2,2,2-trifluoroethyl 2-(6-methoxy-2-naphthyl)propanoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2,2,2-trifluoroethyl 2-(6-methoxy-2-naphthyl)propanoate
• 英文别名: (R,S)-naproxen 2,2,2-trifluoroethyl ester；2,2,2-Trifluoroethyl 2-(6-methoxynaphthalen-2-yl)propanoate
• 化学式: C₁₆H₁₅F₃O₃
• 分子量: 312.289
• InChiKey: AZJVFESZLRUKQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  甲醇 、 2,2,2-trifluoroethyl 2-(6-methoxy-2-naphthyl)propanoate 在 Candida antarctica lipase B 作用下， 以 甲基叔丁基醚 为溶剂， 反应 7.0h， 生成 (R)-naproxen 2,2,2-trifluoroethyl ester 、 (R)-naproxen methyl ester 、 (S)-萘普生2,2,2-三氟乙酯
  参考文献：
  名称：

  Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides

  摘要：

  With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45 degrees C) as the model system, the enzyme enantioselectivity in terms of V-R/V-S = 105.8 and specific activity for the fast-reacting (R)-azolide V-R/(E-t) = 0.979 mmol/(h g) were greatly improved in comparison with V-R/V-S = 8.0 and V-R/(E-t) = 0.113 mmol/(h g) of using (R,S)-naproxenyl 2,2,2-trifluoroethyl ester as the substrate. The resolution strategy was successfully extended to other (R,S)-profenyl 1,2,4-triazolides and lipases from Candida rugosa (Lipase MY) and Carica papaya (CPL) having opposite enantioselectivity to CALB. Moreover, the kinetic constants were estimated, compared with those obtained via hydrolysis, and employed for modeling time-course conversions of (R,S)-naproxenyl 1,2,4-triazolide in anhydrous MTBE. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, as well as easy product separation from the remaining substrate via reactive extraction demonstrate merits of using (R,S)-azolides but not the corresponding esters for the alcoholytic resolution. (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2009.11.001
• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 在 吡啶 、 氯化亚砜 作用下， 以 苯 为溶剂， 反应 5.5h， 生成 2,2,2-trifluoroethyl 2-(6-methoxy-2-naphthyl)propanoate
  参考文献：
  名称：

  皱纹假丝酵母脂肪酶催化的硫代酯交换反应或在有机溶剂中水解制备（RS）-2-芳基丙酸硫酯的酶解反应

  摘要：

  通过使用脂肪酶催化的硫代酯交换反应或在有机溶剂中水解反应，开发了一种酶促拆分工艺，可从相应的外消旋硫酯生产（S）-萘普生酯，（S）-萘普生或（S）-布洛芬。当含有吸电子基团的活化萘普生硫酯为底物时，酶活性大大提高。与其他脂肪酶不同的是，假丝酵母与相应的含氧类似物相比，脂肪酶可识别硫酯的硫部分，并产生较低的酶活性。在各种条件下，即反应类型（硫代酯交换或水解），溶剂（异辛烷或环己烷），底物（萘普生或布洛芬硫酯）和脂肪酶来源的不同组合下，进一步比较了酶的性能。

  DOI：

  10.1016/s0957-4166(98)00296-1

文献信息

• Trifluoroacetaldehyde <i>N</i>-Tosylhydrazone as a Precursor of Trifluorodiazoethane in Reactions of Insertion into the Heteroatom–Hydrogen Bond
  作者：Vladimir S. Ostrovskii、Irina P. Beletskaya、Igor D. Titanyuk

  DOI：10.1021/acs.orglett.9b03471

  日期：2019.11.15

  volatility, storage instability, toxicity, and explosiveness. We report the application of trifluoroacetaldehyde N-tosylhydrazone as a CF3CHN2 precursor capable of generating in situ trifluorodiazoethane under mild basic conditions. Copper-catalyzed P–H, O–H, S–H, and C–H insertion reactions of trifluoroacetaldehyde N-tosylhydrazone revealed its wide applicability in the synthesis of trifluoroethyl-containing

  三氟重氮乙烷是一种被广泛研究的三氟乙基化试剂，适用于制备大量的含氟有机分子。然而，CF 3 CHN 2具有一些缺点，例如挥发性，储存不稳定性，毒性和爆炸性。我们报告了三氟乙醛N-甲苯磺酰as作为CF 3 CHN 2前体的应用，该前体能够在温和的碱性条件下原位生成三氟重氮乙烷。铜催化的三氟乙醛N-甲苯磺酰hydr的PH，OH，SH和CH插入反应表明了其在含三氟乙基物质合成中的广泛应用。
• Racemization and hydrolysis of (<i>S</i>)-naproxen 2,2,2-trifluoroethyl ester in non-polar solvents by strong neutral bases: implication for ion-pair kinetic basicity and hydrolysis
  作者：Han-Yuan Lin、Eddy Lay、Wen-Yen Wen、Hamza Dewi、Yu-Chi Cheng、Shau-Wei Tsai

