4-(benzo[b]thiophen-3-yl)-morpholine | 56639-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 4-(benzo[b]thiophen-3-yl)-morpholine
• 英文别名: 4-(benzo[b]thiophen-3-yl)morpholine；3-N-morpholinobenzo[b]thiophene；4-benzo[b]thien-3-ylmorpholine；4-benzo[b]thiophen-3-yl-morpholine；3-Morpholino-thionaphten；Morpholine, 4-benzo[b]thien-3-yl-；4-(1-benzothiophen-3-yl)morpholine
• CAS: 56639-83-9
• 化学式: C₁₂H₁₃NOS
• 分子量: 219.307
• InChiKey: KAVVKSVOHIAWDY-UHFFFAOYSA-N

物化性质

• 熔点：
  64-66 °C
• 沸点：
  382.8±32.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-溴苯腈 、 4-(benzo[b]thiophen-3-yl)-morpholine 在 二环己烷并-18-冠醚-6 、 palladium diacetate 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 以65%的产率得到2-(3-Morpholin-4-yl-benzo[b]thiophen-2-yl)-benzonitrile
  参考文献：
  名称：

  Efficient Access to 2-Aryl-3-Substituted Benzo[b]thiophenes

  摘要：

  Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo [b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.

  DOI：

  10.1021/jo0500378
• 作为产物：
  描述：

  3-溴苯并噻吩亚砜 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 3.5h， 生成 4-(benzo[b]thiophen-3-yl)-morpholine
  参考文献：
  名称：

  Efficient Access to 2-Aryl-3-Substituted Benzo[b]thiophenes

  摘要：

  Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo [b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.

  DOI：

  10.1021/jo0500378

文献信息

• Cobalt-Catalyzed Electrophilic Amination of Aryl- and Heteroarylzinc Pivalates with <i>N</i> -Hydroxylamine Benzoates
  作者：Yi-Hung Chen、Simon Graßl、Paul Knochel

  DOI：10.1002/anie.201710931

  日期：2018.1.22

  Aryl‐ and heteroarylzinc pivalates can be aminated with O‐benzoylhydroxylamines at 25 °C within 2–4 h in the presence of 2.5–5.0 % CoCl2⋅2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields. This electrophilic amination also provides access to diarylamines and aryl(heteroaryl)amines. A new tuberculosis drug candidate (Q203) was prepared in six steps and 56 %

  芳基-和三甲基乙酸盐heteroarylzinc可胺化以Ó在存在-benzoylhydroxylamines在25℃下2-4小时内2.5-5.0％氯化钴2 ⋅2的LiCl以提供相应的以良好的收率叔芳基化或heteroarylated胺。这种亲电胺化作用还提供了二芳基胺和芳基（杂芳基）胺的通道。使用该钴催化的胺化反应作为关键步骤，可以分六个步骤制备新的候选结核病药物（Q203），使总收率达到56％。
• A Heteroarylamine Library: Indium-Catalyzed Nucleophilic Aromatic Substitution of Alkoxyheteroarenes with Amines
  作者：Kyohei Yonekura、Yasuhiro Yoshimura、Mizuri Akehi、Teruhisa Tsuchimoto

  DOI：10.1002/adsc.201701452

  日期：2018.3.20

  five‐membered heteroaryl electrophiles fused with/without a benzene ring were found to couple with amines to produce heteroarylamines with broad structural diversity. The heteroarylamine formation proceeds through the cleavage of a heteroaryl−OMe bond by the nucleophilic attack of the amine based on the nucleophilic aromatic substitution (SNAr) reaction. In contrast to the corresponding traditional SNAr amination

  在铟路易斯酸催化下，与/不与苯环稠合的富电子五元杂芳基亲电试剂与胺偶合生成具有广泛结构多样性的杂芳基胺。通过基于亲核芳香取代（S胺的亲核攻击，通过杂芳基- OME键的裂解的杂芳基形成前进Ñ AR）反应。与相应的传统S N Ar胺形成对比，目前基于S N Ar的杂芳基胺化反应无需依赖具有吸电子基团的杂芳基亲电子试剂和亲核性增强的金属酰胺。对NO 2，Br，I，CF 3等官能团的高度相容性观察到CN，CO 2 Et，吡啶基，噻唑基，C = C和OH基团，从而表明该方法的实用性和可靠性。机理研究表明，在此过程中，杂芳基环上可能会形成碳-铟键。
• Efficient Pd-Catalyzed Amination of Heteroaryl Halides
  作者：Mark D. Charles、Phillip Schultz、Stephen L. Buchwald

  DOI：10.1021/ol0514754

  日期：2005.9.1

  The Pd-catalyzed amination of a variety of heteroaryl halides has been accomplished by utilizing bulky electron-rich biaryl phosphine ligands. In particular, we report the first couplings of amines with chloro- and bromoindoles bearing a free NH, as well as the first Pd-catalyzed aminations of a 5-halopyrimidine.
• Buchwald‐Hartwig Amination of Coordinating Heterocycles Enabled by Large‐but‐Flexible Pd‐BIAN‐NHC Catalysts**
  作者：Dong‐Hui Li、Xiao‐Bing Lan、A‐Xiang Song、Md. Mahbubur Rahman、Chang Xu、Fei‐Dong Huang、Roman Szostak、Michal Szostak、Feng‐Shou Liu

  DOI：10.1002/chem.202103341

  日期：2022.1.19

  AbstractA new class of large‐but‐flexible Pd‐BIAN‐NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N‐heterocyclic carbene) has been rationally designed to enable the challenging Buchwald‐Hartwig amination of coordinating heterocycles. This robust class of BIAN‐NHC catalysts permits cross‐coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron‐deficient heterocycles containing multiple heteroatoms with BIAN‐INon (N,N′‐bis(2,6‐di(4‐heptyl)phenyl)‐7H‐acenaphtho[1,2‐d]imidazol‐8‐ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN‐NHC scaffold.
• Efficient Access to 2-Aryl-3-Substituted Benzo[<i>b</i>]thiophenes
  作者：Emilie David、Julie Perrin、Stéphane Pellet-Rostaing、Jérémie Fournier dit Chabert、Marc Lemaire

  DOI：10.1021/jo0500378

  日期：2005.4.1

  Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo [b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.