6-bromo-4-(bromomethyl)-2H-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6-bromo-4-(bromomethyl)-2H-chromen-2-one
• 英文别名: 6-Bromo-4-(bromomethyl)chromen-2-one
• 化学式: C₁₀H₆Br₂O₂
• 分子量: 317.964
• InChiKey: SBJFICWWVJDYEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-4-(bromomethyl)-2H-chromen-2-one 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 丙酮 、 叔丁醇 为溶剂， 反应 10.25h， 生成 7-[[1-[(6-Bromo-2-oxo-chromen-4-yl)methyl]triazol-4-yl]methoxy]-4-methyl-chromen-2-one
  参考文献：
  名称：

  Click Chemistry Approach for Bis-Chromenyl Triazole Hybrids and Their Antitubercular Activity

  摘要：

  1,4‐Disubstituted bis‐chromenyl triazole hybrids 5a–m have been synthesized in a three‐step reaction sequence from 4‐(bromomethyl)‐2H‐chromen‐2‐ones 3a–m. The intermediate azides 4a–m underwent a regioselective 1,3‐dipolar cycloaddition with a 2H‐chromen‐2‐one linked acetylenic dipolarophile in the presence of Cu (II)/ascorbate/water/n‐butanol reaction medium. Three compounds 5h–j exhibited 6.25 μg/mL MIC against M. tuberculosis. Among the compounds screened for antifungal activity, lowest MIC of 6.25 μg/mL was observed for 5c against A. niger that also exhibited DNA cleavage observed by agarose gel electrophoresis. All the compounds were moderately active against both Gram‐positive and Gram‐negative bacterial strains. The cytotoxic effect of potent compounds on normal cells (V79 and HBL100) was assessed by MTT assay.

  DOI：

  10.1111/j.1747-0285.2012.01441.x
• 作为产物：
  描述：

  4-溴乙酰乙酸乙酯 、 苯酚 在 tetra-N-butylammonium tribromide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 以86%的产率得到6-bromo-4-(bromomethyl)-2H-chromen-2-one
  参考文献：
  名称：

  三丁基四溴化铵作为选择性溴化剂和高效溴化氢的生成剂，合成6-溴香豆素

  摘要：

  通过苯酚，4-取代的乙酰乙酸酯和四丁基三溴化铵（TBATB）在CH 2 Cl 2 -MeOH中的三组分反应，可以简单，高效地一锅合成6-溴香豆素。

  DOI：

  10.1002/jccs.200900090

文献信息

• Synthesis of Coumarin-benzotriazole Hybrids and Evaluation of their Anti-tubercular Activity
  作者：Sachin P. Ambekar、Chakrabhavi Dhananjaya Mohan、Arunkumar Shirahatti、Mahesh K. Kumar、Shobith Rangappa、Surender Mohan、Basappa、Obelannavar Kotresh、Kanchugarakoppal S. Rangappa

  DOI：10.2174/1570178614666170710125501

  日期：2017.12.11

  Background: Tuberculosis is one of the top ranked airborne infectious diseases caused by the bacillus Mycobacterium tuberculosis with high mortality rate from a single infectious agent. In the present article, we aimed to synthesize oxadiazole-coumarin-triazole based small molecules and evaluate for their possible anti-mycobacterial activity. Method: Herein, we describe the facile synthesis of 5-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)-1,3,4- oxadiazole-2-thiol-tethered substituted 4-(bromomethyl)-7-methyl-2H-chromen-2-one derivatives and evaluated for their anti-mycobacterial activity against H37Rv strain of M. tuberculosis. We also evaluated the cytotoxic effect of new compounds on normal cells. Results: Among the 14 novel oxadiazole-coumarin-triazole derivatives, 4-((5-((1H-benzo[d][1,2,3]triazol-1- yl)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-6-methoxy-2H-chromen-2-one (5f) displayed good antimycobacterial activity towards M. tuberculosis with an MIC value of 15.5 µM. Pyrazinamide was used as reference drug. Our investigation also revealed that, 5f is not cytotoxic to normal cells. Conclusion: In summary, the findings suggested that novel 1,3,4-oxadiazole coumarin-triazole hybrids are promising antimycobacterial agents against M. tuberculosis.

