(R)-N-(2,4-dichlorophenyl)methylene-2-methylpropane-2-sulfinamide | 1015198-52-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-N-(2,4-dichlorophenyl)methylene-2-methylpropane-2-sulfinamide
• 英文别名: (R)-N-[(2,4-dichlorophenyl)methylidene]-2-methylpropane-2-sulfinamide
• CAS: 1015198-52-3
• 化学式: C₁₁H₁₃Cl₂NOS
• 分子量: 278.202
• InChiKey: LMHRIUHAOBJYCN-MRXNPFEDSA-N

物化性质

• 沸点：
  391.7±52.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  48.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-N-(2,4-dichlorophenyl)methylene-2-methylpropane-2-sulfinamide 在 盐酸 、 potassium carbonate 、 苯硫酚 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 8.0h， 生成 1-[(S)-(2,4-dichlorophenyl)(p-tolyl)methyl]piperazine
  参考文献：
  名称：

  Asymmetric synthesis and biological evaluation of N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide as hCB1 receptor antagonists

  摘要：

  We recently discovered and reported a novel series of benzhydrylpiperazine derivatives bearing an asymmetric carbon atom that are potent and selective hCB1 inverse agonists. In the present study, we used Davis-Ellmann-type sulfonamide chemistry to asymmetrically synthesize two enantiomers of the most potent racemic N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide [14]. Enantiomer separation and configuration assignment were carried out. Our results indicate that the R-configuration is the more active enantiomer, displaying enhanced antagonistic activity for hCB1 receptor, better oral bioavailability, and greater efficacy in the reduction of body weight in diet-induced obese mice. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.030
• 作为产物：
  描述：

  2,4-二氯苯甲醛 、 (R)-(+)-叔丁基亚磺酰胺 在 titanium(IV) isopropylate 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以93%的产率得到(R)-N-(2,4-dichlorophenyl)methylene-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  Asymmetric synthesis and biological evaluation of N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide as hCB1 receptor antagonists

  摘要：

  We recently discovered and reported a novel series of benzhydrylpiperazine derivatives bearing an asymmetric carbon atom that are potent and selective hCB1 inverse agonists. In the present study, we used Davis-Ellmann-type sulfonamide chemistry to asymmetrically synthesize two enantiomers of the most potent racemic N-cyclohexyl-4-[1-(2,4-dichlorophenyl)-1-(p-tolyl)methyl]piperazine-1-carboxamide [14]. Enantiomer separation and configuration assignment were carried out. Our results indicate that the R-configuration is the more active enantiomer, displaying enhanced antagonistic activity for hCB1 receptor, better oral bioavailability, and greater efficacy in the reduction of body weight in diet-induced obese mice. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.030

文献信息

• Dramatic lithium chloride effect on the reaction stereocontrol in Zn-mediated asymmetric cinnamylation: highly practical synthesis of β-aryl homoallylic amines
  作者：Min Liu、An Shen、Xing-Wen Sun、Fei Deng、Ming-Hua Xu、Guo-Qiang Lin

  DOI：10.1039/c0cc03230a

  日期：——

  An extremely mild and practical approach for the preparation of enantiomerically enriched beta-aryl substituted homoallylic amines bearing two adjacent stereogenic centers was realized by room temperature zinc-mediated highly stereoselective cinnamylation of N-sulfinyl imines.

  通过室温锌介导的N-亚磺酰基亚胺的高度立体选择性肉桂基化，实现了一种极其温和且实用的方法，用于制备带有两个相邻立体异构中心的对映异构体富集的β-芳基取代的均烯丙基胺。
• Highly Stereoselective Trichloromethylation of N-(tert-Butylsulfinyl)aldimines: Facile Synthesis of Chiral α-Trichloromethylamines
  作者：Ya Li、Yunlv Cao、Jiaying Gu、Wei Wang、Han Wang、Tao Zheng、Zhihua Sun

  DOI：10.1002/ejoc.201001495

  日期：2011.2

  The first highly stereoselective and facile synthesis of α-trichloromethylamines is described by using a nucleophilic trichloromethylation strategy. With tetrabutylammonium triphenyldifluorosilicate (TBAT) as the mediator, the trichloromethyl anion (CCl 3 ― ) from TMSCCl 3 can be transferred to N-(tert-butylsulfinyl)aldimines in excellent yields and with high diastereoselectivity (≥99:1 dr).

