1,3-Dihydro-1-(phenylmethyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1,3-Dihydro-1-(phenylmethyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one
• 英文别名: 1-benzyl-5-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one；1-benzyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2(3H)-one；1-benzyl-5-(trifluoromethyl)-2,3-dihydro-1H-1,3-benzodiazol-2-one；3-benzyl-6-(trifluoromethyl)-1H-benzimidazol-2-one
• 化学式: C₁₅H₁₁F₃N₂O
• mdl: MFCD07296471
• 分子量: 292.26
• InChiKey: KJGSMBYKAQHDEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-三氟甲基-1,3-二氢-苯并咪唑-2-酮 在 盐酸 、 sodium hydride 、 potassium carbonate 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 28.25h， 生成 1,3-Dihydro-1-(phenylmethyl)-5-(trifluoromethyl)-2H-benzimidazol-2-one
  参考文献：
  名称：

  Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives

  摘要：

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.

  DOI：

  10.1021/jo00111a014

文献信息

• Tandem C/N-Difunctionalization of Nitroarenes: Reductive Amination and Annulation by a Ring Expansion/Contraction Sequence
  作者：Gen Li、Marissa N. Lavagnino、Siraj Z. Ali、Shicheng Hu、Alexander T. Radosevich

  DOI：10.1021/jacs.2c12450

  日期：2023.1.11

  A synthetic method for the reductive transformation of nitroarenes into ortho-aminated and -annulated products is reported. The method operates via the exhaustive deoxygenation of nitroarenes by an organophosphorus catalyst and a mild terminal reductant to access aryl nitrenes, which after ring expansion, are trapped by amine nucleophiles to give dearomatized 2-amino-3H-azepines. Treatment of these

  报道了一种将硝基芳烃还原转化为邻位胺化和环化产物的合成方法。该方法通过有机磷催化剂和温和的末端还原剂对硝基芳烃进行彻底脱氧，得到芳基氮宾，芳基氮宾在扩环后被胺亲核试剂捕获，得到脱芳构化的2-氨基-3H-氮杂平。用酰基亲电子试剂处理这些扩环中间体会引发 6π 电环化，挤出氮原子并恢复苯环的芳香性，从而通过 C–H 官能化生成 2-氨基苯胺和苯并咪唑产物。
• Regioselective Synthesis of Benzimidazolones via Cascade C–N Coupling of Monosubstituted Ureas
  作者：Johannes B. Ernst、Nicholas E. S. Tay、Nathan T. Jui、Stephen L. Buchwald

  DOI：10.1021/ol501531q

  日期：2014.7.18

  A direct method for the regioselective construction of benzimidazolones is reported wherein a single palladium catalyst is employed to couple monosubstituted urea substrates with differentially substituted 1,2-dihaloaromatic systems. In this method, the catalyst is able to promote a cascade of two discrete chemoselective C-N bond-forming processes that allows the highly selective and predictable formation of complex heterocycles from simple, readily available starting materials.
• Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives
  作者：Nicholas A. Meanwell、Sing Yuen Sit、Jinnian Gao、Henry S. Wong、Qi Gao、Denis R. St. Laurent、Neelakantan Balasubramanian

  DOI：10.1021/jo00111a014

  日期：1995.3

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.