2-cyclohexyl-1-(2-methoxy-phenyl)ethanone | 1281318-51-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-cyclohexyl-1-(2-methoxy-phenyl)ethanone
• 英文别名: 2-Cyclohexyl-1-(2-methoxyphenyl)ethanone
• CAS: 1281318-51-1
• 化学式: C₁₅H₂₀O₂
• 分子量: 232.323
• InChiKey: VIQYVQWLKPMZDG-UHFFFAOYSA-N

物化性质

• 沸点：
  347.0±15.0 °C(Predicted)
• 密度：
  1.021±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-cyclohexyl-1-(2-methoxy-phenyl)ethanone 在 甲烷磺酸 、 palladium on carbon 、 氢溴酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 正庚烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 35.0~75.0 ℃ 、230.0 kPa 条件下， 反应 1.0h， 生成 3-环己基-2-(2-羟苯基)-1H-吲哚-6-羧酸甲酯
  参考文献：
  名称：

  An Efficient Process for the Large-Scale Synthesis of a 2,3,6-Trisubstituted Indole

  摘要：

  The efficient synthesis of a key trisubstituted indole intermediate 1 is described. The synthetic route required the use of an aryl Grignard reagent which was not commercially available, and the large-scale formation of this fragment and the thermal evaluation for this step is presented. The key step in the sequence was a Truce-Smiles rearrangement to provide an advanced ketone intermediate which, upon reduction, cyclized to the desired indole 1. Design of experiment (DoE) optimization of this reduction is also presented. In total >50 kg of target indole 1 were synthesized in 55% overall yield over five steps using this new route.

  DOI：

  10.1021/op300303p
• 作为产物：
  描述：

  环己基乙酸 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.17h， 生成 2-cyclohexyl-1-(2-methoxy-phenyl)ethanone
  参考文献：
  名称：

  An Efficient Process for the Large-Scale Synthesis of a 2,3,6-Trisubstituted Indole

  摘要：

  The efficient synthesis of a key trisubstituted indole intermediate 1 is described. The synthetic route required the use of an aryl Grignard reagent which was not commercially available, and the large-scale formation of this fragment and the thermal evaluation for this step is presented. The key step in the sequence was a Truce-Smiles rearrangement to provide an advanced ketone intermediate which, upon reduction, cyclized to the desired indole 1. Design of experiment (DoE) optimization of this reduction is also presented. In total >50 kg of target indole 1 were synthesized in 55% overall yield over five steps using this new route.

  DOI：

  10.1021/op300303p

文献信息

• Ruthenium-Catalyzed Direct Cross-Coupling of Secondary Alcohols to β-Disubstituted Ketones
  作者：Subramanian Thiyagarajan、Chidambaram Gunanathan

  DOI：10.1055/s-0037-1611912

  日期：2019.11

  prevalent in biologically active compounds and in pharmaceuticals. A ruthenium-catalyzed direct synthesis of β-disubstituted ketones by cross-coupling of two different secondary alcohols is reported. This new protocol was applied to the synthesis of variety of β-disubstituted ketones from various cyclic, acyclic, symmetrical, and unsymmetrical secondary alcohols. An amine–amide metal–ligand cooperation

  β-二取代的酮官能团在生物活性化合物和药物中很普遍。报道了通过两种不同仲醇的交叉偶联在钌催化下直接合成 β-二取代酮。这一新协议被应用于从各种环状、无环、对称和不对称仲醇合成各种 β-二取代酮。Ru催化剂中的胺-酰胺金属-配体合作促进了选择性序列中共价键的活化和形成以提供产物。动力学和氘标记实验表明脂肪醇比苄基仲醇氧化得更快。在机械和动力学研究的基础上提出了一种合理的机制。水和 H2 是这种仲醇选择性交叉偶联的唯一副产物。1 引言 2 醇的催化自偶联或交叉偶联和选择性挑战 3 β-二取代酮合成的最新进展 4 钌催化仲醇交叉偶联的范围 5 机理研究和建议的机理 6 结论
• Catalytic Cross-Coupling of Secondary Alcohols
  作者：Subramanian Thiyagarajan、Chidambaram Gunanathan

  DOI：10.1021/jacs.9b00025

  日期：2019.3.6

  assimilating to provide the cross-coupled products. Reactions are sensitive to steric hindrance. This new C-C bond forming methodology requires low catalyst load and catalytic amount of base. Notably, the reaction produces H2 and H2O as the only byproducts making the protocol greener, atom economical and environmentally benign.

