- Role of Cage Return and Solvent Viscosity in the Temperature-Dependent Kinetics of Benzylic Bromination
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The effect of temperature on both the kinetic isotope effect in the homolytic abstraction of benzylic hydrogen by bromine and the competitive brominations of toluene and a ring-substituted toluene was interpreted as being due not only to the activation parameters involved in abstraction but upon the viscosity dependence of the kinetic results.Internal cage return was shown to be viscosity dependent, and the resultant kinetic isotope effect was corrected to account for cage reversal.The viscosity dependence in the relative rates of competitive bromination of toluene and p-chlorotoluene showed an inverse correlation to that obtained with temperature.The nonmonotonic Arrhenius plot previously reported could be explained on the basis of these two opposing effects, as well as the fact that over the range of temperature previously reported the reaction mixtures became nonhomogeneous.
- Tanner, Dennis D.,Nam, Hguyen H.
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- Synthesis, inhibition properties against xanthine oxidase and molecular docking studies of dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives
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This study focused on synthesis various dimethyl N-benzyl-1H-1,2,3-triazole-4,5-dicarboxylate and (N-benzyl-1H-1,2,3-triazole-4,5-diyl)dimethanol derivatives under the conditions of green chemistry without the use of solvent and catalysts. Their inhibition properties were also investigated on xanthine oxidase (XO) activity. All dimethanol and dicarboxylate derivatives exhibited significant inhibition activities with IC50 values ranging from 0.71 to 2.25 μM. Especially, (1-(3-bromobenzyl)-1H-1,2,3-triazole-4,5-diyl)dimethanol (5c) and dimethyl 1-(4-chlorobenzyl)-1H-1,2,3-triazole-4,5-dicarboxylate (6 g) compounds were found to be the most promising derivatives on the XO enzyme inhibition with IC50 values 0.71 and 0.73 μM, respectively. Moreover, the double docking procedure was to evaluate compound modes of inhibition and their interactions with the protein (XO) at atomic level. Surprisingly, the docking results showed a good correlation with IC50 [correlation coefficient (R2 = 0.7455)]. Also, the docking results exhibited that the 5c, 6f and 6 g have lowest docking scores ?4.790, ?4.755, and ?4.730, respectively. These data were in agreement with the IC50 values. These results give promising beginning stages to assist in the improvement of novel and powerful inhibitor against XO.
- Yagiz, Güler,Noma, Samir Abbas Ali,Altundas, Aliye,Al-khafaji, Khattab,Taskin-Tok, Tugba,Ates, Burhan
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- Synthesis, Docking, and Biological activities of novel Metacetamol embedded [1,2,3]-triazole derivatives
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ERα controls the breast tissue development and progression of breast cancer. In our search for novel compounds to target Estrogen Receptor Alpha Ligand-Binding Domain, we identified “N-(3-((1H-1,2,3-triazol-4-yl)methoxy)phenyl)acetamide” derivatives as lead compounds. The Docking studies indicated good docking score for Metacetamol derivatives when docked into the 1XP6. A series of metacetamol derivatives have been synthesized, characterized and evaluated for cytotoxicity, anti bacterial and anti oxidant activities. Among the tested twelve hybrid compounds, “7a, 7g, 7h and 7i” derivatives showed promising cytotoxicity with IC50 value of 50 value of 30 μM, whereas Compounds “7a, 7b, 7c, 7d, 7g, 7j, 7k and 7l” showed moderate anti bacterial activity with the MIC value of 300 μM.
- Battu, Satyanarayana,Joolakanti, Hima Bindhu,Kamepalli, Ramanjaneyulu,Miryala, Jeevanreddy
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- [1,3]-Claisen rearrangement via removable functional group mediated radical stabilization
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A thermal O-to-C [1,3]-rearrangement of α-hydroxy acid derived enol ethers was achieved under mild conditions. The 2-aminothiophenol protection of carboxylic acids facilitates formation of the [1,3] precursor and its thermal rearrangement via stabilization of a radical intermediate. Experimental and theoretical evidence for dissociative radical pair formation, its captodative stability via aminothiophenol, and a unique solvent effect are presented. The aminothiophenol was deprotected from rearrangement products as well as after derivatization to useful synthons.
- Alam, Md Nirshad,Dash, Soumya Ranjan,Mukherjee, Anirban,Pandole, Satish,Marelli, Udaya Kiran,Vanka, Kumar,Maity, Pradip
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supporting information
p. 890 - 895
(2021/02/01)
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- Thiourea-Catalyzed C?F Bond Activation: Amination of Benzylic Fluorides
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We describe the first thiourea-catalyzed C?F bond activation. The use of a thiourea catalyst and Ti(OiPr)4 as a fluoride scavenger allows the amination of benzylic fluorides to proceed in moderate to excellent yields. Preliminary results with S- and O-based nucleophiles are also presented. DFT calculations reveal the importance of hydrogen bonds between the catalyst and the fluorine atom of the substrate to lower the activation energy during the transition state.
