2-(2-(fluoromethyl)phenyl)ethylamine | 1279558-77-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-(fluoromethyl)phenyl)ethylamine
• 英文别名: 2-(2-fluoromethylphenyl)ethylamine；2-[2-(Fluoromethyl)phenyl]ethanamine
• CAS: 1279558-77-8
• 化学式: C₉H₁₂FN
• 分子量: 153.199
• InChiKey: RNTFEWBCAUQZLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 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：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-甲基苯乙胺 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 silver fluoride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.5h， 生成 2-(2-(fluoromethyl)phenyl)ethylamine
  参考文献：
  名称：

  Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F]fluoromethyl-phenylalanine

  摘要：

  无载体添加的(n.c.a.) 2-[18F]氟甲基-l-苯丙氨酸在水溶液中对水解非常敏感。通过添加钙离子 (0.04 M)，该问题部分得到解决，使其货架期延长至至少6小时。本文详细研究了去氟反应，以阐明其机制。因此，合成了2-[18F]FMP和4-[18F]FMP的L和D对映体，以及2-[18F]氟甲基-苯乙胺和4-[18F]氟甲基-苯乙胺，这两者都是氨基酸类的去羧基‘模拟’分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，获得了高的总体产率和>99%的放射化学纯度。通过高效液相色谱(HPLC)研究了所有化合物的去氟速率。n.c.a 2-[18F]FMP的L对映体去氟速率是D对映体和2-[18F]氟甲基-苯乙胺的七倍。4-[18F]FMP和4-[18F]氟甲基-苯乙胺的两个对映体均表现出稳定性。根据这些数据，得出了反应机制，涉及两种不同的分子内相互作用。首先，胺与苯基氟之间的相互作用削弱了碳-氟键。其次，羧基与其中一个苯基氢原子形成的第二个氢桥使氟原子对水解的敏感性进一步增强。后者的相互作用引入了额外的手性中心。这种手性中心的形成概率在n.c.a. 2-[18F]FMP的L和D对映体之间存在显著差异，这解释了水解速率的差异。版权所有 © 2010 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1811

文献信息

• Mechanistic approach of the difference in hydrolysis rate between the 2- and 4-isomers of no-carrier-added [18F]fluoromethyl-L-phenylalanine
  作者：Ken Kersemans、John Mertens、Frank De Proft、Paul Geerlings

  DOI：10.1002/jlcr.1852

  日期：2011.4

  No-carrier-added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine (2-[18F]FMP) was found to be very sensitive to hydrolysis in aqueous solutions. In this paper, the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, besides 2-[18F]FMP and 4-[18F]FMP, 2-[18F]fluoromethyl-phenethylamine (2-[18F]FMPAM) and 4-[18F]FMPAM were synthesized, both ‘mimetic’ molecules of the decarboxylated amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The defluorination rate of 2-[18F]FMLP at 50°C was approximately 300 times faster than that of n.c.a. 4-[18F]FMLP. The defluorination rate of 2-[18F]FMPAM is somewhat lower than of 2-[18F]FMP but still very high in comparison with 4-[18F]FMPAM, which is virtually stable. It allowed to elucidate the reaction mechanism ruled by two distinct intramolecular interactions. First, the hydrogen bond interaction between the amine and the benzylic fluorine weakening the carbon–fluorine bond. Secondly, the formation of a second hydrogen bond between the carboxyl oxygen atom and one of the benzylic hydrogen atoms rendering the benzyl fluoride group even more susceptible to hydrolysis. Copyright © 2010 John Wiley & Sons, Ltd.

