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CAS No. :7466-54-8 MDL No. :MFCD00014755
Formula : C8H10N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :QMGXWNSSMGAHCA-UHFFFAOYSA-N
M.W : 166.18 Pubchem ID :24051
Synonyms :

Safety of [ 7466-54-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 7466-54-8 ]

* 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 [ 7466-54-8 ]

[ 7466-54-8 ] Synthesis Path-Downstream   1~66

  • 1
  • [ 506-68-3 ]
  • [ 7466-54-8 ]
  • [ 5711-59-1 ]
YieldReaction ConditionsOperation in experiment
With potassium hydrogencarbonate
  • 2
  • [ 606-45-1 ]
  • [ 7466-54-8 ]
YieldReaction ConditionsOperation in experiment
94% With hydrazine hydrate monohydrate In ethanol for 4h; Reflux;
92% With hydrazine hydrate monohydrate In ethanol at 80℃; for 1h; Inert atmosphere;
90% With hydrazine hydrate monohydrate for 5h; Heating;
87% With hydrazine monohydrate In ethanol for 0.216667h; Reflux; Microwave irradiation;
84% With hydrazine monohydrate In methanol for 6h; Reflux; 4.2. Synthesis of 2-methoxybenzohydrazide (2) Methyl 2-methoxybenzoate (1) (50 mmol, 8.31 g) and 50 mL ofhydrazine hydrate were mixed in methanol (100 mL). The mixturewas refluxed for 6 h. Methanol was then evaporated and theproduct formed was being rinsed with plenty of water to removeexcess hydrazine hydrate. The product formed was left to dry atroom temperature and yielded 94% (7.82 g).
81% With hydrazine hydrate monohydrate In ethanol for 2.5h; Reflux; 5.1.1. General procedure for the preparation of benzohydrazides(4-13) General procedure: Various benzohydrazides 5-7 and 9-13 were obtained accordingto known procedures [40,65] except for benzohydrazides 4and 8 which were commercially available. A solution of the methylbenzoate (1 equiv) in ethanol was added dropwise to 65% hydrazinemonohydrate (5 equiv). The reaction mixture was then heatedunder reflux and stirred overnight. The reaction progress was followedup by TLC. Crude product was collected by filtration aftercooling of the reaction medium and finally washed with coldethanol unless specified otherwise. The desired benzohydrazides were used without any further purification.The analysis of spectral data (1H and 13C NMR), the yields, HRMS,Mp and Rf of these precursors are presented in SupplementaryInformation.
81% With hydrazine monohydrate In ethanol for 2.5h; Reflux; 4.1.1. General procedure for the preparation of benzohydrazidesprecursors (1-5) General procedure: The benzohydrazides 2 and 3 were obtained according to known procedures [34,66] and benzohydrazides 1, 4 and 5 were commercially available. A solution of the methyl benzoate (1 equiv)in ethanol was added dropwise to 65% hydrazine monohydrate (5equiv). The reaction mixture was then heated under reflux and stirred overnight. The reaction progress was followed up by TLC. Crude product was collected by filtration after cooling of the reaction medium and finally washed with cold ethanol unless specified otherwise. The desired benzohydrazides were used without any further purification.
73% With hydrazine hydrate monohydrate In ethanol for 6h; Heating;
With hydrazine hydrate monohydrate
With hydrazine In ethanol for 12h; Heating;
With hydrazine hydrate monohydrate
With hydrazine In ethanol for 12h; Inert atmosphere; Reflux;
With hydrazine In ethanol; lithium hydroxide monohydrate for 8h; Reflux;
With hydrazine hydrate monohydrate Reflux;
With hydrazine hydrate monohydrate In ethanol Reflux;
With hydrazine hydrate monohydrate In ethanol at 70℃; for 3h;
With hydrazine hydrate monohydrate In methanol for 6h; Reflux;
With hydrazine hydrate monohydrate In methanol Reflux;
With hydrazine hydrate monohydrate In ethanol Reflux; General procedure for the synthesis of the hydrazide ligands General procedure: Different substituted carboxylic acids (20 mmol) (A) were stirred with thionyl chloride (100 mmol) in dry methanol (75 ml) or 5-6 h to synthesize corresponding methyl esters (B) (Scheme1). After extraction of esters in chloroform, solvent was evaporated and esters (66 mmol) were refluxed with hydrazine hydrate(330 mmol) in ethanol (75 ml) for 4-5 h. A solid was obtained upon removal of the solvent by rotary evaporation. The resulting solid was washed with hexane to afford hydrazide ligand (C). The spectral and analytical data are given below.
With hydrazine hydrate monohydrate In methanol
With hydrazine hydrate monohydrate In methanol for 5h; Reflux; General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C.
With hydrazine hydrate monohydrate for 6h; Reflux;
With hydrazine hydrate monohydrate
With diazenium hydroxide In methanol for 6h; Reflux;
With hydrazine hydrate monohydrate In ethanol Reflux;
With hydrazine monohydrate In methanol Reflux;
With hydrazine hydrate monohydrate In methanol at 85℃; for 14h;
With hydrazine monohydrate In methanol at 65℃; for 4h; General Procedure 2: The Formation of Hydrazide General procedure: To a solution of esters (2a~2t, 1.0 equiv.), furan-2-carbonyl chloride (7a, 1.0 equiv.) orthiophene-2-carbonyl chloride (7b, 1.0 equiv.) in MeOH (2 mL/1 mmol) was added hydrazine hydrate(1 mL/1 mmol), then the mixture was allowed to reach 65 C and stirred for 4 h. After completion(monitored by TLC), the organic solvent was removed and extracted three times with ethyl acetate,the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to givethe corresponding hydrazides (3a~3t, 8a, or 8b) in high yields, which were taken up for the next stepwithout any purification.
With hydrazine monohydrate
With hydrazine hydrate monohydrate In methanol at 0 - 20℃; for 4h; 4.3 General procedure for the synthesis of compounds 3a-3q General procedure: Compound 2a was dissolved in methanol and the mixture was cooled in an ice bath. Hydrazine hydrate (3 eq.) was added dropwise at 0°C. The resulting reaction mixture was stirred at room temperature for 4h. The reaction progress was monitored by TLC (MeOH/DCM=1:20) until it was completed. A crude solid 3a was obtained by filtering and washing with ice methanol, which was used to the next step without further purification. Preparation method of 3b∼3q was same as 3a.
With hydrazine hydrate monohydrate In ethanol
With hydrazine hydrate monohydrate In ethanol at 90℃;

Reference: [1]Location in patent: scheme or table Kubo, Yuji; Minowa, Yu; Shoda, Takayuki; Takeshita, Kimiya [Tetrahedron Letters, 2010, vol. 51, # 12, p. 1600 - 1602]
[2]Bolli, Martin H.; Boss, Christoph; Brotschi, Christine; Gatfield, John; Heidmann, Bibia; Jenck, Francois; Roch, Catherine; Sifferlen, Thierry; Treiber, Alexander; Williams, Jodi T. [ChemMedChem, 2020]
[3]Khan, Khalid Mohammad; Rasheed, Maimona; Ullah, Zia; Hayat, Safdar; Kaukab, Farhana; Choudhary, M. Iqbal; Ur-Rahman, Atta; Perveen, Shahnaz [Bioorganic and Medicinal Chemistry, 2003, vol. 11, # 7, p. 1381 - 1387]
[4]Zaheer, Muhammad; Zia-Ur-Rehman, Muhammad; Rahman, Salma; Ahmed, Naveed; Chaudhary, Muhammad Nawaz [Journal of the Chilean Chemical Society, 2012, vol. 57, # 4, p. 1492 - 1496]
[5]Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Anouar, El Hassane; Selvaraj, Manikandan; Jamil, Waqas; Ali, Muhammad; Kashif, Syed Muhammad; Rahim, Fazal; Khan, Khalid Mohammed; Adenan, Mohd Ilham [European Journal of Medicinal Chemistry, 2017, vol. 126, p. 1021 - 1033]
[6]Ameryckx, Alice; Thabault, Léopold; Pochet, Lionel; Leimanis, Serge; Poupaert, Jacques H.; Wouters, Johan; Joris, Bernard; Van Bambeke, Françoise; Frédérick, Raphaël [European Journal of Medicinal Chemistry, 2018, vol. 159, p. 324 - 338]
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[13]Location in patent: experimental part Jiang, Qian-Qian; Darhkijav, Burenkhangai; Liu, Hao; Wang, Fang; Li, Zhao; Jiang, Yun-Bao [Chemistry - An Asian Journal, 2010, vol. 5, # 3, p. 543 - 549]
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[17]Taha, Muhammad; Baharudin, Mohd Syukri; Ismail, Nor Hadiani; Khan, Khalid Mohammed; Jaafar, Faridahanim Mohd; Samreen; Siddiqui, Salman; Choudhary, M. Iqbal [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 11, p. 3463 - 3466]
[18]Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Maqsood, Muhammad Rizwan; Rama, Nasim Hasan; Lee, Ki-Hwan; Seo, Sung-Yum [Bulletin of the Korean Chemical Society, 2012, vol. 33, # 12, p. 3943 - 3949]
[19]Ain, Qurrat Ul; Ashiq, Uzma; Jamal, Rifat Ara; Mahrooof-Tahir, Mohammad [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 115, p. 683 - 689]
[20]Li, Pei; Yin, Juan; Xu, Weiming; Wu, Jian; He, Ming; Hu, Deyu; Yang, Song; Song, Baoan [Chemical Biology and Drug Design, 2013, vol. 82, # 5, p. 546 - 556] Shi, Zhichuan; Zhao, Zhigang; Huang, Meiwei; Fu, Xiaolin [Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1320 - 1327] Dong, Liangrun; Song, Baojing; Wu, Jian; Wu, Zengxue; Zhu, Yunying; Chen, Xuewen; Hu, Deyu [Phosphorus, Sulfur and Silicon and the Related Elements, 2016, vol. 191, # 6, p. 904 - 907] Cao, Xiao; Liu, Fang; Liu, Liwei; Liu, Tingting; Peng, Feng; Wang, Qifan; Xie, Chengwei; Xue, Wei; Yang, Jinsong [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 37, p. 11085 - 11094]
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  • 3
  • [ 7335-26-4 ]
  • [ 7466-54-8 ]
YieldReaction ConditionsOperation in experiment
78% With hydrazine hydrate In ethanol; water Reflux; Synthesis of benzohydrazides General procedure: Hydrazides (30-58) were synthesized by one pot conventionalmethod24 Benzoic acid or its derivative (10 mmol) was dissolvedin ethanol (20 mL). Sulfuric acid (3 N, 2 mL) was added and thereaction contents were refluxed for six hours. The reaction wasmonitored with TLC. After the completion of the reaction, the reactionmixture was neutralized by adding solid NaHCO3, and filteredto remove excess of NaHCO3. In the neutralized reaction mixture which contains ethyl ester, hydrazine monohydrate (1.5 mL,3 mmol) was added and refluxed for 3-6 h to complete the reaction.Ethanol and unreacted hydrazine were removed by distillationupto 1/3 volume. The reaction contents were cooled, filteredand recrystallized from methanol to obtain the desired hydrazidecrystals (see Supporting information).