  背景：结核病是由结核分枝杆菌引起的高度致死性空气传播传染病之一。在本文中，我们的目标是合成基于噁二唑-香豆素-三唑的小分子并评估它们可能的抗结核活性。 方法：在此，我们描述了5-((1H-苯并[d][1,2,3]三唑-1-基)甲基)-1,3,4-噁二唑-2-硫醇缀合的取代4-(溴甲基)-7-甲基-2H-色烯-2-酮衍生物的简易合成，并评估了它们对M. tuberculosis H37Rv菌株的抗结核活性。我们还评估了新化合物对正常细胞的细胞毒性效应。 结果：在14种新型噁二唑-香豆素-三唑衍生物中，4-((5-((1H-苯并[d][1,2,3]三唑-1-基)甲基)-1,3,4-噁二唑-2-基硫)甲基)-6-甲氧基-2H-色烯-2-酮(5f)显示出对M. tuberculosis的良好抗菌活性，MIC值为15.5 µM。利福平被用作参考药物。我们的研究还揭示，5f对正常细胞没有细胞毒性。 结论：总之，研究结果表明，新型1,3,4-噁二唑香豆素-三唑杂化物是针对M. tuberculosis有前景的抗结核药物。
• Click chemistry approach for the regioselective synthesis of iso-indoline-1,3-dione-linked 1,4 and 1,5 coumarinyl 1,2,3-triazoles and their photophysical properties
  作者：Ashish Anand、Manohar V. Kulkarni

  DOI：10.1080/00397911.2017.1283524

  日期：2017.4.3

  ABSTRACT Copper-catalyzed reaction of N-propargyl isoindoline-1,3-dione and 4-azidomethyl coumarins / 4-azidomethyl-1-aza coumarins under click chemistry conditions afforded 1,4-disubstituted 1,2,3-triazoles, whereas ruthenium catalysis yielded isomeric 1,5-disubstituted 1,2,3-triazoles. The two regioisomers have been distinguished by NOE studies. UV absorption for a given pair of isomers exhibited

  摘要 在点击化学条件下，N-炔丙基异吲哚啉-1,3-二酮和 4-叠氮甲基香豆素/4-叠氮甲基-1-氮杂香豆素在铜催化下反应得到 1,4-二取代 1,2,3-三唑，而钌催化产生异构的 1,5-二取代的 1,2,3-三唑。两种区域异构体已通过 NOE 研究区分开来。一对给定异构体的紫外吸收显示出相似的趋势，而荧光测量显示出相当大的差异。还对叠氮化物与铜和钌的相互作用进行了光物理研究。图形概要
• Synthesis, antimicrobial and DNA cleavage studies of some 4-aryloxymethylcoumarins obtained by reaction of 4-bromomethylcoumarins with bidentate nucleophiles
  作者：Shabana Banu N. Makandar、Mahantesha Basanagouda、Manohar V. Kulkarni、Pranesha、Vijaykumar P. Rasal

  DOI：10.1007/s00044-011-9785-z

  日期：2012.9

  and 3-diethylaminophenol have been used to generate 4-aryloxymethylcoumarins. All the compounds have been analyzed by spectral methods and subjected to preliminary antibacterial, antifungal and DNA cleavage studies. The results showed that the compounds bearing methoxy, chloro and bromo substituents at C6-position of coumarin showed higher activity. Graphical Abstract Symmetrical bidentate nucleophiles