- Houle, Camille,Savoie, Paul R.,Davies, Clotilde,Jardel, Damien,Champagne, Pier Alexandre,Bibal, Brigitte,Paquin, Jean-Fran?ois
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supporting information
p. 10620 - 10625
(2020/07/24)
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- Thiourea-Mediated Halogenation of Alcohols
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The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
- Mohite, Amar R.,Phatake, Ravindra S.,Dubey, Pooja,Agbaria, Mohamed,Shames, Alexander I.,Lemcoff, N. Gabriel,Reany, Ofer
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p. 12901 - 12911
(2020/11/26)
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- Synthesis of Alkyl Halides from Aldehydes via Deformylative Halogenation
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An unprecedented deformylative halogenation of aldehydes to alkyl halides is presented. Under oxidative conditions, 1,4-dihydropyridine (DHP), derived from an aldehyde, generated a C(sp3)- radical that coupled with a halogen radical that was generated from inexpensive and atom-economical halogen sources (NaBr, NaI, or HCl), to yield an alkyl halide. Because of the mild conditions, a wide range of functional groups were tolerated, and excellent site selectivity was achieved.
- Liang, Shengzong,Kumon, Tatsuya,Angnes, Ricardo A.,Sanchez, Melissa,Xu, Bo,Hammond, Gerald B.
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supporting information
p. 3848 - 3854
(2019/05/24)
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- Photochemical benzylic bromination in continuous flow using BrCCl3 and its application to telescoped p-methoxybenzyl protection
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BrCCl3 represents a rarely used benzylic brominating reagent with complementary reactivity to other reagents. Its reactivity has been revisited in continuous flow, revealing compatibility with electron-rich aromatic substrates. This has brought about the development of a p-methoxybenzyl bromide generator for PMB protection, which was successfully demonstrated on a pharmaceutically relevant intermediate on 11 g scale, giving 91% yield and a PMB-Br space-time-yield of 1.27 kg L?1 h?1
- Otake, Yuma,Williams, Jason D.,Rincón, Juan A.,De Frutos, Oscar,Mateos, Carlos,Kappe, C. Oliver
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supporting information
p. 1384 - 1388
(2019/02/14)
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- An efficient conversion of alcohols to alkyl bromides using pyridinium based ionic liquids: A green alternative to appel reaction
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Pyridinium based ionic liquids namely 4-alkylpyridinium bromides were prepared and used for the conversion of alcohols to alkyl bromides in the presence of p-toluenesulphonic acid in the absence of volatile organic compounds. This solvent free procedure promises to be a much improved and environmentally benign alternative to the Appel reaction.
- Das, Pranab J.,Das, Jupitara,Das, Dimpee
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p. 651 - 654
(2018/02/09)
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- Visible-Light-Driven Oxidative Mono- and Dibromination of Benzylic sp 3 C-H Bonds with Potassium Bromide/Oxone at Room Temperature
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Benzylic sp 3 C-H bonds have been successfully brominated with potassium bromide by using Oxone as an oxidant in water/dichloromethane under visible light at room temperature. Toluene, ethylbenzene and other alkylbenzenes bearing an electron-withdrawing group, such as Br, Cl, COMe, CO 2 Et, CO 2 H, CN or NO 2, provide the corresponding benzylic monobromides in good to excellent yields in this reaction. Dibromides can also be produced in the presence of excess potassium bromide in a prolonged reaction time. Control of the illuminance of visible light (~500 lux) is crucial to achieving both high yield and high selectivity in these brominations. Mono- and difluorides can be conveniently prepared through nucleophilic substitutions of the benzylic bromides with potassium fluoride.
- Zhao, Mengdi,Li, Meiqi,Lu, Wenjun
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supporting information
p. 4933 - 4939
(2018/12/14)
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- Design, synthesis and neuroprotective activities of novel cinnamide derivatives containing benzylpiperazine moiety
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A new series of cinnamide derivatives 6a–l were synthesized by the reaction of acyl chlorides with various substituted benzylpiperazines. The structures were characterized by 1H NMR, 13C NMR, and HRMS. The potential neuroprotective activities of cinnamide analogs were evaluated in differentiated rat pheochromocytoma cells (PC12 cells) and in mice subjected to acute cerebral ischemia. Among the series, 6a, 6b, and 6c, featuring a 1,3-benzodioxole moiety, showed potent neuroprotection both in vivo and in vitro. The three compounds were selected and further studied to determine their mechanism of action. MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with 6a, 6b, and 6c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke.
