tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol;Reflux; Synthesis of Mannich base derivatives AS1 , AS2. AS3. AS4, AS5, AS6 and AS70.1 mol of trimethoxy benzaldehyde was added to the solution of 0.1 mol of acid appropriate acid hydrazide in 20 ml of methanol. The mixture was stirred for 1 to 2 hours in an ice bath. The cold solution of 1.0 mol of 1 -cyclopropyl-7-[(1 S,6S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6- fluoro-8-methoxy-4-oxo-quinoline-3-carboxylic acid or <strong>[151096-09-2]moxifloxacin</strong> was added drop wise to the mixture while stirring. The resulting mixture was refluxed for 5 to 8 hours on a steam bath. The refluxed mixture was then subjected to evaporation using a solvent and the residue obtained was recrystallized from ethanol.
  • 22
  • [ 59938-06-6 ]
  • [ 4664-55-5 ]
  • [ 1398075-93-8 ]
  • 23
  • [ 31162-25-1 ]
  • [ 4664-55-5 ]
  • 1-(phenoxyacetyl)-4-(4-phenylbenzyl)-thiosemicarbazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide at 55℃; for 1.5h; 4.3.21. General procedure for acylthiosemicarbazide 1, 10-48, 53 synthesis (procedure D) General procedure: To a solution of 0.25 M di-pyridyl-thiocarbonate in DMF (stored on molecular sieves 3A) (1.05 eq) was added 0.1 M amine (free base) 0.1 M in DMF (1 eq). The reaction mixture was heated at 55 °C for 1.5 h. Then a solution of hydrazide (free base) 0.1 M in DMF (1eq) was added. The reaction mixture was heated at 55 °C for another 1.5 h. Solvent was removed under reduced pressure. The residue was dissolved in EtOAc and the organic layer washed with water (3×20 mL) to remove pyridone, dried over MgSO4 and concentrated under reduced pressure to give the desired compound. When needed, the compound was purified by preparative HPLC.
  • 24
  • C11H19NS [ No CAS ]
  • [ 4664-55-5 ]
  • [ 1489288-39-2 ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide at 55℃; for 1.5h; 4.3.21. General procedure for acylthiosemicarbazide 1, 10-48, 53 synthesis (procedure D) General procedure: To a solution of 0.25 M di-pyridyl-thiocarbonate in DMF (stored on molecular sieves 3A) (1.05 eq) was added 0.1 M amine (free base) 0.1 M in DMF (1 eq). The reaction mixture was heated at 55 °C for 1.5 h. Then a solution of hydrazide (free base) 0.1 M in DMF (1eq) was added. The reaction mixture was heated at 55 °C for another 1.5 h. Solvent was removed under reduced pressure. The residue was dissolved in EtOAc and the organic layer washed with water (3×20 mL) to remove pyridone, dried over MgSO4 and concentrated under reduced pressure to give the desired compound. When needed, the compound was purified by preparative HPLC.
  • 25
  • [ 22106-37-2 ]
  • [ 4664-55-5 ]
  • N'-(1-(4-(1H-pyrrol-1-yl)phenyl)ethylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With acetic acid In ethanol Reflux; 4.7. General procedure for the synthesis of pyrrole hydrazones (4a-z and 5a-z) General procedure: An ethanolic solution of 4-(1H-pyrrol-1-yl)-acetophenone (2) (0.93 g, 0.005 mol) or 4-(2,5-dimethyl-1H-pyrrol-1-yl)-acetophenone (3) (1.07 g, 0.005 mol) was added to a hot ethanolic solution of hydrazides (0.005 mol) in the presence of catalytic amount of acetic acid and the mixture was heated under reflux for 2-4 h and then cooled in an ice bath. The yellow or brown flakes separated were filtered, washed repeatedly with ethanol, dried in vacuum and purified using column chromatography (ethyl acetate:petroleum ether; 6:4) to afford the final compound.
  • 26
  • [ 83935-45-9 ]
  • [ 4664-55-5 ]
  • N'-(1-(4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)ethylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With acetic acid In ethanol Reflux; 4.7. General procedure for the synthesis of pyrrole hydrazones (4a-z and 5a-z) General procedure: An ethanolic solution of 4-(1H-pyrrol-1-yl)-acetophenone (2) (0.93 g, 0.005 mol) or 4-(2,5-dimethyl-1H-pyrrol-1-yl)-acetophenone (3) (1.07 g, 0.005 mol) was added to a hot ethanolic solution of hydrazides (0.005 mol) in the presence of catalytic amount of acetic acid and the mixture was heated under reflux for 2-4 h and then cooled in an ice bath. The yellow or brown flakes separated were filtered, washed repeatedly with ethanol, dried in vacuum and purified using column chromatography (ethyl acetate:petroleum ether; 6:4) to afford the final compound.
  • 27
  • [ 38501-87-0 ]
  • [ 4664-55-5 ]
  • C21H17N5O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With acetic acid In ethanol for 8h; Synthesis and characterize: Compound L was prepared by mixing azosalicylic aldehyde (270 mg, 0.1 mol) and 2-phenoxyacetohydrazide (166 mg, 0.1 mol) in absolute alcohol (40 mL) under stir in room temperature for 8 h with 0.2 mL HAc as catalyst, then the crude product was purified by recrystallisation from ethanol to give compound L. Compound L was obtained as a yellowish solid. Sensor L: (Yield: 78 %), m.p.: 203-205 °C. 1H NMR (DMSO-d6, 400 MHz ppm) δ: 11.94 (s, 1H, OH), 11.68 (s, 1H, NH), 8.71 (s,1H, N=CH), 8.39-8.08 (m, 4H, Ar-CH), 7.89-7.67 (m, 3H,Ar-CH), 7.35-7 (m, 5H, Ar-CH), 5.15 (s, 1H, CH), 4.7 (s, 1H,CH); IR (KBr, nmax, cm-1): 3428 (-OH), 3162 (N-H), 1672(C=N-H); MS/(EI): m/z 420.2 (M + H)+. Anal. Calc. for C21H17N5O5: C, 59.97; H, 4.05; N, 16.66. Found: C, 59.88; H,4.12; N, 16.45.
  • 28
  • [ 933-88-0 ]
  • [ 4664-55-5 ]
  • 2-(o-tolyl)-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With indium(III) chloride In 1,2-dimethoxyethane at 100℃; for 16h; General procedure for 2,5-substituted-1,3,4-Oxadiazoles (3a-l) General procedure: To the solution of carboxylic acid hydrazide (1a-l)(1.1 mmol) in (DME, 4 mL) was added InCl3 (20 mol %)followed by o-toloyl chloride (2) (1.1 mmol), the obtained mixture was heated to 100 °C for 16 h. Progress of reactionwas monitored by TLC and after completion of the reaction,mixture was evaporated under vacuum. Resulting residuewas quenched with saturated Na2CO3 (10 mL), and extractedwith ether. Then the obtained organic layer was dried overNa2SO4 and then distilled in vacuum, the residue was purifiedby silica gel column chromatography using in 10-25%EtOAc in hexane to obtain 1,3,4-oxadiazole (3a-l) with75-88% yields. All the compounds were further confirmedwith literature data.[32,35]
77% With camphor-10-sulfonic acid In 1,4-dioxane at 100℃; for 16h;
  • 29
  • [ 3949-36-8 ]
  • [ 4664-55-5 ]
  • (E)-N’-(1-(2-oxo-2H-chromen-3-yl)ethylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% In ethanol for 6h; Reflux; Synthesis of Coumarin Derivatives (L1-7) General procedure: Compounds L1-7 were prepared by similar procedures. In atypical synthesis of L1, 3-acetyl coumarin (4 mmol, 0.75 g)was dissolved in 30 mL absolute ethanol in a 150 mL threeneckflask, then phenoxyacetohydrazide (4 mmol, 0.66 g) in20 mL absolute ethanol was added dropwise with constant stirringand finally heated under reflux for 6 h. A light yellow solidwas precipitated, filtered and dried in vacuum. The light yellowcrystal was purified by recrystallization from ethyl acetate
  • 30
  • 6-chloro-8-methoxy-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester [ No CAS ]
  • [ 4664-55-5 ]
  • C23H21N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
8.6 mg With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 2h; 33 To lactam 64 (51.8 mg, 0.172 mmol) and N,N-dimethyl-/?-toluidine (93.0 mg, 0.688 mmol) stirring in chlorobenzene (1 ml) under nitrogen was added POCl3 (52.7 mg, 0.344 mmol). The reaction was then heated at 135°C for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (228.4 mg, 1.36 mmol) was added in situ to the imino-chloride 65, followed by DIPEA (90 ul). The reaction was stirred at room temperature for 30 min, then heated at 100°C for 90 min. The reaction mixture was cooled, saturated NaHC03 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgS04. After filtration and concentration, the product as Compound 55 was isolated by ISCO flash column chromatography (RediSep 4 g column, 1 to 10 % MeOH in DCM as eluting gradient) as a white solid, Wt: 8.6 mg. MS: [M+l] = 432. 1H-NMR (500 MHz, CDC13) δ: 7.81 (s, 1H), 7.71 (d, 1H, J=3.5 Hz), 7.52 (d, 1H, J=9.0 Hz), 7.32 (m, 2H), 7.21 (dd, 1H, J=2.5, 8.5 Hz), 7.11 (d, 2H, J=8.5 Hz), 7.02 (m, 1H), 5.44 (s, 2H), 4.38 (q, 2H, J=7.5 Hz), 3.94 (s, 3H), 1.39 (t, 3H, J=7.0 Hz).