  DOI：10.1002/poc.741

  日期：2004.5

  investigation of the racemization of (S)-naproxen 2,2,2-trifluoroethyl ester was conducted in the non-polar solvents isooctane, cyclohexane and n-hexane. The second-order interconversion constant as representing the ion-pair kinetic basicity in isooctane was first estimated and correlated with the equilibrium ion-pair basicity pKip in tetrahydrofuran, giving slopes of 0.768 and 0.689 for non-phosphazene and phosphazene

  通过使用强碱中性作为催化剂，（的外消旋化的详细调查小号） -萘普生2,2,2-三氟乙基酯在非极性溶剂中进行异辛烷，环己烷和Ñ正己烷。首先估算了代表异辛烷中离子对动力学碱性的二阶互变常数，并将其与四氢呋喃中的平衡离子对碱性p K ip关联，非磷腈和磷腈碱的斜率分别为0.768和0.689，在布朗斯台德相关性中。将该结果与（S）-萘普生2,2,2-三氟乙基硫代酯的结果进行了进一步比较，显示出约1–2个数量级的增强。相应的含硫类似物。非极性溶剂的影响较小（即异辛烷，Ñ上己烷和环己烷）被发现。外消旋和（水解的动力学分析小号） -萘普生2,2,2-三氟乙基酯在异辛烷和Ñ含有7-甲基-1,5,7-三氮杂二环-己烷[4.4.0]癸-5-烯和水建议通过碱进行亲核水解，其中四面体中间体I R1和I S1的分解是限速步骤，水解常数k hy与碱和离子对浓度的乘积成比例。版权所有©2004 John Wiley＆Sons，Ltd
• Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides
  作者：An-Chi Wu、Pei-Yun Wang、Yi-Sheng Lin、Min-Fang Kao、Jin-Ru Chen、Jyun-Fen Ciou、Shau-Wei Tsai

  DOI：10.1016/j.molcatb.2009.11.001

  日期：2010.3

  With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45 degrees C) as the model system, the enzyme enantioselectivity in terms of V-R/V-S = 105.8 and specific activity for the fast-reacting (R)-azolide V-R/(E-t) = 0.979 mmol/(h g) were greatly improved in comparison with V-R/V-S = 8.0 and V-R/(E-t) = 0.113 mmol/(h g) of using (R,S)-naproxenyl 2,2,2-trifluoroethyl ester as the substrate. The resolution strategy was successfully extended to other (R,S)-profenyl 1,2,4-triazolides and lipases from Candida rugosa (Lipase MY) and Carica papaya (CPL) having opposite enantioselectivity to CALB. Moreover, the kinetic constants were estimated, compared with those obtained via hydrolysis, and employed for modeling time-course conversions of (R,S)-naproxenyl 1,2,4-triazolide in anhydrous MTBE. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, as well as easy product separation from the remaining substrate via reactive extraction demonstrate merits of using (R,S)-azolides but not the corresponding esters for the alcoholytic resolution. (C) 2009 Elsevier B.V. All rights reserved.
• Enzymatic resolution of (RS)-2-arylpropionic acid thioesters by Candida rugosa lipase-catalyzed thiotransesterification or hydrolysis in organic solvents
  作者：Chun-Sheng Chang、Shau-Wei Tsai、Chun-Nan Lin

  DOI：10.1016/s0957-4166(98)00296-1

  日期：1998.8

  An enzymatic resolution process was developed to produce (S)-naproxen ester, (S)-naproxen or (S)-ibuprofen from the corresponding racemic thioesters by using lipase-catalyzed thiotransesterification or hydrolysis in organic solvents. Enzyme activity is greatly enhanced when activated naproxen thioesters containing an electron-withdrawing group are the substrates. Unlike other lipases, Candida rugosa

  通过使用脂肪酶催化的硫代酯交换反应或在有机溶剂中水解反应，开发了一种酶促拆分工艺，可从相应的外消旋硫酯生产（S）-萘普生酯，（S）-萘普生或（S）-布洛芬。当含有吸电子基团的活化萘普生硫酯为底物时，酶活性大大提高。与其他脂肪酶不同的是，假丝酵母与相应的含氧类似物相比，脂肪酶可识别硫酯的硫部分，并产生较低的酶活性。在各种条件下，即反应类型（硫代酯交换或水解），溶剂（异辛烷或环己烷），底物（萘普生或布洛芬硫酯）和脂肪酶来源的不同组合下，进一步比较了酶的性能。