With hydrazine hydrate
With hydrazine hydrate for 0.05h; Microwave irradiation;
With hydrazine In ethanol for 16h; Reflux; Inert atmosphere;
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate
With hydrazine hydrate for 0.05h; Microwave irradiation;
With hydrazine hydrate
With hydrazine hydrate In ethanol Microwave irradiation;
With hydrazine hydrate Microwave irradiation; Reflux;
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate for 6h; Reflux;
With hydrazine hydrate In ethanol Reflux; Synthesis of Hydrazide Ligands General procedure: Hydrazide ligands (1-12) were synthesized by reportedmethod [28,29]. Ethylbenzoate (25 mmol) was dissolved inethanol (75 mL), and then hydrazine hydrate (100 mmol)was added and the mixture refluxed for 5 h. The solid obtainedwas washed with hexane to afford the hydrazide.Other ligands were prepared from their respective esters. Theanalytical data of benzohydrazide (1), M.P. 116 °C; 2-fluorobenzohydrazide (2), M.P. 74 °C; 2-methoxybenzohydrazide(3), M.P. 83 °C; 2-aminobenzohydrazide (4), M.P.124 °C; 4-phenylsemicarbazide (5), M.P. 125 °C; 3-aminobenzohydrazide(6), M.P. 79°C; 4-aminobenzohydrazide (7),M.P. 229 °C; 3-methoxybenzohydrazide (8), M.P. 94 °C; 3-fluorobenzohydrazide (9), M.P. 138 °C; 3-iodobenzohydrazide(10), M.P. 141 °C; 4-iodobenzohydrazide (11) M.P.170 °C and 3-bromobenzohydrazide (12) M.P. 160 °C; werereported previously [28,30].
With hydrazine hydrate Reflux;
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate In methanol Reflux; 2.3. Procedure for the synthesis of different aralkyl/aryl acidhydrazides (3a-o) General procedure: The ethyl esters (0.15 mol; 2a-o) were taken in 250 mL round bottom flask.About 30 mL of methanol was added to the flask and homogenized by stirringat room temperature. Hydrazine hydrate (80%; 0.15 mol) was introduced to theflask drop wise and the reaction apparatus was refluxed for 5-6 hrs. Reactionprogress was confirmed by thin layer chromatography. n-Hexane and ethylacetate (3:2). At the end of reaction, excess of solvent was evaporated andresidue was poured into the ice cold water. Precipitates of acid hydrazides werefiltered, washed with water and dried. Re-crystallization of acid hydrazides wasperformed by using methanol.
With hydrazine In ethanol Reflux; General Procedures for Synthesis of Aryl/AralkylCarbohydrazides (IIIa-n) General procedure: The synthesized aryl/aralkyl esters (IIa-n)(3.5 mL) were diluted in 250 mL ethanol followed byaddition of 4.8 mL 80% hydrazine. Refluxing wascontinued for 4-6 h. After monitoring by TLC, icecold distilled H2O was poured to acquire the precipitatesof (IIIa-n), which were filtered and washed offwith cold distilled H2O [18, 19].
With hydrazine hydrate Reflux;
With hydrazine hydrate In ethanol Reflux; General procedure for synthesis of (un)substituted-benzohydrazides (VIa-n). General procedure: Ethyl ester (Va-n) (0.04 mol) was refluxed with 80% N2H4 · H2O(7.2 mL) for 3-4 h in 20 mL EtOH in a round-bottom flask (100 mL). The reaction was monitored by TLC. At completion, excess ice-cold distilled water (60 mL) was added to get the precipitate, which was filtered, washed with distilled water, and dried to acquire title compounds (VIa-n) [18, 19].
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate In ethanol for 6h; Reflux;
With hydrazine hydrate In ethanol
With hydrazine hydrate In ethanol 5.b b: The aromatic ester obtained in a is completely dissolved in an appropriate amount of absolute ethanol, and 3.5 g of 80% hydrazine hydrate is added dropwise, and the product is concentrated and dried.
With hydrazine hydrate In ethanol Reflux;
With hydrazine hydrate Reflux;

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[2]Kalb; Gross [Chemische Berichte, 1926, vol. 59, p. 733]
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[18]Aziz-ur-Rehman; Arif; Abbasi; Siddiqui; Rasool; Shah [Russian Journal of Bioorganic Chemistry, 2017, vol. 43, # 3, p. 328 - 339][Bioorg. Khim., 2017, vol. 43, # 3, p. 328 - 339,12]
[19]Xu; Wang; Luo; Yu; Guo; Fu; Zhao; Wu [RSC Advances, 2018, vol. 8, # 12, p. 6306 - 6314]
[20]Abbasi; Ramzan; Aziz-ur-Rehman; Siddiqui; Shah; Hassan; Seo; Ashraf; Mirza; Ismail [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 6, p. 801 - 811][Bioorg. Khim., 2018, vol. 44, # 6, p. 801 - 811,11]
[21]Guo, Yong; Xu, Ting; Bao, Chongnan; Liu, Zhiyan; Fan, Jiangping; Yang, Ruige; Qin, Shangshang [European Journal of Pharmaceutical Sciences, 2019, vol. 136]
[22]Wu, Shaojie; Zhang, Wenhui; Qi, Le; Ren, Yinghui; Ma, Haixia [Journal of Molecular Structure, 2019, vol. 1197, p. 171 - 182]
[23]Jin, Ruyi; Wang, Yanyan; Guo, Hui; Long, Xu; Li, Jiajia; Yue, Shijun; Zhang, Shuan; Zhang, Guanghui; Meng, Qinghua; Wang, Chuan; Yan, Hao; Tang, Yuping; Zhou, Sha [Journal of Molecular Structure, 2020, vol. 1202]
[24]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - CN112125860, 2020, A Location in patent: Paragraph 0100; 0104
[25]Kant, Rajni; Yang, Ming-Hui; Tseng, Chih-Hua; Yen, Chia-Hung; Li, Wei-You; Tyan, Yu-Chang; Chen, Marcelo; Tzeng, Cherng-Chyi; Chen, Wei-Cheng; You, Kaiting; Wang, Wen-Chieh; Chen, Yeh-Long; Chen, Yi-Ming Arthur [Journal of Medicinal Chemistry, 2021, vol. 64, # 13, p. 8992 - 9009] Guo, Yong; Meng, Jie-Ru; Liu, Jia-Zheng; Xu, Ting; Zheng, Zhi-Yuan; Jiang, Zhi-Hong; Bai, Li-Ping [Pharmaceuticals, 2021, vol. 14, # 9]
[26]Cheng, Wanqing; Fan, Jiangping; Guo, Yong; Han, Meiyue; Ma, Nannan; Yan, Xiaoting; Yang, Ruige [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 51, p. 15544 - 15553]
  • 4
  • [ 42466-67-1 ]
  • [ 7466-54-8 ]
  • 2-cyano-3-[<i>N</i>'-(2-methoxy-benzoyl)-hydrazino]-acrylic acid ethyl ester [ No CAS ]
  • 5
  • [ 75-15-0 ]
  • [ 7466-54-8 ]
  • [ 69844-25-3 ]
YieldReaction ConditionsOperation in experiment
68% In N,N-dimethyl-formamide at 40 - 70℃; Inert atmosphere; 4.9 4.1.2. General procedure for synthesis of 5-substituted 1,3,4-oxadiazole-2-thiols General procedure: To a solution of acid hydrazide in anhydrous 5-15mL of DMF, carbon disulfide (2.5mL/mmol) was added at room temperature and under a nitrogen atmosphere. The reaction mixture was then heated to 40°C for 15min and then to 70°C for 4-8h until the reaction was completed. After completion, the reaction mixture was cooled to room temperature and poured dropwise into ice cold water. The solids formed were separated by filtration, washed with water and dried in vacuo.
With potassium hydroxide In ethanol Heating;
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol for 2h; Inert atmosphere; Reflux; Stage #2: With hydrogenchloride In water Inert atmosphere;
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol for 24h; Reflux; Stage #2: With hydrogenchloride
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol for 24h; Reflux; Stage #2: With hydrogenchloride In water 4.2. General procedure for the synthesis of 5-phenyl-1,3,4-oxadiazole-2-thiol derivatives General procedure: Then equimolar portions of the appropriately substituted benzoylhydrazine (5 mmol) and potassium hydroxide (5 mmol) were dissolved in 20 mL of 95% ethanol. The mixture was allowed to stir for several minutes at room temperature and then carbon disulfide (7.5 mmol) was slowly added dropwise to the reaction system via a self-equalizing addition funnel while the mixture was heated to reflux. After 24 h, the solvent was completely removed under reduced pressure. The residue obtained was dissolved in water (50 mL) and diluted hydrochloric acid was added to adjust the pH values of the solution to 5-6. Then the precipitate was collected by filtering under reduced pressure, washed with water for several times and dried without further purification.
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol for 24h; Reflux; Stage #2: With hydrogenchloride In ethanol; water
With potassium hydroxide In ethanol Reflux;
In ethanol for 5h; Reflux;
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol Reflux; Stage #2: With hydrogenchloride In ethanol; water
With potassium hydroxide In ethanol Reflux;
With potassium hydroxide In ethanol for 20h; Reflux;
With potassium hydroxide In ethanol Reflux; 2.4. Procedure for the synthesis of 5-substituted-1,3,4-oxadiazol-2-thiols (4a-o) General procedure: The aralkyl/aryl acid hydrazides (0.01 mol; 3a-o) were dissolved in 20 mLabsolute C2H5OH in a 250 mL of round bottom flask. Solid KOH (0.02 mol)and carbon disulphide (0.02 mol) were added to reaction flask. The reactioncontents were refluxed for 4-5 hrs with continuous stirring. H2S was evolvedduring the completion of reaction. Completion of reaction was confirmed bythin layer chromatography by using n-hexane and ethyl acetate (3:2) as mobilephase to develop a chromatogram. After confirmation, cold distilled water wasadded to the flask contents along with the addition of dilute HCl (pH 4-5).Precipitates of title compounds were filtered, washed with distilled waterand dried. To obtain the pure products, precipitates were recrystallized frommethanol.