  摘要 使间苯二酚等对称的双齿亲核试剂与4-溴甲基香豆素级联反应，通过室温烯丙基亲核取代反应获得单和双-4-芳氧基甲基香豆素。不对称的亲核试剂，例如3-乙酰氨基苯酚和3-二乙基氨基苯酚已经用于产生4-芳氧基甲基香豆素。所有化合物均已通过光谱方法进行了分析，并已进行了初步的抗菌，抗真菌和DNA裂解研究。结果表明，在香豆素的C6-位带有甲氧基，氯和溴取代基的化合物显示出更高的活性。 图形概要 已经使对称的双齿亲核试剂如间苯二酚和不对称的亲核试剂3-乙酰氨基苯酚和3-二乙基氨基苯酚以级联的方式与4-溴甲基香豆素反应以获得相应的4-芳氧基甲基香豆素。所有化合物均已通过光谱方法进行了分析，并已进行了初步的抗菌，抗真菌和DNA裂解研究。
• An efficient and catalyst free methylthiolation of 4-(bromomethyl)-2<i>H</i>-chromen-2-ones with DMSO
  作者：Bahubali M. Chougala、Samundeeswari S、Megharaja Holiyachi、Nirmala S. Naik、Lokesh A. Shastri、Vinay A Sunagar

  DOI：10.1080/10426507.2017.1290628

  日期：2017.7.3

  efficient protocol has been established for the methylthiolation of structurally diverse 4-bromomethyl-2H-chromen-2-ones using dimethyl sulfoxide (DMSO) as methylthiolation source at higher temperature. The experimental method is highly economical and provides excellent yields of highly pure products which do not require further purification. All novel 4-[(methylthio)methyl]-2H-chromen-2-ones were characterized

  图形摘要 摘要 使用二甲基亚砜 (DMSO) 作为甲基硫醇化源在较高温度下对结构多样的 4-溴甲基-2H-chromen-2-ones 进行甲基硫醇化已经建立了第一个简单、无金属且有效的协议。该实验方法非常经济，并且提供了不需要进一步纯化的高纯度产品的极好收率。所有新型 4-[(甲硫基) 甲基]-2H-chromen-2-ones 的特点是 1H、13C 核磁共振和单晶 X 射线分析。
• Biscoumarin–pyrimidine conjugates as potent anticancer agents and binding mechanism of hit candidate with human serum albumin
  作者：Dinesh S. Reddy、Manasa Kongot、Vishal Singh、Md. Abrar Siddiquee、Rajan Patel、Nitin K. Singhal、Fernando Avecilla、Amit Kumar

  DOI：10.1002/ardp.202000181

  日期：2021.1

  magnetic resonance). In addition, the structure of compound 1d (1,3‐bis[(7‐chloro‐2‐oxo‐2H‐chromen‐4‐yl)methyl]‐5‐methylpyrimidine‐2,4(1H,3H)‐dione) was established through X‐ray crystallography. Compounds 1a–l were screened for in vitro anticancer activity against C6 rat glioma cells. Among the screened compounds, 1,3‐bis[(6‐chloro‐2‐oxo‐2H‐chromen‐4‐yl)methyl]‐5‐methylpyrimidine‐2,4(1H,3H)‐dione (1c)

  在我们不断努力开发具有治疗活性的香豆素类化合物的过程中，通过取代的 4-溴甲基香豆素与胸腺嘧啶的 SN2 反应合成了一系列新的 C4-C4' 双香豆素-嘧啶缀合物（1a-l）。所有化合物均使用光谱技术进行表征，即衰减全反射红外 (ATR-IR)、CHN 元素分析以及 1H 和 13C NMR（核磁共振）。此外，化合物1d的结构（1,3-双[（7-氯-2-氧代-2H-色烯-4-基）甲基]-5-甲基嘧啶-2,4（1H,3H）-二酮）是通过 X 射线晶体学建立的。筛选化合物 1a-l 对 C6 大鼠神经胶质瘤细胞的体外抗癌活性。在筛选的化合物中，1,3-双[(6-chloro-2-oxo-2H-chromen-4-yl)methyl]-5-methylpyrimidine-2,4(1H, 3H)-二酮 (1c) 被确定为最佳的抗增殖候选药物，其 IC50 值为 4.85 μM。发现所有化合物 (1a-l)