1,4-二甲氧基-2-(甲氧基甲基)苯 | 103441-37-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1,4-二甲氧基-2-(甲氧基甲基)苯
• 中文别名: 尼达尼布杂质63
• 英文名称: 1,4-dimethoxy-2-methoxymethyl-benzene
• 英文别名: 1,4-Dimethoxy-2-methoxymethyl-benzol；1,4-Dimethoxy-2-(methoxymethyl)benzene
• CAS: 103441-37-8
• 化学式: C₁₀H₁₄O₃
• 分子量: 182.219
• InChiKey: BLXSVSMHJMOYMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,4-二甲氧基-2-(甲氧基甲基)苯 在 ammonium cerium (IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 以50%的产率得到4,4'-bis(methoxymethyl)-[1,1'-bi(cyclohexane)]-3,3',6,6'-tetraene-2,2',5,5'-tetraone
  参考文献：
  名称：

  硝酸铈铵氧化 1,4-二甲氧基苯衍生物的电子效应

  摘要：

  摘要 已经发现存在于 1,4-二甲氧基苯衍生物中的取代基的电子性质对这些底物是否可以使用硝酸铈铵 (CAN) 氧化成二醌具有深远的影响。特别是，在取代基的 Hammett σ p值与用 CAN 处理二甲氧基苯衍生物时获得的相应二醌的产率之间似乎存在相关性。该信息可以帮助预测给定的底物是否会在这种氧化时产生二醌。

  DOI：

  10.1080/00397911.2022.2095209
• 作为产物：
  描述：

  2,5-二甲氧基甲苯 在 四氯化碳 、 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 生成 1,4-二甲氧基-2-(甲氧基甲基)苯
  参考文献：
  名称：

  Green et al., Journal of the Chemical Society, 1959, p. 3362,3369

  摘要：

  DOI：

文献信息

• Improved Synthesis of Diquinones
  作者：Brian Love、Jeffrey Bonner-Stewart、Lori Forrest

  DOI：10.1055/s-0028-1087937

  日期：——

  Preparation of a series of substituted diquinones is reported. In most examples, inverse order of addition (addition of a dimethoxybenzene derivative to a CAN solution) has been found to produce higher yields of diquinones than the traditional protocol in which the oxidant is added to the arene.

  报道了一系列取代双奎诺的制备。在大多数例子中，发现逆序加料（将一个二甲氧基苯衍生物加入CAN溶液）比传统方法（将氧化剂加入芳烃）能够产生更高的双奎诺产率。
• Structural Effects on the OH−-Promoted Fragmentation of Methoxy-Substituted 1-Arylalkanol Radical Cations in Aqueous Solution: The Role of Oxygen Acidity
  作者：Enrico Baciocchi、Massimo Bietti、Maria Francesca Gerini、Laura Manduchi、Michela Salamone、Steen Steenken

  DOI：10.1002/1521-3765(20010401)7:7<1408::aid-chem1408>3.0.co;2-m

  日期：2001.4.1

  corresponding cumyl alcohol radical cations; this suggests a mechanism in which a key role is played by the oxygen acidity as well as by the strength of the scissile C-C bond: a radical zwitterion is formed which undergoes a rate-determining C-C bond cleavage, coupled with the intramolecular ET. Finally, oxygen acidity also determines the reactivity of the radical cations of 2-(3,4-dimethoxyphenyl)ethanol

  动力学和产物研究，由OH诱导，H 2 O由一些二和三甲氧基取代的1-芳基烷醇（ArCH（OH）R * +）以及2-和3-（3， 4-二甲氧基苯基）链烷醇已经通过使用脉冲-和γ-辐解技术进行。在1-芳基链烷醇体系中，自由基阳离子3,4-（MeO）2C6H3CH2-OH * +的分解速率比其甲基醚的分解速率高两个数量级。这表明侧链OH基团在衰变过程中的关键作用（氧酸度）。但是，与该α-非氘代对应物相比，该自由基阳离子具有相当大的氘动力学同位素效应（3.7）。提出了一种机制，其中快速的OH去质子化导致自由基两性离子，然后进行速率确定的1,2-H移位，偶联至侧链至环的分子内电子转移（ET）步骤。该概念也将重要的作用归因于该ET的能量屏障，该能量屏障应取决于环中正电荷的稳定性，并因此取决于甲氧基的数量和位置。在相似的实验基础上，对于2,5-（MeO）2C6H3CH2OH * +提出了与3,4-（MeO）2C6H3CH2OH
• Selective nitration versus oxidative dealkylation of hydroquinone ethers with nitrogen dioxide
  作者：R. Rathore、E. Bosch、J.K. Kochi