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol Reflux; Stage #2: With hydrogenchloride
With hydrazine hydrate; potassium hydroxide In ethanol Reflux; General procedure for synthesis of 5-((un)substituted-phenyl)-1,3,4-oxadiazol-2-thiols (VIIa-n). General procedure: Solid KOH (0.03 mol) was dissolved in 25 mL EtOH on reflux in a 100 mL round-bottom flask. (Un)Substituted-benzohydrazide (VIa-n) (0.03 mol) was refluxed with CS2 (0.06 mol) in this basified EtOH for 5-6 h. The reaction was monitored by TLC. At completion, excess ice-cold distilled water (60 mL) wasadded to form homogeneous solution. pH was adjusted to 5-6 by pouring dilute HCl; precipitatethus formed was filtered, washed with distilled water and dried. The formed products (VIIa-n) were also re-crystallized from EtOH [18, 19].
With potassium hydroxide In ethanol; water at 95℃; for 16h; Inert atmosphere;
Stage #1: carbon disulfide; 2-methoxybenzoylhydrazine With sodium hydroxide Stage #2: With hydrogenchloride
Stage #1: 2-methoxybenzoylhydrazine With potassium hydroxide In ethanol for 0.166667h; Inert atmosphere; Stage #2: carbon disulfide In ethanol Reflux; Stage #3: In water at 70 - 80℃; 4.1.2 General synthetic procedure for the key intermediate 5(a-c): General procedure: The intermediate 5(a-c) were synthesized by two step reaction. Firstly, to a 100mL flask was added the intermediate compound 3(a-b) (1mmol) and milled potassium hydroxide (1.1mmol) in ethanol (5mL), stirred for 10min under nitrogen atmosphere. Later, slowly added carbon disulphide (2mmol) to the reaction mixture, solid will observed (if necessary, add ethanol) and heated to reflux for 4-5 h. The reaction progress was detected by using TLC technique. After completion of the reaction, the reaction mass was cooled to room temperature and concentrated under reduced pressure to afford a crude solid 4(a-d). The obtained crude solid was taken as such for further step. (0029) The obtained crude intermediate 4(a-d) was taken in water and heated to reflux at 70-80°C for 7-8 h. After completion of the reaction, the reaction mixture was gradually brought to room temperature followed cooled to 0 to 5°C. Then neutralised with 10% hydrochloric acid solution, the precipitated solid was filtered, and several times washed with cold water. The obtained solid was dried and used as it is for next step.
With potassium hydroxide In ethanol for 7h; Reflux;
With potassium hydroxide In ethanol for 12h; Reflux;

Reference: [1]Kummari, Lalith K.; Butler, Mark S.; Furlong, Emily; Blundell, Ross; Nouwens, Amanda; Silva, Alberto B.; Kappler, Ulrike; Fraser, James A.; Kobe, Bostjan; Cooper, Matthew A.; Robertson, Avril A.B. [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 20, p. 5408 - 5419]
[2]Chao, Shu-Jun; Hui, Xin-Ping; Li, Shuo; Qiu, Zao-Zao; Xu, Peng-Fei; Zhang, Zi-Yi; Wang, Qin; Guan, Zuo-Wu [Journal of the Chinese Chemical Society, 2005, vol. 52, # 3, p. 539 - 544]
[3]Location in patent: experimental part Rai, Ganesha; Kenyon, Victor; Jadhav, Ajit; Schultz, Lena; Armstrong, Michelle; Jameson, J. Brian; Hoobler, Eric; Leister, William; Simeonov, Anton; Holman, Theodore R.; Maloney, David J. [Journal of Medicinal Chemistry, 2010, vol. 53, # 20, p. 7392 - 7404]
[4]Location in patent: scheme or table Zheng, Qing-Zhong; Zhang, Xiao-Min; Xu, Ying; Cheng, Kui; Jiao, Qing-Cai; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 22, p. 7836 - 7841]
[5]Location in patent: experimental part Liu, Kai; Lu, Xiang; Zhang, Hong-Jia; Sun, Juan; Zhu, Hai-Liang [European Journal of Medicinal Chemistry, 2012, vol. 47, # 1, p. 473 - 478]
[6]Location in patent: scheme or table Zhang, Li-Rong; Liu, Zhi-Jun; Zhang, Hui; Sun, Jian; Luo, Yin; Zhao, Ting-Ting; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3615 - 3621]
[7]Du, Qian-Ru; Li, Dong-Dong; Pi, Ya-Zhou; Li, Jing-Ran; Sun, Jian; Fang, Fei; Zhong, Wei-Qing; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297]
[8]Deora, Girdhar Singh; Karthikeyan, Chandrabose; Moorthy, N. S. Hari Narayana; Rathore, Vandana; Rawat, Arun K.; Tamrakar, Akhilesh K.; Srivastava; Trivedi, Piyush [Medicinal Chemistry Research, 2013, vol. 22, # 11, p. 5344 - 5348]
[9]Li, Pei; Yin, Juan; Xu, Weiming; Wu, Jian; He, Ming; Hu, Deyu; Yang, Song; Song, Baoan [Chemical Biology and Drug Design, 2013, vol. 82, # 5, p. 546 - 556]
[10]Ahmed, Muhammad Naeem; Yasin, Khawaja Ansar; Hameed, Shahid; Ayub, Khurshid; Haq, Ihsan-ul; Tahir, M. Nawaz; Mahmood, Tariq [Journal of Molecular Structure, 2017, vol. 1129, p. 50 - 59]
[11]Wang, Zi-Zhen; Sun, Wen-Xue; Wang, Xue; Zhang, Ya-Han; Qiu, Han-Yue; Qi, Jin-Liang; Pang, Yan-Jun; Lu, Gui-Hua; Wang, Xiao-Ming; Yu, Fu-Gen; Yang, Yong-Hua [Chemical Biology and Drug Design, 2017, vol. 90, # 2, p. 236 - 243]
[12]Aziz-Ur-Rehman; Ahtzaz, Samreen; Abbasi, Muhammad Athar; Siddiqui, Sabahat Zahra; Rasool, Shahid; Ahmad, Irshad [Journal of the Chilean Chemical Society, 2017, vol. 62, # 1, p. 3370 - 3375]
[13]Aziz-ur-Rehman; Arif; Abbasi; Siddiqui; Rasool; Shah [Russian Journal of Bioorganic Chemistry, 2017, vol. 43, # 3, p. 328 - 339][Bioorg. Khim., 2017, vol. 43, # 3, p. 328 - 339,12]
[14]Abbasi; Ramzan; Aziz-ur-Rehman; Siddiqui; Shah; Hassan; Seo; Ashraf; Mirza; Ismail [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 6, p. 801 - 811][Bioorg. Khim., 2018, vol. 44, # 6, p. 801 - 811,11]
[15]Kahl, Dylan J.; Hutchings, Kim M.; Lisabeth, Erika Mathes; Haak, Andrew J.; Leipprandt, Jeffrey R.; Dexheimer, Thomas; Khanna, Dinesh; Tsou, Pei-Suen; Campbell, Phillip L.; Fox, David A.; Wen, Bo; Sun, Duxin; Bailie, Marc; Neubig, Richard R.; Larsen, Scott D. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4350 - 4369]
[16]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]
[17]Vanjare, Balasaheb D.; Choi, Nam Gyu; Mahajan, Prasad G.; Raza, Hussain; Hassan, Mubashir; Han, Yohan; Yu, Seon-Mi; Kim, Song Ja; Seo, Sung-Yum; Lee, Ki Hwan [Bioorganic and Medicinal Chemistry, 2021, vol. 41]
[18]Cao, Xiao; Liu, Fang; Liu, Liwei; Liu, Tingting; Peng, Feng; Wang, Qifan; Xie, Chengwei; Xue, Wei; Yang, Jinsong [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 37, p. 11085 - 11094]
[19]Cheng, Wanqing; Fan, Jiangping; Guo, Yong; Han, Meiyue; Ma, Nannan; Yan, Xiaoting; Yang, Ruige [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 51, p. 15544 - 15553]
  • 6
  • [ 943130-42-5 ]
  • [ 7466-54-8 ]
  • 2-(5-cyclopropyl-3-phenyl-isoxazol-4-yl)-5-(2-methoxy-phenyl)-[1,3,4]oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With 2-chloro-1,3-dimethyl imidazolium chloride; triethylamine In dichloromethane at 20℃; for 18h; 69.c To a suspension of 5-cyclopropyl-3-phenyl-isoxazole-4-carboxylic acid (236 mg, 1.03 mmol) in dichloromethane (2 mL) were added 2-methoxybenzhydrazide (205 mg, 1.24 mmol), 2-chloro-l,3-dimethylimidazolium chloride (383 mg, 2.26 mmol) and triethylamine (0.52 ml, 5.15 mmol) at ambient temperature. The resuting suspension was stirred for 18 h at this temperature before diluting with dichloromethane (20 ml) and washing with water (20 mL) and brine (20 mL). The aqueous layers were extracted with dichlormethane and the combined organic layers dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane = 70:10:20 to 40:40:20) afforded the title compound ( 121 mg, 33%) as a white solid. MS: m/e = 360.2 [M+H]+.
  • 7
  • [ 75-15-0 ]
  • [ 7466-54-8 ]
  • [ 61019-31-6 ]
YieldReaction ConditionsOperation in experiment
60% With potassium hydroxide for 0.5h; 2.4.2. Synthesis of potassium N-aroylhydrazine carbodithioate General procedure: Potassium N-(pyridine-2-carbonyl)-hydrazine carbodithioate [K+(H2L)-] and potassium N'-(2-methoxybenzoyl)]-hydrazine carbodithioate [K+(H2L')-] were prepared by adding CS2 (1.5 mL, 25 mmol) dropwise to a suspension of picolinic acid hydrazide (2.7 g, 20 mmol) or 2-methoxy benzoic acid hydrazide (3.32 g, 20 mmol) in methanol (30 mL) in the presence of potassium hydroxide (1.2 g, 20 mmol). The reaction mixtures were stirred continuously for 30 min and the solids which separated were filtered off, washed with 10% (v/v) mixture of ethanol ether and dried.
