3-叔丁基-4-羟基-5-甲基苯甲醛 | 10537-77-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-叔丁基-4-羟基-5-甲基苯甲醛
• 英文名称: 3-tert-butyl-4-hydroxy-5-methylbenzaldehyde
• 英文别名: 3-t-butyl-4-hydroxy-5-methylbenzaldehyde；4-Hydroxy-3-tert-butyl-5-methyl-benzaldehyd；4-hydroxy-3-methyl-5-(1,1-dimethylethyl)benzaldehyde
• CAS: 10537-77-6
• 化学式: C₁₂H₁₆O₂
• 分子量: 192.258
• InChiKey: IOFKLPGWURTFMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-叔丁基-4-羟基-5-甲基苯甲醛 以88%的产率得到
  参考文献：
  名称：

  GOOT H. VAN DER; ERIKS J. C.; RHIJN-VAN DER SCHAAR P. J. VAN; ZUINDERVELD+, EUR. J. MED. CHEM.-CHIM. THER., 1978, 13, NO 5, 425-428

  摘要：

  DOI：
• 作为产物：
  描述：

  2,4-二甲基-6-叔丁基苯酚 在 copper diacetate 、 乙二醇 作用下， 反应 12.0h， 以84%的产率得到3-叔丁基-4-羟基-5-甲基苯甲醛
  参考文献：
  名称：

  Cu（OAc）2催化的远位苄基C（sp 3）-H氧基官能化，在无配体和无添加剂条件下，以受阻的对羟基在环境空气中作为末端氧化剂，指导C O的形成

  摘要：

  已经开发了一种受阻的对羟基定向的远程苄基C（sp 3）–H氧官能团，用于将2,6-二取代的4-甲酚，4-烷基苯酚，4-羟基苄醇和4-羟基苄基烷基醚直接转化为各种芳族羰基化合物。由乙二醇介导的无配体和无添加剂的Cu（OAc）2催化的大气氧化作用，可以使伯苄基和仲苄基官能化，形成简便，原子经济且对环境无害的C O形成。由于4-羟基苯甲醛和4-羟基苯酮的药物重要性，因此该方法对于基础研究和实际应用均具有重要价值。

  DOI：

  10.1039/c3gc41946k

文献信息

• Environmentally Friendly and Highly Efficient Co(OAc)₂-Catalyzed Aerobic Oxidation to Access 2,6-Di-Electron-Donating Group Substituted 4-Hydroxybenzaldehydes
  作者：Jian-An Jiang、Jia-Lei Du、Zhong-Nan Zhang、Jiao-Jiao Zhai、Ya-Fei Ji

  DOI：10.1080/00397911.2013.813052

  日期：2014.5.19

  developed for selectively preparing a series of valuable 2,6-dialkyl-, dialkoxyl-, and alkoxylalkyl-substituted 4-hydroxybenzaldehydes from corresponding 4-cresols in good to excellent yields, using a catalytic system of Co(OAc)2 · 4H2O (1.0 mol%)–NaOH (1.0 equiv)–O2 (1.0 atm) in aqueous ethylene glycol (EG/H2O = 20/1, v/v) at 50 °C. Furthermore, a plausible mechanism was proposed for the direct oxyfunctionalization

  摘要 开发了一种高效、绿色的好氧氧化，用于从相应的 4-甲酚中选择性地制备一系列有价值的 2,6-二烷基-、二烷氧基-和烷氧基烷基-取代的 4-羟基苯甲醛，使用催化系统。 Co(OAc)2 · 4H2O (1.0 mol%)–NaOH (1.0 equiv)–O2 (1.0 atm) 在乙二醇水溶液 (EG/H2O = 20/1, v/v) 中的浓度为 50 °C。此外，提出了一种将芳香甲基直接氧基官能化为醛基的合理机制。图形概要
• The Oxidation of 2,4,6-Trimethylphenol with Molecular Oxygen Catalyzed by a Copper(II)-Oxime or Copper(II)-Amine System.
  作者：Masao Shimizu、Yoshihito Watanabe、Hideo Orita、Takashi Hayakawa、Katsuomi Takehira

  DOI：10.1246/bcsj.66.251

  日期：——

  2,4,6-Trimethylphenol (1a) was selectively oxidized to 3,5-dimethyl-4-hydroxybenzaldehyde (2a) by molecular oxygen in the presence of a copper(II) chloride-oxime or copper(II) chloride-amine catalyst in alcohol at ambient temperature. When an acid was present in the catalyst system, the formation of both 2,6-dimethyl-p-benzoquinone (3) and a formaldehyde dialkyl acetal was accelerated. It is likely that 2a is produced by way of the formation of a quinonemethide intermediate, followed by a repeated 1,6-addition of alcohol on the intermediate to form a 4-(alkoxymethyl)-2,6-dimethylphenol (5a), and then 3,5-dimethyl-4-hydroxybenzaldehyde dialkyl acetal, which would be hydrolyzed to 2a. When the reaction time was shortened, 5a was isolated in good yield. Oxidations of the other p-methyl-substituted phenols were also examined using the present oxidation system.

