4-methoxy-2,5-dimethylbenzonitrile | 64400-49-3

• 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-methoxy-2,5-dimethylbenzonitrile
• CAS: 64400-49-3
• 化学式: C₁₀H₁₁NO
• mdl: MFCD00053416
• 分子量: 161.203
• InChiKey: ZYHLPXFNLCESEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  4-methoxy-2,5-dimethylbenzonitrile 在 三甲基铝 、 碳酸氢钠 作用下， 以 异丙醇 为溶剂， 反应 40.5h， 生成 4,5-dihydro-4-hydroxy-2-(4-methoxy-2,5-dimethylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225
• 作为产物：
  描述：

  2,5-二甲基对茴香醛 在 吡啶 、 盐酸羟胺 作用下， 生成 4-methoxy-2,5-dimethylbenzonitrile
  参考文献：
  名称：

  1,2-Diarylimidazoles as Potent, Cyclooxygenase-2 Selective, and Orally Active Antiinflammatory Agents

  摘要：

  Series of 1,2-diarylimidazoles has been synthesized and found to contain highly potent and selective inhibitors of the human COX-2 enzyme. The paper describes a short synthesis of the target 1,2-diarylimidazoles starting with aryl nitriles. Different portions of the diarylimidazole (I) were modified to establish SAR. Systematic variations of the substituents in the aryl ring B have yielded very potent (IC50 = 10-100 nm) and selective (1000-12500) inhibitors of the COX-2 enzyme. The study on the influence of substituents in the imidazole ring established that a CF3 group at position 4 gives the optimum oral activity. A number of the diarylimidazoles showed excellent inhibition in the adjuvant induced arthritis model (e.g., ED50 = 0.02 mph for 22 and 34). The diarylimidazoles are also potent inhibitors of carrageenan-induced edema (ED50 = 9-30 mph) sind hyperalgesia (ED50 = 11-40 mpk). Several orally active diarylimidazoles show no GI toxicity in the rat and mouse up to 200 mpk.

  DOI：

  10.1021/jm9700225

文献信息

• Acetonitrile as a Cyanating Reagent: Cu-Catalyzed Cyanation of Arenes
  作者：Yamin Zhu、Mengdi Zhao、Wenkui Lu、Linyi Li、Zengming Shen

  DOI：10.1021/acs.orglett.5b00886

  日期：2015.6.5

  A novel approach to the Cu-catalyzed cyanation of simple arenes using acetonitrile as an attractive cyano source has been documented. The C–H functionalization of arenes without directing groups involves a sequential iodination/cyanation to give the desired aromatic nitriles in good yields. A highly efficient Cu/TEMPO system for acetonitrile C–CN bond cleavage has been discovered. TEMPO is used as

  已有文献报道使用乙腈作为有吸引力的氰基源，对简单的芳烃进行铜催化的氰化反应的新方法。不带引导基团的芳烃的C–H功能化涉及顺序的碘化/氰化，以高收率得到所需的芳族腈。已经发现了用于乙腈C-CN键裂解的高效Cu / TEMPO系统。TEMPO用作廉价的氧化剂，可使反应在铜中催化。此外，已将TEMPOCH 2 CN 6鉴定为活性氰化剂，并显示出高的形成-CN部分的反应性。
• Iron(II)‐Catalyzed Direct Cyanation of Arenes with Aryl(cyano)iodonium Triflates
  作者：Zhibin Shu、Wenzhi Ji、Xi Wang、Yujing Zhou、Yan Zhang、Jianbo Wang

  DOI：10.1002/anie.201309791

  日期：2014.2.17

  A direct oxidative cyanation of arenes under FeII catalysis with 3,5‐di(trifluoromethyl)phenyl(cyano)iodonium triflate (DFCT) as the cyanating agent has been developed. The reaction is applicable to wide range of aromatic substrates, including polycyclic structures and heteroaromatic compounds.

  已经开发了在Fe II催化下使用3,5-二（三氟甲基）苯基（氰基）碘化三氟甲磺酸盐（DFCT）作为氰化剂的芳烃直接氧化氰化反应。该反应适用于多种芳族底物，包括多环结构和杂芳族化合物。
• Convenient Conversion of Aldoximes into Nitriles with <i>N</i>-Chlorosuccinimide and Pyridine
  作者：W. Gołebiewski、Mirosaw Gucma

  DOI：10.1055/s-2008-1067106

  日期：——

  Benzaldehyde oximes substituted with electron-donating groups are dehydrated to the corresponding benzonitriles by N-chlorosuccinimide/pyridine in acetonitrile. Benzaldehyde oxime itself and alkanal oximes afford the corresponding aldehydes.

  用电子供给基团取代的苯甲醛肟在乙腈中通过N-氯琥珀酰亚胺/吡啶脱水得到相应的苯腈。苯甲醛肟本身和烷醛肟则生成相应的醛。
• Arylthioamides as H₂S Donors: <scp>l</scp>-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo
  作者：Alma Martelli、Lara Testai、Valentina Citi、Alice Marino、Isabella Pugliesi、Elisabetta Barresi、Giulia Nesi、Simona Rapposelli、Sabrina Taliani、Federico Da Settimo、Maria C. Breschi、Vincenzo Calderone

  DOI：10.1021/ml400239a

  日期：2013.10.10

  A small library of arylthioamides 1-12 was easily synthesized, and their H2S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as L-cysteine. A number of arylthioamides (1-3 and 7) showed a slow and L-cysteine-dependent H2S-releasing mechanism, similar to that exhibited by the reference slow H2S-releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of arylthioamides 1-3 and 7 as H2S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.
• 8-(4-Methoxyphenyl)pyrazolo[1,5-<i>a</i>]-1,3,5-triazines: Selective and Centrally Active Corticotropin-Releasing Factor Receptor-1 (CRF₁) Antagonists
  作者：Paul J. Gilligan、Liqi He、Todd Clarke、Parcharee Tivitmahaisoon、Snjezana Lelas、Yu-Wen Li、Karen Heman、Lawrence Fitzgerald、Keith Miller、Ge Zhang、Anne Marshall、Carol Krause、John McElroy、Kathyrn Ward、Helen Shen、Harvey Wong、Scott Grossman、Gregory Nemeth、Robert Zaczek、Stephen P. Arneric、Paul Hartig、David W. Robertson、George Trainor

  DOI：10.1021/jm9000242

  日期：2009.5.14

  This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discovery of analogue 12-3. which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 4.7 +/- 2.0 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 12-3 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 12-3 has been advanced to clinical trials.