  通过使用亲核三氯甲基化策略描述了 α-三氯甲基胺的第一个高度立体选择性和简便的合成。以三苯基二氟硅酸四丁基铵 (TBAT) 作为介质，TMSCCl 3 中的三氯甲基阴离子 (CCl 3 ― ) 可以以优异的收率和高非对映选择性 (≥99:1 dr) 转移到 N-(叔丁基亚磺酰基) 醛亚胺中。
• Remarkable Salt Effect on In-Mediated Allylation of <i>N</i>-<i>tert</i>-Butanesulfinyl Imines in Aqueous Media:  Highly Practical Asymmetric Synthesis of Chiral Homoallylic Amines and Isoindolinones
  作者：Xing-Wen Sun、Min Liu、Ming-Hua Xu、Guo-Qiang Lin

  DOI：10.1021/ol8001514

  日期：2008.3.1

  A highly practical and efficient asymmetric synthesis of chiral homoallylic amines by In-mediated allylation of chiral N-tert-butanesulfinyl imines in aqueous media at room temperature was developed. With 2-formylbenzoate imine substrates, the method allows the highly enantioselective achievement of a variety of pharmacologically important 3-allyl isoindolinone compounds.

  通过在室温下在水性介质中手性N-叔丁烷亚磺酰基亚胺的介导烯丙基化，开发了一种高度实用，高效的不对称手性均胺合成方法。使用2-甲酰基苯甲酸酯亚胺底物，该方法可以实现多种对药理学很重要的3-烯丙基异吲哚满酮化合物的高度对映选择性。
• Highly Efficient Asymmetric Synthesis of Vinylic Amino Alcohols by Zn-Promoted Benzoyloxyallylation of Chiral<i>N</i>-<i>tert</i>-Butanesulfinyl Imines: Facile and Rapid Access to (−)-Cytoxazone
  作者：Min Liu、Xing-Wen Sun、Ming-Hua Xu、Guo-Qiang Lin

  DOI：10.1002/chem.200900801

  日期：2009.10.5

  An efficient and convenient α‐hydroxyallylation approach for the asymmetric synthesis of a variety of β‐amino‐α‐vinyl alcohols has been successfully developed. A wide range of vinylic amino alcohol derivatives could be obtained in very good yields and with excellent diastereomeric ratios of up to 99:1 in favor of anti isomers by highly diastereoselective Zn‐promoted benzoyloxyallylation of chiral

  已经成功开发了一种有效且方便的α-羟基化方法，用于多种β-氨基-α-乙烯基醇的不对称合成。赞成1：可以在非常良好的产率和具有高达的非对映体优良比率获得宽范围的乙烯类的氨基醇衍生物的99反异构体通过手性高度非对映锌促进的benzoyloxyallylation ñ -叔-butanesulfinyl亚胺与3- bromopropenyl在室温下苯甲酸酯。特别是，观察到两个新的立体生成中心的出色对映体诱导，ee高达98％ 。该方法为高度立体选择性的亚胺直接α-羟基化提供了一条新途径。此外，该方法的合成价值还通过尚未报道的（-）-cytoxazone的最简明，最直接的合成得到了证明。
• Highly Stereoselective and Practical Synthesis of α-Trichloromethyl Amines and 2,2-Dichloroaziridines from Chloroform
  作者：Ya Li、Tao Zheng、Wei Wang、Wei Xu、Yingchao Ma、Sishi Zhang、Han Wang、Zhihua Sun

  DOI：10.1002/adsc.201100713

  日期：2012.2

  A highly stereoselective and practical synthesis of α-trichloromethyl amines by nucleophilic trichloromethylation of N-(tert-butylsulfinyl)imines with chloroform was achieved. The obtained α-trichloromethyl amines can be further transformed into chiral 2,2-dichloroaziridines through an intramolecular nucleophilic substitution methodology. 2,2-Dichloroaziridines can also be produced directly from chloroform

  通过N-（叔丁基亚磺酰基）亚胺与氯仿的亲核三氯甲基化，实现了高度立体选择性和实用的α-三氯甲基胺的合成。可以通过分子内亲核取代方法将获得的α-三氯甲基胺进一步转化为手性2，2-二氯氮丙啶。也可以通过一锅法由氯仿和N-（叔丁基亚磺酰基）亚胺直接生产2，2-二氯氮丙啶。