8.6 mg With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 2h; 33 To lactam 64 (51.8 mg, 0.172 mmol) and N,Ndimethyl-v-toluidine (93.0 mg, 0.688 mmol) stirring in chiorobenzene (1 ml) under nitrogen was added POC13 (52.7 mg, 0.344 mmol). The reaction was then heated at 135° C. for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (228.4 mg, 1.36 mmol) was added in situ to the imino-chloride 65, followed by DIPEA (90 ul). The reaction was stirred at room temperature for 30 mm, then heated at 100° C. for 90 mm. The reaction mixture was cooled, saturated NaHCO3 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over Mg504. Afier filtration and concentration, the product as Compound 55 was isolated by ISCO flash column chromatography (RediSep 4 g column, 1 to 10% MeOH in DCM as eluting gradient) as a white solid, Wt: 8.6 mg. MS: [M+1]=432. ‘H-NMR (500 MHz, CDC13) ö: 7.81 (s, 1H), 7.71 (d, 1H, J=3.5 Hz), 7.52 (d, 1H, J=9.0 Hz), 7.32 (m, 2H), 7.21 (dd, 1H, J=2.5, 8.5 Hz), 7.11 (d, 2H, J=8.5 Hz), 7.02 (m, 1H), 5.44 (s, 2H), 4.38 (q, 2H, J=7.5 Hz), 3.94 (s, 3H), 1.39 (t, 3H, J=7.0 Hz).
8.6 mg With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 2h; Inert atmosphere; 33 To lactam 64 (51.8 mg, 0.172 mmol) and N,N-dimethyl-p-toluidine (93.0 mg, 0.688 mmol) stirring in chlorobenzene (1 ml) under nitrogen was added POCb (52.7 mg, 0.344 mmol). The reaction was then heated at l35°C for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (228.4 mg, 1.36 mmol) was added in situ to the imino-chloride 65, followed by DIPEA (90 ul). The reaction was stirred at room temperature for 30 min, then heated at l00°C for 90 min. The reaction mixture was cooled, saturated NaHCCh (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgSCL. After filtration and concentration, the product as Compound 55 was isolated by ISCO flash column chromatography ( RediSep 4 g column, 1 to 10 % MeOH in DCM as eluting gradient) as a white solid, Wt: 8.6 mg. MS: [M+l] = 432. 1H-NMR (500 MHz, CDC13) d: 7.81 (s, 1H), 7.71 (d, 1H, J=3.5 Hz), 7.52 (d, 1H, J=9.0 Hz), 7.32 (m, 2H), 7.21 (dd, 1H, J=2.5, 8.5 Hz), 7.11 (d, 2H, J=8.5 Hz), 7.02 (m, 1H), 5.44 (s, 2H), 4.38 (q, 2H, J=7.5 Hz), 3.94 (s, 3H), 1.39 (t, 3H, J=7.0 Hz).
  • 31
  • C14H11ClFN3O2 [ No CAS ]
  • [ 4664-55-5 ]
  • C22H18FN5O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 1.5h; 80 To lactam (209.1 mg, 0.723 mmol) and N,N-dimethyl-/?-toluidine (234.7 mg, 1.74 mmol) stirring in chlorobenzene (2.5 mL) under nitrogen was added POCI3 (133.0 mg, 0.867 mmol). The reaction was then heated at 135°C for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (189.0 mg, 1.08 mmol) was added, followed by DIPEA (0.455 mL). The reaction was stirred at room temperature for 30 min, then heated at 100°C for 60 min. The reaction mixture was cooled, saturated NH4C1 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgS04. After filtration and concentration, the product was isolated by ISCO flash column chromatography using 0 to 10% MeOH in EtOAc, wt: 116.7mg (36%) of Compound 137 as a yellowish filmy solid. MS: [M+l] = 420.
36% With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 1.5h; 80 Example 80: Synthesis of Compound 137: To lactam (209.1 mg, 0.723 mmol) and N,N-dimethyl-p-toluidine (234.7 mg, 1.74 mmol) stirring in chlorobenzene (2.5 mL) under nitrogen was added POC13 (133.0 mg, 0.867 mmol). The reaction was then heated at 13 5°C for 2 h. Upon cooling to roomtemperature, phenoxy acetic acid hydrazide (189.0 mg, 1.08 mmol) was added, followed by DIPEA (0.455 mL). The reaction was stirred at room temperature for 30 mm, then heated at 100°C for 60 mm. The reaction mixture was cooled, saturated NH4C1 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgSO4. After filtration and concentration, the product wasisolated by ISCO flash column chromatography using 0 to 10% MeOH in EtOAc, wt:116.7mg (36%) of Compound 137 as a yellowish filmy solid. MS: [M+1] = 420.
36% In chlorobenzene at 20 - 100℃; for 1.5h; 80 To lactam (209.1 mg, 0.723 mmol) and N,Ndimethyl-p-toluidine (234.7 mg, 1.74 mmol) stirring in chiorobenzene (2.5 mL) under nitrogen was added POC13 (133.0 mg, 0.867 mmol). The reaction was then heated at 135° C. for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (189.0 mg, 1.08 mmol) was added, followed by DIPEA (0.455 mL). The reaction was stirred at room temperature for 30 mm, then heated at 100° C. for 60 mm. The reaction mixture was cooled, saturated NH4C1 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over Mg504. Afier filtration and concentration, the product was isolated by ISCO flash column chromatography using 0 to 10% MeOH in EtOAc, wt: 116.7mg (36%) of Compound 137 as a yellowish filmy solid. MS: [M+1]=420.
116.7 mg In chlorobenzene at 20 - 100℃; for 1.5h; Inert atmosphere; 80 To lactam (209.1 mg, 0.723 mmol) and N,N-dimethyl-p-toluidine (234.7 mg, 1.74 mmol) stirring in chlorobenzene (2.5 mL) under nitrogen was added POCb (133.0 mg, 0.867 mmol). The reaction was then heated at l35°C for 2 h. Upon cooling to room temperature, phenoxy acetic acid hydrazide (189.0 mg, 1.08 mmol) was added, followed by DIPEA (0.455 mL). The reaction was stirred at room temperature for 30 min, then heated at l00°C for 60 min. The reaction mixture was cooled, saturated NH4Cl (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgS04. After filtration and concentration, the product was isolated by ISCO flash column chromatography using 0 to 10% MeOH in EtOAc, wt: 1 l6.7mg (36%) of Compound 137 as a yellowish filmy solid. MS: [M+l] = 420.

  • 32
  • C15H13N5O3 [ No CAS ]
  • [ 4664-55-5 ]
  • C23H19N7O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% Stage #1: C15H13N5O3 With Dimethyl-p-toluidine; trichlorophosphate In chlorobenzene at 135℃; for 3h; Inert atmosphere; Stage #2: phenoxyacetyl hydrazine With N-ethyl-N,N-diisopropylamine In chlorobenzene at 10℃; for 14h; 89 Example 89: Synthesis of Compound 162: Phosphorous oxychloride (29.9 mg, 0.195 mmol) was added to a solution of the above obtained lactam (22.5 mg, 0.0723 mmol) and N,N-dimethyl-p-toluidine (51.8 mg, 0.3 83 mmol) stirring in chlorobenzene (0.45 mL) under nitrogen atmosphere. The reaction mixture was heated at 13 5°C for 3 h, then cooled to RT. Diisopropylethylamine (75.7 mg, 0.586 mmol) and phenoxyacetic hydrazide (50.1 mg, 0.302 mmol) was added,and the reaction mixture was heated at 100°C for 14 h, cooled to RT, and partitioned between sat. NH4C1 and EtOAc. Aq. Layer was separated and extracted with EtOAc; combined EtOAc solution was washed with brine, and dried over Mg504. Upon filtration and concentration, the product Compound 162 was isolated by silica gel column chromatography using a gradient elution of 0 to 10% MeOH in EtOAc as a yellowishsolid. Wt: 11.8mg (37%). MS: [M+1] = 442.
37% Stage #1: C15H13N5O3 With Dimethyl-p-toluidine; trichlorophosphate In chlorobenzene at 135℃; for 3h; Inert atmosphere; Stage #2: phenoxyacetyl hydrazine With N-ethyl-N,N-diisopropylamine In chlorobenzene at 100℃; for 14h; 89 Phosphorous oxychloride (29.9 mg, 0.195 mmol) was added to a solution of the above obtained lactam (22.5 mg, 0.0723 mmol) and N,N-dimethyl-p-toluidine (51.8 mg, 0.383 mmol) stirring in chlorobenzene (0.45 mL) under nitrogen atmosphere. The reaction mixture was heated at 135° C. for 3 h, then cooled to RT. Diisopropylethylamine (75.7 mg, 0.586 mmol) and phenoxyacetic hydrazide (50.1 mg, 0.302 mmol) was added, and the reaction mixture was heated at 100° C. for 14 h, cooled to RT, and partitioned between sat. NH4C1 and EtOAc. Aq. Layer was separated and extracted with EtOAc; combined EtOAc solution was washed with brine, and dried over Mg504. Upon filtration and concentration, the product Compound 162 was isolated by silica gel column chromatography using a gradient elution of 0 to 10% MeOH in EtOAc as a yellowish solid. Wt:11.8 mg (37%). MS: [M+1]442.
