methyl 2-methoxy-2-(4-nitrophenyl)acetate | 129918-92-9

• 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: methyl 2-methoxy-2-(4-nitrophenyl)acetate
• 英文别名: 4-Nitro-α-methoxy-phenylessigsaeure-methylester；α-Methoxy-4-nitrophenylessigsaeuremethylester
• CAS: 129918-92-9；59845-70-4
• 化学式: C₁₀H₁₁NO₅
• 分子量: 225.201
• InChiKey: XNNGAXLWDZQVGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methoxy-(4-nitro-phenyl)-acetic acid	129918-95-2	C9H9NO5	211.174
  对硝基苯乙酸甲酯	methyl (4-nitrophenyl)acetate	2945-08-6	C9H9NO4	195.175

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	methyl 2-(4-aminophenyl)-2-methoxyacetate	91012-55-4	C10H13NO3	195.218
  ——	methyl 2-(4-(3-chloropropylsulfonamido)phenyl)-2-methoxyacetate	1333472-54-0	C13H18ClNO5S	335.809

反应信息

• 作为反应物：
  描述：

  methyl 2-methoxy-2-(4-nitrophenyl)acetate 在 盐酸 、 叠氮基三甲基硅烷 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三苯基膦 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia

  摘要：

  A series of 2-methoxyacylhydrazones were optimized to yield compounds with high affinity for PDE10A. Several compounds demonstrated efficacy in animal models of schizophrenia, including conditioned avoidance response and a pro-psychotic phencyclidine hyperactivity model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.007
• 作为产物：
  描述：

  对硝基苯乙酸甲酯 在 4-乙酰氨基苯磺酰叠氮 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 methyl 2-methoxy-2-(4-nitrophenyl)acetate
  参考文献：
  名称：

  二氧化硅负载的HClO 4促进重氮化合物催化的无溶剂和无金属的O–H插入反应

  摘要：

  在重氮羰基化合物存在下，无溶剂的O–H插入反应在非常温和的条件下进行。与使用乙酸铑二聚体的传统金属催化形式不同，此方法使用环保的二氧化硅负载的HClO 4作为催化剂。仅需0.3 mol％的这种布朗斯台德酸催化剂，也可以循环使用几次，以确保在O–H插入反应中获得非常高的收率（最高97％）。反应设置简单，可以在室温下仅1小时内制备43种α-羟基和α-烷氧基酯/酮。

  DOI：

  10.1039/c8gc02574f

文献信息

• Mechanistic studies of direct and sensitized photolysis of methyl (4-nitrophenyl)diazoacetate in the presence of an electron-donating amine: photochemical generation of the diazoalkane radical anion
  作者：Tadashi Mizushima、Go Monden、Shigeru Murata、Kunihiko Ishii、Hiro-o Hamaguchi

  DOI：10.1039/b202800j

  日期：2002.6.27

  The direct and perylene-sensitized photolysis of methyl (4-nitrophenyl)diazoacetate (1) in the presence of an electron-donating amine was investigated by the characterization of reaction products and by the direct observation of reactive species using a laser flash photolysis technique. In the direct photolysis of 1 in the presence of N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD), electron transfer from TMPD occurs and the photoproducts are obtained through an intermediate other than the carbene 3, which we suppose to be the carbene radical anion 3−˙. In the perylene-sensitized photolysis of 1 in the presence of an amine having a large electron-donating ability such as N,N-dimethylaniline and TMPD, the radical anion of 1 can be generated by perylene-mediated electron transfer from the amine to 1. The resulting 1−˙ appears to undergo extrusion of dinitrogen to give 3−˙ smoothly, the behavior of which is dependent on the amine employed as an additive. The product studies revealed that 3−˙ reacts readily with O2 to give the ketoester 5 or abstracts hydrogen atoms to give the ester 7, which is not inconsistent with the theoretical prediction that 3−˙ has a σ radical character in its electronic structure.

