6-chloro-2-phenyl-benzo[d][1,3]oxazin-4-one | 7033-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 6-chloro-2-phenyl-benzo[d][1,3]oxazin-4-one
• 英文别名: 6-chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one；6-chloro-2-phenyl-4H-3,1-benzoxazin-4-one；6-chloro-2-phenyl-3,1-benzoxazin-4-one
• CAS: 7033-51-4
• 化学式: C₁₄H₈ClNO₂
• mdl: MFCD00640544
• 分子量: 257.676
• InChiKey: RQDCQRFZYXJXMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-chloro-2-phenyl-benzo[d][1,3]oxazin-4-one 在 sodium hydroxide 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 5.66h， 生成 4-chloro-2-(2'-thienylcarbonyl)-N-bromoacetylaniline
  参考文献：
  名称：

  Syntheses of 5-thienyl and 5-furyl-substituted benzodiazepines: probes of the pharmacophore for benzodiazepine receptor agonists

  摘要：

  The synthesis of 5-thienyl- and 5-furyl-substituted benzodiazepines is described. These compounds were employed to probe the lipophilic pocket (L(3)) of the benzodiazepine receptor (BzR) and to determine the effect of occupation of L(3) on biological activity. Of the new analogs synthesized, the 5-(2-thienyl)-benzodiazepines 6a and 7a displayed high affinity for the BzR (IC50 28 and 18 nM, respectively) and exhibited both anticonvulsant (ED(50) approximate to 9 and 3 mg/kg) and muscle relaxant (ED(50) approximate to 10 and 7 mg/kg) activity. The 5-(3-thienyl)benzodiazepines 6d and 7d displayed only moderate affinity for the BzR (IC50 140 and 110 nM) and exhibited no biological activity (no anticonvulsant or muscle relaxant activity) at doses up to 40 mg/kg. The 5-(2-furyl)benzodiazepines (6b, 7b, 19b and 20b) exhibit low affinities for the BzR. These in vitro and in vivo findings are consistent with our model suggesting that pocket L(3) is very sensitive to lipophilic effects. Thus, decreasing the lipophilicity of functional groups which occupy this region decreases ligand affinity at BzR. The 2'-halogen (F or Cl) substituent of the 5-phenylbenzodiazepines increases ligand affinity in vitro because the active conformation of the phenyl N(4)=C(5)-C(1')=C(2') moiety is syn rather than anti. The syn conformation permits the 2'-halogen (F or Cl) atom to interact at the hydrogen bonding site H-2 and form a stable three-centered hydrogen bond in the proposed ligand binding cleft. The 3-thienyl and 2-furyl groups decrease the lipophilicity of the substituent which occupies L(3) but do not form a hydrogen bond at H-2, thus resulting in a diminished affinity at BzR.

  DOI：

  10.1016/0223-5234(96)88259-6
• 作为产物：
  描述：

  苯甲羟肟酸 在 silver hexafluoroantimonate 、 carbonyl(η-5-cyclopentadienyl)diiodocobalt(III) 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 6-chloro-2-phenyl-benzo[d][1,3]oxazin-4-one
  参考文献：
  名称：

  通过Cp * Co（III）催化的C–H活化直接合成苯并恶嗪酮，并与二恶唑酮环化磺化ox盐。

  摘要：

  通过Cp * Co（III）催化的C–H活化和sulf代氧鎓叶立德与二恶唑酮之间的[3 + 3]环化反应，开发了苯并恶嗪酮的高度新颖和直接的合成方法。该反应在无碱条件下进行，并能耐受各种官能团。从各种容易获得的亚砜基砜和二恶唑酮开始，可以一步合成32％-75％收率的各种苯并恶嗪酮。

  DOI：

  10.1016/j.cclet.2020.09.020

文献信息

• Carbonylative Synthesis of Phthalimides and Benzoxazinones by Using Phenyl Formate as a Carbon Monoxide Source
  作者：Sujit P. Chavan、Bhalchandra M. Bhanage