With potassium hydroxide In ethanol at 20℃; for 12h;
With potassium hydroxide In ethanol Inert atmosphere;
With potassium hydroxide In ethanol at 20℃; for 12h;
Stage #1: 2-methoxybenzoylhydrazine With potassium hydroxide In methanol for 0.25h; Stage #2: carbon disulfide at 20 - 25℃; for 3h;
With potassium hydroxide In ethanol
With potassium hydroxide In ethanol
With potassium hydroxide In methanol at 0 - 5℃; Synthesis of 3-Substituted 4-Amino-5-aryl-3H-1,2,4-triazole-3-thiones 5a-j. Potassium hydroxide (0.125 mol) was dissolved in dry methanol (50 mL). To the solution, aryl acid hydrazide 3a-j (0.125 mol) was added and cooled the solution in ice. To this, carbon disulfide (0.125 mol) was added in small portions with constant stirring. The solid product of potassium dithiocarbazate 4a-j was formed, filtered, washed with chilled diethyl ether, dried and was taken in water (20 mL) and hydrazine hydrate (0.250 mol) was added, and followed by refluxed for 10-12 h. The reaction mixture turned to green with evolution of hydrogensulfide and finally it became homogeneous. It was then poured in ice and acidified with 37% hydrochloric acid. The white precipitates was filtered, washed with cold water and recrystallized from aqueous methanol.
With potassium hydroxide In methanol at 20℃; Reflux; General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C.
With potassium hydroxide In ethanol at 20℃; for 15h;
With potassium hydroxide In methanol at 0℃; General procedure: Potassium hydroxide (0.125 mol, 1eq) was dissolved in drymethanol (50 mL). To the solution, substituted acid hydrazides 3(0.125 mol, 1eq) was added and cooled the solution in ice. To this,carbon disulfide (0.125 mol, 1eq) was added with constant stirringfor 1e2 h. The solid product of potassium salt of hydrazinecarbodithioates5 formed, was filtered, washed with chilled diethyl etherand dried. It was directly used for next step without further purification.The potassium salt of hydrazinecarbodithioates 5 wastaken in deionized water (50 mL) and hydrazine hydrate(0.250 mol) was added, followed by reflux overnight. The reactionmixture turned to yellowish green with evolution of hydrogensulfide and finally it became homogeneous. It was then poured incrushed ice and neutralized with hydrochloric acid to afford whiteprecipitates of substituted triazole derivatives 6 which was filtered,washed with cold water and crystallized on methanol.
With potassium hydroxide at 20℃;
With potassium hydroxide In ethanol
With potassium hydroxide In ethanol at 20 - 25℃; for 3h; 5.c c: Dissolve the hydrazide obtained in b in anhydrous ethanol, add dropwise an anhydrous ethanol solution containing 1.25g KOH after it is completely dissolved, and slowly add CS2 until a white solid is produced. The amount of CS2 is 1.2mL. After reacting at 20-25°C for 3 hours, it was filtered off with suction and washed with absolute ethanol several times.

Reference: [1]Location in patent: experimental part Bharty; Bharti; Dani; Dulare; Bharati; Singh [Journal of Molecular Structure, 2012, vol. 1011, p. 34 - 41]
[2]Skoumbourdis, Amanda P.; Huang, Ruili; Southall, Noel; Leister, William; Guo, Vicky; Cho, Ming-Hsuang; Inglese, James; Nirenberg, Marshall; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 4, p. 1297 - 1303]
[3]Skoumbourdis, Amanda P.; LeClair, Christopher A.; Stefan, Eduard; Turjanski, Adrian G.; Maguire, William; Titus, Steven A.; Huang, Ruili; Auld, Douglas S.; Inglese, James; Austin, Christopher P.; Michnick, Stephen W.; Xia, Menghang; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 13, p. 3686 - 3692]
[4]Location in patent: scheme or table Baeeri, Maryam; Foroumadi, Alireza; Motamedi, Maryam; Yahya-Meymandi, Azadeh; Firoozpour, Loghman; Ostad, Seyed N.; Shafiee, Abbas; Souzangarzadeh, Saeid; Abdollahi, Mohammad [Chemical Biology and Drug Design, 2011, vol. 78, # 3, p. 438 - 444]
[5]Location in patent: experimental part Chhabria, Mahesh T.; Suhagia, Bhanubhai N.; Brahmkshatriya, Pathik S.; Raval, Priyesha M. [Arzneimittel-Forschung/Drug Research, 2011, vol. 61, # 8, p. 452 - 457]
[6]Location in patent: scheme or table Yang, Jie; Zhao, Zhigang; Li, Hui [Journal of Chemical Research, 2012, vol. 36, # 7, p. 383 - 386]
[7]Singh, Mamata; Bharty, Manoj K.; Singh, Aarti; Kashyap, Sujata; Singh, Udai P.; Singh, Nand K. [Transition Metal Chemistry, 2012, vol. 37, # 8, p. 695 - 703] Shi, Zhichuan; Zhao, Zhigang; Huang, Meiwei; Fu, Xiaolin [Comptes Rendus Chimie, 2015, vol. 18, # 12, p. 1320 - 1327]
[8]Rafiq, Muhammad; Saleem, Muhammad; Hanif, Muhammad; Maqsood, Muhammad Rizwan; Rama, Nasim Hasan; Lee, Ki-Hwan; Seo, Sung-Yum [Bulletin of the Korean Chemical Society, 2012, vol. 33, # 12, p. 3943 - 3949]
[9]Li, Liangjing; Ding, Hao; Wang, Baogang; Yu, Shichong; Zou, Yan; Chai, Xiaoyun; Wu, Qiuye [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 1, p. 192 - 194]
[10]Xie, Wenlin; Zhang, Jingai; Ma, Xiaojing; Yang, Wenqian; Zhou, Ying; Tang, Xufu; Zou, Yan; Li, Hui; He, Jingjing; Xie, Shimin; Zhao, Yunhui; Liu, Fengping [Chemical Biology and Drug Design, 2015, vol. 86, # 5, p. 1087 - 1092]
[11]Rafiq, Muhammad; Saleem, Muhammad; Jabeen, Farukh; Hanif, Muhammad; Seo, Sung-Yum; Kang, Sung Kwon; Lee, Ki Hwan [Journal of Molecular Structure, 2017, vol. 1138, p. 177 - 191]
[12]Jin, Ru-Yi; Zeng, Chu-Yue; Liang, Xu-Hua; Sun, Xiao-Hong; Liu, Yuan-Fa; Wang, Yan-Yan; Zhou, Sha [Bioorganic Chemistry, 2018, vol. 80, p. 253 - 260]
[13]Jin, Ruyi; Wang, Yanyan; Guo, Hui; Long, Xu; Li, Jiajia; Yue, Shijun; Zhang, Shuan; Zhang, Guanghui; Meng, Qinghua; Wang, Chuan; Yan, Hao; Tang, Yuping; Zhou, Sha [Journal of Molecular Structure, 2020, vol. 1202]
[14]Current Patent Assignee: NORTHWESTERN UNIVERSITY (ILLINOIS) - CN112125860, 2020, A Location in patent: Paragraph 0100; 0105
  • 8
  • [ 1051929-62-4 ]
  • [ 7466-54-8 ]
  • [ 1051929-64-6 ]
YieldReaction ConditionsOperation in experiment
37.3% With 2-chloro-1,3-dimethylimidazolinium chloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h; 13.2 Step 2 tert-butyl 4-(5-(5-(2-methoxyphenyl)-1 ,3,4-oxadiazol-2-yl)-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)piperidine-1 -carboxylate (102); [0278] Triethylamine (0 46 mL, 3 3 mmol) was added to a solution of 101 (300 mg, 0 826 mmol), 2-methoxybenzhydride (137 mg, 0 826 mmol) and 2-Chloro-1 ,3-dimethylimidazolinium chloride (279 mg, 1 651 mmol) in DMF (4 13 mL) The mixture was stirred for 16h at room temperature, then saturated NaHCO3 was added and the mixture was extracted with EtOAc After work-up the residue was purified via Biotage (5% to 40% EtOAc/Hexane, 25M column) to give 102 (152 mg, 37 3% yield) as white solid LRMS (ESI) calc 493 5, found 494 4 (MH)+
  • 9
  • [ 1051928-71-2 ]
  • [ 7466-54-8 ]
  • (S)-tert-butyl 1-((4-(5-(2-(2-methoxybenzoyl)hydrazinecarbonyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 20h; 1j.1 Example 1j; (S)-2-amino-N-((4-(5-(5-(2-methoxyphenyl)-1 ,3,4-oxadiazol-2-yl)-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)thiophen-2-yl)methyl)propanamide (18); Step 1 (S)-tert-butyl 1 -((4-(5-(2-(2-methoxybenzoyl)hydrazinecarbonyl)-3-(trifluoromethyl)-1 H- pyrazol-1-yl)thiophen-2-yl)methylamino)-1-oxopropan-2-ylcarbamate (16); [0192] To a solution of 2-methoxybenzhydrazide (0 040 g, 0 238 mmol) and compound 7 (preparation described in scheme 2 example 1 c, step 7) (0 1 1 g, 0 238 mmol) in dichloromethane (2ml_) under nitrogen was added EDC (0 046 g, 0 238 mmol) followed by DMAP (5 81 mg, 0 048 mmol) The reaction was left to stir for 16 hours at room temperature Another portion of EDC (20mg, 0 104mmol) was added and the reaction continued for 4 hours The solvent was then removed on the rotary evaporator and the crude purified by silica gel column chromatography with a Biotage 12M column and a gradient of 0-5% methanol in dichloromethane to give compound 16 as a yellow crust (73 7mg, 51 %) LRMS (ESI) calc 610 2, found 51 1 2 (MH-BoC)+, 633 3 (MNa)+
  • 10
  • [ 7466-54-8 ]
  • [ 1204-75-7 ]
  • [ 1186469-90-8 ]
YieldReaction ConditionsOperation in experiment
95% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dimethyl sulfoxide; for 16h; To compound 2a (150mg, 0.79mmol) was added 2- methoxybenzohydrazide (171 mg, I .Ommol), EDCI (228mg, 1.19mmol), HOBt (161mg, 1.19mmol), and DMSO (6mL) and the solution was stirred for 16h. To the solution was added H2O (15OmL), stirred for 20min, filtered solid, and dried to yield compound 49b (255mg, 95%).
  • 11
  • [ 579-75-9 ]
  • [ 7466-54-8 ]
YieldReaction ConditionsOperation in experiment
95% Stage #1: 2-Methoxybenzoic acid With oxalyl dichloride In methanol; chloroform; N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere; Stage #2: With hydrazine hydrate In methanol; ethanol; chloroform; N,N-dimethyl-formamide at 100℃; for 2h; Microwave irradiation; 138.138-1 Example 138-1: Synthesis of 2-methoxy benzohydrazide 2-methoxy-benzoic acid(4 g, 26.3 mmol) in chloroform (50 ml) solution of an argon atmosphere, was added dropwise oxalyl chloride (2.42 ml, 27.6 mmol) at room temperature. DMF (20 μl, 0.26 mmol) was stirred for 2 hours was dropped. It was added dropwise methanol (25 ml),After stirring overnight, it was concentrated to dryness under reduced pressure.Ethanol of the residue (4 ml) solution in hydrazine monohydrate (3.83 ml, 79mmol)It was dropped, under microwave irradiation,It was stirred for 2 hours at 100 . After it was concentrated to dryness under reduced pressure, saturated brine, saturated aqueous sodium hydrogen carbonate solution was added, followed by extraction with chloroform. Dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To give the title compound (4.16 g, 95%).
