(4,5-dichloro-2-nitrobenzyl)triphenylphosphonium bromide

• 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: (4,5-dichloro-2-nitrobenzyl)triphenylphosphonium bromide
• 英文别名: (4,5-Dichloro-2-nitrophenyl)methyl-triphenylphosphanium;bromide
• 化学式: Br*C₂₅H₁₉Cl₂NO₂P
• 分子量: 547.215
• InChiKey: BMDNYCKENHWDCI-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4,5-dichloro-2-nitrobenzyl)triphenylphosphonium bromide 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 17.0h， 生成 (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)-1,2-dideoxy-3,4-O-isopropylidene-D-allo-1-enitol
  参考文献：
  名称：

  Convergent Synthesis of Polyhalogenated Quinoline C-Nucleosides as Potential Antiviral Agents

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. We proposed to synthesize 2-halo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of TCRB. The synthesis used Wittig reactions in two key steps. The first Wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)-1,2-dideoxy-3,4-O-isopropylidene-D-allo-1-enitol (5) as the basic skeleton for the target compounds. The following electrophile-mediated intramolecular cyclization of the cis-alkene (5) was found to afford (1S,2S)-2,5-anhydro-1-bromo-6-O-(tert-butyldimethylsilyl)-1-deoxy-1-(4,5-dichloro-2-nitrophenyl)-3,4-O-isopropylidene-D-allitol (8) as the major product. This alpha-stereoselectivity was contrary to the literature precedence. A double-bond isomerization was established to be the cause of the unexpected stereochemistry. The bromo group of 8 was displaced by a hydroxyl group. Oxidation of the hydroxy group and the reduction of a phenylnitro group provided (2S)-1-(2-amino-4,5-dichlorophenyl)-2,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-isopropylidene-D-allose (11), which was subjected to the second Wittig reaction with a phosphacumulene to construct 4-[5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-alpha-D-ribofuranosyl]-6,7-dichloroquinolin-2-one (13). Halogenation followed by deprotection of 13 and led to the synthesis of 4-(alpha-D-ribofuranosyl)-2,6,7-trichloroquinoline (17) as the major product. The 2-aminophenone alpha-nucleoside (11) was successfully anomerized to the beta-anomer (19), which led to the synthesis of the targeted 2-chloro- and 2-bromo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines (18 and 21, respectively).

  DOI：

  10.1021/jo020643s
• 作为产物：
  描述：

  4,5-二氯-2-硝基甲苯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 甲苯 、 苯 为溶剂， 反应 110.0h， 生成 (4,5-dichloro-2-nitrobenzyl)triphenylphosphonium bromide
  参考文献：
  名称：

  Convergent Synthesis of Polyhalogenated Quinoline C-Nucleosides as Potential Antiviral Agents

  摘要：

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. We proposed to synthesize 2-halo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of TCRB. The synthesis used Wittig reactions in two key steps. The first Wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)-1,2-dideoxy-3,4-O-isopropylidene-D-allo-1-enitol (5) as the basic skeleton for the target compounds. The following electrophile-mediated intramolecular cyclization of the cis-alkene (5) was found to afford (1S,2S)-2,5-anhydro-1-bromo-6-O-(tert-butyldimethylsilyl)-1-deoxy-1-(4,5-dichloro-2-nitrophenyl)-3,4-O-isopropylidene-D-allitol (8) as the major product. This alpha-stereoselectivity was contrary to the literature precedence. A double-bond isomerization was established to be the cause of the unexpected stereochemistry. The bromo group of 8 was displaced by a hydroxyl group. Oxidation of the hydroxy group and the reduction of a phenylnitro group provided (2S)-1-(2-amino-4,5-dichlorophenyl)-2,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-isopropylidene-D-allose (11), which was subjected to the second Wittig reaction with a phosphacumulene to construct 4-[5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-alpha-D-ribofuranosyl]-6,7-dichloroquinolin-2-one (13). Halogenation followed by deprotection of 13 and led to the synthesis of 4-(alpha-D-ribofuranosyl)-2,6,7-trichloroquinoline (17) as the major product. The 2-aminophenone alpha-nucleoside (11) was successfully anomerized to the beta-anomer (19), which led to the synthesis of the targeted 2-chloro- and 2-bromo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines (18 and 21, respectively).

  DOI：

  10.1021/jo020643s

文献信息

• Convergent Synthesis of Polyhalogenated Quinoline <i>C-</i>Nucleosides as Potential Antiviral Agents
  作者：Jiong J. Chen、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jo020643s

  日期：2003.5.1

  2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. We proposed to synthesize 2-halo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of TCRB. The synthesis used Wittig reactions in two key steps. The first Wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)-1,2-dideoxy-3,4-O-isopropylidene-D-allo-1-enitol (5) as the basic skeleton for the target compounds. The following electrophile-mediated intramolecular cyclization of the cis-alkene (5) was found to afford (1S,2S)-2,5-anhydro-1-bromo-6-O-(tert-butyldimethylsilyl)-1-deoxy-1-(4,5-dichloro-2-nitrophenyl)-3,4-O-isopropylidene-D-allitol (8) as the major product. This alpha-stereoselectivity was contrary to the literature precedence. A double-bond isomerization was established to be the cause of the unexpected stereochemistry. The bromo group of 8 was displaced by a hydroxyl group. Oxidation of the hydroxy group and the reduction of a phenylnitro group provided (2S)-1-(2-amino-4,5-dichlorophenyl)-2,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-isopropylidene-D-allose (11), which was subjected to the second Wittig reaction with a phosphacumulene to construct 4-[5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-alpha-D-ribofuranosyl]-6,7-dichloroquinolin-2-one (13). Halogenation followed by deprotection of 13 and led to the synthesis of 4-(alpha-D-ribofuranosyl)-2,6,7-trichloroquinoline (17) as the major product. The 2-aminophenone alpha-nucleoside (11) was successfully anomerized to the beta-anomer (19), which led to the synthesis of the targeted 2-chloro- and 2-bromo-6,7-dichloro-4-(beta-D-ribofuranosyl)quinolines (18 and 21, respectively).