- Zhong, Yan,Li, Xiaofeng,Zhang, Aixia,Xu, Yi,Li, Ping,Wu, Bin
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p. 1366 - 1373
(2018/02/28)
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- Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors
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In our endeavour towards the development of potent cytotoxic agents, a series of some new curcumin inspired indole analogues, in which indole and phenyl moieties are linked on either sides of 1,5-diaryl-1,4-pentadien-3-one system have been synthesized and characterized by spectral data. All the newly synthesized analogues were tested for their cytotoxic potential against a panel of eight cancer cell lines namely, lung (A549), breast (MDA-MB-231, BT549 and 4T1), prostate (PC-3, DU145), gastric (HGC-27) and cervical (HeLa). Notably, among all the compounds tested, compounds 11c, 11d and 11f showed potent growth inhibition on PC-3 and BT549 with IC50values in the range of 3.12–6.34?μM and 4.69–8.72?μM respectively. The most active compound (11c) was also tested on RWPE-1 (normal prostate) cells and was found to be safe compared to the PC-3?cells. In tubulin polymerization assay, compounds 11c and 11f effectively inhibited microtubule assembly with IC50values of 10.21?±?0.10 and 8.83?±?0.06?μM respectively. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Moreover, DAPI and acridine orange/ethidium bromide staining studies indicated that compounds 11c and 11f can induce apoptosis in PC-3?cells. Further flow-cytometry analysis revealed that compound 11c arrests PC-3?cells in G2/M phase of the cell cycle while compound 11f treatment resulted in moderate increase in the G2/M population. Additionally, the treatment by these compounds led to the impairment of mitochondrial membrane potential (DΨm) in PC-3?cells.
- Sri Ramya,Angapelly, Srinivas,Guntuku, Lalita,Singh Digwal, Chander,Nagendra Babu, Bathini,Naidu,Kamal, Ahmed
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p. 100 - 114
(2016/12/30)
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- PROCESS FOR THE PREPARATION OF ORGANIC HALIDES
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The present invention provides a halo-de-carboxylation process for the preparation of organic chlorides, organic bromides and mixtures thereof, from their corresponding carboxylic acids, using a chlorinating agent selected from trichloroisocyanuric acid (TCCA), dichloroisocyanuric acid (DCCA), or combination thereof, and a brominating agent.
- -
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Paragraph 00163
(2017/08/01)
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- PROCESS FOR THE PREPARATION OF ORGANIC BROMIDES
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The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.
- -
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Paragraph 00168
(2017/07/28)
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- Synthesis of Novel Triazole-incorporated Isatin Derivatives as Antifungal, Antitubercular, and Antioxidant Agents and Molecular Docking Study
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A library of 1,2,3-triazoles efficiently prepared via click chemistry and evaluated for their antifungal, antitubercular, antioxidant, cytotoxicity, molecular docking and ADME prediction.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Nawale, Laxman,Arkile, Manisha,Sarkar, Dhiman,Shingate, Bapurao B.
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p. 413 - 421
(2017/02/03)
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- Method for preparing benzyl bromide
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The invention provides a method for preparing benzyl bromide. The method comprises the following steps: by taking bromine released from a redox reaction between bromates and negative bromide ions in the presence of an acid as a bromine source in an organic solvent, carrying out a benzyl radical substitution reaction with a methylbenzene compound shown as a formula I under initiation of an initiator, thereby obtaining a corresponding benzyl bromide compound shown a formula II, wherein in the formula II, m represents the number of Br and is equal to 1 or 2; when m is equal to 1, the formula II shows a benzyl monobromo compound; and when m is equal to 2, the formula II shows a benzyl dibromo compound. The reaction is carried out in an organic solvent, the initiator is combined and used, the radical substitution reaction is high in selectivity and wide in substrate application range, the substituent group replacing methylbenzene may be an electron-withdrawing group or an electron-donating group and can give extremely high yield on strong electron-donating groups (such as methoxy group). Moreover, the method disclosed by the invention is also applicable to preparation of benzyl dibromo compounds, and the product yield is high.
- -
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Paragraph 0037-0039
(2017/10/05)
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- Synthesis and bioactivity of novel triazole incorporated benzothiazinone derivatives as antitubercular and antioxidant agent
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In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and M. bovis BCG, a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34-29.37 μg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG. The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 14.14-47.11 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and in silico study suggest that the triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Arkile, Manisha,Khedkar, Vijay M.,Jadhav, Nandadeep,Sarkar, Dhiman,Shingate, Bapurao B.
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p. 561 - 569
(2016/01/09)
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- Synthesis, biological evaluation and molecular docking of novel coumarin incorporated triazoles as antitubercular, antioxidant and antimicrobial agents
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A series of new coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular activity in vitro against Mycobacterium tuberculosis H37Ra, antioxidant activity by DPPH radical scavenging assay, antimicrobial activity in vitro against three gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus and Bacillus cereus) and three gram-negative bacteria (Escherichia coli, Pseudomonas fluorescens and Flavobacterium devorans as well as three fungi (Aspergillus niger, Penicillium chrysogenum and Curvularia lunata). The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antitubercular, antioxidant, antibacterial and antifungal efficacy in comparison with reference drugs. Furthermore, docking study has been performed against DprE1 enzyme of M. tuberculosis that showed good binding interactions. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates. Graphical Abstract: New coumarin-based 1,2,3-triazole derivatives were designed, synthesized and evaluated for their antitubercular, antioxidant, antibacterial and antifungal activity. Some of the coumarin-based triazole derivatives displayed comparable or even better efficacy in comparison with reference drugs. Molecular docking study has been performed against DprE1 enzyme of Mycobacterium tuberculosis showed good binding interactions.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Shingate, Bapurao B.,Kalam Khan, Firoz A.,Sangshetti, Jaiprakash N.,Khedkar, Vijay M.,Nawale, Laxman,Sarkar, Dhiman,Navale, Govinda R.,Shinde, Sandip S.
