2-methyl-4-(4-(methylthio)phenyl)but-3-yn-2-ol | 124153-81-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-methyl-4-(4-(methylthio)phenyl)but-3-yn-2-ol
• 英文别名: 2-Methyl-4-(4-methylsulfanyl-phenyl)-but-3-yn-2-ol；2-methyl-4-(4-methylsulfanylphenyl)but-3-yn-2-ol
• CAS: 124153-81-7
• 化学式: C₁₂H₁₄OS
• 分子量: 206.309
• InChiKey: IFKSCJVXNSJMER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-4-(4-(methylthio)phenyl)but-3-yn-2-ol 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 苯 为溶剂， 反应 1.05h， 生成 3-(4-methylsulfanylphenyl)-1-phenylprop-2-yn-1-ol
  参考文献：
  名称：

  1,3-二芳基丙-2-yn-1-ones的合成及其与构效关系的研究：环氧合酶和脂氧合酶的双重抑制剂。

  摘要：

  设计，合成和评估了一组具有C-3 p-SO2Me COX-2药效基团的1,3-二芳基丙-2-yn-1-ones（13、17、23、26和27），作为潜在的双重抑制剂环氧合酶1/2（COX-1 / 2）和5 / 15-脂氧合酶（5 / 15-LOX）具有体内抗炎和镇痛作用。在这类化合物中，3-（4-甲磺酰基苯基）-1-（4-氟苯基）丙-2-炔-1-酮（13h）被确定为有效和选择性的COX-2抑制剂（COX-2 IC50 = 0.1 microM； SI = 300），效力比罗非昔布高5倍（COX-2 IC50 = 0.5 microM； SI> 200）。在大鼠角叉菜胶诱导的爪水肿测定中，口服30 mg / kg剂量后3 h，13h表现出中等的抗炎活性（炎症抑制26％）。相关的双重COX-1 / 2和5 / 15-LOX抑制剂3-（4-甲磺酰基苯基）-1-（4-氰基苯基）丙-2-炔-1-酮（13g，COX-1

  DOI：

  10.1021/jm0510474
• 作为产物：
  描述：

  苯乙炔 在 正丁基锂 、 potassium tert-butylate 作用下， 反应 2.17h， 生成 2-methyl-4-(4-(methylthio)phenyl)but-3-yn-2-ol
  参考文献：
  名称：

  Experimental and theoretical study of the dimetalation of phenylacetylene and (1-naphthyl)acetylene

  摘要：

  DOI：

  10.1021/jo00291a041

文献信息

• NIS/HFIP‐Mediated Synthesis of Indene‐Based β‐Iodoalkenyl Sulfides from Propargylic Sulfides
  作者：Noelia Velasco、Clara Martínez‐Núñez、Manuel A. Fernández‐Rodríguez、Roberto Sanz、Samuel Suárez‐Pantiga

  DOI：10.1002/adsc.202200613

  日期：2022.9.6

  A tandem 1,3-sulfur migration followed by iodocyclization reaction of propargylic sulfides in the presence of NIS in HFIP has been developed to synthesize indene-based β-iodoalkenyl sulfides. The choice of the reaction media is crucial to promote the reaction. The proposed mechanism involving the initial NIS activation by HFIP and favoring the sulfur migration of the starting propargylic thioether

  已经开发了串联 1,3-硫迁移，然后在 HFIP 中在 NIS 存在下进行炔丙基硫化物的碘环化反应，以合成茚基 β-碘烯基硫化物。反应介质的选择对于促进反应至关重要。所提出的机制涉及 HFIP 的初始 NIS 活化和有利于起始炔丙基硫醚通过阳离子中间体的硫迁移得到实验支持。此外，已证明选择的茚基 β-碘烯基硫化物作为后续 C-C 键形成反应的结构单元的适用性。
• Rhenium-Catalyzed Decarboxylative Coupling of Cyclic Enol Carbonates with Silyl Enol Ethers and Ketene Silyl Acetals
  作者：Yoichi Dokai、Aoi Fujioka、Kodai Saito、Tohru Yamada

  DOI：10.1021/acs.orglett.3c00543

  日期：——

  carbon dioxide onto propargyl alcohols, with silyl enol ethers including ketene silyl acetals, was developed to afford 1,4-dicarbonyl compounds in good-to-high yields. As the plausible reaction mechanism, it was proposed that the decarboxylative formation of an oxyallyl cation intermediate or its equivalent and the sequential nucleophilic addition of silyl enol ethers proceeded to afford 1,4-dicarbonyl