85% With hydrazine at 250℃; Microwave irradiation; 1 6.2.1. Microwave assisted synthesis of acyl hydrazides General procedure: Acyl hydrazides were synthesized in excellent yields from thereaction of substituted aryl acids (0.010 mol) with hydrazine hydrate(0.012 mol) in absence of organic solvents under microwaveirradiation (300 W, 250 C) for 4e8 min. Spectral analysis of thesynthesized hydrazides are consistent with the proposed structuresand with those reported [58].
78% Stage #1: 2-Methoxybenzoic acid With sulfuric acid In ethanol for 6h; Reflux; Stage #2: With hydrazine hydrate; sodium hydrogencarbonate; acetic acid Reflux;
Multi-step reaction with 2 steps 1: thionyl chloride / 0.07 h / Microwave irradiation 2: hydrazine hydrate / 0.05 h / Microwave irradiation
Multi-step reaction with 2 steps 1: thionyl chloride 2: hydrazine hydrate
Stage #1: 2-Methoxybenzoic acid With sulfuric acid at 20℃; for 12h; Stage #2: With hydrazine for 12h; Reflux;
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: thionyl chloride / Microwave irradiation 2: hydrazine hydrate / Microwave irradiation; Reflux
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 0.3 h / Reflux; Microwave irradiation 2: hydrazine hydrate / ethanol / 0.22 h / Reflux; Microwave irradiation
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / methanol / Reflux
Multi-step reaction with 2 steps 1: 8 h / Reflux 2: hydrazine hydrate / 6 h / Reflux
Multi-step reaction with 2 steps 1: thionyl chloride / 20 °C 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / methanol
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate
Multi-step reaction with 2 steps 1: sulfuric acid / water / 6 h / Reflux 2: hydrazine hydrate / water; ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / methanol
Multi-step reaction with 2 steps 1: thionyl chloride / 20 °C 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: Reflux 2: hydrazine hydrate / Reflux
Multi-step reaction with 2 steps 1: trichlorophosphate / 1,2-dichloro-ethane / 3 h / Reflux 2: triethylamine; hydrazine hydrate / acetonitrile / 3 h / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / water / 12 h / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / methanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 85 °C 2: hydrazine hydrate / methanol / 14 h / 85 °C
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate / ethanol / 6 h / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / ethanol
Multi-step reaction with 2 steps 1: thionyl chloride / 1 h / 40 °C 2: hydrazine hydrate / methanol / 4 h / 65 °C
Multi-step reaction with 2 steps 1: thionyl chloride / methanol / 1 h / 40 °C 2: hydrazine hydrate / methanol / 4 h / 65 °C
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate
Multi-step reaction with 2 steps 1: sulfuric acid / 8 h / Reflux 2: hydrazine hydrate / methanol / 4 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid / 24 h / Reflux 2: hydrazine hydrate / ethanol / Reflux
Multi-step reaction with 2 steps 1: sulfuric acid 2: hydrazine hydrate / ethanol
Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / Reflux

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  • 12
  • [ 7466-54-8 ]
  • [ 2284-20-0 ]
  • [ 483283-17-6 ]
YieldReaction ConditionsOperation in experiment
In ethanol for 8h; Reflux; 1.a 2-methoxybenzoyl hydrazide (Lancaster; 0.2 mol) was dissolved in ethanol (100 mL). 4-methoxyphenyl isothiocyanate (Acros; 0.22 mol) was added to this solution. The mixture was maintained under reflux stirring for 8 hours. A control TLC performed after this time showed the formation of the thioureido intermediate. A 15% aqueous solution of KOH (0.24 mol.) was added at this point. The resulting mixture was reflux heated under stirring for 20 h. On completion of the reaction (TLC control) the reaction mixture was concentrated at low pressure. The residue obtained was diluted with water (200 mL) and acidified at pH 4.5 with 2N HC1. The precipitate formed was separated by filtration, washed with water and dried. The crude product was crystallised with dimethylformamide, giving 4-(4-mefhoxyphenyl)-5-(2- methoxyphenyl)-4H-[l,2,4]triazol-3 -thiol (46 g, 74%).
  • 13
  • [ 7466-54-8 ]
  • [ 86265-88-5 ]
  • N'-(3-bromo-4-chlorobenzylidene)-2-methoxybenzohydrazide [ No CAS ]
  • 14
  • [ 7466-54-8 ]
  • [ 5711-59-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ethanol / 70 °C 2: sodium hydroxide; potassium iodide; iodine; water / ethanol / 70 °C
  • 15
  • [ 7466-54-8 ]
  • [ 148-53-8 ]
  • [ 309939-68-2 ]
YieldReaction ConditionsOperation in experiment
93% In methanol
93% In methanol
87% In methanol at 20℃; for 0.5h; Synthesis of H2L1: 3-Methoxysalicylaldehyde (1.0 mmol, 0.152 g) and 2-methoxybenzohydrazide (1.0 mmol, 0.166 g) were dissolved in methanol (30 mL) with stirring. The mixture was stirred for about 30 min at room temperature to give a colorless solution. The solvent was evaporated to give colorless crystalline product of H2L1.
  • 16
  • [ 492-88-6 ]
  • [ 7466-54-8 ]
  • [ 443966-26-5 ]
YieldReaction ConditionsOperation in experiment
92% In methanol at 20℃; for 0.5h; Synthesis of H2L2 3-Ethoxysalicylaldehyde (1.0 mmol, 0.166 g) and 2-methoxybenzohydrazide (1.0 mmol, 0.166 g) were dissolved in methanol (30 mL) with stirring. The mixture was stirred for about 30 min at room temperature to give a colorless solution. The solvent was evaporated to give colorless crystalline product of H2L2.
In methanol at 20℃;
  • 17
  • [ 7466-54-8 ]
  • [ 94695-48-4 ]
  • [ 1542993-14-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine In chloroform at 20℃; for 2h;
  • 18
  • [ 7466-54-8 ]
  • [ 98-88-4 ]
  • [ 6781-63-1 ]
YieldReaction ConditionsOperation in experiment
95% With triethylamine In chloroform at 20℃; for 2h;
95% With triethylamine In chloroform at 20℃; for 2h;
With triethylamine In chloroform at 20℃; for 2h; Inert atmosphere; Synthesis of the ancillary ligands (HLX) General procedure: 5-fluoro-benzoyl chloride (1.58 g, 10 mmol) was added dropwise to a solution of 2-methoxybenzohydrazine (1.66 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in chloroform (20 mL) at room temperature. The mixture was stirred for 2 h and then filtered. The solid was washed with water and ethanol to give N-(4-fluorobenzoyl)-2-methoxybenzohydrazine (2.59 g, 90%yield). A mixture of N-(4-fluorobenzoyl)-2-methoxybenzo-hydrazine and POCl3 (20 mL) in a 50 mL flask was refluxed under nitrogen for 5 h. The excessive POCl3 was then distilled out, and the residue was poured into water. The crude solid product was purified by recrystallization from chloroform/hexane to give 2-(4-fluorophenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole (2.30 g, 85% yield). Then, to a mixture of 2-(4-fluorophenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole (2.30 g) in 50 mL CH2Cl2 at 78C was added BBr3 (12.5 g, 50 mmol in 20 mL CH2Cl2) dropwise. The mixture was stirred for 24 h at 78 C and the resulting solution was poured into water, extracted with CH2Cl2 (50 mL 3 times) and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and recrystallization of the residue from ethanol gave colorless crystal of 2-(5-(4-fluoro-phenyl)-1,3,4-oxadiazol-2-yl)phenol (HFPOP) with 87% yield.
In chloroform at 20℃; for 1h; General syntheses of 2-(5-phenyl-1,3,4-thiadiazol-2-yl)-phenol derivatives (L4 - L6) 2-Methoxybenzohydrazide (10 mmol) was dissolved in 50 mL CHCl3, and benzoyl chloride (10 mmol) was added dropwise for 1 h at room temperature. Then, the solvent was removed under vacuum gave benzoyl-2-methoxybenzohydrazine as pale yellow solid with high yield. Benzoyl-2-methoxybenzohydrazine (3.7 mmol) and phosphorus pentasulfide (4.4 mmol) were stirred in 40 mL dimethylbenzene at 140 °C for 3 h. Water (about 20 mL) was added till no more gas generated. The mixture was washed with water (40 mL x 3 times) and then dried over anhydrous sodium sulfate. Silica column chromatography purification (petroleum ether:EtOAc 4: 1 as eluent) gave white powder. The powder was dissolved in CH2Cl2 followed by adding BBr3 carefully at -78 °C and stirred at room temperature for 20 h. Colorless crystal was recrystallized from ethanol. In order to be easier for further reactions, the ligand was reacted with equivalent KOH to give KLX (LX represents the ancillary ligand).
Inert atmosphere;

  • 19
  • [ 7466-54-8 ]
  • [ 18233-24-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 °C 2: trichlorophosphate / 5 h / Inert atmosphere; Reflux 3: boron tribromide / dichloromethane / 24 h / -78 °C
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 °C / Inert atmosphere 2: trichlorophosphate / 5 h / Reflux; Inert atmosphere 3: boron tribromide / dichloromethane / 24 h / -78 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: chloroform / 1 h / 20 °C 2: trichlorophosphate 3: boron tribromide / dichloromethane / 20 h / -78 °C
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 °C 2: trichlorophosphate / 5 h / Reflux; Inert atmosphere 3: boron tribromide / dichloromethane / 24 h / -78 °C
Multi-step reaction with 3 steps 1: triethylamine / chloroform / 2 h / 20 °C 2: trichlorophosphate / 5 h / Inert atmosphere; Reflux 3: boron tribromide / dichloromethane / 24 h / -78 °C / Inert atmosphere

  • 21
  • [ 7466-54-8 ]
  • [ 1711-07-5 ]
  • [ 331988-91-1 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In chloroform at 20℃; for 2h; Inert atmosphere; Synthesis of the ancillary ligands (HLX) 5-fluoro-benzoyl chloride (1.58 g, 10 mmol) was added dropwise to a solution of 2-methoxybenzohydrazine (1.66 g, 10 mmol) and triethylamine (1.01 g, 10 mmol) in chloroform (20 mL) at room temperature. The mixture was stirred for 2 h and then filtered. The solid was washed with water and ethanol to give N-(4-fluorobenzoyl)-2-methoxybenzohydrazine (2.59 g, 90%yield). A mixture of N-(4-fluorobenzoyl)-2-methoxybenzo-hydrazine and POCl3 (20 mL) in a 50 mL flask was refluxed under nitrogen for 5 h. The excessive POCl3 was then distilled out, and the residue was poured into water. The crude solid product was purified by recrystallization from chloroform/hexane to give 2-(4-fluorophenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole (2.30 g, 85% yield). Then, to a mixture of 2-(4-fluorophenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole (2.30 g) in 50 mL CH2Cl2 at 78C was added BBr3 (12.5 g, 50 mmol in 20 mL CH2Cl2) dropwise. The mixture was stirred for 24 h at 78 C and the resulting solution was poured into water, extracted with CH2Cl2 (50 mL 3 times) and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and recrystallization of the residue from ethanol gave colorless crystal of 2-(5-(4-fluoro-phenyl)-1,3,4-oxadiazol-2-yl)phenol (HFPOP) with 87% yield.