  2,4,6-三甲基苯酚（1a）在铜（II）氯化物-肟或铜（II）氯化物-胺催化剂的存在下，利用分子氧在酒精中于室温下可选择性地氧化为3,5-二甲基-4-羟基苯甲醛（2a）。当催化剂体系中存在酸时，2,6-二甲基对苯醌（3）和甲醛二烷基缩醛的形成会加速。2a很可能是通过形成醌亚甲基中间体，随后在中间体上重复进行1,6-加成反应，生成4-（烷氧基甲基）-2,6-二甲基苯酚（5a），然后形成3,5-二甲基-4-羟基苯甲醛二烷基缩醛，最终水解为2a。当反应时间缩短时，5a可以高收率地分离出来。通过本氧化体系对其他对位甲基取代苯酚的氧化反应进行了研究。
• Process for preparing cephalosporin derivatives
  申请人：Sankyo Company Limited

  公开号：US04016155A1

  公开（公告）日：1977-04-05

  Process for preparing .beta.-lactam antibiotic substances useful as intermediate for various cephalosporin or penicillin derivatives, which comprises oxidation of 7-benzylideneaminocephem or 6-benzylideneaminopenam compounds capable of being converted to their quinoid forms by oxidation followed by reaction with lower alkanols.

  制备β-内酰胺类抗生素物质的过程，用作各种头孢菌素或青霉素衍生物的中间体，包括氧化7-苄基亚氨基头孢菌素或6-苄基亚氨基青霉素化合物，这些化合物能够通过氧化转化为它们的喹诺醌形式，然后与较低的烷醇发生反应。
• Studies on styrene derivatives. I. Synthesis and antiinflammatory activities of .ALPHA.-benzylidene-.GAMMA.-butyrolactone derivatives.
  作者：IKUO KATSUMI、HIDEO KONDO、KATSUJI YAMASHITA、TAKAYOSHI HIDAKA、KAZUNORI HOSOE、TOSHIAKI YAMASHITA、KIYOSHI WATANABE

  DOI：10.1248/cpb.34.121

  日期：——

  Two α-benzylidene-γ-butyrolactones, α-(3, 5-dimethyl-4-hydroxybenzylidene)-γ-butyrolactone and α-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), were found to have platelet aggregation inhibitory activity; the latter also had potent antiinflammatory activity and inhibited not only prostaglandin synthetase (PGS) but also 5-lipoxygenase. Further α-benzylidene-γ-butyrolactones were synthesized, and tested for antiinflammatory activity in carrageenin-induced rat paw edema assay (CPE) and for PGS inhibitory activity. It was found that the structural combination of a tert-butyl group at the 3 position, an alkyl group at the 5 position and an oxygen atom at the Δ position in α-benzylidene-γ-butyrolactone is necessary for antiinflammatory activity, and that rather broad structural variation is possible for inhibitors of PGS. The structural requirements for antiinflammatory activity in the CPE assay also seem to be partial requirements for inhibitory activity against PGS.

  两种α-苄叉基-γ-丁内酯，即α-(3, 5-二甲基-4-羟基苄叉基)-γ-丁内酯和α-(3, 5-二叔丁基-4-羟基苄叉基)-γ-丁内酯（KME-4），被发现具有血小板聚集抑制活性；后者还具有强效的抗炎活性，不仅抑制前列腺素合成酶（PGS），还抑制5-脂氧合酶。进一步合成了α-苄叉基-γ-丁内酯，并测试了它们在卡拉胶诱导的大鼠足跖水肿试验（CPE）中的抗炎活性和PGS抑制活性。研究发现，在α-苄叉基-γ-丁内酯中，3位叔丁基、5位烷基和Δ位氧原子的结构组合对发挥抗炎活性是必要的，而且对PGS抑制剂来说，其结构变化非常广泛。在CPE试验中对发挥抗炎活性的结构要求似乎也是对PGS抑制活性的部分要求。
• Selective Oxidation of Phenols to Hydroxybenzaldehydes and Benzoquinones with Dioxygen Catalyzed by Polymer-Supported Copper
  作者：Ken Takaki、Yohei Shimasaki、Tetsuya Shishido、Katsuomi Takehira

  DOI：10.1246/bcsj.75.311

  日期：2002.2

  Oxidation of 2,6-disubstituted 4-methylphenols with dioxygen by using a CuCl2-poly(4-methyl-4′-vinyl-2,2′-bipyridine) catalyst gave the corresponding 4-hydroxybenzaldehydes in high yields. The activity of the catalyst and the selectivity of the products significantly depended on the reaction conditions and the composition of the catalyst. When the molar ratio of the bipyridine unit of the polymer ligand to Cu was unity, i.e., N/Cu = 2, the best results were obtained. Moreover, the reaction is likely to be promoted by coordination of the products to the catalyst. Similarly, 2,3,6-trimethylphenol and related compounds were converted to p-benzoquinones selectively with a CuCl2-poly(4-vinylpyridine) catalyst. These polymer-supported catalysts were readily recovered and are reusable without noticeable decrease of their activity.

  用CuCl2-聚(4-甲基-4'-乙烯基-2,2'-吡啶)催化剂与氧气氧化2,6-二取代4-甲基苯酚，得到了相应的4-羟基苯甲醛，高收率。催化剂的活性和产物的选择性显著依赖于反应条件和催化剂的组成。当聚合物配体的双吡啶单元与铜的摩尔比为1，即N/Cu = 2时，获得最佳结果。此外，反应可能通过产物与催化剂的配位得到促进。同样，2,3,6-三甲基苯酚及相关化合物在CuCl2-聚(4-乙烯基吡啶)催化剂的作用下选择性转化为对苯醌。这些聚合物支撑的催化剂容易回收，且在不显著降低活性的情况下可重复使用。