  通过将二氧化碳固定到炔丙醇上制备的环状烯醇碳酸酯与甲硅烷基烯醇醚（包括乙烯酮甲硅烷基缩醛）进行路易斯酸催化的脱羧偶联，以良好至高产率提供 1,4-二羰基化合物。作为似是而非的反应机理，有人提出氧烯丙基阳离子中间体或其等价物的脱羧形成和甲硅烷基烯醇醚的顺序亲核加成进行以提供1,4-二羰基产物。此外，所获得的-1,4-二羰基化合物的合成效用也通过将它们应用于多取代杂环的构建得到了证明。
• Desulfitative Sonogashira cross-coupling of thiopyronin for the synthesis of NIR arylacetylene-containing rhodamines
  作者：Guangshuai Zhou、Nathaniel Finney、Yali Wang

  DOI：10.1039/d3cc05995b

  日期：2024.3.12

  A classical, safe and efficient red-shift strategy contributing to NIR arylacetylene-containing rhodamines has been developed via the desulfitative Sonogashira cross-coupling reaction of thiopyronin for the first time, exhibiting a broad substrate scope with good yields. In addition, compound 3m shows great potential for application as a singlet oxygen probe, demonstrating the practicality of the method

  首次通过硫代吡罗宁的脱硫 Sonogashira 交叉偶联反应开发了一种经典、安全且高效的红移策略，有助于产生近红外芳基乙炔含罗丹明，该策略具有广泛的底物范围和良好的产率。此外，化合物3m显示出作为单线态氧探针的巨大应用潜力，证明了该方法的实用性。
• Pd/C-mediated coupling of aryl halides with terminal alkynes in water
  作者：Venkateswara Rao Batchu、Venkataraman Subramanian、Karuppasamy Parasuraman、Nalivela Kumara Swamy、Sanjeev Kumar、Manojit Pal

  DOI：10.1016/j.tet.2005.06.056

  日期：2005.10

  2-Aminoethanol facilitated the alkynylation of aryl halides (Sonogashira reaction) under palladium/charcoal-copper catalysis in water affording a mild and practical method for the synthesis of arylalkynes. A variety of terminal alkynes were coupled with aryl iodides and bromides possessing no hydrophilic functional groups to give the coupled products in good to excellent yields. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis and cyclooxygenase inhibitory activities of linear 1-(methanesulfonylphenyl or benzenesulfonamido)-2-(pyridyl)acetylene regioisomers
  作者：Morshed Alam Chowdhury、Ying Dong、Qiao-Hong Chen、Khaled R.A. Abdellatif、Edward E. Knaus

  DOI：10.1016/j.bmc.2007.11.003

  日期：2008.2.15

  A group of 1-(aminosulfonylphenyl and methylsulfonylphenyl)-2-(pyridyl) acetylene regioisomers were designed such that a COX-2 SO2NH2 pharmacophore was located at the para-position of the phenyl ring, or a SO2Me pharmacophore was placed at the ortho-, meta- or para-position of the phenyl ring, on an acetylene template (scaffold). The point of attachment of the pyridyl ring to the acetylene linker was simultaneously varied (2-pyridyl, 3-pyridyl, 4-pyridyl, 3-methyl- 2-pyridyl) to determine the combined effects of positional, steric, and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. These target linear 1-(phenyl)-2-(pyridyl) acetylenes were synthesized via a palladium-catalyzed Sonogashira cross-coupling reaction. Structure-activity relationship (SAR) data (IC50 values) acquired by determination of the in vitro ability of the title compounds to inhibit the COX-1 and COX-2 isozymes showed that the position of the COX-2 SO2NH2 or SO2Me pharmacophore on the phenyl ring, and the point of attachment of the pyridyl ring to the acetylene linker, were either individual, or collective, determinants of COX-2 inhibitory potency and selectivity. A number of compounds discovered in this study, particularly 1-(4-aminosulfonylphenyl)-2-(3-methyl-2-pyridyl) acetylene (22), 1-(3-methanesulfonylphenyl)-2-(2-pyridyl) acetylene (27), 1-(3methanesulfonylphenyl)-2-(4-pyridyl)acetylene (29), 1-(4-methanesulfonylphenyl)-2-(2-pyridyl)acetylene (30), and 1-(4-methanesulfonylphenyl)2-(3-pyridyl)acetylene (31), exhibit potent (IC50 = 0.04-0.33 mu M range) and selective (SI = 18 to > 312 range) COX-2 inhibitory activities, that compare favorably with the reference drug celecoxib (COX-2 IC50 = 0.07 mu M; COX-2 SI = 473). The sulfonamide (22), and methylsulfonyl (27 and 31), compounds exhibited anti-inflammatory activities (ID50 = 59.9-76.6 mg/kg range) that were intermediate in potency between the reference drugs aspirin (ID50 = 128.7 mg/kg) and celecoxib (ID50 = 10.8 mg/kg). (c) 2007 Elsevier Ltd. All rights reserved.