9-(氟甲基)-9H-芴 | 502897-85-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: 9-(氟甲基)-9H-芴
• 英文名称: 9-(fluoromethyl)fluorene
• 英文别名: 9H-Fluorene, 9-(fluoromethyl)-；9-(fluoromethyl)-9H-fluorene
• CAS: 502897-85-0
• 化学式: C₁₄H₁₁F
• 分子量: 198.24
• InChiKey: PWATVXXDZGPHSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2903999090

反应信息

• 作为产物：
  描述：

  9-芴甲醇 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以58%的产率得到9-(氟甲基)-9H-芴
  参考文献：
  名称：

  Comparing Isotope Effects and Rates for the Methanolic Sodium Methoxide Reactions of 9-R-Fluorene to Those for p-CF3C6H4CHClR (R = CH2Cl, CH2F and CF3)

  摘要：

  报道了与9-(氯甲基)芴和9-(氟甲基)芴的甲醇钠甲醇醇促进的脱卤代反应相关的动力学初级同位素效应和激活参数，并与对-p-CF3C6H4CHClCH2Cl和对-p-CF3C6H4CHClCH2F进行了比较。在25°C下，芴基化合物的元素效应kHCl/kHF = 4，仅为苄基化合物所获得的值kHCl/kHF = 54的十分之一。还报道了9-(三氟甲基)芴的甲醇钠甲醇醇反应的激活参数，用于氘交换和脱氟反应，并与对-p-CF3C6H4CHClCF3进行了比较。在两种情况下，交换反应比消除反应快；然而，在芴基系统中，交换的激活熵∆S≠ = -14 eu和消除的激活熵∆S≠ = +10 eu之间存在很大差异；然而，苄基系统的∆S≠为12-13 eu。9-(氯甲基)芴和9-(氟甲基)芴的消除速度比对-p-CF3C6H4CHClCH2X的速度快80至1,000倍。在25°C下，9-(三氟甲基)芴的反应对脱氟反应有利，比对-p-CF3C6H4CHClCF3有利200,000倍，对交换有利1,000倍；然而，由于激活熵的巨大差异，交换反应在-50°C下有利10^7。

  DOI：

  10.1135/cccc20021505

文献信息

• Stepwise and Concerted Solvolytic Elimination and Substitution Reactions:  E1 Reaction via a Primary Carbocation
  作者：Qingshui Meng、Alf Thibblin

  DOI：10.1021/ja970362f

  日期：1997.5.1

  (1-NHCOMe). Kinetic studies of the corresponding ring-substituted compounds 2-X and 3-X show that the rate of elimination increases with increasing acidity of the substrate, Bronsted α > 0. The small kinetic deuterium isotope effects measured for the elimination reactions of the brosylates 1-OBs and 3-OBs, kH/kD = 2.0 ± 0.1 and 2.8 ± 0.1, respectively, suggest significant amounts of E1 reaction. The bimolecular

  9-(X-甲基)芴 (1-X, X = I, Br, OBs) 在 25 vol% 乙腈水溶液中的溶剂分解得到消除产物 9-亚甲基芴和取代产物 9-(羟甲基)芴 (1- OH) 和 9-(乙酰氨基甲基)芴 (1-NHCOMe)。相应的环取代化合物 2-X 和 3-X 的动力学研究表明，消除速率随着底物酸度的增加而增加，Bronsted α > 0。对溴磺酸盐 1 的消除反应测量的小动力学氘同位素效应-OB 和 3-OB，kH/kD = 2.0 ± 0.1 和 2.8 ± 0.1，分别表明 E1 反应的显着量。溴化物与添加的碱的双分子反应可能是不可逆的 E1cB 类型，与卤化物的反应相反，卤化物的反应与添加的碱以及溶剂水发生 E2 反应。
• IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20140206675A1

  公开（公告）日：2014-07-24

  In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -, L 2 -, and L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination nation with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

