2-[anilino(phenyl)methyl]-1-cyclohexanone

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-[anilino(phenyl)methyl]-1-cyclohexanone
• 英文别名: 2-(phenyl(phenylamino)methyl)cyclohexanone；syn-2-[1'-phenyl-1'-(N-phenyl)amino]methylcyclohexanone；2-(phenyl(phenylamino)methyl)cyclohexan-1-one；(2S)-2-[(S)-anilino(phenyl)methyl]cyclohexan-1-one
• 化学式: C₁₉H₂₁NO
• 分子量: 279.382
• InChiKey: ITYLIHBJQIGSFJ-IEBWSBKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  环己酮 在 2,2,2-三氟乙醇 、 silver trifluoromethanesulfonate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 (S)-(-)-5,5-双(二苯膦基)-4,4-双-1,3-苯并间二氧杂环戊烯 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 2-[anilino(phenyl)methyl]-1-cyclohexanone
  参考文献：
  名称：

  通过手性银醇盐催化对映选择性曼尼希型反应

  摘要：

  在2,2,2-三氟乙醇存在下，以SEGPHOS·AgOTf为手性预催化剂，以N，N-二异丙基乙胺为基础预催化剂，实现了三氯乙酸烯基酯与醛亚胺的Mannich型催化不对称反应。通过原位产生的手性烯醇银，以中等至高产率合成选择性地获得了ee高达99％以上的旋光性β-氨基酮。

  DOI：

  10.1021/ol403075u

文献信息

• Salicylato Titanocene Complexes as Cooperative Organometallic Lewis Acid and Brønsted Acid Catalysts for Three-Component Mannich Reactions
  作者：Ya Wu、Chun Chen、Gai Jia、Xuyang Zhu、Huaming Sun、Guofang Zhang、Weiqiang Zhang、Ziwei Gao

  DOI：10.1002/chem.201402438

  日期：2014.7.7

  A binary acid system has been developed that features an air‐stable organometallic precursor, titanocene dichloride, and simple organic cooperative Brønsted acids, which allowed for mild and highly efficient Mannich reactions of both aryl and alkyl ketones with excellent yields and satisfactory diastereoselectivity. Mechanistic studies, including 1H NMR titration, X‐ray structure analyses as well as

  已经开发了一种二元酸体系，其特征是具有空气稳定性的有机金属前体，二茂钛二氯化物和简单的有机协作布朗斯台德酸，可实现芳基和烷基酮的温和高效的曼尼希反应，并具有优异的收率和令人满意的非对映选择性。机理研究，包括1 H NMR滴定，X射线结构分析以及催化活性物质的分离，阐明了这种新的二元酸体系的巨大协同作用。
• Brønsted Acid-Catalyzed Mannich-Type Reactions in Aqueous Media
  作者：Takahiko Akiyama、Jun Takaya、Hirotaka Kagoshima

  DOI：10.1002/1615-4169(200206)344:3/4<338::aid-adsc338>3.0.co;2-o

  日期：2002.6

  aldimines took place smoothly in aqueous organic solvent to afford β-aminocarbonyl compounds in high yields. The HBF4-catalyzed Mannich-type reaction also proceeded smoothly in water without organic solvent in the presence of a surfactant. A three-component synthesis starting from aldehyde, amine, and silyl enolate was successfully realized by means of a Bronsted acid in aqueous media.

  HBF4催化的甲硅烷基烯醇化物与醛亚胺的曼尼希型反应在水性有机溶剂中顺利进行，以高产率得到β-氨基羰基化合物。在表面活性剂存在下， 催化的曼尼希型反应在没有有机溶剂的水中也能顺利进行。借助布朗斯台德酸在水性介质中成功实现了从醛、胺和烯醇甲硅烷基开始的三组分合成。
• Pronounced Catalytic Effect of a Micellar Solution of Sodium Dodecylsulfate (SDS) Upon a Three-Component Reaction of Aldehydes, Amines, and Ketones Under Neutral Conditions
  作者：Abbas Ali Jafari、Fatemeh Moradgholi、Fatemeh Tamaddon

  DOI：10.1002/ejoc.200801037

  日期：2009.3

  A micellar solution of anionic, cationic or neutral surfactants can be used as an excellent medium for three-component Mannich reactions of aldehydes, amines, and ketones at room temperature. Sodium dodecylsulfate turned out to efficiently catalyze the reaction in neutral pure water (pH ≈ 7), and the corresponding desired β-amino ketones precipitate while the reactions proceedes. This method provides