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p. 790 - 804
(2016/03/08)
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- 1,2,3-Triazole tethered acetophenones: Synthesis, bioevaluation and molecular docking study
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A small focused library of eighteen new 1,2,3-triazole tethered acetophenones has been efficiently prepared via click chemistry approach and evaluated for their antifungal and antioxidant activity. The antifungal activity was evaluated against five human pathogenic fungal strains: Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger, and Cryptococcus neoformans. Among the synthesized compounds, 9c, 9i, and 9p found to be more potent antifungal agents that the reference standard. These 1,2,3-triazole based derivatives were also evaluated for antioxidant activity, and compound 9h was found to be the most potent antioxidant as compared to the standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential as good oral drug candidates.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khedkar, Vijay M.,Jha, Prakash C.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 1058 - 1063
(2016/07/29)
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- 1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents
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A series of novel ethyl-7-((1-(benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxylates 8a-h as potential antifungal agents were synthesized via click chemistry. The antifungal activity was evaluated against five human pathogenic fungal strains, such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compound 8c, 8d, 8e and 8h were found to be equipotent against C. albicans when compared with miconazole and compound 8f was found to be two-fold more active compared with miconazole and equipotent to fluconazole against C. albicans. The coumarin-based triazole derivatives were also evaluated for antioxidant activity and compound 8a was found to be potent antioxidant when compared with standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 295 - 301
(2018/03/22)
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- An efficient and selective method for the iodination and bromination of alcohols under mild conditions
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A straightforward and effective procedure for the conversion of a variety of alcohols into the corresponding alkyl iodides and bromides is described using KX/P2O5 (X = I, Br). The reactions were easily carried out in acetonitrile under mild conditions. Using this method, the selective conversion of benzylic alcohols in the presence of aliphatic alcohols was achieved.
- Khazdooz, Leila,Zarei, Amin,Aghaei, Hamidreza,Azizi, Ghobad,Gheisari, Mohammad Mehdi
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p. 168 - 171
(2015/12/30)
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- 1,2,3-Triazole derivatives as antitubercular agents: synthesis, biological evaluation and molecular docking study
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Searching for new active molecules against Mycobacterium tuberculosis (MTB) H37Ra, a small focused library of 1,2,3-triazoles has been efficiently prepared via a click chemistry approach. The newly synthesized compounds were tested against drug-sensitive MTB. Several derivatives were found to be promising inhibitors of MTB characterized by lower MIC values (5.8-29.9 μg mL-1). Among all the synthesized 31 compounds, 15e was the most active compound against MTB. Based on the results from the anti-tubercular activity, SAR for the synthesized series has been developed. The active compounds from the anti-tubercular study were further tested for anti-proliferative activity against THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity against these three cell lines except THP-1 at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activities with an IC50 range of 10.1-37.3 μg mL-1. The molecular docking study of the synthesized compounds was performed against the DprE1 enzyme of MTB to understand the binding interactions. Moreover, the synthesized compounds were also analysed for ADME properties and all the experimental results promote us to consider this series as a starting point for the development of novel and more potent anti-tubercular agents in the future.
- Shaikh, Mubarak H.,Subhedar, Dnyaneshwar D.,Nawale, Laxman,Sarkar, Dhiman,Kalam Khan, Firoz A.,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
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p. 1104 - 1116
(2015/06/25)
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- Clay-Supported Cu(II) Catalyst: An Efficient, Heterogeneous, and Recyclable Catalyst for Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Alloxan-Derived Terminal Alkyne and Substituted Azides Using Click Chemistry
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A novel series of alloxan-derived 1,4-disubstituted 1,2,3-triazoles was synthesized in excellent yields under catalytic conditions using a click reaction strategy through 1,3-dipolar cycloaddition. Their structures have been ascertained on the basis of spectroanalytical and elemental analysis data. Synthesis of hybrid compounds with varying substitutions in the triazole ring was achieved by reaction between alloxan-derived terminal alkyne and a pertinent azide derivative in the presence of clay-Cu(II) as the catalyst in methanolic medium. Also, comparative evaluation of various catalytic systems [viz., CuI, CuSO4, CuI-zeolite, K10Ti, and clay-Cu(II)] was investigated. Of these catalytic systems, clay-Cu(II) was observed to be the best. The catalyst was recyclable for several runs without showing significant loss in its activity. The good selectivity, cost-efficiency, short reaction time, milder reaction conditions, and simple workup procedure are the added salient features of this synthetic protocol.
- Dubey, Nitin,Sharma, Pratibha,Kumar, Ashok
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p. 2608 - 2626
(2015/11/28)
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- Uranyl Schiff base complexes as new heterogeneous catalysts for halogen exchange reactions between alkyl halides and elemental halogens
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Mild and effective procedure for the halogen exchange reaction of alkyl halides with elemental iodine and bromine catalyzed with uranyl Schiff base complexes in various aprotic solvents was developed. Corresponding alkyl bromides and iodides were obtained with high yields within 20—70 min. The structures of the target products were confirmed by physical and spectroscopic data.
