1-fluoro-4-[(methoxymethoxy)methyl]benzene | 104620-55-5

• 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-4-[(methoxymethoxy)methyl]benzene
• 英文别名: Benzene, 1-fluoro-4-[(methoxymethoxy)methyl]-；1-fluoro-4-(methoxymethoxymethyl)benzene
• CAS: 104620-55-5
• 化学式: C₉H₁₁FO₂
• 分子量: 170.184
• InChiKey: PKJNLJURKIDHRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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：

  1-fluoro-4-[(methoxymethoxy)methyl]benzene 在 三氯化硼 作用下， 以 正己烷 、 正戊烷 为溶剂， 反应 1.0h， 以41%的产率得到1-(chloromethoxymethyl)-4-fluorobenzene
  参考文献：
  名称：

  Quaternary salts of 2-[(hydroxyimino)methyl]imidazole. 3. Synthesis and evaluation of (alkenyloxy)-, (alkynyloxy)-, and (aralykyloxy)methyl quaternarized 2-[(hydroxyimino)methyl]-1-alkylimidazolium halides as reactivators and therapy for soman intoxication

  摘要：

  A series of structurally related monosubstituted 1-[(alkenyloxy)methyl]-, 1-[(alkynyloxy)methyl]-, and 1-[(aralkyloxy)methyl]-2-[(hydroxyimino)methyl]-3-methyli midazolium halides were prepared and evaluated. All new compounds were characterized with respect to (hydroxyimino)methyl acid dissociation constant, nucleophilicity, and octanol-buffer partition coefficient. The alkynyloxy-substituted compounds were also evaluated in vitro with respect to reversible inhibition of human erythrocyte (RBC) acetylcholinesterase (AChE) and kinetics of reactivation of human AChE inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP). In vivo evaluation in mice revealed that coadministration of alkynyloxy-substituted imidazolium compounds with atropine sulfate provided significant protection against a 2 x LD50 challenge of GD. For the alkynyloxy-substituted imidazolium drugs there is a direct relationship between in vitro and in vivo activity: the most potent in vivo compounds against GD proved to be potent in vitro reactivators against EPMP-inhibited human AChE. These results differ from the observations made on the sterically hindered imidazolium compounds (see previous article) and suggest that several antidotal mechanisms of protective action may be applicable for the imidazolium aldoxime family of therapeutics. The ability of the alkynyloxy substituents to provide life-saving protection against GD intoxication was not transferable to the pyridinium or triazolium heteroaromatic ring systems.

  DOI：

  10.1021/jm00122a035
• 作为产物：
  描述：

  对氟苯甲醇 、 二甲醇缩甲醛 在 aluminum hydrogen sulfate 作用下， 反应 0.86h， 以85%的产率得到1-fluoro-4-[(methoxymethoxy)methyl]benzene
  参考文献：
  名称：

  无溶剂条件下金属硫酸氢盐催化醇的甲氧基甲基化

  摘要：

  在金属硫酸氢盐 M(HSO 4 ) n 存在下，在室温和无溶剂条件下，使用甲醛二甲氧基缩醛对多种醇进行甲氧基甲基化。以高产率和纯度获得甲氧基甲基醚（MOM-醚）。

  DOI：

  10.1002/jccs.200700153

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。
• High-valent [SnIV(Br8TPP)(OTf)2] as a highly efficient and reusable catalyst for selective methoxymethylation of alcohols and phenols: The effect of substituted bromines on the catalytic activity
  作者：Majid Moghadam、Shahram Tangestaninejad、Valiollah Mirkhani、Iraj Mohammadpoor-Baltork、Mostafa Khajehzadeh、Farshid Kosari、Mehdi Araghi

  DOI：10.1016/j.poly.2009.07.041

  日期：2010.1

  tin(IV)octabromotetraphenylporphyrinato trifluoromethanesulfonate, [SnIV(Br8TPP)(OTf)2], was used for selective methoxymethylation of alcohols and phenols with formaldehyde dimethyl acetal (FDMA) at room temperature. Different primary, secondary and tertiary alcohols as well as phenols were converted to their corresponding methoxymethyl ethers with FMDA in the presence of an electron deficient tin(IV) porphyrin

  摘要在室温下，高价锡（IV）八溴四苯基卟啉三氟甲烷磺酸盐[SnIV（Br8TPP）（OTf）2]用于用甲醛二甲基乙缩醛（FDMA）对醇和酚进行选择性甲氧基甲基化。在缺电子的锡（IV）卟啉存在下，使用FMDA将不同的伯，仲和叔醇以及苯酚转化为相应的甲氧基甲基醚。催化剂被重复使用了几次，而活性没有明显损失。
• <i>N,N,N′,N′</i>-Tetrabromobenzene-1,3-Disulfonamide and Poly(<i>N</i>-Bromo-<i>N</i>-Ethyl-Benzene-1,3-Disulfonamide) as Efficient Catalysts for the Methoxymethylation of Alcohols under Solvent-Free Conditions
  作者：Ramin Ghorbani-Vaghei、Mohammad Ali Zolfigol、Mostafa Amiri、Hojat Veisi

  DOI：10.1002/jccs.200800092

  日期：2008.6

  Methoxymethylation of a variety of alcohols was performed using formaldehyde dimethyl acetal in the presence of N,N,N',Ν'-tetrabromobenzene-1,3-disulfonamide [TBBDA] and poly(N-bromo-N-ethyl-benzene-l,3-disulfonamide) [PBBS] as catalysts at room temperature and solvent-free conditions. The methoxymethyl ethers (MOM-ethers) were obtained with good to excellent yields.

  在 N,N,N',N'-四溴苯-1,3-二磺酰胺 [TBBDA] 和聚 (N-溴-N-乙基-苯-1) 存在下使用甲醛二甲基缩醛对各种醇进行甲氧基甲基化,3-二磺酰胺) [PBBS] 在室温和无溶剂条件下作为催化剂。以良好至优异的产率获得甲氧基甲基醚（MOM-醚）。
• Cleavage of methoxymethyl ethers with boron trichloride. A convenient, versatile preparation of chloromethyl ether derivatives
  作者：Dane A. Goff、Ralph N. Harris、Jeffrey C. Bottaro、Clifford D. Bedford

  DOI：10.1021/jo00374a040

  日期：1986.11
• 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.