11.8 mg Stage #1: C15H13N5O3 With Dimethyl-p-toluidine; trichlorophosphate In chlorobenzene at 135℃; for 3h; Inert atmosphere; Stage #2: phenoxyacetyl hydrazine With N-ethyl-N,N-diisopropylamine In chlorobenzene at 100℃; for 14h; 89 Phosphorous oxychloride (29.9 mg, 0.195 mmol) was added to a solution of the above obtained lactam (22.5 mg, 0.0723 mmol) and N,N-dimethyl-/?-toluidine (51.8 mg, 0.383 mmol) stirring in chlorobenzene (0.45 mL) under nitrogen atmosphere. The reaction mixture was heated at 135°C for 3 h, then cooled to RT. Diisopropylethylamine (75.7 mg, 0.586 mmol) and phenoxyacetic hydrazide (50.1 mg, 0.302 mmol) was added, and the reaction mixture was heated at 100°C for 14 h, cooled to RT, and partitioned between sat. NH4C1 and EtOAc. Aq. Layer was separated and extracted with EtOAc; combined EtOAc solution was washed with brine, and dried over MgS04. Upon filtration and concentration, the product Compound 162 was isolated by silica gel column chromatography using a gradient elution of 0 to 10% MeOH in EtOAc as a yellowish solid. Wt: 11.8 mg (37%). MS: [M+l] = 442.
11.8 mg Stage #1: C15H13N5O3 With Dimethyl-p-toluidine; trichlorophosphate In chlorobenzene at 135℃; for 3h; Inert atmosphere; Stage #2: phenoxyacetyl hydrazine With N-ethyl-N,N-diisopropylamine In chlorobenzene at 100℃; for 14h; Inert atmosphere; 89 Phosphorous oxychloride (29.9 mg, 0.195 mmol) was added to a solution of the above obtained lactam (22.5 mg, 0.0723 mmol) and N,N-dimethyl-p-toluidine (51.8 mg, 0.383 mmol) stirring in chlorobenzene (0.45 mL) under nitrogen atmosphere. The reaction mixture was heated at l35°C for 3 h, then cooled to RT. Diisopropyl ethylamine (75.7 mg, 0.586 mmol) and phenoxyacetic hydrazide (50.1 mg, 0.302 mmol) was added, and the reaction mixture was heated at l00°C for 14 h, cooled to RT, and partitioned between sat. NH4Cl and EtOAc. Aq. Layer was separated and extracted with EtOAc; combined EtOAc solution was washed with brine, and dried over MgS04. Upon filtration and concentration, the product Compound 162 was isolated by silica gel column chromatography using a gradient elution of 0 to 10% MeOH in EtOAc as a yellowish solid. Wt: 11.8 mg (37%). MS: [M+l] = 442.

  • 33
  • [ 458-37-7 ]
  • [ 4664-55-5 ]
  • 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With acetic acid for 12h; Reflux; General method for the synthesis of 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl-(aryl)methanone analogues (3a-j) General procedure: 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione (curcumin) (0.005 mol) and aryl hydrazides(0.005 mol) were refluxed in glacial acetic acid (AcOH)for 12 h. The progress of reaction was monitored throughout by TLC plates (silica gel G) using mobilephase, hexane/ethylacetate (6:4), and the spots wereidentified by iodine vapours or UV light. The excess ofsolvent was removed under reduced pressure, and then thereaction mixture was then poured into the crushed ice. Thesolid mass was filtered, washed, dried, and recrystallizedwith ethanol furnished the title of 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl-(aryl)methanone analogues(3a-j).
  • 34
  • [ 91-56-5 ]
  • [ 4664-55-5 ]
  • N'-(2-oxoindolin-3-ylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid In ethanol at 90℃; General Procedure for the Synthesis of schiff bases 3a-3g and 6a-6g.1-6 General procedure: A mixture of isatin 1 (1.47 g, 10.0 mmol, 1.0 equiv) and benzohydrazides 2a (2.0 g, 15.0 mmol,1.5 equiv) dissolved in ethanol (50 mL) was refluxed in presence of few drops of acetic acid for3 h. Progress of reaction was monitored by TLC and refluxing continued till disappearance ofstarting material (3h). Resulting product mixture was cooled to room temperature then suspendedin ice cold water. The resulting suspension mixture was filtered and washed with water and driedin vaccuo to get almost pure product 3a (2.15 g) in 81% yield. The product 3a recrystallizedusing absolute ethanol to get pure product which was used for condensing with benzoin in nextstep. All other schiff base compounds 3b-3g and 6a-6g were synthesized by adopting samereation protocol using corresponding benzohydrazides 2b-2g and phenoxyacetohydrazides 5a-5g respectively in good yield. All the prepared schiff base compounds were characterized byNMR, IR spectroscopy and mass spectrometry data which were consistence with the datareported in literature.
  • 35
  • [ 50-00-0 ]
  • [ 42407-86-3 ]
  • [ 4664-55-5 ]
  • N′,N′-bis((2-oxo-3-(p-tolylimino)indolin-1-yl)methyl)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% In ethanol for 1h; Heating; 3.13 Synthesis of the bis(Mannich bases) 21a, b General procedure: A solution of 20 (0.94 g, 4 mmol), isonicotinic hydrazide(0.27 g, 2 mmol) or phenoxyacetohydrazide (0.33 g,2 mmol), and formalin (36%, 0.40 mL, 5 mmol) in ethanol(50 mL) was heated over a steam bath for 1 h. The product obtained on cooling was filtered and washed with boiling ethyl acetate (3 × 10 mL) to give 21a, b.
  • 36
  • 8-Methoxy-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester [ No CAS ]
  • [ 4664-55-5 ]
  • C23H21N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
8.6mg Stage #1: 8-Methoxy-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester With Dimethyl-p-toluidine; trichlorophosphate In chlorobenzene at 135℃; for 2h; Inert atmosphere; Stage #2: phenoxyacetyl hydrazine With N-ethyl-N,N-diisopropylamine In chlorobenzene at 20 - 100℃; for 2h; 33 Example 33: Synthesis of Compound 55: To lactam 64(51.8mg, 0.172 mmol) and N,N-dimethyl-p-toluidine (93.0 mg,0.688 mmol) stirring in chlorobenzene (1 ml) under nitrogen was added POC13 (52.7 mg,0.344 mmol). The reaction was then heated at 13 5°C for 2 h. Upon cooling to roomtemperature, phenoxy acetic acid hydrazide (228.4 mg, 1.36 mmol) was added in situ tothe imino-chloride 65, followed by DIPEA (90 ul). The reaction was stirred at roomtemperature for 30 mm, then heated at 100°C for 90 mm. The reaction mixture was cooled, saturated NaHCO3 (aq.) was added, and extracted with ethyl acetate three times; combined organic layer was washed with brine, and dried over MgSO4. After filtration and concentration, the product as Compound 55 was isolated by ISCO flash columnchromatography (Red/Sep 4 g column, 1 to 10 % MeOH in DCM as eluting gradient) as a white solid, Wt: 8.6 mg. MS: [M+1] = 432. ‘H-NIVIR (500 MHz, CDC13) ö: 7.81 (s, 1H), 7.71 (d, 1H, J=3.5 Hz), 7.52 (d, 1H, J=9.0 Hz), 7.32 (m, 2H), 7.21 (dd, 1H, J=2.5,8.5 Hz), 7.11 (d, 2H, J=8.5 Hz), 7.02 (m, 1H), 5.44 (s, 2H), 4.38 (q, 2H, J7.5 Hz), 3.94 (s, 3H), 1.39 (t, 3H, J7.0 Hz).
  • 37
  • [ 75-15-0 ]
  • [ 4664-55-5 ]
  • 2-mercapto-5-((phenoxy)methyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide In ethanol at 80℃; 3.2.2. Synthesis of the Key Intermediate 2-Thiol-5-Substituted-1,3,4-Oxadiazole/Thiadiazole (3) General procedure: For X=O (3I), to a 100 mL three necked rounded-bottomed flask was added a solution ofintermediate 2 (0.009 mol, 1 eq.) and KOH (0.0108 mol, 1.2 eq.) in 50 mL absolute ethanol.This mixture was first digested and then a diluted solution carbon disulfide (0.0108 mol, 1.2 eq) in 10 mLof absolute ethanol was slowly added. The resulting mixture was stirred for 1-2 h and then refluxedat 80 °C till a homogeneous solution was obtained [19]. The alcohol was removed under reducedpressure on a rotary evaporator. The solution was washed with added brine followed by treatmentwith dilute hydrochloric acid solution. The pH was adjusted to 5-6 when a precipitate appearedwhich was subsequently filtered to afford a white solid 5-(phenoxymethyl)-1,3,4-oxadiazole-2-thiol (3I) ( yield 60%-75%). For X=S (3II), to a 100 mL three necked rounded-bottomed flask was added a solution ofintermediate 2 (0.009 mol, 1 eq.), and KOH (0.0108 mol, 1.2 eq.) in 50 mL of absolute ethanol.This mixture was first digested and then a diluted solution carbon disulfide (0.0108 mol, 1.2 eq)in 10 mL of absolute ethanol was slowly added. The resulting mixture was stirred for 5-6 h and thenfiltered through celite. The filtrate was concentrated in vacuo. The crude potassium 2-(2-phenoxyacetyl)hydrazinecarbodithioate (2-3) was washed with absolute ethanol alcohol and used directly in the nextstep for the preparation of 3II. 2-3(0.01 mol) was crushed into small powder and then slowly addedto 50 mL H2SO4 (98%). An exothermic reaction ensued, the solution was stirred on an ice salt bathfor 2 h, and the temperature was kept temperature below 5 °C in order to control the violence of thereaction. The progress of the reaction was monitored by TLC; the reaction was quenched by addingcrushed ice equivalent to 200 mL of water. A white precipitate appeared which was filtered and thenwashed with water. The solid was subsequently dissolved in 10% NaOH solution and filtered again.The filtrate was then acidified with hydrochloric acid (HCl) to afford a white solid which was filteredto obtain the desired 5-(phenoxymethyl)-1,3,4-thiadiazole-2-thiol 3II.
