24123-67-9Relevant academic research and scientific papers
Method for preparing alpha,alpha-dichloroketone under solvent-free condition
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Page/Page column 5-6, (2021/06/21)
The invention provides a method for synthesizing an alpha,alpha-dichloroketone compound by taking methyl ketone and sulfonyl chloride as raw materials. The method comprises the following steps: heating a reaction mixture of methyl ketone and sulfonyl chloride to 80 DEG C under a dry air condition, stirring for 4-8 hours, after the reaction is finished, removing sulfonyl chloride from the obtained mixture, and carrying out silica gel column chromatography separation by taking ethyl acetate-hexane as an eluent to obtain the alpha,alpha-dichloroketone compound. The synthesis method provided by the invention has the advantages of extremely high chemical reactivity and selectivity, simple and easily available raw materials, low price, simple operation, no need of any catalyst and solvent, reduction of the synthesis cost and the pollution of organic solvents to the environment, greenness, economy and the like.
Solvent-free preparation of α,α-dichloroketones with sulfuryl chloride
Tu, Dewei,Luo, Juan,Jiang, Wengao,Tang, Qiang
supporting information, (2021/09/15)
An efficient and facile method is reported for the synthesis of a series of α,α-dichloroketones. The direct dichlorination of methyl ketones and 1,3-dicarbonyls using an excess amount of sulfuryl chloride affords the corresponding gem-dichloro compounds in moderate to excellent yields. Moreover, the protocol features high yields, broad substrate scope, and simple reaction conditions without using any catalysts and solvents.
Modular and Chemoselective Strategy for Accessing (Distinct) α,α-Dihaloketones from Weinreb Amides and Dihalomethyllithiums
Malik, Monika,Pace, Vittorio,Senatore, Raffaele,Touqeer, Saad,Urban, Ernst
supporting information, p. 5056 - 5061 (2020/10/21)
The selective transfer of diversely functionalized dihalomethyllithiums (LiCHBrCl, LiCHClI, LiCHBrI, LiCHCl2, LiCHBr2, LiCHFI) to Weinreb amides for preparing gem-dihaloketones in one synthetic operation is reported. The capability of these amides as acylating agents and, the wide availability of dihalomethanes as pronucleophiles, enable a straightforward route to the title compounds under full chemocontrol. No racemization phenomena were evidenced in the case of optically active materials. Additionally, tolerance to sensitive functional groups (esters, amides, halogens, olefins etc.) was uniformly noticed, thus making this conceptually intuitive strategy flexible and tunable by the operator. (Figure presented.).
Electrochemical synthesis of α,α-dihaloacetophenones from terminal alkyne derivatives
Li, Zhibin,Sun, Qi,Qian, Peng,Hu, Kangfei,Zha, Zhenggen,Wang, Zhiyong
supporting information, p. 1855 - 1858 (2020/03/10)
By virtue of electrochemistry, a series of α,α-dihaloacetophenones were easily obtained with good to excellent yields. This electrochemical procedure was taken in a divided cell with constant current in aqueous media. The reaction can be carried out smoothly at room temperature under metal and oxidant free condition, which provides an eco-friendly synthesis for the α,α-dihaloacetophenone derivatives.
Visible-light-promoted oxidative halogenation of alkynes
Li, Yiming,Mou, Tao,Lu, Lingling,Jiang, Xuefeng
supporting information, p. 14299 - 14302 (2019/12/02)
In nature, halogenation promotes the biological activity of secondary metabolites, especially geminal dihalogenation. Related natural molecules have been studied for decades. In recent years, their diversified vital activities have been explored for treating various diseases, which call for efficient and divergent synthetic strategies to facilitate drug discovery. Here we report a catalyst-free oxidative halogenation achieved under ambient conditions (halide ion, air, water, visible light, room temperature, and normal pressure). Constitutionally, electron transfer between the oxygen and halide ion is shuttled via simple conjugated molecules, in which phenylacetylene works as both reactant and catalyst. Synthetically, it provides a highly compatible late-stage transformation strategy to build up dihaloacetophenones (DHAPs).
