2-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]aniline | 209850-74-8

• 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: 2-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]aniline
• 英文别名: (S)-2-(4-methyl-4,5-dihydrooxazol-2-yl)benzenamine；(S)-2-(4-methyl-4,5-dihydrooxazol-2-yl)-aniline；(S)-2-(4-methyl-4,5-dihydrooxazol-2-yl)aniline；S-2-(4-methyloxazol-2-yl)aniline
• CAS: 209850-74-8
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: WPJQSSOGCLGFDI-ZETCQYMHSA-N

物化性质

• 沸点：
  325.1±25.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]aniline 在 吡啶 、 4 A molecular sieve 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 4-thiobenzyl-21,6-bis[2-((4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]carbamoylpyridine
  参考文献：
  名称：

  Dynamic Helical Chirality of an Intramolecularly Hydrogen-Bonded Bisoxazoline

  摘要：

  The synthesis and conformational properties of 2,6-bis-[2-((4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]carbam oylpyridines, 2, have been described. Bisoxazoline 2a was prepared in five steps from 2-nitrobenzoyl chloride in an overall yield of 71%. In contrast to related structures such as 1, bisoxazoline 2a exhibits a highly biased P-type helical conformation in solution and in the solid state. In the crystal lattice, 2a further assembles into a left-handed helical superstructure aligned along the crystallographic c axis. The barrier to helical interconversion, as measured by line-shape analysis of the temperature-dependent H-1 NMR spectra of thiobenzyl derivative 2b, was determined to be quite low (DeltaG(double dagger) = 12.3 kcal/mol), indicating the presence of a highly dynamic helical chirality.

  DOI：

  10.1021/jo026496f
• 作为产物：
  描述：

  邻硝基苯甲酸 在 palladium on activated charcoal 氯化亚砜 、 草酰氯 、 4 A molecular sieve 、 氢气 、 sodium hydride 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 26.5h， 生成 2-[(4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]aniline
  参考文献：
  名称：

  Dynamic Helical Chirality of an Intramolecularly Hydrogen-Bonded Bisoxazoline

  摘要：

  The synthesis and conformational properties of 2,6-bis-[2-((4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]carbam oylpyridines, 2, have been described. Bisoxazoline 2a was prepared in five steps from 2-nitrobenzoyl chloride in an overall yield of 71%. In contrast to related structures such as 1, bisoxazoline 2a exhibits a highly biased P-type helical conformation in solution and in the solid state. In the crystal lattice, 2a further assembles into a left-handed helical superstructure aligned along the crystallographic c axis. The barrier to helical interconversion, as measured by line-shape analysis of the temperature-dependent H-1 NMR spectra of thiobenzyl derivative 2b, was determined to be quite low (DeltaG(double dagger) = 12.3 kcal/mol), indicating the presence of a highly dynamic helical chirality.

  DOI：

  10.1021/jo026496f

文献信息

• Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines
  作者：Shengkun Li、Dangdang Li、Taifeng Xiao、ShaSha Zhang、Zehua Song、Hongyu Ma

  DOI：10.1021/acs.jafc.6b03464

  日期：2016.11.23

  plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.

  手性极大地影响了农药的生物学和药理特性，并将导致不必要的环境负荷和不希望的生态影响。没有证明对映体纯琥珀酸脱氢酶抑制剂（SDHIs）的结构和活性之间的关系（SAR）。基于商业上的SDHIs，恶唑啉天然产物和有机合成中的多种恶唑啉配体，人们首先致力于探索手性SDHIs及其初步机理。对带有手性烟碱酰胺4ag的微调提供了更有望的抗solani solani，Botrytis cinerea和Sclerotiania sclerotiorum杀真菌剂的选择，并使用EC50个值分别为0.58、0.42和2.10 mg / L。对体内生物测定和分子对接进行了研究，以分别探讨其在实际应用中的潜力和在作用机理上的新颖性。出乎意料的分子对接模型在与氨基酸残基的结合位点上显示出不同的手性作用。这种手性烟酰胺还具有易于合成和成本效益的特点。随着手性的引入，它将为商业SDHI杀菌剂提供有力的补充。
• Copper-Mediated Diastereoselective C–H Thiolation of Ferrocenes
  作者：Wei-Jun Kong、Qian Shao、Ming-Hong Li、Zeng-Le Zhou、Hui Xu、Hui-Xiong Dai、Jin-Quan Yu