With potassium hydroxide In ethanol at 70 - 80℃; 11.2 Step 2:Phenoxyacetylhydrazine,Potassium hydroxide was cast in a 100 mL three-necked round bottom flask,And anhydrous ethanol as solvent,After the solid is completely dissolved,Dropping carbon disulfide(Molar ratio: phenoxyacetylhydrazide: potassium hydroxide: carbon disulfide = 1: 1.3: 1.3),And then heated to reflux(70 to 80 ° C)TLC tracks the progress of the reaction(Reaction time: 6-8 h)After the raw material point disappears,Stop the reaction,The ethanol was distilled off under reduced pressure,Then add 80 mL of water,Filter to remove impurities,The filtrate was adjusted to pH 4 with 5% dilute hydrochloric acid to give 2-mercapto-5 - ((phenoxy) methyl) -1,3,4-oxadiazole;
Stage #1: carbon disulfide; phenoxyacetyl hydrazine With potassium hydroxide In ethanol Stage #2: With hydrogenchloride In water
Stage #1: carbon disulfide; phenoxyacetyl hydrazine With potassium hydroxide In ethanol Reflux; Stage #2: With hydrogenchloride In water

  • 38
  • [ 122-88-3 ]
  • [ 4664-55-5 ]
  • 2-(4-chlorophenoxy)-N'-(2-phenoxyacetyl)acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With Vilsmeier reagent; triethylamine; In acetonitrile; at 20℃; for 6h; Acylhydrazines 2-5 (1.0 mmol) was added to a solution of carboxylic acid (1.5 mmol), Vilsmeier reagent (1.5 mmol) and Et3N (5.0 mmol) in dry CH3CN(15 mL) at room temperature and the mixture was stirred 6 h. Saturated NaHCO3 (20 mL) was added and the mixture was extracted with EtOAc (3 9 15 mL). The organic layer was washed with brine (20 mL), dried (Na2SO4), filtered and the solvent was removed under reduced pressure to give the crude products. The crude residues were purified by crystallization from ethanol 95 %. The data for 19 hasbeen previously reported [35]. 2-(4-Chlorophenoxy)-N0-(2-phenoxyacetyl)acetohydrazide (17) White solid. mp:130-132 C. IR (KBr) cm-1: 1635 (CO), 3199 (NH); 1H NMR d 4.61, 4.64 (2 CH2,2 s, 4H), 6.84-7.32 (ArH, m, 9H), 9.72, 9.87 (2 NH, 2 s, 2H); 13C NMR d 60.3,65.9 (CH2) 115.9, 116.0, 122.3, 126.9, 129.0, 129.5, 157.1, 159.4 (aromatic carbons)168.9, 176.4 (CO). Anal. Calcd for C16H15ClN2O4: C, 57.41; H, 4.52; N, 8.37.Found: C, 57.55; H, 4.69; N, 8.44.
  • 39
  • [ 625-45-6 ]
  • [ 4664-55-5 ]
  • 2-methoxy-N'-(2-phenoxyacetyl)acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With Vilsmeier reagent; triethylamine; In acetonitrile; at 20℃; for 6h; General procedure: Acylhydrazines 2-5 (1.0 mmol) was added to a solution of carboxylic acid (1.5 mmol), Vilsmeier reagent (1.5 mmol) and Et3N (5.0 mmol) in dry CH3CN(15 mL) at room temperature and the mixture was stirred 6 h. Saturated NaHCO3 (20 mL) was added and the mixture was extracted with EtOAc (3 9 15 mL). The organic layer was washed with brine (20 mL), dried (Na2SO4), filtered and the solvent was removed under reduced pressure to give the crude products. The crude residues were purified by crystallization from ethanol 95 %. The data for 19 hasbeen previously reported [35].
  • 40
  • [ 105-39-5 ]
  • [ 108-95-2 ]
  • [ 4664-55-5 ]
YieldReaction ConditionsOperation in experiment
Stage #1: phenol With potassium carbonate In ethanol for 0.0833333h; Stage #2: chloroacetic acid ethyl ester In ethanol Reflux; Stage #3: With hydrazine hydrate In ethanol at 20℃; for 1h; 11.1 first step:The phenol,Potassium carbonate was cast in a 100 mL three-necked round bottom flask,And anhydrous ethanol as solvent,After stirring for 5 min, ethyl chloroacetate was added dropwise,Heating reflux,TLC followed the reaction process (1 ~ 2 h)After the raw material point disappears,Add 80% hydrazine hydrate(Molar ratio: phenol: potassium carbonate: ethyl chloroacetate: hydrazine hydrate = 1: 1.4: 1: 2)Room temperature reaction,TLC followed the reaction process (reaction time: 1 h),After the raw material point disappears,Stop the reaction,The ethanol was distilled off under reduced pressure,After cooling,Water washing filter,To obtain the intermediate phenoxyacetylhydrazide;
  • 41
  • [ 122-88-3 ]
  • [ 4664-55-5 ]
  • 2-({4-chlorophenoxy}methyl)-5-(phenoxymethyl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% General procedure: Acylhydrazines 2a-f (1.0 mmol) was added to a solution of corresponding carboxylic acid (1.2 mmol), Vilsmeier reagent (1.2 mmol) and Et3N (2.5 mmol) in dry THF (20 mL) at room temperature. After 2 h Vilsmeier reagent (1.0 mmol) Et3N (2.0 mmol )and Lawesson's reagent (2.0 mmol) was added and the mixture was stirred at room temperature 13 h. Saturated NaHCO3 (20 mL) was added and the mixture was extracted with EtOAc (3 20 mL). The organic layer was washed with brine (20 mL), dried (Na2SO4),filtered and the solvent was removed under reduced pressure togive the crude products. The crude residues were purified by crystallization from 95% ethanol.
  • 42
  • [ 625-45-6 ]
  • [ 4664-55-5 ]
  • 2-(methoxymethyl)-5-(phenoxymethyl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: 2-methoxyacetic acid; phenoxyacetyl hydrazine With N-(1-chloroethylidene)-N-methylmethanaminium chloride; triethylamine In tetrahydrofuran at 20℃; for 2h; Stage #2: With Lawessons reagent; N-(1-chloroethylidene)-N-methylmethanaminium chloride; triethylamine In tetrahydrofuran at 20℃; for 13h; 4.4. General procedure for one-pot synthesis of asymmetrical 1,3,4-thiadiazoles 5k-v General procedure: Acylhydrazines 2a-f (1.0 mmol) was added to a solution of corresponding carboxylic acid (1.2 mmol), Vilsmeier reagent (1.2 mmol) and Et3N (2.5 mmol) in dry THF (20 mL) at room temperature. After 2 h Vilsmeier reagent (1.0 mmol) Et3N (2.0 mmol )and Lawesson's reagent (2.0 mmol) was added and the mixture was stirred at room temperature 13 h. Saturated NaHCO3 (20 mL) was added and the mixture was extracted with EtOAc (3 20 mL). The organic layer was washed with brine (20 mL), dried (Na2SO4),filtered and the solvent was removed under reduced pressure togive the crude products. The crude residues were purified by crystallization from 95% ethanol.
  • 43
  • [ 122-88-3 ]
  • [ 4664-55-5 ]
  • 2-((4-chlorophenoxy)methyl)-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
  • 44
  • C13H13ClN2O [ No CAS ]
  • [ 4664-55-5 ]
  • C21H22N4O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With triethylamine In ethyl acetate at 20℃; 6 Example 6 Preparation of the target product Phenoxyacetohydrazide (0.0018 mol), (Et) 3N, and ethyl acetate (10 mL) were sequentially added to a 50 mL reaction flask,Then a mixed solution of the acid chloride and ethyl acetate obtained in Example 1 was added dropwise to the reaction flask,After stirring at room temperature overnight, a solid precipitated point plate monitoring, raw material reaction is complete, suction filtration, washing, a light solid powder, the product was obtained in 79% yield.