Dichloroacetophenones targeting at pyruvate dehydrogenase kinase 1 with improved selectivity and antiproliferative activity: Synthesis and structure-activity relationships
Zhang, Shao-Lin,Yang, Zheng,Hu, Xiaohui,Tam, Kin Yip
supporting information, p. 3441 - 3445 (2018/09/29)
Dichloroacetophenone is a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor with suboptimal kinase selectivity. Herein, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones. Structure-activity relationship analyses (SARs) enabled us to identify three potent compounds, namely 54, 55, and 64, which inhibited PDK1 function, activated pyruvate dehydrogenase complex, and reduced the proliferation of NCI-H1975 cells. Mitochondrial bioenergetics assay suggested that 54, 55, and 64 enhanced the oxidative phosphorylation in cancer cells, which might contribute to the observed anti-proliferation effects. Collectively, these results suggested that 54, 55, and 64 could be promising compounds for the development of potent PDK1 inhibitors.
Method for removal of methanamide by dichlorination
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Paragraph 0020-0025; 0050; 0051; 0052; 0053; 0054; 0070-0074, (2017/10/12)
A method for removal of methanamide by dichlorination is disclosed, according to the method, a finished product is obtained by removal of methanamide by dichlorination by one-step-reaction of various beta-carbonyl amide derivatives as raw materials, 2,2,6,6-Tetramethylpiperidinooxy (TEMPO) and an alkali as additives and N-chlorosuccinimide as a reagent in a reaction solvent, and then concentration and purification. According to the method, synthesis of an alpha-dichloroacetophenone derivative can be realized for the first time by a method of removal of methanamide by fracturation of carbon-carbon single bond. The method is novel and unique, has certain universality, is mild in reaction conditions, low in requirement of production equipment, and simple in technology, has the advantages of high efficiency, simple operation, high safety, economy and environmentally-friendliness; high-quality diverse alpha-dichloroacetophenone derivative products can be prepared by the method, and the products prepared by the method are important drug synthesis intermediates and material intermediates, can be widely used in the synthesis of heterocycles, unsaturated acids, acetylene alcohols and other compounds and cyclopropanation, and have wide market prospects.
One-pot dichlorinative deamidation of primary β-ketoamides
Zheng, Congke,Zhang, Xiaohui,Ijaz Hussain, Muhammad,Huang, Mingming,Liu, Qing,Xiong, Yan,Zhu, Xiangming
, p. 574 - 577 (2017/01/16)
An approach to the dichlorinative deamidation of primary β-ketoamides through ketonic cleavage is described, and a series of α,α-dichloroketones were furnished mostly in the presence of TEMPO. Based on control experiments, a mechanism involving tandem dichlorination and deamidation is proposed to interpret the observed reactivity.
A novel β-(oxy)alkyl radical during copper(I)-mediated stereoselective synthesis of (Z)-ene-1,4-diones in a reaction of 2,2,2-trichloro-1-phenylethanone
Ram, Ram N.,Tittal, Ram K.
supporting information, p. 2437 - 2440 (2016/05/19)
A novel β-(oxy)alkyl radical derived from trichloro methyl compound containing neither a suitably located C-C multiple bond nor a leaving group or a H-atom at the β-position of the radical in a reaction of 2,2,2-trichloro-1-phenyl-ethanone with 2 mol equiv each of CuCl and bpy in refluxing DCE under a N2 atm underwent intramolecular heterolysis (just like formation of intact radical cation-anion pair) during stereoselective radical dimerization to Z-ene-1,4-dione along with small amount of reductive dechlorination product. The stereochemistry was established by X-ray diffraction spectroscopy of various solid crystalline products.
Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
Kedziora, Kinga,Bisogno, Fabricio R.,Lavandera, Ivan,Gotor-Fernandez, Vicente,Montejo-Bernardo, Jose,Garcia-Granda, Santiago,Kroutil, Wolfgang,Gotor, Vicente
, p. 1066 - 1072 (2014/05/06)
Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR).