  • 22
  • [ 7466-54-8 ]
  • C39H60O8 [ No CAS ]
  • C47H68N2O9 [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With phosphotungstic acid In N,N-dimethyl-formamide at 60℃; for 4h; 3.6.1. Brevenal Derivatives General procedure: In a typical reaction, brevenal was dissolved in DMF and the hydrazide (2 eq) was added, followed by addition of a catalytic amount of tungstophosphoric acid. The reaction mixture was heated at 60 °C for 4 h. The solvents were evaporated under vacuum and the residue was taken up in methanol. The mixture was filtered through a 0.2 μm nylon filter and subjected to purification by HPLC. Desired products were positively identified by HRMS mass spectrometry and NMR. Spectroscopic data collected for all compounds can be found in the supplementary data document.
  • 23
  • [ 7466-54-8 ]
  • [ 933-88-0 ]
  • 2-(2-methoxyphenyl)-5-(o-tolyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With camphor-10-sulfonic acid In 1,4-dioxane at 100℃; for 16h;
79% 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]
  • 24
  • [ 824-42-0 ]
  • [ 7466-54-8 ]
  • (E)-N′-(2-hydroxy-3-methylbenzylidene)-2-methoxybenzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% In methanol at 20℃; for 0.5h; 2.2. Synthesis of the hydrazones The hydrazones were synthesized as follows. To a stirred methanolic solution (30 mL) of 2-methoxybenzohydrazide (0.02 mol) was added a methanolic solution (20 mL) of3-bromosalicylaldehyde or 3-methylsalicylaldehyde (0.02 mol). The mixtures were stirred for 30 min at room temperature and left to slowly evaporate to give colorless crystalline products, which were recrystallized from methanol and dried under vacuum in the presenceof anhydrous CaCl2. For HLa: Yield 83%. IR data (cm-1): 3447, 3311, 1659, 1605, 1516, 1473, 1393, 1344,1283, 1235, 1174, 1135, 1011, 939, 793, 750, 667, 552, 518. UV-vis data (MeOH, λmax,nm): 292, 328. Anal. Calcd for C15H13BrN2O3: C, 51.6; H, 3.7; N, 8.0. Found: C, 51.7; H,3.9; N, 7.9%. 1H NMR (300 MHz, d6-DMSO): δ 12.58 (s, 1H), 11.91 (s, 1H), 8.54 (s, 1H),7.69 (dd, J = 7.6, 1.7 Hz, 1H), 7.63 (dd, J = 7.9, 1.3 Hz, 1H), 7.55 (m, 1H), 7.47 (dd,J = 7.7, 1.4 Hz, 1H), 7.20 (d, 1H), 7.09 (t, 1H), 6.91 (t, 1H), 3.90 (s, 3H). For HLb: Yield87%. IR data (cm-1): 3453, 3305, 1651, 1608, 1525, 1470, 1398, 1353, 1292, 1245, 1172,1152, 1020, 973, 888, 745, 521. UV-vis data (MeOH, λmax, nm): 292, 332. Anal. Calcd forC16H16N2O3: C, 67.6; H, 5.7; N, 9.8. Found: C, 67.4; H, 5.6; N, 10.0%. 1H NMR(300 MHz, d6-DMSO): δ 11.90 (s, 1H), 11.75 (s, 1H), 8.51 (s, 1H), 7.68 (dd, J = 7.6,1.7 Hz, 1H), 7.54 (m, 1H), 7.3-7.0 (m, 4H), 6.85 (t, 1H), 3.90 (s, 3H), 2.04 (s, 3H).
  • 25
  • [ 7466-54-8 ]
  • [ 219861-08-2 ]
  • (S)-3-{1-(4-fluorophenyl)-5-[5-(2-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-1,3-dihydroisobenzofuran-1-yl}-N,N-dimethylpropan-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With potassium carbonate In butan-1-ol at 150℃; 26 Synthesis of escitalopram triazoles General procedure: The triazoles of escitalopram (60-88) were synthesized byfollowing a reported method for triazole formation.25 A mixtureof a benzohydrazide (33 mmol), escitalopram (59-oxalate,10 mmol) and K2CO3 (0.5 mmol) in n-butanol (2 mL) was heatedat 150 C for 5-6 h. The reaction was monitored with TLC. Afterthe completion of the reaction, the solvent was removed underreduced pressure. Finally, the triazole derivatives of escitalopram(60-88) were purified with column chromatography using solventsystem CH3OH/CH3Cl = 60:40 and finally with preparative thinlayer chromatography.
  • 26
  • [ 7466-54-8 ]
  • [ 139-85-5 ]
  • 4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzene-1,2-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 27
  • [ 7466-54-8 ]
  • [ 123-08-0 ]
  • 4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 28
  • [ 7466-54-8 ]
  • [ 90-02-8 ]
  • 2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 29
  • [ 673-22-3 ]
  • [ 7466-54-8 ]
  • 5-methoxy-2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 30
  • [ 672-13-9 ]
  • [ 7466-54-8 ]
  • 4-methoxy-2-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 31
  • [ 621-59-0 ]
  • [ 7466-54-8 ]
  • 2-methoxy-5-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 32
  • [ 2973-78-6 ]
  • [ 7466-54-8 ]
  • 2-bromo-4-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 33
  • [ 7466-54-8 ]
  • [ 138490-94-5 ]
  • 2-iodo-6-methoxy-3-(5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl)phenol [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 34
  • [ 7466-54-8 ]
  • [ 120-14-9 ]
  • 2-(3,4-dimethoxyphenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 35
  • [ 7311-34-4 ]
  • [ 7466-54-8 ]
  • 2-(3,5-dimethoxyphenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 36
  • [ 7466-54-8 ]
  • [ 123-11-5 ]
  • [ 93014-12-1 ]
YieldReaction ConditionsOperation in experiment
68% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 37
  • [ 1121-60-4 ]
  • [ 7466-54-8 ]
  • 2-(2-methoxyphenyl)-5-(pyridin-2-yl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 38
  • [ 500-22-1 ]
  • [ 7466-54-8 ]
  • 2-(2-methoxyphenyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 39
  • [ 872-85-5 ]
  • [ 7466-54-8 ]
  • 2-(2-methoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 40
  • [ 98-03-3 ]
  • [ 7466-54-8 ]
  • 2-(2-methoxyphenyl)-5-(thiophen-2-yl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 41
  • [ 7466-54-8 ]
  • [ 1571-08-0 ]
  • [ 1424272-40-1 ]
YieldReaction ConditionsOperation in experiment
51% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 42
  • [ 7466-54-8 ]
  • [ 555-16-8 ]
  • 2-(2-methoxyphenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 43
  • [ 7466-54-8 ]
  • [ 77771-02-9 ]
  • 2-(3-bromo-4-fluorophenyl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With [bis(acetoxy)iodo]benzene; In dichloromethane; at 20℃; General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 44
  • [ 7466-54-8 ]
  • [ 459-57-4 ]
  • [ 666208-24-8 ]
YieldReaction ConditionsOperation in experiment
65% With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; Synthesis 2-(2-methoxyphenyl)-5-phenyl-1,3,4-oxadiazole (1-25) General procedure: A mixture of 2-methoxybenzohydrazide and benzaldehyde derivatives (1 mmol) each and equivalent amount of PhI(OAc)2 was stirred in dichloromethane (10 ml) at room temperature. The solvent was evaporated and the residue was washed with diethyl ether, filtered, dried and then crystallized from ethanol to afford desired compounds 1-25.
  • 45
  • [ 7466-54-8 ]
  • [ 4659-45-4 ]
  • 2-methoxy-N'-(2,6-dichlorobenzoyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With triethylamine In acetonitrile at 20℃; Reflux; 2-Methoxy-N'-(2,6-dichlorobenzoyl)benzohydrazide (2b) General procedure: 2 mL of triethylamine and 0.73 g (0.004 mol) of 2,6-dichlorobenzoyl chloride in 15 mL of anhydrous acetonitrile were added to a stirred solution of 0.39 g (0.003 mol) of salicylic acid hydrazide 1a in 20 mL of anhydrous acetonitrile. The reaction mixture was incubated at room temperature overnight and then refluxed during 10 h. The solvent was removed in vacuum; the oily residue was washed with water (2 ×10 mL), dried, and purified by chromatography on silica gel (0.063-0.200 μm; ethyl acetate-petroleum ether, 1 : 5 as eluent) collecting the fraction with Rf=0.70. After distilling off the solvent, the product was recrystallized from propan-2-ol. Yield 0.73 g (85%), colorless crystals, mp 139-140 °C. IR spectrum, ν, cm-1: 763, 792, 855, 1005, 1010, 1156, 1158, 1236, 1249, 1360, 1467, 1466, 1491, 1499, 1564, 1594, 1598(C=C); 1668, 1701 (C=O); 3037 (NH), 3280 (OH). 1H NMR spectrum (CDCl3), δ, ppm: 7.08-7.12 m (2H, HAr), 7.23-7.39 m (4H, HAr), 7.57 and 7.61 d.d (1H, HAr, J1 = 7.5, J2 = 7.6 Hz), 10.40 d (1H, NH, J =7.6 Hz), 11.21 d (H, NH, J = 7.6 Hz). 13C NMR spectrum (DMSO-d6), δ, ppm: 116.15, 116.46, 118.84, 128.63, 129.37, 132.02, 132.38, 133.79, 133.99, 159.69, 160.15 (C=O), 161.35 (C=O). Found, %: C 51.80; H 3.06; N 8.60. C14H10Cl2N2O3. Calculated, %: C 51.72; H 3.10; N 8.62.