  DOI：10.1016/s0040-4020(01)81329-6

  日期：1994.1

  Various alkyl-substituted p-dialkoxybenzenes (ArH) react readily with nitrogen dioxide (NO2) in dichloromethane solution via either nitration (ArNO2) or oxidative dealkylation to quinones (Q). Spectral transients indicate that these coupled processes from the dialkoxybenzene radical cation (ArH+·) formed as the common reactive intermediate from electron-transfer in the disproprtionated precursor [ArH

  各种烷基取代的对二烷氧基苯（ArH）可以通过硝化（ArNO 2）或氧化脱烷基化成醌（Q）与二氯甲烷溶液中的二氧化氮（NO 2）反应。光谱瞬变指示来自二烷氧基苯自由基阳离子这些耦合过程（ARH +·形成为从disproprtionated前体电子转移常见的反应中间体）ARH，NO + ] N0 3 - 。在快速的后续步骤中。ARH +·经历均裂耦合与NO 2（这会导致芳烃硝化）和NO的亲核攻击3 -（这导致氧化脱烷基）。这样，通过溶剂极性和添加的硝酸盐可以有效地调节硝化和氧化脱烷基之间的竞争。
• (THIO)MORPHOLINE DERIVATIVES AS S1P MODULATORS
  申请人：Iwema Bakker Wouter I.

  公开号：US20120220552A1

  公开（公告）日：2012-08-30

  The present disclosure relates to (thio)morpholine derivatives of the formula (I) wherein R1 is selected from cyano, (2-4C)alkynyl, (1-4C)alkyl, (3-6C)cycloalkyl, (4-6C)cycloalkenyl, (6-8C)bicycloalkyl, (8-10C)bicyclic group, each optionally substituted with (1-4C)alkyl, phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (2-4C)alkynyl, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino, —SO 2 -(1-4C)alkyl, —CO-(1-4C)alkyl, —CO—O-(1-4C)alkyl, —NH—CO-(1-4C)alkyl and (3-6C)cycloalkyl, phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl, monocyclic heterocycle optionally substituted with halogen, (1-4C)alkyl or with phenyl optionally substituted with (1-4C)alkyl, and bicyclic heterocycle optionally substituted with (1-4C)alkyl; A is selected from —CO—O—, —O—CO—, —NH—CO—, —CO—NH, —C═C—, —CCH 3 —O— and the linking group —Y—(CH 2 ) n —X— wherein Y is attached to R1 and selected from a bond, —O—, —S—, —SO—, —SO 2 —, —CH 2 —O—, —CO—, —O—CO—, —CO—O—, —CO—NH—, —NH—CO—, —C═C— and —C≡C—; n is an integer from 1 to 10; and X is attached to the phenylene/pyridyl group and selected from a bond, —O—, —S—, —SO—, —SO 2 —, —NH, —CO—, —C═C— and —C≡C—; ring structure B optionally contains one nitrogen atom; R2 is H, (1-4C)alkyl optionally substituted with one or more fluoro atoms, (1-4C)alkoxy optionally substituted with one or more fluoro atoms, or halogen; and R3 is (1-4C)alkylene-R5 wherein the alkylene group may be substituted with (CH 2 ) 2 to form a cyclopropyl moiety or one or two halogen atoms, or R3 is (3-6C)cycloalkylene-R5 or —CO—CH 2 —R5, wherein R5 is —OH, —PO 3 H 2 , —OPO 3 H 2 , —COOH, —COO(1-4C)alkyl or tetrazol-5-yl; R4 is H or (1-4C)alkyl; R6 is one or more substituents independently selected from H, (1-4C)alkyl or oxo; W is —O—, —S—, —SO— or —SO 2 —; or a pharmaceutically acceptable salt, a solvate or hydrate thereof; with the proviso that the derivative of formula (I) is not 2-(4-ethylphenyl)-4-morpholinoethanol or 4-[4-(2-hydroxyethyl)-2-morpholinyl]benzeneacetonitrile or a pharmaceutically acceptable salt, a solvate or hydrate thereof. The compounds of the disclosure have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of S1P receptor mediated diseases and conditions.