- Naeimi,Nazifi
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p. 1814 - 1818
(2016/05/11)
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- Application of "click" chemistry in solid phase synthesis of alkyl halides
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A convenient and highly selective microwave assisted procedure for the conversion of allylic, benzylic and aliphatic alcohols to their corresponding halides using polymer-bound triphenylphosphine and iodine is presented. In case of symmetrical diols, mono-iodination product is obtained in very high yield. Additionally, highly regioselective behavior is observed in our procedure. Simplicity in operation, no column chromatography required for the purification of the products, recyclability of the reagents used, short reaction times and good to excellent yields are the advantages of our protocol. Most functional groups remain unaffected under our reaction condition.
- Das, Diparjun,Chanda, Tridib,Rokhum, Lalthazuala
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p. 775 - 783
(2016/01/20)
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- Generation of α-imino gold carbenes through gold-catalyzed intermolecular reaction of azides with ynamides
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The generation of α-imino gold carbenes via gold-catalyzed intermolecular reaction of azides and ynamides is disclosed. This new methodology allows for highly regioselective access to valuable 2-aminoindoles and 3-amino-β-carbolines in generally good to excellent yields. A mechanistic rationale for this tandem reaction, especially for the observed high regioselectivity, is supported by DFT calculations.
- Shu, Chao,Wang, Yong-Heng,Zhou, Bo,Li, Xin-Ling,Ping, Yi-Fan,Lu, Xin,Ye, Long-Wu
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supporting information
p. 9567 - 9570
(2015/08/18)
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- Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents
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A series of pyrazolo-triazole hybrids were designed and synthesized by combining the 1,3-diphenyl pyrazole and triazole scaffolds to obtain (1-benzyl-1H-1,2,3-triazol-4-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methanones. All the synthesized compounds were screened for their anticancer activity against four tumor cell lines, viz. HT-29 (colon), PC-3 (prostate), A549 (lung), and U87MG (glioblastoma) cells. Most of the tested compounds showed moderate to potent cell growth inhibition on different cancer cells, in particular, the compounds 17, 23, and 29 exhibited promising cytotoxicity against these cell lines with the IC50 values in the range of 0.86-3.72 μM. In addition, the potential mechanism of cell growth inhibition and apoptotic induction by these compounds was investigated in U87MG cancer cells using cell-based assays, including wound healing assay, flow cytometry, Hoechst staining, acridine orange/ethidium bromide staining, Annexin V-FITC/propidium Iodide dual staining, Rhodamine 123 staining, and carboxy-DCFDA staining. The results indicate that the compounds induce apoptosis in U87MG cells via mitochondrial pathway through up-regulation of pro-apoptotic (Bax) and down-regulation of anti-apoptotic (Bcl-2) genes. Based on these studies, three compounds 17, 23 and 29 have been identified as promising new molecules that have the potential to be developed as leads.
- Srinivasa Reddy,Kulhari, Hitesh,Ganga Reddy,Subba Rao,Bansal, Vipul,Kamal, Ahmed,Shukla, Ravi
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p. 10136 - 10149
(2015/10/20)
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- Microreactor-mediated benzylic bromination in concentrated solar radiation
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Sunlight-induced bromination of benzylic compounds was conducted in a capillary microreactor, resulting in mono-brominated compounds with yields of up to 94%. These reactions can be considered to be eco-friendly since they were carried out without an artificial light source or additional temperature control. In addition, up to 257.9mmol could be produced daily using cost-effective molecular bromine, which leads to potential improvement of industrial processes.
- Kim, Young Joon,Jeong, Myung Jin,Kim, Ji Eun,In, Insik,Park, Chan Pil
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p. 1653 - 1656
(2015/11/10)
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- Tribromoisocyanuric acid as a green reagent for benzylic bromination of alkylarenes
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The reaction of diverse alkylarenes with tribromoisocyanuric acid (0.34 mol equiv) in reflux EtOAc in the absence of any catalysts or light irradiation produced the corresponding benzyl bromides in 53-88% yield.
- De Almeida, Leonardo S.,Esteves, Pierre M.,De Mattos, Marcio C.S.
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p. 6843 - 6845
(2015/11/27)
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- Palladium(0)-catalyzed cyclopropanation of benzyl bromides via C(sp 3)-H bond activation
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A novel and highly efficient Pd(0)-catalyzed domino reaction to prepare cyclopropane derivatives has been established. The process involves a Heck-type coupling reaction and a C(sp3)-H bond activation. Preliminary DFT calculations suggest that a four-membered palladacycle intermediate is involved. This journal is the Partner Organisations 2014.
