1,1,1,3-tetrafluoro-4-phenyl-2,4-butanedione | 188817-19-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,1,1,3-tetrafluoro-4-phenyl-2,4-butanedione
• 英文别名: 2,4,4,4-tetrafluoro-1-phenyl-1,3-butanedione；2,4,4,4-tetrafluoro-1-phenylbutane-1,3-dione
• CAS: 188817-19-8
• 化学式: C₁₀H₆F₄O₂
• 分子量: 234.15
• InChiKey: QQUDLIURQFHDCA-UHFFFAOYSA-N

物化性质

• 沸点：
  252.5±35.0 °C(Predicted)
• 密度：
  1.351±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-磺酰胺基苯肼盐酸盐 、 1,1,1,3-tetrafluoro-4-phenyl-2,4-butanedione 以 乙醇 为溶剂， 反应 15.0h， 生成 4-[4-fluoro-5-phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)

  摘要：

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

  DOI：

  10.1021/jm960803q
• 作为产物：
  描述：

  2-羟基苯乙酮 在 2,6-二甲基吡啶 、 四丁基氟化铵 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.83h， 生成 1,1,1,3-tetrafluoro-4-phenyl-2,4-butanedione
  参考文献：
  名称：

  Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class of Cyclooxygenase-2 Inhibitors:  Identification of 4-[5-(4-Methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, Celecoxib)

  摘要：

  A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of ii (4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

  DOI：

  10.1021/jm960803q

文献信息

• Synthesis of fluorinated heterocycles
  作者：Joseph C. Sloop、Carl L. Bumgardner、W.David Loehle

  DOI：10.1016/s0022-1139(02)00221-x

  日期：2002.12

  Selected 1,3-diketones having a trifluoromethyl group and/or a fluorine in the 2-position were condensed with aromatic hydrazines, hydroxylamine, urea, thiourea, guanidine, and substituted anilines producing pyrazoles, isoxazoles, pyrimidines, and quinolines, respectively, in yields ranging from 27 to 87%.

  将选定的在2位具有三氟甲基和/或氟的1,3-二酮与芳族肼，羟胺，尿素，硫脲，胍和取代的苯胺缩合，分别生成吡唑，异恶唑，嘧啶和喹啉。产率从27％到87％。
• Microwave-mediated pyrazole fluorinations using selectfluor^®
  作者：Joseph C. Sloop、James L. Jackson、Robert D. Schmidt

  DOI：10.1002/hc.20556

  日期：——

  Microwave-mediated electrophilic fluorinations and a new single-pot condensation en route to ring-fluorinated pyrazoles were examined: The monofluorination by these methods was successful for a variety of pyrazoles, with yields ranging from 13% to 75%. While electrophilic aromatic fluorination of 3-CF3 pyrazoles proved largely ineffective, development of a single-pot process overcame this limitation

  研究了微波介导的亲电氟化和一种新的单锅缩合在环氟化吡唑的过程中：通过这些方法的单氟化对各种吡唑是成功的，产率范围为 13% 到 75%。虽然 3-CF3 吡唑的亲电芳族氟化被证明在很大程度上是无效的，但单锅法的发展克服了这一限制。微波介导的反应具有区域选择性；杂环的环氟化优先发生在苯基和烷基取代基上。当需要时，烷基侧链氟化可以通过反应物比率进行调节。单锅法，包括 H-TEDA 的酸催化，生产 4-氟吡唑类产品。© 2009 Wiley Periodicals, Inc. 杂原子化学 20:341–345, 2009; 在线发表于 Wiley InterScience (www.interscience. wiley.com）。DOI 10.1002/hc.20556
• Electron-Deficient Aryl β-Diketones: Synthesis and Novel Tautomeric Preferences
  作者：Joseph C. Sloop、Paul D. Boyle、Augustus W. Fountain、William F. Pearman、Jacob A. Swann

  DOI：10.1002/ejoc.201001451

  日期：2011.2

  suggest a single, chelated cis-enol isomer that is conjugated with the aryl ring. In polar aprotic solvents, nonfluorinated aryl β-diketones equilibrate rapidly from the chelated cis-enol form to a tautomeric mixture of cis-chelated enol and a substantial proportion of the diketone form, trifluoromethylated aryl β-diketones show only limited equilibration from the chelated cis-enol to the diketone form

  使用克莱森和亲电氟化方法制备氟化芳基β-二酮。这些化合物的酮-烯醇和烯醇-烯醇互变异构在固态、纯液体和极性非质子溶液中通过结晶学和光谱学进行了检测。纯液体光谱测量以及选定的缺电子芳基 β-二酮的单晶 X 射线晶体学结果表明，存在与芳环共轭的单一螯合顺式烯醇异构体。在极性非质子溶剂中，非氟化芳基 β-二酮从螯合顺式烯醇形式迅速平衡为顺式螯合烯醇和大部分二酮形式的互变异构混合物，三氟甲基化芳基 β-二酮仅显示有限的螯合顺式平衡-烯醇到二酮形式，
• Ring-fluorinated pyrazoles
  作者：Carl L. Bumgardner、Joseph C. Sloop

  DOI：10.1016/s0022-1139(00)81096-9

  日期：1992.2

  2-Fluoro-1,3-diketones react with phenylhydrazine to yield ring-fluorinated pyrazoles in high yield. An isoxazole is produced when 2-fluoro-1,3-diphenyl-1,3-propandione is treated with hydroxylamine hydrochloride.
• cAMP REPORTERS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：EP1791972A2

  公开（公告）日：2007-06-06