N-benzyl-2-hydroxy-5-nitrobenzamide | 13156-81-5

• 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: N-benzyl-2-hydroxy-5-nitrobenzamide
• 英文别名: N-benzyl-5-nitrosalicylamide；N-Benzyl-2-hydroxy-5-nitrobenzamid
• CAS: 13156-81-5
• 化学式: C₁₄H₁₂N₂O₄
• mdl: MFCD07021463
• 分子量: 272.26
• InChiKey: DBRHRPYVJWBDJS-UHFFFAOYSA-N

物化性质

• 熔点：
  152-154 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  502.9±50.0 °C(Predicted)
• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-benzyl-2-hydroxy-5-nitrobenzamide 在 叔丁基过氧化氢 、 caesium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 以90%的产率得到2-hydroxy-6-nitro-2-phenyl-2,3-dihydro-4H-benzo[e][1,3-]-oxaz-in-4-one
  参考文献：
  名称：

  与酰胺氮原子相邻的C（sp 3）H键的分子内官能化：2-羟基-苯并恶嗪酮衍生物的无金属合成

  摘要：

  一个分子内的C（sp 3）H键功能与酰胺氮原子相邻已成功开发了在环境友好的条件下合成2-羟基苯并恶嗪酮衍生物。该方法无金属催化剂，底物范围宽，收率高。此外，在反应过程中还提出了自由基机理。另外，大多数目标化合物对MCF-7和Hela细胞表现出有效的抗增殖活性。

  DOI：

  10.1016/j.tet.2017.09.001
• 作为产物：
  描述：

  2-氯-5-硝基苯甲酸 在 copper(l) iodide 、 氯化亚砜 、 1,10-菲罗啉 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 N-benzyl-2-hydroxy-5-nitrobenzamide
  参考文献：
  名称：

  一种高效的铜催化水中2-羟基苯甲酰胺合成方法

  摘要：

  摘要 首次描述了在纯净水中使用碘化铜/ 1,10-菲咯啉和碱金属氢氧化钾，从2-氯苯甲酰胺底物制备2-羟基苯甲酰胺的有效铜催化合成方法。通过该反应，获得了一系列带有官能团（例如氟，氯，碘，甲氧基，酰胺和醇）的2-羟基苯甲酰胺，收率为33–96％。发现其他芳族2-氯芳基酰胺，例如萘，吡啶和噻吩与反应同样相容。提出该反应通过形成铜-酰胺络合物进行，这可以促进水中的羟基化。总体而言，提出了关于铜在水中的羟基化反应的第一份报道，以及合成2-羟基苯甲酰胺的第一条催化路线。 首次描述了在纯净水中使用碘化铜/ 1,10-菲咯啉和碱金属氢氧化钾，从2-氯苯甲酰胺底物制备2-羟基苯甲酰胺的有效铜催化合成方法。通过该反应，获得了一系列带有官能团（例如氟，氯，碘，甲氧基，酰胺和醇）的2-羟基苯甲酰胺，收率为33–96％。发现其他芳族2-氯芳基酰胺，例如萘，吡啶和噻吩与反应同样相容。提出该反应通过形成铜-酰胺络合

  DOI：

  10.1055/s-0031-1289755

文献信息

• Structure-Activity Relationships of N-benzylsalicylamides for Inhibition of Photosynthetic Electron Transport
  作者：Katarina Kralova、Milan Perina、Karel Waisser、Josef Jampilek

  DOI：10.2174/1573406410666140815125004

  日期：2015.1.30

  Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 μmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 μmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 μmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 μmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 μmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett σ constants of the substituents on the acyl fragment (R1 = H, 5-OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R2 = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters π 1 and ▂of individual substituents) and electronic properties of the substituents on the acyl (σ1) and the benzylamide fragments (σ2), the contribution of σ1 being more significant than that of σ2.

  研究了61种环取代的N-苄基水杨酰胺对菠菜叶绿体中光合电子传递(PET)的抑制作用。这些化合物的抑制能力以IC50值表示，范围从2.0到425.3 μmol/L。评估的化合物中有几种可被视为有效的PET抑制剂；其中包括N-(3,4-二氯苄基)-2-羟基-5-硝基苯甲酰胺(IC50 = 2.0 μmol/L)、3,5-二溴-N-(3,4-二氯苄基)-2-羟基苯甲酰胺(IC50 = 2.3 μmol/L)和3,5-二溴-N-(4-氯苄基)-2-羟基苯甲酰胺(IC50 = 2.6 μmol/L)，这些活性与标准敌草隆(IC50 = 1.9 μmol/L)相当。PET抑制活性随着化合物亲脂性的增加以及酰基片段(R1 = H, 5-O , 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-O , 4-Cl, 3,5-Cl和3,5-Br)和苄胺片段(R2 = H, 4-O , 4- , 4-F, 4-Cl和3,4-Cl)上取代基的Hammett σ常数之和的增加而大致线性增加。基于评估的结构-PET抑制活性关系(QSAR)证实，这些化合物的抑制活性依赖于亲脂性(log P或分布参数π1和▂)以及酰基(σ1)和苄胺片段(σ2)上取代基的电子性质，其中σ1的贡献比σ2更为显著。
• On the Relationship between the Structure and Antimycobacterial Activity of Substituted N-Benzylsalicylamides
  作者：Karel Waisser、Milan Peřina、Věra Klimešová、Jarmila Kaustová

