1-fluoro-3-[(methoxymethoxy)methyl]benzene | 481075-27-8

• 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: 1-fluoro-3-[(methoxymethoxy)methyl]benzene
• 英文别名: 1-Fluoro-3-(methoxymethoxymethyl)benzene
• CAS: 481075-27-8
• 化学式: C₉H₁₁FO₂
• 分子量: 170.184
• InChiKey: TWHUZABPXRGDKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  二氧化碳 、 1-fluoro-3-[(methoxymethoxy)methyl]benzene 在 五甲基二乙烯三胺 、 仲丁基锂 作用下， 以 四氢呋喃 、 环己烷 为溶剂， 反应 2.0h， 以15%的产率得到2-氟-4-(羟基甲基)苯甲酸
  参考文献：
  名称：

  Fluoro- or Trifluoromethyl-Substituted Benzyl and Phenethyl Alcohols: Substrates for Metal-Mediated Site-Selective Functionalization

  摘要：

  It was possible to functionalize the three fluorobenzyl alcohols and the three 2-(fluorophenyl)ethanols by metalation and subsequent carboxylation, the prototype electrophilic trapping reaction. Thisopropylsilyl (TIPS) outperformed methoxymethyl (MOM) as an O-protective group making seven new fluorobenzoic acids accessible in 63% average yield. Moreover, the TIPS group tolerates weakly basic and acidic media and, therefore, may facilitate further structural eldboration. The unprotected alcohols reacted more sluggishly and were unable to provide two of the targeted products (acids 1 and 2). The yield averaged only 46% in the five other cases (acids 3-7). The direct metalation of fluorinated benzyl and phenethyl alcohols remains nevertheless an attractive option because of its operational simplicity. All three (trifluoromethyl) benzyl alcohols and two of the three (trifluoromethyl)phenethyl alcohol isomers were successfully submitted to the metalation/functionalization sequence. These five starting materials gave rise to a total of nine new benzoic acids or lactones (compounds 8-14 and 17-18). Despite the poor yields (31% on average), the organometallic methods employed are, in general, extremely selective, economical and easy to perform.

  DOI：

  10.1002/1099-0690(200208)2002:15<2508::aid-ejoc2508>3.0.co;2-c
• 作为产物：
  描述：

  3-氟苄醇 、 氯甲基甲基醚 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以71%的产率得到1-fluoro-3-[(methoxymethoxy)methyl]benzene
  参考文献：
  名称：

  Fluoro- or Trifluoromethyl-Substituted Benzyl and Phenethyl Alcohols: Substrates for Metal-Mediated Site-Selective Functionalization

  摘要：

  It was possible to functionalize the three fluorobenzyl alcohols and the three 2-(fluorophenyl)ethanols by metalation and subsequent carboxylation, the prototype electrophilic trapping reaction. Thisopropylsilyl (TIPS) outperformed methoxymethyl (MOM) as an O-protective group making seven new fluorobenzoic acids accessible in 63% average yield. Moreover, the TIPS group tolerates weakly basic and acidic media and, therefore, may facilitate further structural eldboration. The unprotected alcohols reacted more sluggishly and were unable to provide two of the targeted products (acids 1 and 2). The yield averaged only 46% in the five other cases (acids 3-7). The direct metalation of fluorinated benzyl and phenethyl alcohols remains nevertheless an attractive option because of its operational simplicity. All three (trifluoromethyl) benzyl alcohols and two of the three (trifluoromethyl)phenethyl alcohol isomers were successfully submitted to the metalation/functionalization sequence. These five starting materials gave rise to a total of nine new benzoic acids or lactones (compounds 8-14 and 17-18). Despite the poor yields (31% on average), the organometallic methods employed are, in general, extremely selective, economical and easy to perform.

  DOI：

  10.1002/1099-0690(200208)2002:15<2508::aid-ejoc2508>3.0.co;2-c

文献信息

• Direct metalation of methoxymethyl arylmethyl ethers: A tin-free approach to the generation of α-alkoxyalkoxy-substituted aryllithiums
  作者：Ugo Azzena、Luisa Pisano、Sarah Mocci

  DOI：10.1016/j.jorganchem.2009.07.007

  日期：2009.10

  arylmethyllithiums was achieved by direct metalation of the corresponding arylmethyl methoxymethyl ethers. While the effect of substituents at the benzylic position is straightforward, substituents located on the aromatic ring promote the set up of a competition between lateral and aromatic metalation, strongly affected by the position and relative ortho directing properties of the new substituent. The proposed methodology

  一系列α-甲氧基甲氧基取代的芳基甲基锂的生成是通过相应的芳基甲基甲氧基甲基醚的直接金属化而实现的。尽管取代基在苄基位置的作用是直接的，但是位于芳环上的取代基促进了侧向和芳族金属化之间的竞争的建立，这受到新取代基的位置和相对邻位取向性质的强烈影响。所提出的方法学允许一种简单的方法来产生各种各样的功能化有机锂试剂。
• Fluoro- or Trifluoromethyl-Substituted Benzyl and Phenethyl Alcohols: Substrates for Metal-Mediated Site-Selective Functionalization
  作者：Elena Marzi、Andrea Spitaleri、Florence Mongin、Manfred Schlosser

  DOI：10.1002/1099-0690(200208)2002:15<2508::aid-ejoc2508>3.0.co;2-c

  日期：2002.8

  It was possible to functionalize the three fluorobenzyl alcohols and the three 2-(fluorophenyl)ethanols by metalation and subsequent carboxylation, the prototype electrophilic trapping reaction. Thisopropylsilyl (TIPS) outperformed methoxymethyl (MOM) as an O-protective group making seven new fluorobenzoic acids accessible in 63% average yield. Moreover, the TIPS group tolerates weakly basic and acidic media and, therefore, may facilitate further structural eldboration. The unprotected alcohols reacted more sluggishly and were unable to provide two of the targeted products (acids 1 and 2). The yield averaged only 46% in the five other cases (acids 3-7). The direct metalation of fluorinated benzyl and phenethyl alcohols remains nevertheless an attractive option because of its operational simplicity. All three (trifluoromethyl) benzyl alcohols and two of the three (trifluoromethyl)phenethyl alcohol isomers were successfully submitted to the metalation/functionalization sequence. These five starting materials gave rise to a total of nine new benzoic acids or lactones (compounds 8-14 and 17-18). Despite the poor yields (31% on average), the organometallic methods employed are, in general, extremely selective, economical and easy to perform.