  DOI：10.1002/ejoc.201500109

  日期：2015.4

  efficient palladium-catalyzed carbonylative cyclization of N-substituted 2-iodobenzamides and 2-iodoanilides was investigated for the synthesis of phthalimides and benzoxazinones, respectively, by using phenyl formate as a CO source. The present catalytic protocol circumvents the use of an expensive phosphine ligand as well as solvent in the case of the phthalimide synthesis. Moreover, mild reaction conditions

  通过使用甲酸苯酯作为 CO 源，研究了一种简单有效的钯催化的 N-取代 2-碘苯甲酰胺和 2-碘苯胺的羰基化环化反应，分别用于合成邻苯二甲酰亚胺和苯并嗪酮。本催化协议在邻苯二甲酰亚胺合成的情况下避免使用昂贵的膦配体以及溶剂。此外，温和的反应条件和对各种官能团的耐受性增强了该方法的普遍适用性。
• A Convenient and General Palladium-Catalyzed Carbonylative Coupling for the Synthesis of 2-Arylbenzoxazinones
  作者：Xiao-Feng Wu、Johannes Schranck、Helfried Neumann、Matthias Beller

  DOI：10.1002/chem.201102254

  日期：2011.10.24

  CO and CO again: A new double carbonylation methodology for the synthesis of 2‐arylbenzoxazinones has been developed (see scheme).

  一氧化碳和一氧化碳：已开发出一种用于合成2-芳基苯并恶嗪酮的新型双羰基化方法（参见方案）。
• Copper-Catalyzed C-N, C-O Coupling Reaction of Arylglyoxylic Acids with Isatins
  作者：Rashmi Prakash、Sanjib Gogoi

  DOI：10.1002/adsc.201600516

  日期：2016.10.6

  The copper(II)‐catalyzed decarboxylative coupling reactions of arylglyoxylic acids with isatins afford 4H‐benzo[d][1,3]oxazin‐4‐ones via decarbonylation and concurrent C–N, C–O bond formation.

  芳基乙醛酸与Isatin的铜（II）催化的脱羧偶联反应通过脱羰作用和同时的C–N，C–O键形成提供4 H-苯并[ d ] [1,3]恶嗪-4-酮。
• One-pot approach to 2-arylbenzoxazinone derivatives from 2-alkynylanilines using copper-mediated tandem reactions
  作者：Mitsuaki Yamashita、Akira Iida

  DOI：10.1016/j.tet.2014.06.056

  日期：2014.9

  describe a one-pot method to obtain a variety of 2-arylbenzoxazinones and N-benzoyl anthranilic acid by using a copper catalyst and molecular oxygen as oxidants. This protocol involves tandem cyclization and oxidative processes of 2-alkynylanilines to afford significant motifs in synthetic and medicinal chemistry with moderate yields. We also demonstrated that combining the Sonogashira coupling and the

  在这项研究中，我们描述了一种一锅法，通过使用铜催化剂和分子氧作为氧化剂来获得各种2-芳基苯并恶嗪酮和N-苯甲酰基邻氨基苯甲酸。该方案涉及2-炔基苯胺的串联环化和氧化过程，以中等产率在合成和药物化学中提供重要的基序。我们还证明，结合Sonogashira偶联和开发的方法，可以从市售的2-碘苯胺和末端乙炔合成2-芳基苯并恶嗪酮衍生物。
• Oxidation of 2-arylindoles for synthesis of 2-arylbenzoxazinones with oxone as the sole oxidant
  作者：Xiao-Li Lian、Hao Lei、Xue-Jing Quan、Zhi-Hui Ren、Yao-Yu Wang、Zheng-Hui Guan

  DOI：10.1039/c3cc44215b

  日期：——

  A novel and efficient method for the oxidation of 2-arylindoles to synthesize 2-arylbenzoxazinones utilizing oxone as the sole oxidant has been developed. The reaction tolerates a wide range of functional groups and allows quick and atom-economical assembly of a variety of valuable 2-arylbenzoxazinones in high yields.

  开发了一种新颖且高效的方法，利用单独的Oxone作为氧化剂，将2-芳基吲哚氧化合成2-芳基苯并噁唑酮。该反应对多种官能团具有良好的耐受性，并能快速且原子经济性地合成多种高产率的有价值2-芳基苯并噁唑酮。