2-chloro-10-butyl-10H-phenothiazine | 6578-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-chloro-10-butyl-10H-phenothiazine
• 英文别名: 10-Butyl-2-chlorophenothiazine
• CAS: 6578-71-8
• 化学式: C₁₆H₁₆ClNS
• 分子量: 289.829
• InChiKey: BEURQLFTRZIQCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  28.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-10-butyl-10H-phenothiazine 、 tetramethylammonium trifluoromethanethiolate 在 1,1'-双(二苯基膦)二茂铁 、 bis(1,5-cyclooctadiene)nickel (0) 、 乙腈 作用下， 以 甲苯 为溶剂， 以86%的产率得到10-butyl-2-((trifluoromethyl)thio)-10H-phenothiazine
  参考文献：
  名称：

  Fundamental Studies and Development of Nickel-Catalyzed Trifluoromethylthiolation of Aryl Chlorides: Active Catalytic Species and Key Roles of Ligand and Traceless MeCN Additive Revealed

  摘要：

  A catalytic protocol to convert aryl and heteroaryl chlorides to the corresponding trifluoromethyl sulfides is reported herein. It relies on a relatively inexpensive Ni(cod)(2)/dppf (cod = 1,5-cyclooctadiene; dppf = 1,1'-bis(diphenylphosphino)ferrocene) catalyst system and the readily accessible coupling reagent (Me4N)SCF3. Our computational and experimental mechanistic data are consistent with a Ni-(0)/Ni-(II) cycle and inconsistent with Ni-(I) as the reactive species. The relevant intermediates were prepared, characterized by X-ray crystallography, and tested for their catalytic competence. This revealed that a monomeric tricoordinate Ni-(I) complex is favored for dppf and Cl whose role was unambiguously assigned as being an off-cycle catalyst deactivation product. Only bidentate ligands with wide bite angles (e.g., dppf) are effective. These bulky ligands render the catalyst resting state as [(P-P)Ni(cod)]. The latter is more reactive than Ni(P-P)(2), which was found to be the resting state for ligands with smaller bite angles and suffers from an initial high-energy dissociation of one ligand prior to oxidative addition, rendering the system unreactive. The key to effective catalysis is hence the presence of a labile auxiliary ligand in the catalyst resting state. For more challenging substrates, high conversions were achieved via the employment of MeCN as a traceless additive. Mechanistic data suggest that its beneficial role lies in decreasing the energetic span, therefore accelerating product formation. Finally, the methodology has been applied to synthetic targets of pharmaceutical relevance.

  DOI：

  10.1021/jacs.5b00538
• 作为产物：
  描述：

  1-碘丁烷 、 2-氯吩噻嗪 在 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以94%的产率得到2-chloro-10-butyl-10H-phenothiazine
  参考文献：
  名称：

  Fundamental Studies and Development of Nickel-Catalyzed Trifluoromethylthiolation of Aryl Chlorides: Active Catalytic Species and Key Roles of Ligand and Traceless MeCN Additive Revealed

  摘要：

  A catalytic protocol to convert aryl and heteroaryl chlorides to the corresponding trifluoromethyl sulfides is reported herein. It relies on a relatively inexpensive Ni(cod)(2)/dppf (cod = 1,5-cyclooctadiene; dppf = 1,1'-bis(diphenylphosphino)ferrocene) catalyst system and the readily accessible coupling reagent (Me4N)SCF3. Our computational and experimental mechanistic data are consistent with a Ni-(0)/Ni-(II) cycle and inconsistent with Ni-(I) as the reactive species. The relevant intermediates were prepared, characterized by X-ray crystallography, and tested for their catalytic competence. This revealed that a monomeric tricoordinate Ni-(I) complex is favored for dppf and Cl whose role was unambiguously assigned as being an off-cycle catalyst deactivation product. Only bidentate ligands with wide bite angles (e.g., dppf) are effective. These bulky ligands render the catalyst resting state as [(P-P)Ni(cod)]. The latter is more reactive than Ni(P-P)(2), which was found to be the resting state for ligands with smaller bite angles and suffers from an initial high-energy dissociation of one ligand prior to oxidative addition, rendering the system unreactive. The key to effective catalysis is hence the presence of a labile auxiliary ligand in the catalyst resting state. For more challenging substrates, high conversions were achieved via the employment of MeCN as a traceless additive. Mechanistic data suggest that its beneficial role lies in decreasing the energetic span, therefore accelerating product formation. Finally, the methodology has been applied to synthetic targets of pharmaceutical relevance.

