8-<4-(trifluoromethyl)phenyl>-1,3,7-trimethylxanthine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-<4-(trifluoromethyl)phenyl>-1,3,7-trimethylxanthine
• 英文别名: 1,3,7-trimethyl-8-(p-(trifluoromethyl)phenyl)-xanthine；1,3,7-trimethyl-8-(p-trifluoromethylphenyl)xanthine；2-(4-trifluoromethylphenyl)caffeine；1,3,7-trimethyl-8-(4-trifluoromethylfenyl)-xanthine；1,3,7-Trimethyl-8-(4-trifluoromethyl-phenyl)-3,7-dihydro-purine-2,6-dione；1,3,7-trimethyl-8-[4-(trifluoromethyl)phenyl]purine-2,6-dione
• 化学式: C₁₅H₁₃F₃N₄O₂
• 分子量: 338.289
• InChiKey: HRXUMICJYDPMMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5,6-二氨基-1,3-二甲基脲嘧啶 在 吡啶 、 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 8-<4-(trifluoromethyl)phenyl>-1,3,7-trimethylxanthine
  参考文献：
  名称：

  Effect of trifluoromethyl and other substituents on activity of xanthines at adenosine receptors

  摘要：

  An aryl p-(trifluoromethyl) substituent increases the affinity of 1,3-disubstituted 8-phenylxanthines at A2a-adenosine receptors, while having little effect on affinity at Al-adenosine receptors. In contrast, an aryl p-(trifluoromethyl) substituent has little effect on affinity of 3,7-disubstituted and 1,3,7-trisubstituted 8-phenylxanthines. An aryl p-sulfo substituent reduces affinity of all 8-phenylxanthines at A1-and A2a-adenosine receptors. An 8-(trifluoromethyl) substituent markedly reduces affinity of 1,3-dialkylxanthines at both A1- and A2a-adenosine receptors. In contrast, 8-(trifluoromethyl)caffeine retains affinity for A2a-adenosine receptors, but does lose affinity for A1-adenosine receptors. 8-Bromo-, 8-acryl-, and 8-pent-1-enylcaffeines are also selective for A2-adenosine receptors, while 8-cyclobutylcaffeine is nonselective. 8-[trans-2-(tert-butyloxycarbonyl)vinylcaffeine is 20-fold selective for Aza vs A1 receptors.

  DOI：

  10.1021/jm00070a007

文献信息

• Palladium-Catalyzed Direct Arylation of N-Heteroarenes with Arylsulfonyl Hydrazides
  作者：Bo Liu、Jian Li、Feijie Song、Jingsong You

  DOI：10.1002/chem.201201450

  日期：2012.8.27

  Hydrazides applied: A palladium‐catalyzed direct CH arylation of heteroarenes, with arylsulfonyl hydrazides as the arylating reagents, has been developed (see scheme). The reaction is chemoselective, in that arylsulfonyl hydrazides containing halogen substituents can be employed without participation of the halogen substituent in the reaction. The method offers a straightforward approach to a variety

  应用的酰肼类：已开发出以芳基磺酰酰肼为芳基化试剂的钯催化杂芳烃的直接CH芳基化（请参阅方案）。该反应是化学选择性的，因为可以使用含有卤素取代基的芳基磺酰肼，而无需卤素取代基参与反应。该方法为各种芳基-杂芳基化合物提供了一种简单的方法。
• Direct multiple C–H bond arylation reaction of heteroarenes catalyzed by cationic palladium complex bearing 1,10-phenanthroline
  作者：Fumitoshi Shibahara、Eiji Yamaguchi、Toshiaki Murai

  DOI：10.1039/b920794e

  日期：——

  A cationic palladium complex bearing 1,10-phenanthroline ligand is found to catalyze direct C–H arylation reactions of heteroarenes with aryl iodides to give mono-, di-, or tri-arylated products selectively.

