(2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol | 1202942-46-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol
• 英文别名: [2-(4-fluorophenyl)-2H-1,2,3-triazol-4-yl]methanol；[2-(4-fluorophenyl)triazol-4-yl]methanol
• CAS: 1202942-46-8
• 化学式: C₉H₈FN₃O
• 分子量: 193.18
• InChiKey: DTGVVQUMDSDLBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol 在 三溴化磷 作用下， 以 乙醚 为溶剂， 生成 4-(bromomethyl)-2-(4-fluorophenyl)-2H-1,2,3-triazole
  参考文献：
  名称：

  Synthesis and Structure−activity Relationships of Antitubercular 2-Nitroimidazooxazines Bearing Heterocyclic Side Chains

  摘要：

  Recently described biphenyl analogues Of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility.

  DOI：

  10.1021/jm901378u
• 作为产物：
  描述：

  2-(4-fluorophenyl)-2H-1,2,3-triazole-4-carbaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 生成 (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol
  参考文献：
  名称：

  Crystal Structures of 2-Phenyl-2H-1,2,3-Triazol-4-Carbaldehyde, an Active α-Glycosidase Inhibition Agent, and (1-Phenyl-1H-1,2,3-Triazol-4-yl)Methyl Benzoate and (2-(4-Fluorophenyl)-2H-1,2,3-Triazole-4-yl)Methanol, Two Moderately Active Compounds

  摘要：

  报告了（1-苯基-1H-1,2,3-三唑-4-基）苯甲酸甲酯 1a、（2-(4-氟苯基)-2H-1,2,3-三唑-4-基）甲醇 2a 和 2-苯基-2H-1,2,3-三唑-4-甲醛 2b 的晶体结构。据最近的报道，化合物 1a 和 2a 表现出温和的 α-糖苷酶抑制活性，而化合物 2b 则表现出更高的活性。在 1a、2a 和 2b 中，三唑环和相连的芳基环之间分别只存在 6.52(4)、14.02(10) 和 2.44(7)° 的小二面角。化合物 2a 和 2b 相对平坦，而化合物 1a 则呈 "V "形，近平面的苯基三唑基-CH2 和苯基-CO2CH2 分子之间的二面角为 88.11(4)°。1a 中的分子间相互作用为 C-H---X（X = N 或 π（三唑）和 π（三唑）---π（苯基））：由（i）C-H---N 氢键组合和（ii）C-H---π 和 π---π 相互作用组合形成两条不同的链。2a 中的分子间相互作用为 C-H-O 和 C-F-π（苯基）：C-H-O 相互作用产生了包含环网的分子片。化合物 1a 在单斜空间群 P21 中结晶，a = 4.5661(5)，b = 10.5573(14)，c = 13.9694(19) Å，β = 90.594(6)°，Z = 2。化合物 2a 在单斜空间群 P21 中结晶，a = 3.7175(7)，b = 10.428(2)，c = 10.化合物 2b 在单斜空间群 P21/c 中结晶，a = 11。4130(5)，b = 4.80280(10)，c = 15.5916(11) 埃，β = 103.373(7)°， Z = 4。(2-(4-氟苯基)-2H-1,2,3-三唑-4-基)甲醇和 2-苯基-2H-1,2,3-三唑-4-甲醛是相对扁平的化合物，而(1-苯基-1H-1,2,3-三唑-4-基)苯甲酸甲酯则呈 "V "形，近平面的苯基三唑基-CH2 和苯基-CO2CH2 分子之间的二面角为 88.11(4) o。

  DOI：

  10.1007/s10870-015-0629-4

文献信息

• Synthesis and Structure−activity Relationships of Antitubercular 2-Nitroimidazooxazines Bearing Heterocyclic Side Chains
  作者：Hamish S. Sutherland、Adrian Blaser、Iveta Kmentova、Scott G. Franzblau、Baojie Wan、Yuehong Wang、Zhenkun Ma、Brian D. Palmer、William A. Denny、Andrew M. Thompson

  DOI：10.1021/jm901378u

  日期：2010.1.28

  Recently described biphenyl analogues Of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying potent new candidates with improved aqueous solubility. The compounds were constructed by coupling the chiral 2-nitroimidazooxazine alcohol with various halomethyl-substituted arylheterocycles, by cycloadditions to a propargyl ether derivative of this alcohol, or by Suzuki couplings on haloheterocyclic methyl ether derivatives. The arylheterocyclic compounds were all more hydrophilic than their corresponding biphenyl analogues, and several showed solubility improvements. 1-Methylpyrazole, 1,3-linked-pyrazole, 2,4-linked-triazole, and tetrazole analogues had 3- to 7-fold higher MIC potencies against replicating M. tb than predicted by their lipophilicities. Two pyrazole analogues were >10-fold more efficacious than the parent drug in a mouse model of acute M. tb infection, and one displayed a 2-fold higher solubility.
• Crystal Structures of 2-Phenyl-2H-1,2,3-Triazol-4-Carbaldehyde, an Active α-Glycosidase Inhibition Agent, and (1-Phenyl-1H-1,2,3-Triazol-4-yl)Methyl Benzoate and (2-(4-Fluorophenyl)-2H-1,2,3-Triazole-4-yl)Methanol, Two Moderately Active Compounds
  作者：Daniel Gonzaga、Fernando C. da Silva、Vitor F. Ferreira、James L. Wardell、Solange M. S. V. Wardell

