3-chlorophenyl thiophen-2-yl ketone | 56824-65-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chlorophenyl thiophen-2-yl ketone
• 英文别名: (3-chlorophenyl)-(thiophen-2-yl)methanone；(3-chlorophenyl)(thien-2-yl)methanone；(3-Chlorophenyl)(thiophen-2-yl)methanone；(3-chlorophenyl)-thiophen-2-ylmethanone
• CAS: 56824-65-8
• 化学式: C₁₁H₇ClOS
• 分子量: 222.695
• InChiKey: LOFRWWQFKLDCQK-UHFFFAOYSA-N

物化性质

• 熔点：
  56-58 °C
• 沸点：
  352.9±22.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  45.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chlorophenyl thiophen-2-yl ketone 在 sodium tetrahydroborate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以94%的产率得到(3-chlorophenyl)-(thiophen-2-yl)methanol
  参考文献：
  名称：

  Novel 1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. A Structure−Activity Relationship Investigation

  摘要：

  1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentration. Replacement of one phenyl ring of 1-[2-(diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings, such as 2-thienyl or 3-pyridinyl, led to novel DAMNIs with increased activity. In HIV-1 WT cell-based assay the racemic 1-{2-{alpha-(thiophen-2-yl)phenylmethoxylethyl}-2-methyl-5-nitroimidazole (7) (EC50 = 0.03 mu M) proved 5 times more active than compound 4. Docking experiments showed that the introduction of a chiral center would not affect the binding of both (R)-7 and (S)-7. The internal scoring function of the Autodock program calculated the same inhibition constant (K-i = 7.9 nM) for the two enantiomers. Compounds 7 (ID50 = 8.25 mu M) were found more active than efavirenz (ID50 = 25 mu M) against the viral RT carrying the K103N mutation, suggesting for these compounds a potential use in efavirenz based anti-AIDS regimens.

  DOI：

  10.1021/jm050273a
• 作为产物：
  描述：

  3-氯苯甲酸 在 三氯化铝 、 氯化亚砜 作用下， 生成 3-chlorophenyl thiophen-2-yl ketone
  参考文献：
  名称：

  五元单杂环苯甲酰基衍生物的红外和核磁共振特性及芳香度指数的测定

  摘要：

  二苯甲酮，2- benzoylthiophenes，2- benzoylpyrroles和2- benzoylfurans，其在具有取代基的米-和p苯甲酰基环的位上制备并在0.1，得到它们的红外和核磁共振光谱中号氯仿d溶液。将每个系列的化学位移值与哈米特取代基参数作图，以得到良好的相关性，但邻位-Hs和-Cs除外。斜率以及化学位移的差异为芳香性指数提供了一组有意义的值。

  DOI：

  10.1002/jhet.5570400504

文献信息

• Substituent Position‐Controlled Stereoselectivity in Enzymatic Reduction of Diaryl‐ and Aryl(heteroaryl)methanones
  作者：Zhining Li、Zexu Wang、Yuhan Wang、Xiaofan Wu、Hong Lu、Zedu Huang、Fener Chen

  DOI：10.1002/adsc.201801543

  日期：2019.4.16

  directing group (bromo group) showcased the potential application of this substrate‐controlled bioreduction reaction. The combined use of substrate engineering and protein engineering, was demonstrated to be a useful strategy in efficiently improving stereoselectivity or switching stereopreference of enzymatic processes.

  我们在这里报告了一种名为KmCR2的新型酮还原酶（KRED）的发现，该酮具有对大体积的二芳基和芳基（杂芳基）甲烷进行生物还原的广泛的底物光谱。芳环上取代基的位置（间位与对位或邻位被揭示出可以控制KmCR2的立体特异性。使用经过精心设计的带有无痕导向基团（溴基）的底物，对二芳基或芳基（杂芳基）甲醇的两种对映异构体进行立体选择性制备，证明了这种底物控制的生物还原反应的潜在应用。底物工程和蛋白质工程的结合使用被证明是有效提高立体选择性或切换酶促过程的立体偏好的有用策略。
• 2-(Trifluoromethylsulfonyloxy)pyridine as a Reagent for the Ketone Synthesis from Carboxylic Acids and Aromatic Hydrocarbons
  作者：Takashi Keumi、Kiichiro Yoshimura、Masakazu Shimada、Hidehiko Kitajima

  DOI：10.1246/bcsj.61.455

  日期：1988.2

  A new reagent 2-(trifluoromethylsulfonyloxy)pyridine (TFOP) was prepared by the reaction of sodium salt of 2-pyridinol with trifluoromethylsulfonyl chloride in dioxane. The compound TFOP in trifluoroacetic acid has been found to intermolecularly dehydrate from benzoic acid and aromatic hydrocarbons to give the corresponding benzophenones in high yield. It was further elucidated, in the reaction of