  阴离子、阳离子或中性表面活性剂的胶束溶液可用作醛、胺和酮在室温下进行三组分曼尼希反应的优良介质。结果证明十二烷基硫酸钠在中性纯水 (pH ≈ 7) 中有效催化反应，并且在反应进行时相应的所需 β-氨基酮沉淀。该方法在温和的反应条件、干净的反应曲线、提高的产率和优异的区域选择性和非对映选择性方面提供了一种新的改进的三组分曼尼希反应，后处理简单。观察到在水中中性条件下点击化学的有趣例子。 (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• Hf(OTf)4 as a Highly Potent Catalyst for the Synthesis of Mannich Bases under Solvent-Free Conditions
  作者：Shuai-Bo Han、Jing-Ying Wei、Xiao-Chong Peng、Rong Liu、Shan-Shan Gong、Qi Sun

  DOI：10.3390/molecules25020388

  日期：——

  Hf(OTf)4 was identified as a highly potent catalyst (0.1–0.5 mol%) for three-component Mannich reaction under solvent-free conditions. Hf(OTf)4-catalyzed Mannich reaction exhibited excellent regioselectivity and diastereoselectivity when alkyl ketones were employed as substrates. 1H NMR tracing of the H/D exchange reaction of ketones in MeOH-d4 indicated that Hf(OTf)4 could significantly promote the

  Hf(OTf)4 被确定为在无溶剂条件下进行三组分曼尼希反应的高效催化剂（0.1-0.5 mol%）。当使用烷基酮作为底物时，Hf(OTf)4 催化的曼尼希反应表现出优异的区域选择性和非对映选择性。酮在 MeOH-d4 中的 H/D 交换反应的 1H NMR 示踪表明 Hf(OTf)4 可以显着促进酮-烯醇互变异构化，从而有助于加快反应速率。
• H3PW12O40 supported on silica-encapsulated γ-Fe2O3 nanoparticles: a novel magnetically-recoverable catalyst for three-component Mannich-type reactions in water
  作者：Ezzat Rafiee、Sara Eavani

  DOI：10.1039/c1gc15291b

  日期：——

  A new type of magnetically-recoverable catalyst was synthesized by the immobilization of H3PW12O40 on the surface of silica-encapsulated γ-Fe2O3 nanoparticles. This catalyst was characterized by transmission electron microscopy (TEM), a laser particle size analyzer, infrared spectroscopy (IR) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results show that the particles are mostly spherical in shape and have an average size of approximately 94 nm. The characterization data derived from IR spectroscopy reveal that H3PW12O40 on the support exists in the Keggin structure. The acidity of the catalyst was measured by a potentiometric titration with n-butylamine. To our surprise, this very strong solid acid catalyst showed an excellent distribution of acid sites, suggesting that the catalyst possesses a higher number of surface active sites compared to its homogeneous analogues. The activity of the catalyst was probed through one-pot three-component Mannich-type reactions of aldehydes, amines and ketones in water at room temperature. The excellent conversions show that the catalyst has strong and sufficient acidic sites, which are responsible for its catalytic performance. After the reaction, the catalyst/product separation could be easily achieved with an external magnetic field, and more than 95% of the catalyst could usually be recovered. The catalyst was reused at least five times without any loss of its high catalytic activity.

  通过将H3PW12O40固定在二氧化硅包覆的γ-Fe2O3纳米颗粒表面，合成了一种新型磁性可回收催化剂。该催化剂通过透射电子显微镜（TEM）、激光粒度分析仪、红外光谱（IR）和电感耦合等离子体原子发射光谱（ICP-AES）进行了表征。结果显示，颗粒主要呈球形，平均尺寸约为94纳米。红外光谱表征数据揭示，负载上的H3PW12O40以Keggin结构存在。催化剂的酸度通过用正丁胺进行的电位滴定法测量。令人惊讶的是，这种非常强的固体酸催化剂显示出优异的酸位点分布，表明催化剂相对于均相类似物具有更高的表面活性位点数量。催化剂的活性通过在水中的室温下进行的一锅法三组分Mannich型反应，即醛、胺和酮的反应来评估。优异的转化率表明，催化剂具有强烈且充分的酸性位点，这是其催化性能的原因。反应后，通过外部磁场可以轻松实现催化剂/产物分离，通常可以回收超过95%的催化剂。该催化剂至少可以重复使用五次，而不会损失其高催化活性。