  DOI：

  10.1021/jacs.5b00538

文献信息

• TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS
  申请人：Mount Sinai School of Medicine

  公开号：EP2744808A2

  公开（公告）日：2014-06-25
• [EN] HEPATITIS C VIRUS ENTRY INHIBITORS<br/>[FR] INHIBITEURS DE LA PÉNÉTRATION DU VIRUS DE L'HÉPATITE C
  申请人：IMMUSOL INC

  公开号：WO2008021745A2

  公开（公告）日：2008-02-21

  [EN] The present invention relates to the use of tricyclic diphenylamine derivative compounds for prevention and/or treatment of Hepatitis C virus (HCV) infection by inhibiting HCV entry into permissive cells.
  [FR] La présente invention concerne l'utilisation de composés dérivés de la diphénylamine tricyclique pour la prévention et/ou le traitement d'une infection par le virus de l'hépatite C (Hepatitis C Virus : HCV) en inhibant la pénétration du HCV dans les cellules permissives.
• [EN] TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS<br/>[FR] COMPOSÉS TRICYCLIQUES EN TANT QU'AGENTS ANTICANCÉREUX
  申请人：MT SINAI SCHOOL OF MEDICINE

  公开号：WO2013025882A2

  公开（公告）日：2013-02-21

  Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of phenothiazine, dibenzoazepine and annulene and similar genera.
• Fundamental Studies and Development of Nickel-Catalyzed Trifluoromethylthiolation of Aryl Chlorides: Active Catalytic Species and Key Roles of Ligand and Traceless MeCN Additive Revealed
  作者：Guoyin Yin、Indrek Kalvet、Ulli Englert、Franziska Schoenebeck

  DOI：10.1021/jacs.5b00538

  日期：2015.4.1

  A catalytic protocol to convert aryl and heteroaryl chlorides to the corresponding trifluoromethyl sulfides is reported herein. It relies on a relatively inexpensive Ni(cod)(2)/dppf (cod = 1,5-cyclooctadiene; dppf = 1,1'-bis(diphenylphosphino)ferrocene) catalyst system and the readily accessible coupling reagent (Me4N)SCF3. Our computational and experimental mechanistic data are consistent with a Ni-(0)/Ni-(II) cycle and inconsistent with Ni-(I) as the reactive species. The relevant intermediates were prepared, characterized by X-ray crystallography, and tested for their catalytic competence. This revealed that a monomeric tricoordinate Ni-(I) complex is favored for dppf and Cl whose role was unambiguously assigned as being an off-cycle catalyst deactivation product. Only bidentate ligands with wide bite angles (e.g., dppf) are effective. These bulky ligands render the catalyst resting state as [(P-P)Ni(cod)]. The latter is more reactive than Ni(P-P)(2), which was found to be the resting state for ligands with smaller bite angles and suffers from an initial high-energy dissociation of one ligand prior to oxidative addition, rendering the system unreactive. The key to effective catalysis is hence the presence of a labile auxiliary ligand in the catalyst resting state. For more challenging substrates, high conversions were achieved via the employment of MeCN as a traceless additive. Mechanistic data suggest that its beneficial role lies in decreasing the energetic span, therefore accelerating product formation. Finally, the methodology has been applied to synthetic targets of pharmaceutical relevance.