  在此，报道了一种前所未有的钌（II）催化的两种不同仲醇与 β-二取代酮的直接交叉偶联。环状、酰基、对称和不对称仲醇与芳香族苄基仲醇选择性偶联以提供酮产品。单一催化剂氧化两种仲醇以提供选择性 β-二取代酮，以扩大该催化协议的范围。通过在 Ru-MACHO 催化剂中起作用的胺-酰胺金属-配体合作，键活化和键形成反应的数量以选择性顺序发生。还观察到产物诱导的非对映选择性。动力学和氘标记实验表明，脂肪族仲醇比苄类仲醇进行氧化反应更快，选择性同化以提供交叉耦合产品。反应对位阻敏感。这种新的 CC 键形成方法需要低催化剂负载和催化量的碱。值得注意的是，该反应产生 H2 和 H2O 作为唯一的副产品，使该协议更加绿色、原子经济和环境友好。
• Cu(II) Promoted C(sp³)−H Activation in Unactivated Cycloalkanes: Oxo‐Alkylation of Styrenes to Synthesize <i>β‐</i>Disubstituted Ketones
  作者：Krishna Mohan Das、Adwitiya Pal、Lakshmi Surya T、Lisa Roy、Arunabha Thakur

  DOI：10.1002/chem.202303776

  日期：2024.2.7

  We report the Cu(II) catalyzed synthesis of β‐disubstituted ketones from styrene via oxo‐alkylation with unactivated cycloalkanes as the alkylating agent in presence of tert‐butylhydroperoxide (TBHP) and 1‐methylimidazole as oxidant and base respectively. β‐disubstituted ketones are known to be synthesized by using either expensive Ru/Ir complexes, or low‐cost metal complexes (e. g., Fe, Mn) with activated species like aldehyde, acid, alcohol, or phthalimide derivatives as the alkylating agent, however, use of unactivated cycloalkanes directly as the alkylating agent remains challenging. A wide range of aliphatic C−H substrates as well as various olefinic arenes and heteroarene (35 substrates including 14 new substrates) are well‐tolerated in this method. Hammett analysis shed more light on the substitution effect in the olefinic part on the overall mechanism. Furthermore, the controlled experiments, kinetic isotope effect study, and theoretical calculations (DFT) enable us to gain deeper insight of mechanistic intricacies of this new simple and atom‐economic methodology.

  摘要 我们报告了在叔丁基过氧化氢（TBHP）和 1-甲基咪唑分别作为氧化剂和碱的存在下，以未活化的环烷烃为烷基化剂，通过氧化-烷基化反应催化苯乙烯合成 β-二取代酮的情况。众所周知，使用昂贵的 Ru/Ir 复合物或低成本的金属复合物（如铁、锰）与醛、酸、醇或邻苯二甲酰亚胺衍生物等活化物作为烷化剂，可以合成 β-二取代酮，但是直接使用未活化的环烷烃作为烷化剂仍然具有挑战性。在这种方法中，广泛的脂肪族 C-H 底物以及各种烯烃炔和杂芳烃（35 种底物，包括 14 种新底物）都能很好地耐受。Hammett 分析进一步揭示了烯烃部分的取代效应对整个机理的影响。此外，对照实验、动力学同位素效应研究和理论计算（DFT）使我们能够更深入地了解这种简单而原子经济的新方法的复杂机理。
• Phosphine‐Free Pincer Ruthenium‐Catalyzed <i>α</i>‐Alkylation of Ketones with Secondary Alcohols to form <i>β</i>‐Branched Ketones
  作者：Dipanjan Bhattacharyya、Priyanka Adhikari、Nitumoni Hazarika、Bikash Kumar Sarmah、Animesh Das

  DOI：10.1002/cctc.202300542

  日期：2023.7.21

  An efficient and expedient method was developed for α-alkylation of aromatic ketones with secondary alcohols to produce β-disubstituted ketones using phosphine-free pincer ruthenium complexes as the catalyst. This selective, catalytic C−C bond forming reaction proceeds with low catalyst load, catalytic amount of base under air and produces H2O as the only by-product, making the process environmentally

  以无膦钳钌配合物为催化剂，开发了一种高效、便捷的芳香酮与仲醇α-烷基化生产β-二取代酮的方法。这种选择性催化 C−C 键形成反应在空气中以低催化剂负载和催化量的碱进行，并产生 H 2 O 作为唯一的副产物，使该过程环境友好且原子效率高。
• An Efficient Process for the Large-Scale Synthesis of a 2,3,6-Trisubstituted Indole
  作者：Anthony D. Alorati、Andrew D. Gibb、Peter R. Mullens、Gavin W. Stewart

  DOI：10.1021/op300303p

  日期：2012.12.21

  The efficient synthesis of a key trisubstituted indole intermediate 1 is described. The synthetic route required the use of an aryl Grignard reagent which was not commercially available, and the large-scale formation of this fragment and the thermal evaluation for this step is presented. The key step in the sequence was a Truce-Smiles rearrangement to provide an advanced ketone intermediate which, upon reduction, cyclized to the desired indole 1. Design of experiment (DoE) optimization of this reduction is also presented. In total >50 kg of target indole 1 were synthesized in 55% overall yield over five steps using this new route.