  DOI：10.1021/acs.organomet.8b00457

  日期：2018.9.10

  The first copper-mediated diastereoselective C–H thiolation of ferrocenes has been developed. A chiral oxazoline directing group with tert-butyl substituent is essential to the high diastereoselectivity ratio and the suppression of overreaction of monothiolated products. This reaction tolerated various functional groups on arylthiols, implying its potential application in N,S-bidentate planar chiral

  已经开发出第一个铜介导的二茂铁非对映选择性C–H硫醇化反应。具有叔丁基取代基的手性恶唑啉指导基团对于高非对映选择性和抑制单硫醇化产物的过度反应是必不可少的。该反应可耐受芳基硫醇上的各种官能团，这暗示其在N，S双齿平面手性配体中的潜在应用。
• Chiral Primary Amine Catalyzed Asymmetric Epoxidation of α-Substituted Acroleins
  作者：Jiuyuan Li、Niankai Fu、Long Zhang、Pengxin Zhou、Sanzhong Luo、Jin-Pei Cheng

  DOI：10.1002/ejoc.201001117

  日期：2010.12

  substrates in asymmetric epoxidation reactions. In this study, chiral primary amines are shown to catalyze the asymmetric epoxidation of α-substituted acroleins, a versatile type of 1,1-disubstituted terminal alkene. Among various chiral primary amines explored, the chiral primary-tertiary vicinal diamine derived from trans-1,2-diphenylethane-1,2-diamine is identified as the optimal catalyst, which, in combination

  1,1-二取代末端烯烃在不对称环氧化反应中仍然是具有挑战性的底物。在这项研究中，手性伯胺被证明可以催化 α-取代丙烯醛的不对称环氧化，这是一种多功能的 1,1-二取代末端烯烃。在探索的各种手性伯胺中，衍生自反式-1,2-二苯基乙烷-1,2-二胺的手性伯-叔邻二胺被确定为最佳催化剂，其与5-磺基水杨酸（5-SSA）结合使用, 表现出良好的催化活性（高达 95% 的产率）和对映选择性（高达 88% ee）。发现 2 M 氯化钠水溶液是最佳反应介质。
• Absolute control of helicity at the C-termini in quinoline oligoamide foldamers by chiral oxazolylaniline moieties
  作者：Dan Zheng、Chengyuan Yu、Lu Zheng、Yulin Zhan、Hua Jiang

  DOI：10.1016/j.cclet.2019.07.061

  日期：2020.3

  Abstract Absolute one-handed chiral quinoline tetramers andoctamers containing different oxazolylanilines at the C-terminus have been synthesized. The absolute one-handed sense and diastereomeric excess values were valued by 1H NMR. X-ray crystal diffractionand CD studies reveal that the S-oxazolylaniline always induces a P-handed helicity and the absolute helicity is driven by the stable three-center

  摘要合成了在C末端含有不同的恶唑基苯胺的单手绝对喹啉四聚体和八聚体。绝对单手有义和非对映异构体过量值通过1 H NMR评估。X-射线晶体衍射和CD研究表明，S-恶唑基苯胺总是诱发P-手螺旋，而绝对螺旋由酰胺中质子与恶唑基苯胺和相邻喹啉环中N原子之间稳定的三中心氢键驱动。CPL调查表明，S-CQn-a⿼d具有CPL活性，其胶凝值取决于其长度。有趣的是，手性中心取代基的大小不同，但是它们对喹啉低酰胺折叠剂的不对称因子gab和glum没有影响。
• Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore
  作者：Lu Zhang、Wei Li、Taifeng Xiao、Zehua Song、René Csuk、Shengkun Li

  DOI：10.1021/acs.jafc.8b02778

  日期：2018.8.29

  toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates

  受成熟的琥珀酸脱氢酶抑制剂（SDHIs）的启发，我们对发现手性抗真菌酰胺的不懈努力转向使用2-（2-恶唑啉基）苯胺作为已知药效团优化其极性区域。脚手架跳跃和生物活性指导的收敛合成使有希望的抗真菌类别的鉴定。取代基和手性的精细调节提供了7种酰胺（1s，1t，2d，2h，2j，3k和2l）作为抗真菌候选物，其EC 50值低于5 mg / L。进行了无环酸手性酰胺作为SDHIs的首次研究，选择2d作为灰葡萄孢的有希望的候选物，其在50 mg / L时的预防效果高达93.9％，优于Boscalid。针对化合物2d及其非对映异构体，模拟了具有不同构型的化合物之间的不同结合模型。合成可及性和成本效益的优势突出了化合物2d作为已知SDHI杀菌剂的良好替代品的实际潜力。