3-Methoxyphenanthro[3,4-b][1]benzothiophene | 354529-49-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: 3-Methoxyphenanthro[3,4-b][1]benzothiophene
• 英文别名: 18-Methoxy-9-thiapentacyclo[11.8.0.02,10.03,8.016,21]henicosa-1(13),2(10),3,5,7,11,14,16(21),17,19-decaene
• CAS: 354529-49-0
• 化学式: C₂₁H₁₄OS
• 分子量: 314.408
• InChiKey: FYMUMDATDNCYFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  37.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Methoxyphenanthro[3,4-b][1]benzothiophene 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以100%的产率得到3-hydroxyphenanthro[3,4-b][1]benzothiophene
  参考文献：
  名称：

  Synthesis of Dihydrodiol Metabolites Implicated in the Mechanism of Carcinogenesis of Phenanthro[4,3-b][1]benzothiophene and Phenanthro[3,4-b][1]benzothiophene, the Polycyclic Sulfur Heterocycles with a “Fjord” Structure

  摘要：

  Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b] [1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b] [1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro [3,4-b] [ 11 benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by H-1 NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.

  DOI：

  10.1021/jo020493l
• 作为产物：
  描述：

  1-溴二苯并噻吩 在 氢氧化钾 、 四(三苯基膦)钯 、 甲烷磺酸 、 cesium fluoride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 52.0h， 生成 3-Methoxyphenanthro[3,4-b][1]benzothiophene
  参考文献：
  名称：

  Synthesis of Dihydrodiol Metabolites Implicated in the Mechanism of Carcinogenesis of Phenanthro[4,3-b][1]benzothiophene and Phenanthro[3,4-b][1]benzothiophene, the Polycyclic Sulfur Heterocycles with a “Fjord” Structure

  摘要：

  Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b] [1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b] [1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro [3,4-b] [ 11 benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by H-1 NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.

  DOI：

  10.1021/jo020493l

文献信息

• Synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b ][1]benzothiophene, a potentially carcinogenic metabolite of sulfur heterocycle phenanthro[3,2-b ][1]benzothiophene
  作者：Subodh Kumar

  DOI：10.1039/b100345n

  日期：——

  The present study describes the synthesis of trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,2-b][1]benzothiophene (3), which is a potential proximate carcinogen of the environmentally occurring potent carcinogen phenanthro[3,2-b][1]benzothiophene (1). Three approaches were investigated for the synthesis of 3. In the first approach, the diarylalkene 9, which was prepared by the Wittig reaction of ylide 7 and aldehyde 8, was subjected to an oxidative photocyclization reaction to produce a mixture of compounds from which 5, a synthetic precursor to 3, was obtained only in trace amounts. The major cyclized product was 10. The second approach entailed the Suzuki cross-coupling reaction of 2-(dihydroxyboryl)-5-methoxybenzaldehyde (12) with 3-bromodibenzothiophene (11) to produce 13 in 92% yield. The aldehyde function of 13 was elongated with trimethylsulfonium iodide in the presence of KOH to generate the ethylene oxide 14, which, after methanesulfonic acid treatment, produced a 1 ∶ 1 mixture of 3-methoxyphenanthro[3,2-b][1]benzothiophene (6) and 3-methoxyphenanthro[1,2-b][1]benzothiophene (15). Only the undesired compound 15 could be isolated in pure form by extracting the mixture with hot ethanol, leaving behind a 7 ∶ 3 mixture of 6 and 15. In the third approach, the Wittig reaction of 7 with 2-bromo-5-methoxybenzaldehyde (16) produced 17 predominantly as the Z-isomer in quantitative yield. Cyclodehydrobromination of 17 with KOH–quinoline at elevated temperature produced a mixture from which 6 and 3-methoxyphenanthro[3,4-b][1]benzothiophene (18) were easily separated by column chromatography in 23 and 51% yields, respectively. The intermediate 6 was conveniently processed to 3 following the reaction sequence: methoxy phenol→o-quinone→dihydrodiol. A relatively polar dihydrodiol obtained by similar processing of the mixture of 6 and 15 was identified as 3.

  本研究描述了反式-3,4-二羟基-3,4-二氢菲并[3,2-b][1]苯并噻吩(3)的合成，这是一种环境中的强致癌物菲并[3,2-b][1]苯并噻吩(1)的潜在前致癌物。我们研究了三种合成3的方法。在第一种方法中，通过Wittig反应制备的二芳基烯烃9与醛7反应，经过氧化光环化反应生成一组化合物，其中合成3的前体5仅以微量形式存在。主要的环化产物是10。第二种方法涉及Suzuki交叉偶联反应，将2-(二羟基硼基)-5-甲氧基苯甲醛(12)与3-溴二苯并噻吩(11)反应，以92%的收率生成13。13的醛基在KOH存在下通过三甲基硫鎓碘延长，生成环氧乙烷14，经过甲磺酸处理后，生成3-甲氧基菲并[3,2-b][1]苯并噻吩(6)和3-甲氧基菲并[1,2-b][1]苯并噻吩(15)的1:1混合物。只有不希望的15能够在用热乙醇提取混合物后以纯形式分离出来，留下7:3的6和15混合物。在第三种方法中，7与2-溴-5-甲氧基苯甲醛(16)经过Wittig反应主要生成Z-异构体17，其收率是定量的。17在高温下通过KOH-喹啉进行环脱溴反应，生成一组混合物，其中6和3-甲氧基菲并[3,4-b][1]苯并噻吩(18)能够通过柱层析分别以23%和51%的收率轻易分离。中间体6通过甲氧基酚→邻醌→二氢二醇的反应序列方便地转化为3。通过类似的处理方法获得的相对极性的二氢二醇确定了为3。
• Synthesis of Dihydrodiol Metabolites Implicated in the Mechanism of Carcinogenesis of Phenanthro[4,3-<i>b</i>][1]benzothiophene and Phenanthro[3,4-<i>b</i>][1]benzothiophene, the Polycyclic Sulfur Heterocycles with a “Fjord” Structure
  作者：Subodh Kumar

  DOI：10.1021/jo020493l

  日期：2002.12.1

  Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b] [1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b] [1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro [3,4-b] [ 11 benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by H-1 NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.