  • 45
  • C16H10ClNO3 [ No CAS ]
  • [ 4664-55-5 ]
  • C24H19N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 35℃; 1.1 General procedure for the preparation of target compounds (d1-d22) General procedure: A mixture of anthranilic acid derivatives (13.23 mmol), phthalic anhydride (2.06g, 13.89 mmol), DMAP (20 mg, 0.13 mmol) and THF (20 mL) was heated under reflux in an oil bath at 70 for 4 h. After completion of the reaction, THF was removed under vacuum to obtain brown liquids. Then ice-cold water (50 mL) was poured into the brown liquids. The precipitate was filtered off and dried to get the crude product a. The crude product a was dissolved in chloroform (50 mL), then thionyl chloride (3.88 g, 29.11 mmol) and catalyst DMF (10 mg, 0.13 mmol) were added. The reaction mixture was heated at 50 for 2 h. AlCl3 (3.46 g, 29.11 mmol) was added to this mixture for 3 additional hours at this temperature. The reaction fixture was poured into ice-cold aqueous acid (100 mL) under stirring. After keeping stirring for 0.5 h, the aqueous phase of the mixture was separated and extracted with chloroform (20 mL×3). Then the organic phase was dried over Na2SO4 and evaporated under vacuum. The residue was purified by crystallization in dichloromethane to afford the pure product b as off-white solids (yield 59 %). Finally, in a dry flask, thionyl chloride (0.51 g, 4.27 mmol) was added to the mixture of the product b (3.56 mmol) and dichloromethane (30 mL). After catalyst DMF (10 mg, 0.13 mmol) was added, the reaction mixture was heated at 35 for about 5 h and then cooled to 0 . Acylhydrazine derivatives (3.48 mmol) were added, and then the solution of triethylamine (1.62 g, 16 mmol) in dichloromethane (5 mL) was added dropwise to this reaction mixture at this temperature, followed by stirring at 35 for a further 10h. After addition of p-toluenesulfonyl chloride (0.75 g, 3.91 mmol), mixture was kept stirring overnight at 35 . After the solvent was evaporated under reduce pressure, ice-cold water (50 mL) was added and filtered off. The filter cake was dried and purified by crystallization to give the pure product d.
  • 46
  • C15H8ClNO3 [ No CAS ]
  • [ 4664-55-5 ]
  • C23H17N3O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane at 35℃; 1.1 General procedure for the preparation of target compounds (d1-d22) General procedure: A mixture of anthranilic acid derivatives (13.23 mmol), phthalic anhydride (2.06g, 13.89 mmol), DMAP (20 mg, 0.13 mmol) and THF (20 mL) was heated under reflux in an oil bath at 70 for 4 h. After completion of the reaction, THF was removed under vacuum to obtain brown liquids. Then ice-cold water (50 mL) was poured into the brown liquids. The precipitate was filtered off and dried to get the crude product a. The crude product a was dissolved in chloroform (50 mL), then thionyl chloride (3.88 g, 29.11 mmol) and catalyst DMF (10 mg, 0.13 mmol) were added. The reaction mixture was heated at 50 for 2 h. AlCl3 (3.46 g, 29.11 mmol) was added to this mixture for 3 additional hours at this temperature. The reaction fixture was poured into ice-cold aqueous acid (100 mL) under stirring. After keeping stirring for 0.5 h, the aqueous phase of the mixture was separated and extracted with chloroform (20 mL×3). Then the organic phase was dried over Na2SO4 and evaporated under vacuum. The residue was purified by crystallization in dichloromethane to afford the pure product b as off-white solids (yield 59 %). Finally, in a dry flask, thionyl chloride (0.51 g, 4.27 mmol) was added to the mixture of the product b (3.56 mmol) and dichloromethane (30 mL). After catalyst DMF (10 mg, 0.13 mmol) was added, the reaction mixture was heated at 35 for about 5 h and then cooled to 0 . Acylhydrazine derivatives (3.48 mmol) were added, and then the solution of triethylamine (1.62 g, 16 mmol) in dichloromethane (5 mL) was added dropwise to this reaction mixture at this temperature, followed by stirring at 35 for a further 10h. After addition of p-toluenesulfonyl chloride (0.75 g, 3.91 mmol), mixture was kept stirring overnight at 35 . After the solvent was evaporated under reduce pressure, ice-cold water (50 mL) was added and filtered off. The filter cake was dried and purified by crystallization to give the pure product d.
  • 47
  • [ 500011-86-9 ]
  • [ 4664-55-5 ]
  • 2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
78.2% With trichlorophosphate for 2h; Reflux; General procedure for the synthesis of title compounds16a-16ad General procedure: Different fresh substituted 2-phenoxyacetohydrazides 14(0.5 mmol), 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (0.5 mmol), and phosphorus oxychloride (3 cm3) were added to a flask. The resultingmixture was stirred for 120 min at refluxing temperature;the resulting mixture was poured into crushed ice, neutralizedwith 10% NaOH, and then filtered and recrystallizedfrom ethanol in good yield.
  • 48
  • [ 163266-02-2 ]
  • [ 4664-55-5 ]
  • 1-(5-hydroxy-3-(o-tolyl)-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% In isopropyl alcohol; at 90℃; General procedure: A mixture of 2-phenylacetohydrazide (1) (0.10?g, 0.67?mmol) and 1,1,1-trifluoro-5-phenylpentane-2,4-dione (3a) (0.14?g, 0.67?mmol) in a solution of i-PrOH (5?mL) was heated at 90?C for 48?h. After cooling to room temperature, EtOAc and water were added. The EtOAc extract was washed with water, brine and dried (Na2SO4). Flash chromatography (petroleum ether/EtOAc; 100:0 to 93:7) followed by recrystallization from Et2O/petroleum ether gave 4 (0.17?g, 71%), mp 122-123?C (Et2O/petroleum ether).
  • 49
  • [ 53764-99-1 ]
  • [ 4664-55-5 ]
  • 1-(5-hydroxy-3-(m-tolyl)-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-phenoxyethan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% In isopropyl alcohol; at 90℃; General procedure: A mixture of 2-phenylacetohydrazide (1) (0.10?g, 0.67?mmol) and 1,1,1-trifluoro-5-phenylpentane-2,4-dione (3a) (0.14?g, 0.67?mmol) in a solution of i-PrOH (5?mL) was heated at 90?C for 48?h. After cooling to room temperature, EtOAc and water were added. The EtOAc extract was washed with water, brine and dried (Na2SO4). Flash chromatography (petroleum ether/EtOAc; 100:0 to 93:7) followed by recrystallization from Et2O/petroleum ether gave 4 (0.17?g, 71%), mp 122-123?C (Et2O/petroleum ether).
  • 50
  • [ 80194-68-9 ]
  • [ 4664-55-5 ]
  • 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate; at 100℃; third step:Will be 0.20gPhenoxyAcetyl hydrazine and 0.25g3-Chloro-5-trifluoromethylpicolinic acid was added to a 50 mL three-necked flask with a thermowell, 4 mL of POCl3 was added, the stirrer was turned on, and the mixture was heated and stirred, followed by heating to 100 C. The progress of the reaction was followed by TCL, and when it was detected that the starting point of the reaction system disappeared, the reaction was stopped.Post-treatment: The reaction solution was slowly introduced into a 250 mL beaker containing ice cubes, and the pH was adjusted to 9-10 with Na2CO3. A large amount of yellow solid was produced at the bottom of the beaker, suction filtered, washed with water several times to neutral, and dried. After separation and purification by column chromatography (P: E = 3:1), the title compound was obtained.
  • 51
  • [ 1421952-02-4 ]
  • [ 4664-55-5 ]
  • 2-(3-(ethylthio)-5-(trifluoromethyl)pyridin-2-yl)-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate at 100℃; 6.3 Step 3: Add 0.17 g of phenoxyacetyl hydrazine and 0.25 g of 3-chloro-5-trifluoromethylpicolinic acid to the temperatureIn a 50 mL three-necked flask of a gauge cannula, 4 ml of LPCl 3 was added, the stirrer was turned on, and the mixture was heated and stirred, followed by heating to 100 ° C.The progress of the reaction was followed by TCL, and when it was detected that the starting point of the reaction system disappeared, the reaction was stopped.[0143] Post-treatment: The reaction solution was slowly introduced into a 250 mL beaker containing ice cubes, and the pH was adjusted to 9-10 with Na2C03.A large amount of yellow solid is produced at the bottom of the beaker, filtered by suction, washed with water several times to neutral, and dried. Then use column chromatography to divideFrom purification (Ρ:Ε = 3:1), the target compound
  • 52
  • 3-(ethanesulfonyl)-5-(trifluoromethyl)pyridine-2-carboxylic acid [ No CAS ]
  • [ 4664-55-5 ]
  • 2-(3-(ethylsulfonyl)-5-(trifluoromethyl)pyridin-2-yl)-5-(phenoxymethyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate at 100℃; 7.3 Step 3: Add 0.15 g of phenoxyacetyl hydrazine and 0.25 g of 3-chloro-5-trifluoromethylpicolinic acid to a 50 mL three-necked flask with a thermowell, add 4 mL of POCl3, turn on the stirrer, and heat. Stir and then heat to 100 °C. The progress of the reaction was followed by TCL, and when it was detected that the starting point of the reaction system disappeared, the reaction was stopped.Post-treatment: The reaction solution was slowly introduced into a 250 mL beaker containing ice cubes, and the pH was adjusted to 9-10 with Na2CO3. A large amount of yellow solid was produced at the bottom of the beaker, suction filtered, washed with water several times to neutral, and dried. After separation and purification by column chromatography (P: E = 3:1), the title compound was obtained.
