939-99-1Relevant articles and documents
Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors
Yan, Yu-Hang,Li, Wenfang,Chen, Wei,Li, Chao,Zhu, Kai-Rong,Deng, Ji,Dai, Qing-Qing,Yang, Ling-Ling,Wang, Zhenling,Li, Guo-Bo
, (2021/11/17)
Production of metallo-β-lactamases (MBLs) in bacterial pathogens is an important cause of resistance to the ‘last-resort’ carbapenem antibiotics. Development of effective MBL inhibitors to reverse carbapenem resistance in Gram-negative bacteria is still needed. We herein report X-ray structure-guided optimization of 1H-imidazole-2-carboxylic acid (ICA) derivatives by considering how to engage with the active-site flexible loops and improve penetration into Gram-negative bacteria. Structure-activity relationship studies revealed the importance of appropriate substituents at ICA 1-position to achieve potent inhibition to class B1 MBLs, particularly the Verona Integron-encoded MBLs (VIMs), mainly by involving ingenious interactions with the flexible active site loops as observed by crystallographic analyses. Of the tested ICA inhibitors, 55 displayed potent synergistic antibacterial activity with meropenem against engineered Escherichia coli strains and even intractable clinically isolated Pseudomonas aeruginosa producing VIM-2 MBL. The morphologic and internal structural changes of bacterial cells after treatment further demonstrated that 55 crossed the outer membrane and reversed the activity of meropenem. Moreover, 55 showed good pharmacokinetic and safety profile in vivo, which could be a potential candidate for combating VIM-mediated Gram-negative carbapenem resistance.
Triazole derivative as well as preparation method and application thereof
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Paragraph 0053; 0060-0061; 0063, (2020/06/09)
The invention relates to a triazole derivative as well as a preparation method and application thereof, which belong to the technical field of organic synthetic drugs. The structure of the triazole derivative is shown as a formula I. In the formula I, R1 and R2 are H, Cl, Br,-CF3,-CH(CH3)2 or -OCH3, and R1 and R2 are not H at the same time. R3 is -CH2 or -COCH2; X and Y are N or C, X and Y are not C at the same time, and X and Y are not N at the same time. The triazole derivative disclosed by the invention has a certain inhibition effect on germs of various crop diseases. Small toxic andside effects on plants are achieved. The preparation method of the triazole derivative is simple.
Organocatalytic Chlorination of Alcohols by P(III)/P(V) Redox Cycling
Longwitz, Lars,Jopp, Stefan,Werner, Thomas
, p. 7863 - 7870 (2019/06/27)
A catalytic system for the chlorination of alcohols under Appel conditions was developed. Benzotrichloride is used as a cheap and readily available chlorinating agent in combination with trioctylphosphane as the catalyst and phenylsilane as the terminal reductant. The reaction has several advantages over other variants of the Appel reaction, e.g., no additional solvent is required and the phosphane reagent is used only in catalytic amounts. In total, 27 different primary, secondary, and tertiary alkyl chlorides were synthesized in yields up to 95%. Under optimized conditions, it was also possible to convert epoxides and an oxetane to the dichlorinated products.
N -Hydroxyphthalimide/benzoquinone-catalyzed chlorination of hydrocarbon C-H bond using N -chlorosuccinimide
Li, Zi-Hao,Fiser, Béla,Jiang, Biao-Lin,Li, Jian-Wei,Xu, Bao-Hua,Zhang, Suo-Jiang
supporting information, p. 3403 - 3408 (2019/04/01)
The direct chlorination of C-H bonds has received considerable attention in recent years. In this work, a metal-free protocol for hydrocarbon C-H bond chlorination with commercially available N-chlorosuccinimide (NCS) catalyzed by N-hydroxyphthalimide (NHPI) with 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ) functioning as an external radical initiator is presented. Aliphatic and benzylic substituents and also heteroaromatic ones were found to be well tolerated. Both the experiments and theoretical analysis indicate that the reaction goes through a process wherein NHPI functions as a catalyst rather than as an initiator. On the other hand, the hydrogen abstraction of the C-H bond conducted by a PINO species rather than the highly reactive N-centered radicals rationalizes the high chemoselectivity of the monochlorination obtained by this protocol as the latter is reactive towards the C(sp3)-H bonds of the monochlorides. The present results could hold promise for further development of a nitroxy-radical system for the highly selective functionalization of the aliphatic and benzylic hydrocarbon C-H.