  • 46
  • [ 7466-54-8 ]
  • [ 62-53-3 ]
  • [ 6833-21-2 ]
YieldReaction ConditionsOperation in experiment
75% With tert.-butylhydroperoxide; iron(III) chloride In water; acetonitrile at 80℃; for 2h; Inert atmosphere; General procedure for preparation of compounds 3 or 4 General procedure: To a Schlenk tube equipped with a rubber septum was successively added acylhydrazine 1 (1 mmol), amine 2 (1 mmol), FeCl3 (16.2 mg, 10 mol %) and acetonitrile (10 mL). The tube was evacuated and purged with argon three times. Then TBHP (70% in H2O (6 mmol), was slowly added and the mixture allowed to stir for 2 hours at 80 oC. After the completion of reaction (indicated by TLC), the reaction mixture was concentrated under reduced pressure and the crude mixture was purified by column chromatography using acetone/petroleum ether (v/v 1:10) as eluent to obtain the pure products 3 or 4.
66% With tert.-butylhydroperoxide; iron(III) chloride In acetonitrile at 80℃; 32 Example 32: Synthesis of N-phenyl-2-methoxybenzamide Using 2-methoxybenzohydrazide and aniline as raw material, the reaction steps are as follows: In the reaction flask was added 0.083 g (0.5 mmol) of 2-methoxybenzohydrazide, aniline 0.0465 g (0.5 mmol), 0.0081 g (0.05 mmol) of iron trichloride, tert-butyl hydroperoxide (0.3 mL, 3 mmol) and 5 mL of acetonitrile at 80 °C; TLC followed the reaction until complete; The crude product obtained after the end of the reaction was separated by column chromatography (petroleum ether: ethyl acetate = 10: 1) to give the object product (yield 66%).
  • 47
  • benzyl 2-(5-bromo-2-methoxybenzoyl)hydrazine carboxylate [ No CAS ]
  • [ 7466-54-8 ]
YieldReaction ConditionsOperation in experiment
49.7% With palladium 10% on activated carbon; hydrogen In methanol; ethyl acetate at 20℃; for 1h; 132.132-2 Example 132-2: Synthesis 2-methoxy benzohydrazide The compound obtained in Example 132-1 (1.048 g, 2.76 mmol) was dissolved in methanol (60 ml), ethyl acetate (40 ml). 10% palladium on carbon (105 mg) was added. Under a hydrogen atmosphere and stirred at room temperature for 1 hour. After the reaction, the reaction mixture was filtered through Celite, and the solvent was evaporated. The residue was purified by silica gel column chromatography (SNAP 50 g, chloroform / methanol) to give the title compound (228 mg, 49.7%) as a yellow solid.
  • 48
  • [ 5683-31-8 ]
  • [ 7466-54-8 ]
  • 2-methoxy-N'-(3-(trimethylsilyl)propionoyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
56.6% 3- (trimethylsilyl)Propyne acid (195 mg, 1.37 mmol) was dissolved in dichloromethane (4 ml). Oxalyl chloride thereto (0.123 ml, 1.44 mmol), and stirred for 2 hours at room temperature was added a DMF (1 drop). The compound obtained in Example 132-2 thereto (228 mg, 1.37 mmol), triethylamine (0.229 ml, 1.64 mmol) and stirred overnight at room temperature added. After the reaction was washed with saturated brine by the addition of chloroform. Dried with magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (SNAP Ultra 25 g, hexane / ethyl acetate) to give the title compound (225 mg, 56.6%) as a white solid.
  • 49
  • [ 2476-35-9 ]
  • [ 7466-54-8 ]
  • 50
  • [ 7466-54-8 ]
  • [ 34374-88-4 ]
  • C33H30N6O9 [ No CAS ]
  • 51
  • [ 7466-54-8 ]
  • [ 18063-02-0 ]
  • 2,6-difluoro-N'-(2-methoxybenzoyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With triethylamine In acetonitrile at 20℃; for 10h; Reflux; 2,6-Difluoro-N'-(2-hydroxybenzoyl)benzohydrazide (2a). General procedure: To a solution of 0.76 g (0.005 mol) of salicylic acid hydrazide 1a in 20 mL of anhydrous acetonitrile were added sequentially 2 mL of triethylamine and 0.88 g (0.005 mol) of 2,6-difluorobenzoyl chloride in 15 mL of anhydrous acetonitrile. The reaction mixture was left to stand at room temperature overnight, and then refluxed for 10 h. The solvent was removed in a vacuum, the oily residue was washed with water (2×10 mL) and dried in air. The target product was isolated by column chromatography on silica gel (0.063-0.200 mm, eluent ethyl acetate-petroleum ether, 1 : 5), collecting the fraction with Rf 0.70. Afterd stilling off the solvent the product was recrystallized from 2-propanol (2×15 mL). Yield 1.17 g (80%), colorless crystals, mp 194-196°C.
  • 52
  • [ 24372-49-4 ]
  • [ 7466-54-8 ]
  • (E)-2-methoxy-N'-((5-morpholinothiophen-2-yl)methylene)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With acetic acid In methanol Reflux; 4.2. Synthetic protocol for morpholinothiophene hydrazones derivatives General procedure: Equimolar quantities (1 mmol) of 5-morpholinothiophene-2- carbaldehyde and appropriate substituted arylhydrazides in methanol (25 mL) were refluxed for 3 h in the presence of catalytic amount of glacial acetic acid. The resulting solid was filtered and crystallized in methanol in good yields.
  • 53
  • [ 7466-54-8 ]
  • [ 938-18-1 ]
  • 2,4,6-trimethyl-N'-(2-methoxybenzoyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With triethylamine In acetonitrile at 20℃; for 27h; Reflux; N'-Benzoyl-2,4,6-trimethylbenzohydrazide (2a). General procedure: To solution of 1.36 g (10 mmol) of benzohydrazide 1 in 20 mL of dried acetonitrile at stirring was added in succession 5 mL of triethylamine and 2.01 g (11 mmol) of 2,4,6-trimethylbenzoyl chloride in 30 mL of dried acetonitrile. The reaction mixture was left for 24 h at room temperature and afterwards it was boiled for 3 h. The solvent was removed in a vacuum, oily residue was washed with water (2 × 10 mL), dried in air, the reaction product was isolated by column chromatography on silica gel (0.063-0.200 mm, eluent ethylacetate-petroleum ether, 1 : 2), collecting fraction with Rf 0.75. After distilling off the solvent the residue was recrystallized from 2-propanol (2 × 15 mL). Yield 2.40 g (85%), colorless crystals, mp. 203-204° (mp. 202-205° [15, 16]). IR spectrum (KBr), ν, cm-1: 3240, 3174 (NH); 1685, 1637 (C=O); 1616, 1599 (C=C); 1551, 1516, 1489, 1461, 1448, 1379, 1259, 1243, 1170, 1103, 1070, 1027, 1002, 986, 847, 784, 782. 1H NMR spectrum (CDCl3), δ, ppm: 2.28 s (3H, 4-CH3), 2.35 s (6H, 2,6-CH3), 6.86 s (2Harom), 7.48 d.d (2Harom, J1 7.9, J2 7.5 Hz), 7.52 d.d (1Harom, J1 7.5, J2 1.4 Hz), 7.83 d.d (2Harom, J1 7.9, J2 1.5 Hz), 8.63 d (1H, NH, J=2.5 Hz), 9.45 d (1H, NH, J=2.5 Hz). 13C NMR spectrum (CDCl3), δ, ppm: 19.92 (2,6-CH3), 21.16 (4-CH3), 123.85 (Carom. quat.), 126.89 (Carom), 128.24 (2Carom), 129.12 (Carom), 131.55 (Carom.quat.), 131.82 (Carom), 135.11 (2Carom.quat.), 139.21 (Carom.quat.), 168.33 (C=O), 173.34 (C=O). Found, %: 72.25; 6.44; N 9.97. C17H18N2O2. Calculated, %: 72.32; 6.43; N 9.92.
  • 54
  • [ 80194-68-9 ]
  • [ 7466-54-8 ]
  • 2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-(2-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]
  • 55
  • [ 7466-54-8 ]
  • [ 1989-53-3 ]
  • N'-(2-methoxybenzoyl)-2,6-dimethoxybenzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With triethylamine In acetonitrile at 20℃; for 27h; Reflux; N'-Benzoyl-2,6-dimethoxybenzohydrazide (2a). General procedure: To a solution of 1.36 g (0.01 mol) of benzoic acid hydrazide 1a in 20 mL of anhydrous acetonitrile, 5 mL of triethylamine and 2.01 g (0.01 mol) of 2,6-dimethoxybenzoic acid chloride in 30 mL of anhydrous acetonitrile were added successively with stirring. The reaction mixture was left for 1 day at room temperature and then refluxed for 3 h. The solvent was distilled off in a vacuum to give an oily residue which was washed with water (2 × 10 mL) and air-dried, whereupon the resulting product was isolated by column chromatography (eluent ethyl acetate-petroleum ether, 1 : 2), with the Rf 0.75-0.78 fraction being collected. After the solvent was distilled off, the product was recrystallized from 2-propanol (2 × 15 mL).
  • 56
  • [ 7466-54-8 ]
  • [ 611-73-4 ]
  • [ 1874-42-6 ]
YieldReaction ConditionsOperation in experiment
83% With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 24h; Sealed tube; Irradiation; General procedure for synthesis of 2,5-diaryl 1,3,4-oxadiazoles and reuse of the catalyst: General procedure: A sealed tube equipped with a magnetic stir bar was charged with acylhydrazine 1 (0.5 mmol), α-keto acid 2 (0.5 mmol), K2CO3 (1 mmol), PANI-g-C3N4-TiO2 (40 mg) and DMF (5.0 mL). The mixture was then irradiated with a 14 W CFL and stirred at room temperature (25 °C) for 24 h. The distance of the reaction vial from the light is about 5 centimeters. After reaction, the mixture was diluted with EtOAc (10 mL) and H2O (5 mL), and the solid catalyst was recovered by centrifugation. The aqueous phase was extracted with EtOAc (5 mL × 3). The collected organic extracts were dried on Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography on silica gel using a mixture of PE/EA (20:1) to give the pure product 3.