  通过2-吡啶醇的钠盐与三氟甲基磺酰氯在二恶烷中反应制备新试剂2-(三氟甲基磺酰氧基)吡啶(TFOP)。已发现三氟乙酸中的化合物 TFOP 从苯甲酸和芳烃中分子间脱水，以高产率得到相应的二苯甲酮。进一步阐明，在芴反应中，多种羧酸可用作与 TFOP/TFA 系统结合的芳族酮合成的酰基前体。这种酰化方法已被用于合成 2-酰基噻吩，通过使用氯化铝作为催化剂的经典 Friedel-Crafts 反应很难以令人满意的收率制备。
• Base cleavage of substituted [phenyl(2-thienyl)methyl]- and [phenyl(2-furyl)methyl]-trimethylsilane. Stabilization of carbanionic centres by 2-thienyl and 2-furyl groups
  作者：Colin Eaborn、Graziella Pirazzini、Giancarlo Seconi、Alfredo Ricci

  DOI：10.1016/s0022-328x(00)81224-3

  日期：1980.6

  Ph(2-furyl)CH2, 29.6; (2-thienyl)2CH2, 27.1. The effect of the 2-Cl substituent in the thiophen ring is close to that of the p-Cl substituent in the benzene ring, and the effects of the p-Me substituents on the benzene ring are very close to those of the 2-Me substituents on the thiophen or furan rings. The product and rate isotope effects (determined by use of MeOD) are consistent with separation of the

  已确定（2-噻吩基）2 CHSiMe 3和化合物Ph（2-噻吩基）CHSiMe 3和Ph（2-呋喃基）CHSiMe 3及其某些衍生物在25°C下的NaOMEMeOH在25°C的裂解速率。在苯基的m-或p-位或杂环基的5-位上的取代基。结果表明，2-噻吩基和2-呋喃基比苯基更有效地稳定了碳负离子中心，并且可以得出以下近似的p K a值：Ph 2 CH 2，33.4； n 2 ＝1。pH值（2-噻吩基）CH 2，30.0; pH值（2-呋喃基）CH 2，29.6; （2-噻吩基）2 CH 2，27.1。噻吩环中2-Cl取代基的作用与苯环中p -Cl取代基的作用接近，苯环中p -Me取代基的作用与2-Me取代物的作用非常接近噻吩或呋喃环上的取代基。产物和速率同位素效应（通过使用MeOD确定）与速率确定步骤中碳负离子的分离是一致的。
• Palladium-Catalyzed Chemoselective Cross-Coupling of Acyl Chlorides and Organostannanes
  作者：Rachel Lerebours、Alejandra Camacho-Soto、Christian Wolf

  DOI：10.1021/jo051257o

  日期：2005.10.1

  and alkynylstannanes proceeds in up to 98% yield using 2.5 mol % of bis(di-tert-butylchlorophosphine)palladium(II) dichloride as the precatalyst. Various functional groups including aryl chlorides and bromides that usually undergo oxidative addition to palladium complexes bearing phosphinous acid or dialkylchlorophosphine ligands are tolerated. This procedure allows convenient ketone formation and

  脂族和芳族酰氯与芳基-，杂芳基-和炔基锡烷的化学选择性交叉偶联使用2.5 mol％的二氯化二（二叔丁基氯膦）钯（II）作为预催化剂，产率高达98％。容许各种官能团，包括通常被氧化成带有亚膦酸或二烷基氯膦配体的钯络合物的氧化加成的芳基氯化物和溴化物。此程序可方便地形成酮，并消除了Friedel-Crafts酰化反应的内在限制，例如取代基导向作用和Lewis酸催化的亲电芳族取代的典型反应活性要求。
• Clotrimazole Scaffold as an Innovative Pharmacophore Towards Potent Antimalarial Agents: Design, Synthesis, and Biological and Structure–Activity Relationship Studies
  作者：Sandra Gemma、Giuseppe Campiani、Stefania Butini、Gagan Kukreja、Salvatore Sanna Coccone、Bhupendra P. Joshi、Marco Persico、Vito Nacci、Isabella Fiorini、Ettore Novellino、Ernesto Fattorusso、Orazio Taglialatela-Scafati、Luisa Savini、Donatella Taramelli、Nicoletta Basilico、Silvia Parapini、Giulia Morace、Vanessa Yardley、Simon Croft、Massimiliano Coletta、Stefano Marini、Caterina Fattorusso

  DOI：10.1021/jm701247k

  日期：2008.3.13

  We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. SAR studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. A selected set of antimalarials was further biologically investigated and displayed low in vitro toxicity on a panel of human and murine cell lines. In vitro, the novel compounds proved to be selective for free heme, as demonstrated in the beta-hematin inhibitory activity assay, and did not show inhibitory activity against 14-alpha-lanosterol demethylase (a fungal P450 cytochrome). Compounds 2, 4e, and 4n exhibited in vivo activity against P. chabaudi after oral administration and thus represent promising antimalarial agents for further preclinical development.