Halogenation through Deoxygenation of Alcohols and Aldehydes
Chen, Jia,Lin, Jin-Hong,Xiao, Ji-Chang
supporting information, p. 3061 - 3064 (2018/05/28)
An efficient reagent system, Ph3P/XCH2CH2X (X = Cl, Br, or I), was very effective for the deoxygenative halogenation (including fluorination) of alcohols (including tertiary alcohols) and aldehydes. The easily available 1,2-dihaloethanes were used as key reagents and halogen sources. The use of (EtO)3P instead of Ph3P could also realize deoxy-halogenation, allowing for a convenient purification process, as the byproduct (EtO)3Pa?O could be removed by aqueous washing. The mild reaction conditions, wide substrate scope, and wide availability of 1,2-dihaloethanes make this protocol attractive for the synthesis of halogenated compounds.
Preparation method for 4-trifluoromethylbenzyl chloride
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Paragraph 0013; 0016, (2018/03/25)
The invention relates to a preparation method for 4-trifluoromethylbenzyl chloride, wherein the preparation method comprises the specific steps: A, adding a proper amount of tetrahydrofuran, magnesium, iodine, bromoethane and p-chlorobenzotrifluoride into a reaction kettle, introducing nitrogen, stirring to rise the temperature to reflux, refluxing for 20 min-40 min, then controlling the temperature at 40 DEG C-60 DEG C, dropping p-trifluoromethyl chlorobenzene, after the dropping is finished, carrying out a heat preservation reaction for 1.5 h-3 h, then cooling to 5 DEG C-15 DEG C, adding a proper amount of paraformaldehyde, then controlling the temperature at 0 DEG C-60 DEG C, carrying out a reaction for 5 h-7 h, then recycling tetrahydrofuran, and carrying out reduced pressure distillation to obtain 4-trifluoromethylbenzyl alcohol; and B, adding a proper amount of hydrochloric acid and 4-trifluoromethylbenzyl alcohol into another reaction kettle, stirring to rise the temperature toreflux, carrying out a heat preservation reaction for 20 h-30 h, cooling to room temperature, stratifying, dehydrating, and carrying out reduced pressure distillation to obtain 4-trifluoromethylbenzylchloride. The preparation method for 4-trifluoromethylbenzyl chloride is simple in route and high in yield.
Preparation method for 3-trifluoromethylbenzyl chloride
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Paragraph 0011; 0012; 0014, (2018/03/25)
The invention relates to a preparation method for 3-trifluoromethylbenzyl chloride. The preparation method comprises the following concrete steps: A, adding a proper amount of dimethyltetrahydrofuran,magnesium, iodine, bromoethane and bromobenzotrifluoride into a reaction vessel, introducing nitrogen, carrying out stirring and heating for refluxing for 20 to 40 min, then controlling a temperatureto be 40 to 60 DEG C, adding bromobenzotrifluoride drop by drop, carrying out a reaction under a heat preserved condition for 1.5 to 3 h, then carrying out cooling to 5 to 15 DEG C, adding a proper amount of paraformaldehyde, then carrying out a reaction with a temperature controlled to be 0 to 60 DEG C for 5 to 7 h, recovering dimethyltetrahydrofuran, and carrying out vacuum rectification so asto obtain trifluoromethylbenzyl methanol; and B, adding a proper amount of hydrochloric acid and trifluoromethylbenzyl methanol into another reaction vessel, carrying out stirring and heating for refluxing, carrying out a heat-preserved reaction for 20 to 30 h, and then successively carrying out cooling to room temperature, layering, dehydration and pressure-reduced distillation so as to obtain 3-trifluoromethylbenzyl chloride. The preparation method for 3-trifluoromethylbenzyl chloride is concise in route and high in yield.
Ferric(III) Chloride Catalyzed Halogenation Reaction of Alcohols and Carboxylic Acids Using α,α-Dichlorodiphenylmethane
Lee, Chang-Hee,Lee, Soo-Min,Min, Byul-Hana,Kim, Dong-Su,Jun, Chul-Ho
supporting information, p. 2468 - 2471 (2018/04/25)
A new method for chlorination of alcohols and carboxylic acids, using α,α-dichlorodiphenylmethane as the chlorinating agent and FeCl3 as the catalyst, was developed. The method enables conversions of various alcohols and carboxylic acids to their corresponding alkyl and acyl chlorides in high yields under mild conditions. Particulary interesting is the observation that the respective alkyl bromides and iodides can be generated from alcohols when either LiBr or LiI are present in the reaction mixtures.
METHOD OF CONVERTING ALCOHOL TO HALIDE
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Page/Page column 51; 98, (2017/01/02)
The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.
Gallium-catalyzed reductive chlorination of carboxylic acids with copper(II) chloride
Sakai, Norio,Nakajima, Takumi,Yoneda, Shinichiro,Konakahara, Takeo,Ogiwara, Yohei
, p. 10619 - 10623 (2015/02/19)
Described herein is the direct chlorination of carboxylic acids using copper(II) chloride via a gallium(III)-catalyzed reduction in the presence of a hydrosiloxane. During this reductive chlorination, the counteranions of CuCl2 functioned as a chloride source.