- Mao, Jiangang,Zhang, Shuo-Qing,Shi, Bing-Feng,Bao, Weiliang
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p. 3692 - 3694
(2014/04/03)
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- CuI-catalyzed coupling of gem-dibromovinylanilides and sulfonamides: An efficient method for the synthesis of 2-amidoindoles and indolo[1,2-a] quinazolines
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A Cu(I)-catalyzed, intermolecular protocol for the synthesis of 2-amidoindoles and tetrahydroindolo[1,2-a]quinazolines in shorter time and high yields is reported. The key highlight of this disclosure is the formation of 2-amidoindole and tetrahydroindolo[1,2-a]quinazoline moieties directly from gem-dibromovinylanilides and sulfonamides in a one-pot fashion through the in situ formation of ynamides followed by a base-promoted intramolecular hydroamidation.
- Kiruthika, Selvarangam E.,Perumal, Paramasivan Thirumalai
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p. 484 - 487
(2014/04/03)
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- Synthesis of pyrrolo-/indolo[1,2-a ]quinolines and naphtho[2,1- b ]thiophenes from gem -dibromovinyls and sulphonamides
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A highly efficient and simple route for the synthesis of pyrrolo-/indolo[1,2-a]quinolines and naphtho[2,1-b]thiophenes from gem-dibromovinyls and sulphonamides is reported. The noteworthy feature of this report is that the methodology involves a two-step protocol to synthesize tri- and tetracyclic heterocycles in a one-pot fashion through the Cu(I)-catalyzed formation of ynamide followed by a Ag(I)-assisted intramolecular hydroarylation. The photophysical properties of representative examples of pyrrolo- and indolo[1,2-a]quinolines in solid and solution states have also been studied.
- Kiruthika, Selvarangam E.,Nandakumar, Avanashiappan,Perumal, Paramasivan Thirumalai
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p. 4424 - 4427
(2015/02/05)
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- A scalable procedure for light-induced benzylic brominations in continuous flow
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A continuous-flow protocol for the bromination of benzylic compounds with N-bromosuccinimide (NBS) is presented. The radical reactions were activated with a readily available household compact fluorescent lamp (CFL) using a simple flow reactor design based on transparent fluorinated ethylene polymer (FEP) tubing. All of the reactions were carried out using acetonitrile as the solvent, thus avoiding hazardous chlorinated solvents such as CCl4. For each substrate, only 1.05 equiv of NBS was necessary to fully transform the benzylic starting material into the corresponding bromide. The general character of the procedure was demonstrated by brominating a diverse set of 19 substrates containing different functional groups. Good to excellent isolated yields were obtained in all cases. The novel flow protocol can be readily scaled to multigram quantities by operating the reactor for longer time periods (throughput 30 mmol h-1), which is not easily possible in batch photochemical reactors. The bromination protocol can also be performed with equal efficiency in a larger flow reactor utilizing a more powerful lamp. For the bromination of phenylacetone as a model, a productivity of 180 mmol h -1 for the desired bromide was achieved.
- Cantillo, David,De Frutos, Oscar,Rincon, Juan A.,Mateos, Carlos,Oliver Kappe
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supporting information
p. 223 - 229
(2014/01/17)
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- One-pot transformation of methylarenes into aromatic aldehydes under metal-free conditions
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On the basis of studies of the transformation of benzylic bromides into the corresponding aromatic aldehydes by treatment with N-methylmorpholine N-oxide, various methylarenes were treated either with DBDMH in the presence of AIBN in acetonitrile at reflux (Method A) or with NBS in CCl4 under irradiation with a tungsten lamp at 30 °C (Method B), followed by treatment with N-methylmorpholine N-oxide to provide aromatic aldehydes in good yields. These methods could be adopted in one-pot transformations of methylarenes into aromatic aldehydes under conditions free of less toxic reagents and transition metals. Copyright
- Tabata, Masayuki,Moriyama, Katsuhiko,Togo, Hideo
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p. 3402 - 3410
(2014/06/09)
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- Carbon–carbon bond formation via benzoyl umpolung attained by photoinduced electron-transfer with benzimidazolines
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A photoreaction between benzoyl compounds, such as benzoylformate derivatives, and 2-(p-anisyl)-1,3-dimethylbenzimidazoline in the presence of allyl bromide was found to give various allylated alcohols. In the reaction of benzoylformates, α-hydroxy ester enolates, for which the negative charge occurs on the carbonyl carbon of benzoyl (umpolung reactivity), are proposed to be generated as intermediates by electron-transfer from benzimidazolines to the photoexcited benzoylformates; these species react with allyl bromide to produce α-allyl-α-hydroxy esters.
- Igarashi, Tomohito,Tayama, Eiji,Iwamoto, Hajime,Hasegawa, Eietsu
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p. 6874 - 6877
(2019/04/10)
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- In situ generated Ph3P(OAc)2as a novel reagent for the efficient acetylation of alcohols and thiols at room temperature
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Ph3P, Br2, and ammonium acetate are used for the in situ generation of Ph3P(OAc)2, which was characterized by different NMR techniques. The Ph3P(OAc)2generated was used as a novel and efficient reagent for the acetylation of alcohols and thiols in acetonitrile at room temperature under homogeneous conditions. This reaction was also performed under heterogeneous conditions using 1,3,2,4- diazadiphosphetidine as an easily prepared, stable, and heterogeneous P(III) compound.