  DOI：10.1007/s10870-015-0629-4

  日期：2016.2

  The crystal structures of (1-phenyl-1H-1,2,3-triazol-4-yl)methyl benzoate, 1a, (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol, 2a, and 2-phenyl-2H-1,2,3-triazol-4-carbaldehyde, 2b, are reported. Compounds 1a and 2a were recently reported to exhibit mild α-glycosidase inhibition activity, while compound 2b exhibited a much greater activity. Only small dihedral angles 6.52(4), 14.02(10) and 2.44(7)° are present between the triazolyl ring and the attached aryl rings in 1a, 2a and 2b, respectively. The relatively flat compounds 2a and 2b contrast with compound 1a, which is “V” shaped, with a dihedral angle between the near planar phenyltriazolyl-CH2 and phenyl-CO2CH2 moieties of 88.11(4)°. The intermolecular interactions in 1a are C–H···X (X = N or π(triazole) and π(triazole) ···π(phenyl): two different chains are formed, from (i) combinations of the C–H···N hydrogen bonds and (ii) combinations of the C–H···π and π···π interactions.. The intermolecular interactions in 2a are C–H···O and C–F···π(phenyl): the C–H···O interactions generate a sheet of molecules, containing a network of rings.·Classical O–H···O hydrogen bonds, and weaker C–H···π(triazolyl) and π(phenyl)···π(triazolyl) interactions are present in 2b: all three interactions together generate a chevron-type arrangement. Compound 1a crystallizes in the monoclinic space group P21 with a = 4.5661(5), b = 10.5573(14), c = 13.9694(19) Å, β = 90.594(6)° and Z = 2. Compound 2a crystallizes in the monoclinic space group P21 with a = 3.7175(7), b = 10.428(2), c = 10.689(3) Å, β = 90.521(6)° and  Z = 2. Compound 2b crystallizes in the monoclinic space group P21/c with a = 11.4130(5), b = 4.80280(10), c = 15.5916(11) Å, β = 103.373(7)° and  Z = 4. The relatively flat compounds, (2-(4-fluorophenyl)-2H-1,2,3-triazole-4-yl)methanol and 2-phenyl-2H-1,2,3-triazol-4-carbaldehyde, contrast with compound (1-phenyl-1H-1,2,3-triazol-4-yl)methyl benzoate, which is “V” shaped, with a dihedral angle between the near planar phenyltriazolyl-CH2 and phenyl-CO2CH2 moieties of 88.11(4) o.

  报告了（1-苯基-1H-1,2,3-三唑-4-基）苯甲酸甲酯 1a、（2-(4-氟苯基)-2H-1,2,3-三唑-4-基）甲醇 2a 和 2-苯基-2H-1,2,3-三唑-4-甲醛 2b 的晶体结构。据最近的报道，化合物 1a 和 2a 表现出温和的 α-糖苷酶抑制活性，而化合物 2b 则表现出更高的活性。在 1a、2a 和 2b 中，三唑环和相连的芳基环之间分别只存在 6.52(4)、14.02(10) 和 2.44(7)° 的小二面角。化合物 2a 和 2b 相对平坦，而化合物 1a 则呈 "V "形，近平面的苯基三唑基-CH2 和苯基-CO2CH2 分子之间的二面角为 88.11(4)°。1a 中的分子间相互作用为 C-H---X（X = N 或 π（三唑）和 π（三唑）---π（苯基））：由（i）C-H---N 氢键组合和（ii）C-H---π 和 π---π 相互作用组合形成两条不同的链。2a 中的分子间相互作用为 C-H-O 和 C-F-π（苯基）：C-H-O 相互作用产生了包含环网的分子片。化合物 1a 在单斜空间群 P21 中结晶，a = 4.5661(5)，b = 10.5573(14)，c = 13.9694(19) Å，β = 90.594(6)°，Z = 2。化合物 2a 在单斜空间群 P21 中结晶，a = 3.7175(7)，b = 10.428(2)，c = 10.化合物 2b 在单斜空间群 P21/c 中结晶，a = 11。4130(5)，b = 4.80280(10)，c = 15.5916(11) 埃，β = 103.373(7)°， Z = 4。(2-(4-氟苯基)-2H-1,2,3-三唑-4-基)甲醇和 2-苯基-2H-1,2,3-三唑-4-甲醛是相对扁平的化合物，而(1-苯基-1H-1,2,3-三唑-4-基)苯甲酸甲酯则呈 "V "形，近平面的苯基三唑基-CH2 和苯基-CO2CH2 分子之间的二面角为 88.11(4) o。