  一种带有1,10-菲咯啉配体的阳离子钯络合物被发现能够催化杂环芳烃与芳基碘化物的直接C–H芳香化反应，从而选择性地生成单芳基、双芳基或三芳基产物。
• Direct Arylation of N-Heteroarenes with Aryldiazonium Salts by Photoredox Catalysis in Water
  作者：Dong Xue、Zhi-Hui Jia、Cong-Jun Zhao、Yan-Yan Zhang、Chao Wang、Jianliang Xiao

  DOI：10.1002/chem.201304120

  日期：2014.3.3

  solvent, an array of xanthenes, thiazole, pyrazine, and pyridazine are compatible with this new arylation approach. The broad substrate scope, mild reaction conditions, and use of water as reaction solvent make this procedure a practical and environmentally friendly method for the synthesis of compounds containing aryl‐heteroaryl motifs.

  已经开发出一种高效的可见光促进的N-杂芳烃与芳基重氮盐在水中的“自由基型”偶联。在室温下将反应继续进行的[Ru（联吡啶）3 ]氯2 ⋅ 6 H 2O作为光敏剂，商用灯泡作为光源。在这些反应条件下，吡啶和各种取代的吡啶是有效的底物，仅形成具有不同区域选择性的单取代产物。使用甲酸水溶液作为溶剂，一系列的黄嘌呤，噻唑，吡嗪和哒嗪与这种新的芳基化方法兼容。广泛的底物范围，温和的反应条件以及使用水作为反应溶剂，使得该程序成为合成具有芳基-杂芳基基序的化合物的实用且环境友好的方法。
• Palladium-Catalyzed Desulfitative CH Arylation of Heteroarenes with Sodium Sulfinates
  作者：Bo Liu、Qiang Guo、Yangyang Cheng、Jingbo Lan、Jingsong You

  DOI：10.1002/chem.201102644

  日期：2011.11.25

  Desulfitative CH arylation: Palladium‐catalyzed desulfitative CH arylation of heteroarenes with sodium sulfinates has been disclosed to construct aryl–heteroaryl bonds without the need for any extra ligands (see scheme).

  DesulfitativeÇ  ħ芳基化：钯催化desulfitativeÇ  H带钠亚磺酸盐杂芳烃的芳基化已经公开于构建体的芳基-杂芳基键，而不需要任何额外的配体（参见方案）。
• Pd-NHC complex catalyzed C-H bond activation reactions of caffeine and 2-isobuthylthiazole
  作者：Nesrin Buğday、Siraj Khan、Sedat Yaşar、Fatih Bulut、Houssem Boulebd、Hande Karabıyık、Hasan Karabıyık、Erdinç Öz、Asim Ur Rehman、İsmail Özdemir

  DOI：10.1016/j.mcat.2022.112590

  日期：2022.9

  A series of new Pd-NHC complexes were synthesized, characterized, and utilized as catalysts on 8-(hetero)arylation of xanthines and C-5 (hetero)arylation of 2-isobuthylthiazole. All the synthesized derivatives were characterized by NMR, Q-TOF-LC/MS, FTIR, and X-ray (for 4a, 5a, and 5b) analysis. In addition, DFT calculations and computational NBO studies for Pd-NHC complexes were examined, and HOMO

  合成、表征了一系列新的 Pd-NHC 配合物，并将其用作黄嘌呤的 8-（杂）芳基化和 2-异丁基噻唑的 C-5（杂）芳基化的催化剂。所有合成的衍生物均通过 NMR、Q-TOF-LC/MS、FTIR 和 X 射线（用于4a、5a和5b）分析进行表征。此外，还检查了 Pd-NHC 配合物的 DFT 计算和计算 NBO 研究，并定义了每个 Pd-NHC 配合物的 HOMO 和 LUMO 能级和电子密度。4a-c和5a-b配合物在CH键活化反应中表现出良好的催化活性。还进行了 DFT 研究以检查 CMD 途径后的反应机制。复合体5a被选为未取代的苯基与咖啡因和2-异丁基噻唑反应的代表性催化剂。尽管配合物的 ΔE 值非常接近，但观察到4a-c和5a-b的催化活性略有不同。由于这种低 ΔE 值促进了（杂）芳基溴化物的氧化加成反应，由于这种催化体系，新的 8-（杂）芳基黄嘌呤和 5-（杂）芳基噻唑衍生物可以以高产率和低催化剂负载量合成