  DOI：10.1135/cccc20031275

  日期：——

  Sixty-six N-benzylsalicylamides substituted in the acyl moiety in positions 3, 4 or 5 and in position 4 on the benzylic aromatic ring were synthesized. The compounds were tested for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium. To evaluate structure-antimycobacterial activity relationships (QSARs), approaches based on the Free-Wilson as well as a combination of the Free-Wilson and Hansch methods were employed (substituent constants were used to describe the influence of the benzyl substituents, indicator parameters were used for the substituents on the acyl moiety). The use of the Hammett constants for benzyl substituents was not important for QSAR equations. The quadratic representation of lipophilicity parameters (π²) was significant only in QSAR equations of antimycobacterial activity against M. avium.

  六十六种在酰基部位3、4或5以及苄芳香环上的位置4处取代的N-苄基水杨酰胺被合成。这些化合物被测试其对结核分枝杆菌、堪萨斯分枝杆菌和埃维分枝杆菌的体外抗结核活性。为了评估结构-抗结核活性关系（QSARs），采用了基于Free-Wilson方法以及Free-Wilson和Hansch方法的组合方法（取代基常数用于描述苄基取代基的影响，指示参数用于酰基部位的取代基）。对于苄基取代基，使用Hammett常数对于QSAR方程并不重要。脂溶性参数（π^2）的二次表示仅在抗结核活性对埃维分枝杆菌的QSAR方程中显著。
• 3-Benzyl-2H-1,3-benzoxazine-2,4(3H)-diones, a new group of antimycobacterial compounds against potentially pathogenic strains
  作者：Karel Waisser、Milan Peřina、Jiřı́ Kuneš、Vera Klimešová、Jarmila Kaustová

  DOI：10.1016/j.farmac.2003.07.004

  日期：2003.11

  A series of derivatives of 3-benzyl-2H-benzoxazine-2,4(3H)-dione substituted in positions 6, 7 or 8 on the benzoxazine, and in positions 3 or 4 on the benzyl moiety was synthesized. The compounds were evaluated for in vitro antimycobacterial activity against Mycobacterium avium and two strains of Mycobacterium kansasii. The disadvantage of the compounds is in their low solubility in water. The antimycobacterial activity of N-benzylsalicylamides correlates with that of 3-benzyl-2H-1,3-benzoxazin-2,4(3H)-diones and depends on the partition coefficients and electronic indexes.
• NOUVEAUX DERIVES DE LA DIHYDROXYBENZYLAMINE, LEUR PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：RHONE-POULENC RORER S.A.

  公开号：EP0641311A1

  公开（公告）日：1995-03-08
• [EN] NOVEL DIHYDROXYBENZYLAMINE DERIVATIVES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME<br/>[FR] NOUVEAUX DERIVES DE LA DIHYDROXYBENZYLAMINE, LEUR PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT
  申请人：——

  公开号：WO1993023364A1

  公开（公告）日：1993-11-25

  [FR] Nouveaux dérivés de la 2,5-dihydroxybenzylamine de formule générale (I), leur préparation et les compositions pharmaceutiques qui les contiennent. Dans la formule générale (I), l'un des symboles R1 ou R2 représente un atome d'hydrogène ou d'halogène ou radical hydroxy, alcoxy, alcoylcarbonyloxy, arylcarbonyloxy, mercapto, alcoylthio, amino, formylamino, alcoylcarbonylamino, arylcarbonylamino et l'autre représente un radical alcoxy, alcoxyméthyle, acyle, arylcarbonyle, alcoyloxycarbonyle, aryloxycarbonyle, alcényloxycarbonyle, carbamoyle ou thiocarbamoyle dont l'atome d'azote est éventuellement substitué par un ou deux radicaux alcoyles ou phényles, les radicaux alcoyles, phényles et aryles étant éventuellement substitués. Les nouveaux produits de formule (I) manifestent une activité antitumorale remarquable.
  [EN] Novel 2,5 dihydroxybenzylamine derivatives of general formula (I), their preparation and pharmaceutical compositions containing same. In general formula (I), one of the symbols R1? or R2? denots a hydrogen or halo atom or a hydroxy, alkoxy, alkylcarbonyloxy arylcarbonyloxy, mercapto, alkylthio, amino, formylamino, alkylcarbonylamino, arylcarbonylamino radical and the other denotes an alkoxy, alkoxymethyl, acyl, arylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, alkenyloxycarbonyl, carbamoyl or thiocarbamoyl radical, the nitrogen atom being optionally substituted by one or two alkyl or phenyl radicals, the alkyl, phenyl and aryl radicals being optionally substituted. The novel products of formula (I) have outstanding tumour prevention activity.