  • 53
  • (E)-N’-(2,6-dimethoxyphenyl)-N-(((1R,2S)-1-methoxy-1-(5-methylpyrimidin-2-yl)propan-2-yl)sulfonyl)carbamimidothioic acid [ No CAS ]
  • [ 4664-55-5 ]
  • (1R,2S)-N-(4-(2,6-dimethoxyphenyl)-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl)-1-methoxy-1-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.061 g Stage #1: (E)-N’-(2,6-dimethoxyphenyl)-N-(((1R,2S)-1-methoxy-1-(5-methylpyrimidin-2-yl)propan-2-yl)sulfonyl)carbamimidothioic acid; phenoxyacetyl hydrazine With silver nitrate In acetonitrile at 20℃; for 0.25h; Cooling with ice; Stage #2: With methanesulfonic acid In 1,4-dioxane at 80℃; for 16h; 48.0 (lR,2S)-N-(4-(2,6-Dimethoxyphenyl)-5-(phenoxymethyl)-4H-l,2,4- triazol-3-yl)-l-methoxy-l-(5-methyl-2-pyrimidinyl)-2-propanesulfonamide, Example 48.0. In a 20 mL scintillation vial, 48.01 (2.50 ml, 0.250 mmol) and 2- phenoxyacetohydrazide (0.042 g, 0.25 mmol, Frontier Scientific Services, Inc., Newark, DE) were mixed. The mixture was cooled in an ice-water bath and silver (I) nitrate (0.085 g, 0.50 mmol) was added. The cold bath was removed, and the brown mixture was stirred at RT. After 15 min, the mixture was filtered through a pad of Celite brand filter agent and washed with ACN. The filtrate was concentrated in Gene Vac into a 20 mL scintillation vial. Dioxane (2 mL) was added to the yellow residue followed by MSA (0.073 g, 0.76 mmol). The mixture was stirred at 80 °C for 16h. The reaction mixture was allowed to cool to RT and concentrated in vacuo. The residue was dissolved in MeOH (2 mL), and the mixture was passed through a PS-carbonate column, eluting with MeOH. The filtrate was concentrated and purified by mass-triggered HPLC to afford 48.0, (0.061 g, 0.11 mmol, 42% yield). NMR (500MHz, DMSO-d6) δ 13.03 (br. s., 1H), 8.63 (s, 2H), 7.44 (t, .7=8.5 Hz, 1H), 7.22 (t, J=7.9 Hz, 2H), 6.91 (t, .7=7.3 Hz, 1H), 6.84 - 6.75 (m, 4H), 4.83 (s, 2H), 4.80 (d, .7=3.4 Hz, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.39 (dd, .7=3.5, 7.0 Hz, 1H), 3.10 (s, 3H), 2.26 (s, 3H), 1.11 (d, .7=7.0 Hz, 3H). LCMS (pos.) m/z: 555.1 (M+H)+.
  • 54
  • [ 108-31-6 ]
  • [ 4664-55-5 ]
  • C12H12N2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid at 20℃; for 1.5h; Heating; (Z)-3-[5-(2-Furyl)-1,3,4-oxadiazol-2-yl]acrylicacid (IV). General procedure: A solution of maleic anhydride (0.02 mol)in CH3COOH (4 mL) was added to a solution of 2-furoic acid hydrazide (0.02 mol) in CH3COOH(5 mL). Immediately, the mixture was warmed and awhite precipitate was formed. The mixture was stirredfor 1.5 h at room temperature. The precipitate was separatedand washed twice with acetic acid and ethanol.Without additional purification, the resulting acylhydrazidewas subjected to the reaction with a solution ofPOCl3 (0.02 mol) in DMF (7 mL). The solution wasstirred for 2 h at room temperature and poured into H2O (50 mL). The precipitate was separated, washedtwice with water and recrystallized from ethanol togive colorless crystals (72%);
  • 55
  • [ 38270-58-5 ]
  • [ 4664-55-5 ]
  • 4-(1-[(2-phenoxy)acetyl]-4,5-dihydro-5-(3-nitrophenyl)-1H-pyrazol-3-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With acetic acid for 10h; Reflux; Synthesis of Pyrazolines General procedure: A solution of chalcone (0.01 mol) and the appropriate aryloxy acetyl hydrazine (0.02 mol) in 20 ml of glacial acetic acid was refluxed for 10 hours and cooled. Excess of solvent was removed under reduced pressure and the reaction mixture was poured into 250 ml ice cold water. The product was filtered, washed with cold water and recrystallized from ethanol.
  • 56
  • [ 3033-96-3 ]
  • [ 4664-55-5 ]
  • C23H19ClN2O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With acetic acid for 10h; Reflux; Synthesis of Pyrazolines General procedure: A solution of chalcone (0.01 mol) and the appropriate aryloxy acetyl hydrazine (0.02 mol) in 20 ml of glacial acetic acid was refluxed for 10 hours and cooled. Excess of solvent was removed under reduced pressure and the reaction mixture was poured into 250 ml ice cold water. The product was filtered, washed with cold water and recrystallized from ethanol.
  • 57
  • [ 91301-03-0 ]
  • [ 4664-55-5 ]
  • N’-[(E)-(2-oxo-1,2-dihydroquinolin-3-yl)methylidene]-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% In ethanol for 5h; Reflux; General method for the synthesis of 2-(substituted)-(2-oxo-1,2-dihydroquinolin-3-yl)methylidene]acetohydrazides (6a-i) General procedure: A mixture of aromatic hydrazide and 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (3) in ethanol was refluxed for 5 h. After completion of the reaction, the reaction mixture was concentrated, cooled and poured in ice cold water; the precipitate so formed was filtered, dried and recrystallized to give the desired compound.
  • 58
  • [ 16794-68-6 ]
  • [ 4664-55-5 ]
  • C17H17N3O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% In acetone at 60℃; for 2h; 3.2. Synthesis of 1,4-Diacylthiosemicarbazide Substrates (1a-1s) General procedure: To a solution of acyl chloride (1.0 equiv.) in 20 mL dry acetone, potassium thiocyanate (1.1equiv.) was added at room temperature. The solution was stirred at room temperature for 0.5 h. Then,relevant acylhydrazine (1.05 equiv.) was added. The reaction was stirred at 60 °C for 2 h until thereaction was complete based on TLC (thin-layer chromatography) (DCM:MeOH = 15:1). Then, it wascooled to room temperature, and concentrated under reduced pressure. The resulting residue waswashed by water and recrystallized in MeOH to give the corresponding intermediate as a white solid.
  • 59
  • [ 36717-27-8 ]
  • [ 4664-55-5 ]
  • N-(2-(2-phenoxyacetyl)hydrazine-1-carbonothioyl)isobutyramide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% In acetone at 60℃; for 2h; 3.2. Synthesis of 1,4-Diacylthiosemicarbazide Substrates (1a-1s) General procedure: To a solution of acyl chloride (1.0 equiv.) in 20 mL dry acetone, potassium thiocyanate (1.1equiv.) was added at room temperature. The solution was stirred at room temperature for 0.5 h. Then,relevant acylhydrazine (1.05 equiv.) was added. The reaction was stirred at 60 °C for 2 h until thereaction was complete based on TLC (thin-layer chromatography) (DCM:MeOH = 15:1). Then, it wascooled to room temperature, and concentrated under reduced pressure. The resulting residue waswashed by water and recrystallized in MeOH to give the corresponding intermediate as a white solid.
  • 60
  • [ 75091-99-5 ]
  • [ 4664-55-5 ]
  • N'-[4-(trifluoromethyl)cyclohexylidene]-2-phenoxyacetohydrazide [ No CAS ]
  • 61
  • [ 104-87-0 ]
  • [ 4664-55-5 ]
  • C16H16N2O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In ethanol; water at 20℃; for 1h; Inert atmosphere; 2-(Benzo[d][1,3]dioxol-5-yloxy)-N`-(4-methylbenzylidene)acetohydrazide (8). General procedure: To a mixture of 7 (150 mg, 0.71 mmol) in EtOH (4 mL) was added 4-methylbenzaldehyde (0.09 mL, 0.79 mmol) and few drops of 37% aq. HCl solution. The reaction mixture was stirred for 1 h at room temperature, then quenched with ice water and saturated aqueous NaHCO3. The reaction mixture was extracted with CH2Cl2, and the organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The resulting solid was washed with Et2O and CH2Cl2 (9:1 v/v) to afford white solid (68-100% yield). 1H NMR (400 MHz, DMSO-d6) δ 11.47 (s, 1H), 8.13 (d, J = 135.4 Hz, 1H), 7.58 (d, J = 7.9 Hz, 2H), 7.25 (t, J = 7.1 Hz, 2H), 6.81 (dd, J = 14.3, 8.5 Hz, 1H), 6.67 (dd, J = 26.2, 2.6 Hz, 1H), 6.39 (ddd, J = 28.3, 8.5, 2.6 Hz, 1H), 5.96 (d, J = 6.0 Hz, 2H), 4.80 (d, J = 188.3 Hz, 2H), 2.33 (s, 3H). HRMS (ESI) m/z calculated for C17H17N2O4+ [M + H]+: 313.1188. Found: 313.1176.
