2-hydroxy-4-(2',6'-difluorobenzyloxy)benzaldehyde | 175436-52-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-hydroxy-4-(2',6'-difluorobenzyloxy)benzaldehyde
• 英文别名: 4-[(2,6-Difluorophenyl)methoxy]-2-hydroxybenzaldehyde
• CAS: 175436-52-9
• 化学式: C₁₄H₁₀F₂O₃
• 分子量: 264.228
• InChiKey: WIGYPQQFQCBOAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3:5,6-di-O-isopropylidene-D-mannose oxime 、 2-hydroxy-4-(2',6'-difluorobenzyloxy)benzaldehyde 在 三正丁胺 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以174.6 g的产率得到2,6-difluoro-N-(2,3:5,6-di-O-isopropylidene-α-D-mannofuranosyl)[2-hydroxy-4-(phenylmethoxy)phenyl]methanimine N-oxide
  参考文献：
  名称：

  Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones

  摘要：

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.

  DOI：

  10.1021/jo9621736
• 作为产物：
  描述：

  2,6-二氟溴苄 、 2,4-二羟基苯甲醛 在 碳酸氢钠 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 16.0h， 生成 2-hydroxy-4-(2',6'-difluorobenzyloxy)benzaldehyde
  参考文献：
  名称：

  Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones

  摘要：

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.

  DOI：

  10.1021/jo9621736

文献信息

• Large scale preparation of 2,4-dihydroxybenzaldehyde using a variation
  申请人：SmithKline Beecham Corporation

  公开号：US05599988A1

  公开（公告）日：1997-02-04

  A novel process for producing chiral hydroxylamines for use as intermediates to make chiral hydroxyureas, which process comprises a tandem condensation-cyclization reaction between a dimethylsulfoxoniurn methylide and an appropriately substituted nitrone bearing a D- or L- mannose chiral auxiliary to yield a compound of Formula (I) as claimed herein.

  一种生产手性羟胺用作制备手性羟基脲的中间体的新工艺，该工艺包括在含有D-或L-甘露糖手性辅助基的适当取代硝酮和二甲基亚砜甲基化物之间进行串联缩合-环化反应，以产生本申请中所述的式(I)化合物。
• The Regioselective 4-Benzylation of 2,4-Dihydroxybenzaldehyde
  作者：Wilford L. Mendelson、Monica Holmes、Jack Dougherty

  DOI：10.1080/00397919608003653

  日期：1996.2

  A regioselective mono-benzylation of the 1-hydroxyl group of 2,4-dihydroxybenzaldehyde (2) to produce 1 under extremely mild basic conditions (NaHCO3 or KF) has been developed. This approach gives improved regioselectivity relative to earlier methods.
• US5599988A
  申请人：——

  公开号：US5599988A

  公开（公告）日：1997-02-04
• [EN] AN ENANTIOSELECTIVE SYNTHESIS OF CERTAIN HYDROXYLAMINES<br/>[FR] SYNTHESE ENANTIOSELECTIVE DE CERTAINES HYDROXYLAMINES
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1996019438A1

  公开（公告）日：1996-06-27

  (EN) A novel process for producing chiral hydroxylamines for use as intermediates to make chiral hydroxyureas, which process comprises a tandem condensation-cyclization reaction between a dimethylsulfoxonium methylide and an appropriately substituted nitrone bearing a D- or L-mannose chiral auxillary to yield a compound of Formula (I) as claimed herein.(FR) L'invention concerne un nouveau procédé pour produire des hydroxylamines chirales destinées à être utilisées comme intermédiaires pour préparer des hydroxyurées chirales. Ce procédé consiste en une réaction simultanée de condensation et de cyclisation entre un diméthylsulfoxonium méthylide et une nitrone substituée d'une manière appropriée par un groupe auxiliaire chiral D- ou L-mannose, pour donner un composé de la formule (I).
• Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones
  作者：Ivan Lantos、Joseph Flisak、Li Liu、Richard Matsuoka、Wilf Mendelson、David Stevenson、Ken Tubman、Lynn Tucker、Wei-Yuan Zhang、Jerry Adams、Margaret Sorenson、Ravi Garigipati、Karl Erhardt、Steve Ross

  DOI：10.1021/jo9621736

  日期：1997.8.1

  An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 39% overall yield. The synthesis is based on a novel tandem nucleophilic addition-intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in > 99% ee.