  无载体添加（n.c.a.）的2-[18F]氟甲基-L-苯丙氨酸（2-[18F]FMP）在水溶液中对水解非常敏感。本文对去氟反应进行了详细研究，以阐明其机制。因此，除了合成2-[18F]FMP和4-[18F]FMP之外，还合成了2-[18F]氟甲基-苯乙胺（2-[18F]FMPAM）和4-[18F]FMPAM，这两者均为去羧化氨基酸类似物的“模拟”分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，得到了高的整体产率和>99%的放射化学纯度。通过高效液相色谱（HPLC）研究了所有化合物的去氟速率。2-[18F]FMLP在50°C的去氟速率大约是n.c.a. 4-[18F]FMLP的300倍。2-[18F]FMPAM的去氟速率略低于2-[18F]FMP，但与几乎稳定的4-[18F]FMPAM相比，仍然非常高。这有助于阐明由两种不同的分子内相互作用主导的反应机制。首先，是胺和苄基氟之间的氢键相互作用，削弱了碳-氟键。其次，羧氧原子与一个苄基氢原子之间形成第二个氢键，使得苄基氟烷基团更易于水解。版权 © 2010 John Wiley & Sons, Ltd.
• US4959379A
  申请人：——

  公开号：US4959379A

  公开（公告）日：1990-09-25
• Mechanistic approach of the difference in non-enzymatic hydrolysis rate between the L and D enantiomers of no-carrier added 2-[18F]fluoromethyl-phenylalanine
  作者：Ken Kersemans、John Mertens、Frank De Proft、Paul Geerlings

  DOI：10.1002/jlcr.1811

  日期：——

  No-carrier added (n.c.a.) 2-[18F]fluoromethyl-l-phenylalanine was found to be very sensitive to hydrolysis in aqueous solutions. This problem was solved partially by the addition of calcium ions (0.04 M), increasing the shelf-life to at least 6 h. In this paper the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, L and D enantiomers of 2-[18F]FMP and 4-[18F]FMP were synthesized, as well as 2-[18F]fluoromethyl-phenethylamine and 4-[18F]fluoromethyl-phenethylamine, both decarboxylated ‘mimetic’ molecules of the amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotboxthree module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The L enantiomer of n.c.a 2-[18F]FMP defluorinated seven times faster than the D enantiomer and 2-[18F]fluoromethyl-phenethylamine. Both enantiomers of 4-[18F]FMP and 4-[18F]fluoromethyl-phenethylamine were stable. From these data, the reaction mechanism, involving two distinct intramolecular interactions, was derived. First, the interaction between the amine and the benzylic fluorine weakens the carbon–fluorine bond. Secondly, the formation of a second hydrogen bridge between the carboxyl group and one of the benzylic hydrogen atoms renders the fluorine atom even more susceptible to hydrolysis. The latter interaction induces an additional chiral center. The probability of its formation differs considerably between L and D enantiomers of n.c.a. 2-[18F]FMP, which explains the difference in hydrolysis rate. Copyright © 2010 John Wiley & Sons, Ltd.

  无载体添加的(n.c.a.) 2-[18F]氟甲基-l-苯丙氨酸在水溶液中对水解非常敏感。通过添加钙离子 (0.04 M)，该问题部分得到解决，使其货架期延长至至少6小时。本文详细研究了去氟反应，以阐明其机制。因此，合成了2-[18F]FMP和4-[18F]FMP的L和D对映体，以及2-[18F]氟甲基-苯乙胺和4-[18F]氟甲基-苯乙胺，这两者都是氨基酸类的去羧基‘模拟’分子。使用定制的Scintomics自动合成热盒三模块进行的放射合成，获得了高的总体产率和>99%的放射化学纯度。通过高效液相色谱(HPLC)研究了所有化合物的去氟速率。n.c.a 2-[18F]FMP的L对映体去氟速率是D对映体和2-[18F]氟甲基-苯乙胺的七倍。4-[18F]FMP和4-[18F]氟甲基-苯乙胺的两个对映体均表现出稳定性。根据这些数据，得出了反应机制，涉及两种不同的分子内相互作用。首先，胺与苯基氟之间的相互作用削弱了碳-氟键。其次，羧基与其中一个苯基氢原子形成的第二个氢桥使氟原子对水解的敏感性进一步增强。后者的相互作用引入了额外的手性中心。这种手性中心的形成概率在n.c.a. 2-[18F]FMP的L和D对映体之间存在显著差异，这解释了水解速率的差异。版权所有 © 2010 John Wiley & Sons, Ltd.