  • 62
  • [ 4664-55-5 ]
  • [ 776298-90-9 ]
  • C28H28N6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c. 3-Methylthio-7-phenoxymethyl-1,8-diphenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one (4a). White solid; Yield: 80%; mp 224-226 °C; 1H NMR (400 MHz, DMSO-d6): δ 7.95 (d, J=8.0 Hz, 2 H), 7.78 (d, J=7.1 Hz, 2 H), 7.63 (dd, J=15.8, 8.0 Hz, 3 H), 7.38 (t, J=7.8 Hz, 2 H), 7.25 (dt, J=20.7, 7.6 Hz, 3 H), 6.98 (t, J=7.3 Hz, 1 H), 6.92 (d, J=8.1 Hz, 2 H), 5.32 (s, 2 H), 2.61 (s, 3 H); 13C NMR (100 MHz, DMSO-d6): δ 157.6, 153.6, 151.1, 150.5, 149.3, 146.4, 138.9, 131.9, 130.5, 130.1, 130.0, 129.4, 127.7, 126.4, 122.4, 120.6, 115.4, 101.2, 60.9, 13.1; HRMS (ESI) calcd for C26H20N6O2S: 481.1447 [M+H]+, found: 481.1441.
  • 63
  • [ 866491-56-7 ]
  • [ 4664-55-5 ]
  • C29H30N6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 64
  • [ 866491-55-6 ]
  • [ 4664-55-5 ]
  • C28H27ClN6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 65
  • C20H16Cl2N4O2S [ No CAS ]
  • [ 4664-55-5 ]
  • C28H26Cl2N6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 66
  • C20H16Cl2N4O2S [ No CAS ]
  • [ 4664-55-5 ]
  • C28H26Cl2N6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 67
  • C20H17N5O4S [ No CAS ]
  • [ 4664-55-5 ]
  • C28H27N7O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 68
  • C21H17F3N4O2S [ No CAS ]
  • [ 4664-55-5 ]
  • C29H27F3N6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 69
  • [ 866491-54-5 ]
  • [ 4664-55-5 ]
  • C28H27ClN6O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In dichloromethane at 20℃; for 2h; Inert atmosphere; General procedure for the synthesis of 3-(methylthio)-7-[(4-substitutedphenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4 General procedure: To a solution of iminophosphorane 1 (2 mmol) in dry dichloromethane (25 mL), aryl isocyanate (2 mmol) was quickly added under nitrogen at room temperature. After 6 h, substituted 2-phenoxyacetohydrazide (2 mmol) was added to the solution, which was stirred for additional 2 h. Then, the solvent was removed under vacuum, and anhydrous ethanol (25 mL) and cat. sodium ethoxide were added to the mixture. After stirring for 8 h at room temperature, the precipitate was collected by filtration and recrystallized from dimethyl sulfoxide to give pure 3-(methylthio)-7-[(4-substituted phenoxy)methyl]-8-(4-substituted phenyl)-1-phenyl-1,8-dihydro-4H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidin-4-one 4. The supplemental materials contains sample 1H and 13C NMR for products 4, together with full characterization data 4b-4m and X-ray crystallography analysis information for 4c.
  • 70
  • [ 2244-16-8 ]
  • [ 4664-55-5 ]
  • 2-phenoxy-N’-[(5R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-ylidene]acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With acetic acid In methanol for 4h; Reflux; 3.2. General procedure to the synthesis of (-)-carvone hydrazones (3a-3e) General procedure: To solution of (-)-carvone (3.0 g, 19.5 mmol) in methanol (75 mL), the equimolaramount (19.5 mmol) of appropriate 4-R-phenoxyacetic acid hydrazides and 3-4 dropsof glacial acetic acid were added. The reaction mixture was refluxed for 4 h, cooledand then was poured into the ice. The solid mass was filtered, dried and purified byrecrystallization from methanol. 2-phenoxy-N’-[(5R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-ylidene]acetohydrazide (3a).1H-NMR (500 MHz, DMSO-d6) d: 1.74 (s, 3H, CH3-9), 1.82 (s, 3H, 3-10), 1.96-2.09(m, 2, C2-4), 2.24-2.33 (m, 2, C2-6), 2.92-2.95 (m, 1, CH-5), 4.78 (s, 1, CH2),4.80 (s, 1, CH2), 5.02 (d, J6.7 Hz, 2, CH2-8), 6.17 (t, 1, CH-3), 6.87 (d, J6.8 Hz,2, Ar-H), 6.92 (t, 1, Ar-H), 7.27 (t, 2, Ar-H), 10.76 (s, 1H, NH).13C-NMR (100 MHz, DMSO-d6) d: 170.2 (CO), 158.7 (Ar-C), 150.6 (C-1), 147.9 (C-8),133.5 (C-2), 132.5 (Ar-C), 129.8 (C-3), 121.1 (Ar-C), 114.8 (Ar-C), 110.5 (C-9), 65.3 (CH2),29.9 (C-6), 29.5 (C-4), 21.2 (C-10), 18.0 (C-7). FT-IR (mmax, cv1): 3475-3416 (N-H), 3178(C-H, Ar), 2970-2916 (C-H), 1697 (CO), 1638 (CN), 1599 (C-C, Ar), 888-689 (C-H, Ar).Raman (mmax, cv1): 3073 (N-H), 3030 (C-H, Ar), 2993-2837 (C-H), 1686 (CO), 1640(CN). MS (FAB) m/z: 299 [MH]. HRMS (ESI-TOF) calculated for C18H22N2O2[MH] 299.3873, found 299.3300. HPLC: tr 7.127 min. M.p. (DSC) onset: 118.58 C,peak max: 119.14 C.
  • 71
  • [ 101913-35-3 ]
  • [ 4664-55-5 ]
  • N'-(4-hydroxy-3-methoxy-5-(morpholinomethyl)benzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% Stage #1: 4‑hydroxy‑3‑methoxy‑5‑(morpholinomethyl)benzaldehyde; phenoxyacetyl hydrazine With acetic acid In ethanol Reflux; Stage #2: for 2h; General procedure for synthesis compounds 5a-e, 6a-e, and 7a-e General procedure: Suitable aldehyde (1-3) (10 mmol) and hydrazide (4a-e)(10 mmol) were dissolved in absolute ethanol (20 mL) and 4-5 drops of acetic acid was added. Reaction mixture was refluxed for 2-3 h. Compounds 5a-e and 6a-e precipitated during the reaction. For compounds 7a-e, half of the solvent was removed under reduced pressure and the mixture wasleft in the freezer overnight and the formed solid was filteredoff. The crude product was recrystallized from ethanol(Fig. 6).
  • 72
  • 4-hydroxy-3-methoxy-5-((3-methylpiperidin-1-yl)methyl)benzaldehyde [ No CAS ]
  • [ 4664-55-5 ]
  • N’-(4-hydroxy-3-methoxy-5-((3-methylpiperidin-1-yl)methyl)benzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% Stage #1: 4-hydroxy-3-methoxy-5-((3-methylpiperidin-1-yl)methyl)benzaldehyde; phenoxyacetyl hydrazine With acetic acid In ethanol Reflux; Stage #2: for 2h; General procedure for synthesis compounds 5a-e, 6a-e, and 7a-e General procedure: Suitable aldehyde (1-3) (10 mmol) and hydrazide (4a-e)(10 mmol) were dissolved in absolute ethanol (20 mL) and 4-5 drops of acetic acid was added. Reaction mixture was refluxed for 2-3 h. Compounds 5a-e and 6a-e precipitated during the reaction. For compounds 7a-e, half of the solvent was removed under reduced pressure and the mixture wasleft in the freezer overnight and the formed solid was filteredoff. The crude product was recrystallized from ethanol(Fig. 6).
  • 73
  • [ 329725-00-0 ]
  • [ 4664-55-5 ]
  • N’-(4-hydroxy-3-methoxy-5-((4-phenylpiperazin-1-yl)methyl)benzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: 4-hydroxy-3-methoxy-5-[(4-phenyl-1-piperazino)-methyl]benzaldehyde; phenoxyacetyl hydrazine With acetic acid In ethanol Reflux; Stage #2: for 2h; General procedure for synthesis compounds 5a-e, 6a-e, and 7a-e General procedure: Suitable aldehyde (1-3) (10 mmol) and hydrazide (4a-e)(10 mmol) were dissolved in absolute ethanol (20 mL) and 4-5 drops of acetic acid was added. Reaction mixture was refluxed for 2-3 h. Compounds 5a-e and 6a-e precipitated during the reaction. For compounds 7a-e, half of the solvent was removed under reduced pressure and the mixture wasleft in the freezer overnight and the formed solid was filteredoff. The crude product was recrystallized from ethanol(Fig. 6).