  • 57
  • [ 7466-54-8 ]
  • 5-(4-(methylthio)phenyl)furan-2-carboxylic acid [ No CAS ]
  • N'-(2-methoxybenzoyl)-5-(4-(methylthio)phenyl)furan-2-carbohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% Stage #1: 5-(4-(methylthio)phenyl)furan-2-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; Stage #2: 2-methoxybenzoylhydrazine In N,N-dimethyl-formamide at 0 - 20℃; 4.1.3 Synthesis of substituted N′-benzoyl-5-phenylfuran-2-carbohydrazide/N′-benzoyl-5-phenylthiophene-2-carbohydrazide (3a-3h) General procedure: 5-Phenylfuran/thiophene-2-carboxylic acid (0.0004mol) was dissolved in 11 DMF (2mL) at room temperature. HOBt (0.00051mol) was added in one portion followed by EDC.HCl (0.00051mol). The mixture was stirred at room temperature and the reaction progress was monitored by TLC until all of the acid was disappeared from the reaction mixture. The resulting mixture was then slowly added to a solution of substituted hydrazide (0.0004mol) in DMF (2mL) while the temperature was maintained at 0-5°C. Then reaction was allowed to stirred at room temperature for 6-10h. After completion of the reaction, the reaction mixture was dissolved in 54 water followed by partitioning with EtOAc (25×4mL). The EtOAc layer was passed over anhydrous sodium sulfate to remove residual water and then dried under vacuum. The crude product was adsorbed and loaded on alumina (70-230 mesh) column, and it was eluted with EtOAc (30-45%) in hexane to give desired compound in yield ranging from 30 to 62%.
  • 58
  • [ 103854-64-4 ]
  • [ 7466-54-8 ]
  • C19H17N3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; at 80℃; for 3h; General procedure: 8-Methoxyquinoline-2-carbaldehyde (25, 0.534 mmol) was refluxedwith various substituted acylhydrazines (0.587 mmol, 1.1 eq) in ethanol(5-10 mL) to get acyl hydrazides of 8-hydroxyquinoline. After completionof reaction, quinoline acyl hydrazides were found as precipitateson cooling to -15 C. Precipitates were washed with coldethanol and dried under vacuum. These acyl hydrazides were used directlyfor one pot synthesis of 2,5-disubstituted-1,3,4-oxadiazole usingiodine/K2CO3 catalysed oxidative cyclization. To the acyl hydrazides(1.0 eq) in DMSO (5-10 mL), K2CO3 (3.0 eq) and iodine (1.2 eq) wereadded in sequence and refluxed at 110 C. After the completion, thereaction mixture was cooled and saturated solution of sodium thiosulfatewas added. The precipitates were collected and dried under highvacuum to get the respective compounds (33-50).
  • 59
  • [ 7466-54-8 ]
  • 1-(3-methylbut-2-en-1-yl)indoline-2,3-dione [ No CAS ]
  • 2-methoxy-N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
88.2% With acetic acid In ethanol at 20℃; for 2h; General method of synthesis of N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene) hydrazine derivatives (S1-S20) General procedure: To intermediate B (0.5 mmol, 109.5 mg) in ethanol (5 mL), substituted benzoyl hydrazine or phenylhydrazine (0.5 mmol) was added. Then 200 μL glacial acetic acid was dripped in. After 2 h, the mixture was filtered and dried. The target compounds S1-S20 was then obtained through silica column (PE:EA = 4:1 v/v). In some cases, ultrasonic vibration can contribute to precipitation. No cis-trans isomerism was found during reaction and NMR data indicated all this series were trans configuration.
  • 60
  • [ 29684-56-8 ]
  • [ 54903-16-1 ]
  • [ 7466-54-8 ]
  • methyl N-({6-[5-(2-methoxyphenyl)-1,3,4-oxadiazol-2-yl]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl}sulfonyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
18% To a dry mixture of 27-1 (2-methoxyphenylhydrazide, 139 mg, 0.837 mmol), 27-2 (benzoxazol-2- one-6-carboxylic acid, 150 mg, 0.837 mmol), and HATU (318 mg, 0.837 mmol) was added THF (10 mL) to yield a hazy reddish solution. DIPEA (0.29 mL, 1.67 mmol) was added and the reaction was stirred at rt for 2 hr. Burgess reagent (499 mg, 2.09 mmol) was added one portion, and the reaction was heated to 60C overnight. An additional 499 mg Burgess reagent was added. and continued heating. After 4 hr, 2N KHSO4 (10 mL) was added and the resulting oily mixture was extracted 3X EtOAc. The combined organics were washed once with water, once with brine, filtered through cotton and concentrated to an orange solid which was purified by reverse phase chromatography, 20% - 60% MeCN/water/0.1% TFA to yield 67 mg 27-3(18%) MJ-T+ = 447.0. ?H NMR (400 MHz, DMSO) 8.02 - 7.97 (3H, m), 7.74 (1H, d, J=8.4 Hz), 7.64 (1H, t, J=8.2 Hz), 7.30 (1H, d, J=8.4 Hz), 7.18 (1H, t, J=7.4 Hz), 3.95 (3H, s), 3.39 (3H, s).
  • 61
  • [ 7466-54-8 ]
  • [ 40782-53-4 ]
  • 2-methoxy-N'-[(4-octyloxyphenyl)carbonyl]benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% Stage #1: 2-methoxybenzoylhydrazine; 4-octyloxybenzoic acid chloride With triethylamine In benzene at 20℃; for 2h; Stage #2: In benzene for 6h; Reflux; 4-Octyloxy-N'-(phenylcarbonyl)benzohydrazide(2a). General procedure: 2 mL of triethylamine and then a solution of 1.34 g(0.005 mol) of 4-octyloxybenzoyl chloride in 20 mL of anhydrous benzene were added at stirring to a solution of 0.68 g (0.005 mol) of benzohydrazide 1a in 50 mLof anhydrous benzene. The reaction mixture was stirred during 2 h at room temperature and then refluxed during 6 h. The solvent was removed in vacuum, and 50 g of crushed ice was added to the oily residue. The formed precipitate was filtered off, washed with water (2×10 mL), dried in air, and recrystallized from isopropanol (2×20 mL).
  • 62
  • [ 7466-54-8 ]
  • [ 228244-04-0 ]
  • (S)-2-[5-(2-methoxyphenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester [ No CAS ]
Reference: [1]ChemMedChem,2020
  • 63
  • [ 7466-54-8 ]
  • [ 50915-97-4 ]
  • 2-(2-methoxyphenyl)-5-(3,4,5-triethoxyphenyl)-1,3,4-oxadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / benzene / 8 h / 20 °C / Reflux 2: thionyl chloride / 5 h / Reflux
  • 64
  • [ 7466-54-8 ]
  • [ 50915-97-4 ]
  • 2-methoxy-N'-[(3,4,5-triethoxyphenyl)carbonyl]benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With triethylamine In benzene at 20℃; for 8h; Reflux; 3,4,5-Triethoxy-N-(phenylcarbonyl)benzohydrazide (2a) Triethylamine (2 mL) and 3,4,5-triethoxybenzoyl chloride (2.72 g, 10 mmol) in anhydrous benzene (20 mL) were sequentially added to a solution of benzhydrazide (1a) (1.36 g, 10 mmol) in anhydrous benzene (50 mL) with stirring. The reaction mixture was stirred for another 2 h at ~20 °C, then refluxed for 6 h. The solvent was evaporated in vacuo and crushed ice (50 g) was added to the oily residue. The formed precipitate was collected by filtration, washed with water (2×10 mL), dried in air, and recrystallized from propan-2-ol (2×20 mL). The yield was 2.38 g (64%)
  • 65
  • [ 7466-54-8 ]
  • [ 1521-38-6 ]
  • 2,3-dimethoxy-N'-(2-methoxybenzoyl)benzohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h; Inert atmosphere; 4.1.16 2,3-Dimethoxy-N′-(2-methoxybenzoyl)benzohydrazide (25) Et3N (3.8mL, 27mmol) was added dropwise to a stirred solution of hydrazide 24 (1.50g, 9.0mmol) and carboxcylic acid 21 (1.64g, 9.0mmol) in CH2Cl2 (45mL) containing EDC·HCl (2.25g, 12mmol) and HOBt (1.59g, 12mmol) at room temperature under argon. After 12h, the reaction was quenched with 3M aqueous HCl (30mL), and the resulting mixture was extracted with EtOAc (3×100mL). The combined extracts were washed successively with saturated aqueous NaHCO3 (2×100mL) and brine (2×100mL), then dried with Na2SO4. The mixture was concentrated in vacuo, and the residue was purified by recrystallization (hexane/EtOAc 1:1) to give 25 (2.47g, 83%) as colorless needles. M.p. 149°C. 1H NMR (400MHz, DMSO-d6): δ=3.85 (3H, s), 3.85 (3H, s), 3.92 (3H, s), 7.08 (1H, t, J=7.6Hz), 7.15-7.23 (4H, m), 7.51-7.55 (1H, m), 7.81 (1H, dd, J=7.6, 1.7Hz), 10.22 (1H, d, J=2.9Hz), 10.38ppm (1H, d, J=2.9Hz). 13C NMR (100MHz, DMSO-d6): δ=55.96, 55.98, 61.3, 112.1, 115.4, 120.6, 120.8, 121.0, 124.2, 127.7, 130.6, 133.0, 146.7, 152.6, 157,1, 163.4, 163.8ppm. FT-IR (KBr): 3855, 3842, 3736, 3691, 3650, 3353 2956 1617, 1571, 1448, 1268, 1184, 1109, 1060, 1015, 978, 962, 877, 817, 760cm-1. HRMS (EI): calcd for C17H18N2O5 330.1216; found 330.1219. Anal. calcd for C17H18N2O5: C 61.81, H 5.49, N 8.48; found C 61.84, H 5.47, N 8.48.
  • 66
  • [ 2290-65-5 ]
  • [ 7466-54-8 ]
  • [ 39631-37-3 ]
YieldReaction ConditionsOperation in experiment
67.37% Stage #1: trimethylsilyl isothiocyanate; 2-methoxybenzoylhydrazine In ethanol at 0 - 90℃; for 4h; Stage #2: With sodium hydroxide In ethanol at 90℃; for 4h; Step-1: 5-(2-methoxyphenyl)-4H-1,2,4-triazole-3-thiol: To a stirred solution of 2-methoxy benzhydrazide (2.5 g, 15.04 mmol) in ethanol (25 mL) at 0 oC, was added trimethylsilyl isothiocyanate (1.97 g, 15.04 mmol) and the reaction was heated at 90 oC for 4h. To the resultant reaction mixture was then added 4M NaOH solution (25 mL) and was further at 90 oC for another 4h. The reaction mixture was then concentrated, diluted with H2O (10 mL) and acidified with HCl (40 mL,4M). The resultant precipitate was filtered and dried under vacuum to afford 5-(2-methoxyphenyl)-4H- 1,2,4-triazole-3-thiol as off-white solid (2.1 g mg, 67.37 %).1H NMR (400 MHz, DMSO) δ 13.61 (s, 1H), 13.11(s, 1H), 7.63 (d, J = 6.4 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 7.04 (t, J = 7.2 Hz, 1H), 3.83 (s, 3H). LC-MS (ESI): m/z 208.1 (M+H)
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