- Iranpoor, Nasser,Firouzabadi, Habib,Elham, Etemadi Davan
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p. 1813 - 1816
(2013/04/24)
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- Synthesis of 2,4-unsubstituted quinoline-3-carboxylic acid ethyl esters from arylmethyl azides via a domino process
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A convenient synthesis of 2,4-unsubstituted quinoline-3-carboxylic acid ethyl esters via a domino process is described. The synthesis employs arylmethyl azides as the precursor which undergoes an acid-promoted rearrangement to give an N-aryl iminium ion. Following the addition with ethyl 3-ethoxyacrylate, intramolecular electrophilic aromatic substitution, elimination and subsequent oxidation, the quinoline products were obtained in moderate to excellent yields.
- Tummatorn, Jumreang,Thongsornkleeb, Charnsak,Ruchirawat, Somsak,Gettongsong, Tanita
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supporting information
p. 1463 - 1467
(2013/05/08)
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- Direct oxidative conversion of methylarenes into aromatic nitriles
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A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.
- Tsuchiya, Daisuke,Kawagoe, Yuhsuke,Moriyama, Katsuhiko,Togo, Hideo
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supporting information
p. 4194 - 4197
(2013/09/12)
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- Preparation of (-)-nutlin-3 using enantioselective organocatalysis at decagram scale
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Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the first enantioselective synthesis of (-)-Nutlin-3 provided a basis to prepare larger amounts of this tool used widely in cancer biology. Key to the decagram-scale synthesis described here was the discovery of a novel bis(amidine) organocatalyst that provides high enantioselectivity at warmer reaction temperature (-20 C) and low catalyst loadings. Further refinements to the procedure led to the synthesis of (-)-Nutlin-3 in a 17 g batch and elimination of all but three chromatographic purifications.
- Davis, Tyler A.,Vilgelm, Anna E.,Richmond, Ann,Johnston, Jeffrey N.
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p. 10605 - 10616
(2013/11/19)
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- Indium-catalyzed reductive bromination of carboxylic acids leading to alkyl bromides
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The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me3SiBr) with a catalytic amount of indium bromide (InBr3) undertook direct bromination of carboxylic acids, which produced the corresponding alkyl bromides in good to excellent yields. The reducing system was tolerant to several functional groups.
- Moriya, Toshimitsu,Yoneda, Shinichiro,Kawana, Keita,Ikeda, Reiko,Konakahara, Takeo,Sakai, Norio
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supporting information
p. 4842 - 4845,4
(2020/09/16)
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- Synthesis of silica bromide as heterogeneous reagent and its application to conversion of alcohols to alkyl bromides
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Silica bromide as heterogeneous reagent is prepared from the reaction of silica gel with PBr3 as a nonhydroscopic, filterable, cheap, and stable yellowish powder that can be stored for months. The results show that the silica bromide is a suitable and efficient reagent for conversion of alcohols to alkyl bromides under mild conditions at room temperature. The easy availability of this reagent makes this simple procedure attractive and a practical alternative to the existing methods.
- Mohanazadeh, Farajollah,Sedrpoushan, Alireza,Zolfigol, Mohammad A.,Veisi, Hojat
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p. 598 - 603,6
(2012/12/11)
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- Polyvinylpyrrolidone-bromine complex: An efficient polymeric reagent for selective preparation of benzyl bromides in the presence of hexamethyldisilane
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Benzylic bromides were conveniently obtained in high yields via the reaction of the corresponding alcohols with crosslinked polyvinylpyrrolidone- bromine complex (PVPP-Br2)/hexamethyldisilane in chloroform at reflux condition. Selective conversion of benzyl alcohol to benzyl bromide in the presence of primary aliphatic alcohols, e.g. 2-phenylethanol was also achieved.
- Mokhtary, Masoud,Lakouraj, Moslem M.
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p. 305 - 309
(2012/10/29)
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- Direct and selective benzylic oxidation of alkylarenes via C-H abstraction using alkali metal bromides
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A direct benzylic oxidation of alkylarenes via C-H bond abstraction was developed using alkali metal bromides and oxidants under mild conditions. This reaction proceeded with excellent selectivity by thermal oxidation or photooxidation to provide a broad range of carbonyl compounds containing electron-deficient aryl carbonyl compounds in high yields.
- Moriyama, Katsuhiko,Takemura, Misato,Togo, Hideo
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supporting information; experimental part
p. 2414 - 2417
(2012/06/18)
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- Efficient organic transformations mediated by ZrOCl28H 2O in Water
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Operationally simple and environmentally benign methods for some organic transformations comprising reductive coupling of sulfonyl chlorides, chemoselective deoxygenation of sulfoxides, and halogenation of alcohols mediated by ZrOCl28H2O/MX in water have been developed.