  在其不同实施例中，本发明提供某些亚氨基噻二嗪二氧化物化合物，包括化合物公式（I）：（I），并包括其立体异构体和药学上可接受的盐，其中R1、R2、R3、R4、R5、R9、环A、环B、m、n、p、-L1-、L2-和L3-各自独立选择并按照定义选定。本发明的新型亚氨基噻二嗪二氧化物化合物出人意料地发现具有预期的性质，这些性质使它们有望成为BACE抑制剂和/或用于治疗和预防与β-淀粉样蛋白（Aβ）产生相关的各种病理的优势。本发明还揭示了包括一个或多个此类化合物（独立和与一个或多个其他活性剂联合使用）的药物组合物，并揭示了用于制备和治疗与淀粉样β（Aβ）蛋白相关的病理，包括阿尔茨海默病的方法。
• DERIVES DE 5-SULFANYL-4H-1,2,4-TRIAZOLES POUR TRAITER LES DÉSORDRES ASSOCIÉS À LA SOMATOSTATINE
  申请人：IPSEN PHARMA

  公开号：EP1465880B1

  公开（公告）日：2009-08-05
• US8932992B2
  申请人：——

  公开号：US8932992B2

  公开（公告）日：2015-01-13
• Comparing Isotope Effects and Rates for the Methanolic Sodium Methoxide Reactions of 9-R-Fluorene to Those for p-CF3C6H4CHClR (R = CH2Cl, CH2F and CF3)
  作者：Heinz F. Koch、William C. Pomerantz、Erik L. Ruggles、Martijn van Laren、Anne-Marie van Roon

  DOI：10.1135/cccc20021505

  日期：——

  Kinetic primary isotope effects and activation parameters associated with the methanolic sodium methoxide-promoted dehydrohalogenation reactions of 9-(chloromethyl)fluorene and 9-(fluoromethyl)fluorene are reported and compared to for p-CF₃C₆H₄CHClCH₂Cl and p-CF₃C₆H₄CHClCH₂F. The element effect, k^HCl/k^HF = 4 at 25 °C, for the fluorenyl compounds is only a tenth of the value, k^HCl/k^HF = 54, obtained for the benzylic compounds. Also reported are the activation parameters for the methanolic sodium methoxide reactions of 9-(trifluoro)methylfluorene for deuterium exchange and dehydrofluorination, and are compared to those for p-CF₃C₆H₄CHClCF₃. In both cases the exchange reaction is faster than the elimination; however, in the fluorenyl system there is a large difference between the entropies of activation for exchange, ∆S^≠ = -14 eu, and elimination, ∆S^≠ = +10 eu; however, the ∆S^≠ of 12-13 eu are the same for the benzylic systems. The eliminations for 9-(chloromethyl)fluorene and 9-(fluoromethyl)fluorene are 80 to 1,000 times faster than those for p-CF₃C₆H₄CHClCH₂X. The reactions of 9-(trifluoromethyl)fluorene are favored over p-CF₃C₆H₄CHClCF₃ by 200,000 for the dehydrofluorination and 1,000 for the exchange at 25 °C; however, due to the large differences in activation entropies, the exchange reaction is favored by 10⁷ at -50 °C.

  报道了与9-(氯甲基)芴和9-(氟甲基)芴的甲醇钠甲醇醇促进的脱卤代反应相关的动力学初级同位素效应和激活参数，并与对-p-CF3C6H4CHClCH2Cl和对-p-CF3C6H4CHClCH2F进行了比较。在25°C下，芴基化合物的元素效应kHCl/kHF = 4，仅为苄基化合物所获得的值kHCl/kHF = 54的十分之一。还报道了9-(三氟甲基)芴的甲醇钠甲醇醇反应的激活参数，用于氘交换和脱氟反应，并与对-p-CF3C6H4CHClCF3进行了比较。在两种情况下，交换反应比消除反应快；然而，在芴基系统中，交换的激活熵∆S≠ = -14 eu和消除的激活熵∆S≠ = +10 eu之间存在很大差异；然而，苄基系统的∆S≠为12-13 eu。9-(氯甲基)芴和9-(氟甲基)芴的消除速度比对-p-CF3C6H4CHClCH2X的速度快80至1,000倍。在25°C下，9-(三氟甲基)芴的反应对脱氟反应有利，比对-p-CF3C6H4CHClCF3有利200,000倍，对交换有利1,000倍；然而，由于激活熵的巨大差异，交换反应在-50°C下有利10^7。