  本公开涉及以下式子的(硫)吗啡啶衍生物(I)： 其中，R1从氰基，(2-4C)炔基，(1-4C)烷基，(3-6C)环烷基，(4-6C)环烯基，(6-8C)双环烷基，(8-10C)双环基中选择，每个基都可以选择性地被(1-4C)烷基，苯基，联苯基，萘基取代，每个基也可以选择性地被一个或多个取代基独立地选择，所述取代基包括卤素，(1-4C)烷基可选择地被一个或多个氟原子取代，(2-4C)炔基，(1-4C)烷氧基可选择性地被一个或多个氟原子取代，氨基，二(1-4C)烷基氨基，—SO2-(1-4C)烷基，—CO-(1-4C)烷基，—CO—O-(1-4C)烷基，—NH—CO-(1-4C)烷基和(3-6C)环烷基，苯基取代为苯氧基，苄基，苄氧基，苯乙基或单环杂环，每个基都可以选择性地被(1-4C)烷基取代，单环杂环可选择性地被卤素，(1-4C)烷基或苯基取代，或双环杂环可选择性地被(1-4C)烷基取代； A从—CO—O—，—O—CO—，—NH—CO—，—CO—NH，—C═C—，—CCH3—O—和连接基—Y—(CH2)n—X—中选择，其中Y连接到R1并从键，—O—，—S—，—SO—，—SO2—，—CH2—O—，—CO—，—O—CO—，—CO—O—，—CO—NH—，—NH—CO—，—C═C—和—C≡C—中选择；n是1到10的整数；X连接到苯基/吡啶基并从键，—O—，—S—，—SO—，—SO2—，—NH，—CO—，—C═C—和—C≡C—中选择；环结构B可选择性地包含一个氮原子； R2为H，(1-4C)烷基可选择性地被一个或多个氟原子取代，(1-4C)烷氧基可选择性地被一个或多个氟原子取代，或卤素； R3为(1-4C)烷基-R5，其中烷基可以被(CH2)2取代以形成环丙基基团或一或两个卤素原子，或R3为(3-6C)环烷基-R5或—CO—CH2—R5，其中R5为—OH，—PO3H2，—OPO3H2，—COOH，—COO(1-4C)烷基或四唑-5-基； R4为H或(1-4C)烷基； R6为一个或多个取代基，独立地选择自H，(1-4C)烷基或氧代基； W为—O—，—S—，—SO—或—SO2—； 或其药学上可接受的盐、溶剂或水合物； 但是，公开的衍生物式(I)不包括2-(4-乙基苯基)-4-吗啡啶基乙醇或4-[4-(2-羟乙基)-2-吗啡啶基]苯乙腈或其药学上可接受的盐、溶剂或水合物。 本公开的化合物具有对S1P受体的亲和力，并可用于治疗、缓解或预防S1P受体介导的疾病和症状。
• Synthetic Study of Selective Benzylic Oxidation
  作者：Wuyi Wang、Tiechao Li、Giorgio Attardo

  DOI：10.1021/jo962172d

  日期：1997.9.1

  Oxidation of bisbenzyl ethers was studied using 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). Compared to other benzylic oxidations such as Kornblum type reaction of benzyl bromides or MnO2 oxidation of benzyl alcohols, DDQ oxidation offered advantages of being mild and highly selective to provide monoaldehyde products. We have explored factors which influence the course of the reaction and exemplified the synthetic value of the approach by preparing a number of aromatic intermediates (7-8, 15-25).