- Jafarpour, Maasoumeh,Rezaeifard, Abdolreza,Heidari, Mahdieh
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experimental part
p. 1470 - 1482
(2011/10/05)
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- Synthesis of benzyl bromides with hexabromoacetone: An alternative path to drug intermediates
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A series of benzyl bromides were efficiently prepared from the corresponding alcohols with Br3CCOCBr3/PPh3 at low temperatures and under neutral conditions. The present protocol was applied to the heterocyclic analogues and to the successful synthesis of the precursor of the antiulcer drug omeprazole, thus furnishing an alternate, mild method for the preparation of these drug intermediates. A significant steric factor was observed throughout both series supporting a SN2 mechanism.
- Joseph, Kara M.,Larraza-Sanchez, Isabel
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experimental part
p. 13 - 16
(2011/02/25)
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- Microwave-assisted benzyl mono- and dibromination in diethyl carbonate as environmentally friendly alternative to radical bromination in carbon tetrachloride
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An environmentally friendly benzyl mono- and di-bromination synthetic procedure was developed that is superior to the classic carbon tetrachloride bromination procedure in both reaction time and isolated yield. This new reaction was performed in diethyl carbonate as reaction media using microwave instead of conventional heating. Both the solvent and the brominating reagent N-bromosuccinimide (prepared from succinimide obtained from the reaction mixture) are recyclable. Practically, the preparation of our target compounds was completed in less than two hours. The Royal Society of Chemistry.
- Pingali, Subramanya R. K.,Upadhyay, Sunil K.,Jursic, Branko S
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experimental part
p. 928 - 933
(2011/05/15)
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- N-Halosuccinimide/SiCl4 as general, mild and efficient systems for the α-monohalogenation of carbonyl compounds and for benzylic halogenation
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Combinations of N-halosuccinimide and tetrachlorosilane in acetonitrile were found to be efficient systems for the selective α-monohalogenation of carbonyl compounds as well as for benzylic halogenation under mild conditions.
- Salama, Tarek A.,Novák, Zoltán
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experimental part
p. 4026 - 4029
(2011/08/09)
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- Synthesis of 3-(o-stilbenyl)sydnone and 3-(o-stilbenyl)-4- substitutedsydnone derivatives and their antitumor evaluation
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A series of novel stilbene-sydnone derivatives were synthesized by the following sequence of reactions: Starting from methyl anthranilate via glycine- and nitrosoglycine derivatives the corresponding 3-(o-carbomethoxyphenyl)-4-H/ Me/Ph-sydnones were prepared and transformed to 3-(o-formylphenyl)-4-H/Me/Ph- sydnones, starting materials for Wittig reaction with various phosphonium salts to stilbenylsydnone derivatives. Final products were evaluated for their cytotoxic properties on five cancer cell lines, whereby the cis-4-methyl-3-[2- [2-(4-methylphenyl)ethenyl]phenyl]sydnone 5 and cis-4-phenyl-3-[2-[2-(4- chlorophenyl)ethenyl]-phenyl]sydnone 10 showed the most pronounced activity. ARKAT-USA, Inc.
- Butkovic, Kristina,Marinic, Zeljko,Sindler-Kulyka, Marija
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experimental part
p. 1 - 15
(2011/09/16)
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- H3PW12O40-[bmim][FeCl4]: A novel and green catalyst-medium system for microwave-promoted selective interconversion of alkoxymethyl ethers into their corresponding nitriles, bromides and iodides
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In the present work, the catalytic activity of 12-tungstophosphoric acid immobilized on [bmim][FeCl4] ionic liquid as a highly efficient and eco-friendly catalytic system for rapid and chemoselective direct conversion of MOM- or EOM-ethers into their corresponding nitriles, bromides and iodides under microwave irradiation is reported. In these reactions, the products are obtained in high yields. The catalyst exhibited remarkable reactivity and was reused several times.
- Mohammadpoor-Baltork, Iraj,Moghadam, Majid,Tangestaninejad, Shahram,Mirkhani, Valiolah,Mirjafari, Arsalan
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experimental part
p. 1468 - 1473
(2011/10/09)
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- Microwave-promoted, one-pot conversion of alkoxymethylated protected alcohols into their corresponding nitriles, bromides, and iodides using [bmim][InCl4] as a green catalyst
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The Lewis acid room temperature ionic liquid, [bmim][InCl4], was found to be an efficient and green catalyst for the highly chemoselective and one-pot conversion of MOM- or EOM-ethers into their corresponding nitriles, bromides, and iodides under microwave irradiation. The procedures are simple, rapid, and high yielding. The catalyst exhibited a remarkable reactivity and is reusable.
- Mirjafari, Arsalan,Mohammadpoor-Baltork, Iraj,Moghadam, Majid,Tangestaninejad, Shahram,Mirkhani, Valiollah,Khosropour, Ahmad Reza
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supporting information; experimental part
p. 3274 - 3276
(2010/07/18)
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- Benzylic bromination of toluene derivatives with boron tribromide
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A facile method for the benzylic bromination of toluene derivatives was developed. Various substituted toluenes were brominated with boron tribromide as bromine source in carbon tetrachloride at room temperature, affording their corresponding benzyl bromides in good yields.
- Chen, Hongbiao,Shen, Litao,Lin, Yuanbin
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experimental part
p. 998 - 1003
(2010/05/18)
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