  • 74
  • [ 100-52-7 ]
  • [ 4664-55-5 ]
  • (E)-N′-benzylidene-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%; m.p. 156.2-57.0 °C; IR(ATR. cm-1): νmax 1678 (C = Oamide); 1403 (C = CAr); 1259(N = C); 1219 and 1086 (C-Oether); 1H NMR (400 MHz.DMSO-d6): δ 4.66 and 5.14 (2H; s; H2); 6.92-7.01 (3H; m;H6; H7; H8); 7.27-7.35 (2H; m; H5; H9); 7.42-7.47 (3H;m; H13; H14; H15); 7.69-7.72 (2H; m; H12; H16); 8.02and 8.34 (1H; s; H10); 11.57 and 11.60 (1H; s; N-H); 13CNMR (100 MHz. DMSO-d6): δ 64.4 and 66.3 (C2); 114.3and 114.5 (C6; C8); 120.6 and 121.2 (C7); 126.8 and 127.0(C12; C16); 128.7 (C13; C15); 129.3 and 129.4 (C5; C9);129.8 and 130.1 (C14); 133.8 and 134.0 (C11); 143.7 and147.8 (C10); 157.6 and 158.1 (C4); 164.2 and 168.9 (C1);HPLC-UV nm (%): 254 (100). ESI-MS: m/z 277.0947 [M+ Na]+, calcd. for C15H14N2NaO2: 277.0946; MW: 254.28
  • 75
  • [ 1122-91-4 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-bromobenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 76
  • [ 459-57-4 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-fluorobenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 77
  • [ 555-16-8 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-nitrobenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 78
  • [ 123-08-0 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-hydroxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 79
  • [ 90-02-8 ]
  • [ 4664-55-5 ]
  • (E)-N′-(2-hydroxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 80
  • [ 139-85-5 ]
  • [ 4664-55-5 ]
  • (E)-N′-(3,4-dihydroxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 81
  • [ 120-14-9 ]
  • [ 4664-55-5 ]
  • (E)-N′-(3,4-dimethoxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 82
  • [ 121-33-5 ]
  • [ 4664-55-5 ]
  • (E)-N′-(4-hydroxy-3-methoxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 83
  • [ 621-59-0 ]
  • [ 4664-55-5 ]
  • (E)-N′-(3-hydroxy-4-methoxybenzylidene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 84
  • [ 86-81-7 ]
  • [ 4664-55-5 ]
  • (E)-2-phenoxy-N′-(3,4,5-trimethoxybenzylidene)acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 85
  • [ 872-85-5 ]
  • [ 4664-55-5 ]
  • (E)-2-phenoxy-N′-(pyridin-4-ylmethylene)acetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 86
  • [ 4701-17-1 ]
  • [ 4664-55-5 ]
  • (E)-N′-((5-bromothiophen-2-yl)methylene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 87
  • [ 698-63-5 ]
  • [ 4664-55-5 ]
  • (E)-N′-((5-nitrofuran-2-yl)methylene)-2-phenoxyacetohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With hydrogenchloride In water Reflux; General procedure for the preparation of NAH (3-19) General procedure: To a solution of 23 (0.400 g; 2.41 mmol; 1.0 eq.) in 30 mLof water, were added the corresponding aromatic aldehydes(2.43 mmol; 1.01 eq.) and hydrochloric acid in catalyticquantity. After the complete reaction, the mixture was cooled e the precipitate was collected by vacuum filtrationand re-crystallized in distilled water. The products wereobtained in yields that varied 50-86%.(E)-N′-Benzylidene-2-phenoxyacetohydrazide (3) [24].White solid (H2O); yield 80%
  • 88
  • C11H14N4OS2 [ No CAS ]
  • [ 4664-55-5 ]
  • 2-ethylthio-4-amino-6-methylthio-5-{3-[1-(phenoxy)methyl]-1H-1,2,4-triazol-5-yl}pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With trifluoroacetic acid In 2-methoxy-ethanol for 10h; Reflux;
With trifluoroacetic acid In 2-methoxy-ethanol Reflux; 4.3. Preparation of 2-(alkylthio)-6-(methylthio)-5-[3-(1-substituted phenoxymethyl)-1H-1,2,4-triazol-5-y) pyrimidin-4-amine General procedure: Intermediate (1 mmol), trifluoroacetic acid (1.0 mL), and substituted 2-phenoxypropanehydrazide (1 mmol) (or 2- phenoxyacetohydrazide 0.1 mmol) in 2-methoxyethanol (15 mL) was refluxed for 8-10 h. Cooled to room temperature, and the pre- cipitate was filtered, washed with diethyl ether, and recrystallized from DMSO to provide pure product
  • 89
  • C12H16N4OS2 [ No CAS ]
  • [ 4664-55-5 ]
  • 2-propylthio-4-amino-6-methylthio-5-{3-[1-(phenoxy)methyl]-1H-1,2,4-triazol-5-yl}pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With trifluoroacetic acid In 2-methoxy-ethanol for 10h; Reflux;
With trifluoroacetic acid In 2-methoxy-ethanol Reflux; 4.3. Preparation of 2-(alkylthio)-6-(methylthio)-5-[3-(1-substituted phenoxymethyl)-1H-1,2,4-triazol-5-y) pyrimidin-4-amine General procedure: Intermediate (1 mmol), trifluoroacetic acid (1.0 mL), and substituted 2-phenoxypropanehydrazide (1 mmol) (or 2- phenoxyacetohydrazide 0.1 mmol) in 2-methoxyethanol (15 mL) was refluxed for 8-10 h. Cooled to room temperature, and the pre- cipitate was filtered, washed with diethyl ether, and recrystallized from DMSO to provide pure product
  • 90
  • C13H18N4OS2 [ No CAS ]
  • [ 4664-55-5 ]
  • 2-butylthio-4-amino-6-methylthio-5-{3-[1-(phenoxy)methyl]-1H-1,2,4-triazol-5-yl}pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With trifluoroacetic acid In 2-methoxy-ethanol for 10h; Reflux;
With trifluoroacetic acid In 2-methoxy-ethanol Reflux; 4.3. Preparation of 2-(alkylthio)-6-(methylthio)-5-[3-(1-substituted phenoxymethyl)-1H-1,2,4-triazol-5-y) pyrimidin-4-amine General procedure: Intermediate (1 mmol), trifluoroacetic acid (1.0 mL), and substituted 2-phenoxypropanehydrazide (1 mmol) (or 2- phenoxyacetohydrazide 0.1 mmol) in 2-methoxyethanol (15 mL) was refluxed for 8-10 h. Cooled to room temperature, and the pre- cipitate was filtered, washed with diethyl ether, and recrystallized from DMSO to provide pure product
  • 91
  • (Z)-2-(5-(2-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid [ No CAS ]
  • [ 4664-55-5 ]
  • (E)-5-(2-methoxybenzylidene)-3-((5-(phenoxymethyl)-1,3,4-oxadiazol-2-yl)methyl)thiazolidine-2,4-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With trichlorophosphate Reflux; (E)-5-(2-methoxybenzylidene)-3-((5-(phenoxymethyl)-1,3,4-oxadiazol-2-yl)methyl)thiazolidine-2,4-dione General procedure: Compound 4 and different aromatic hydrazides in the equimolar ratio were refluxed in phosphoryl chloride (20 mL) for 12-15 h. After reaction completion, the reaction was poured onto crushed ice and neutralized with sodium bicarbonate solution, filtered, washed, and dried. The purification of final compounds was done by recrystallization using petroleum ether and dichloromethane (Scheme 2).
  • 92
  • [ 104-87-0 ]
  • [ 4664-55-5 ]
  • 2-(phenoxymethyl)-5-p-tolyl-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-methyl-benzaldehyde; phenoxyacetyl hydrazine With sodium acetate for 0.166667h; Stage #2: With iodine; potassium carbonate In 1,4-dioxane at 100℃; for 6h; Synthesis of 2-(phenoxymethyl)-5-p-tolyl-1,3,4-oxadiazole General procedure: Phenoxyhdrazide was mixed with p-tolualdehyde in a round bottom flask and stirred with heating mantle followed by the addition of sodium acetate (0.5 mmol) dropwise after 10 min. The solvent of the reaction mixture was evaporated under reduced pressure. Further, a mixture of K2CO3 (2.5 mmol) and I2 (1.5 mmol) was poured into the resultant mixture using 10 mL of 1,4-dioxane as solvent. Then the whole obtained mixture was put on heating mantle for 6 h at 100 °C (monitored by TLC, 2-3 h). The reaction mixture was cooled overnight and then dried with 10% Na2S2O3 and produce with CH2Cl2/MeOH (20:2, 20 mL × 5). Na2SO4 was used as a drying agent for the organic layer and purification was done through silica gel column chromatography using a mixture of ethyl acetate and petroleum ether as mobile phase to afford the corresponding 2-(phenoxymethyl)-5-p-tolyl-1,3,4-oxadiazole yield 85-99% [9]. IR (KBr, max cm-1): 1305.06 (C = N), 2957.19, 2835.29 (CH2), 3057.57, 1208.26, 1179.38 and 1208.26 (arom. str. C-O-C), 2853.74 (arom. CH3). 1H NMR (DMSO-d6): δ 6.944- 8.30 (m) 9H, 5.122 (S) 2H, 2.33 (S) 3H.
  • 93
  • [ 55149-83-2 ]
  • [ 4664-55-5 ]
  • C12H15N3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In ethanol at 20℃; for 12h; Synthesis of ethyl 1,2,4-triazole-3-carboxylates 1a-t (General method). General procedure: Acyl hydrazide 5a-t (25.0 mmol) wasadded to a solution of ethyl 2-ethoxy-2-iminoacetatehydrochloride (6) (4.50 g, 25.0 mmol) and Et3N (4.20 ml,3.07 g, 30.3 mmol) in anhydrous EtOH (50 ml), andobtained solution was stirred at room temperature for 12 h.The formed ethyl 2-(2-acylhydrazono)-2-aminoacetate intermediate2a-t was filtered, washed with EtOH (3×20 ml),and dispersed (except for acetate 2a) in Ph2O (50 ml). Theresulting mixture was brought to boil and refluxed for1 min. After the temperature of the reaction mixture haddropped to 40°C, it was filtered. Thus obtained crudeproduct was washed with hexane (3×50 ml) andrecrystallized from PhMe to give the title compound 1b-t.Compound 1a was prepared by solvent-free melting ofacetate 2a at 150°C for 2 min.
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