  通过反应产物表征和激光闪光光解技术直接观察活性物种，研究了在电子供体胺存在下，甲基（4-硝基苯基）重氮乙酸酯（1）的直接和苊醌敏化光解反应。在直接光解1的过程中，当有N,N,N′,N′-四甲基-p-苯二胺（TMPD）存在时，发生从TMPD的电子转移，光产物是通过中间体产生的，而非卡宾3，我们推测该中间体为卡宾自由基阴离子3−˙。在苊醌敏化下，当存在强电子供体胺如N,N-二甲基苯胺和TMPD时，可通过苊醌介导的从胺到1的电子转移生成1的自由基阴离子。所生成的1−˙看似能顺利排出二氮生成3−˙，其行为取决于所添加的胺。产物研究表明，3−˙易于与氧气反应生成酮酯5或抽取氢原子生成酯7，这与理论预测3−˙在其电子结构中具有σ自由基特性是一致的。
• Neighboring group participation in carbene chemistry. Effect of neighboring carboxylate group on carbene reactivities
  作者：Hideo Tomioka、Katsuyuki Hirai、Kazuo Tabayashi、Shigeru Murata、Yasuji Izawa、Satoshi Inagaki、Takehiko Okajima

  DOI：10.1021/ja00177a033

  日期：1990.10

  the relative reactivities (k OH /k add ) being 0.3-0.5. In marked contrast, the «carboxylate» carbene generated from the sodium salt of the diazoacetate under the same conditions produces mostly the OH insertion product at the expense of the cyclopropanes, k OH /k add being >100. The marked effect of the carboxylate group is nicely explained in terms of the participation by the neighboring carboxylate

  （烷氧基羰基）卡宾的反应性显示出显着变化，因为一个人用羧酸酯基团取代了酯基团。因此，（甲氧基羰基）-或羧基（4-硝基苯基）卡宾，通过相应的重氮化合物在 2-甲基-2-丁烯和甲醇的二元混合物中的光解产生，将环加成产物提供给丁烯，而 OH 将产物插入到甲醇，相对反应性（k OH /k add ）为0.3-0.5。与此形成鲜明对比的是，在相同条件下由重氮乙酸钠盐生成的“羧酸盐”卡宾主要产生 OH 插入产物，但会消耗环丙烷，k OH /k add 大于 100。羧酸根的显着效果很好地解释了相邻羧酸根的参与，
• Photoreaction of Methyl (<i>p</i>-Nitrophenyl)diazoacetate in the Presence of an Electron-Donating Amine: Evidence for Intermediacy of the Carbene Radical Anion
  作者：Tadashi Mizushima、Shingo Ikeda、Shigeru Murata、Kunihiko Ishii、Hiro-o Hamaguchi

  DOI：10.1246/cl.2000.1282

  日期：2000.11

  by the addition of an electron-donating amine, where the formation of the products derived from the carbene was quenched completely. On the basis of the direct observation of transient species and the dependence of the products on amine concentration, the reaction scheme involving a single electron transfer to afford the carbene radical anion is proposed.

  通过添加给电子胺，（对硝基苯基）重氮乙酸甲酯在 MeCN-MeOH (9:1) 中的光解产物分布发生了显着变化，其中由卡宾衍生的产物的形成被完全淬灭。在对瞬态物种的直接观察和产物对胺浓度的依赖性的基础上，提出了涉及单电子转移以提供卡宾自由基阴离子的反应方案。
• PDE10 INHIBITORS AND RELATED COMPOSITIONS AND METHODS
  申请人：Cutshall Neil S.

  公开号：US20110224202A1

  公开（公告）日：2011-09-15

  Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

  揭示了抑制PDE10的化合物，对治疗多种疾病有用，包括（但不限于）精神病、焦虑、运动障碍和/或神经系统疾病，如帕金森病、亨廷顿病、阿尔茨海默病、脑炎、恐惧症、癫痫、失语症、贝尔氏面瘫、脑瘫、睡眠障碍、疼痛、抽动综合征、精神分裂症、妄想症、药物诱发的精神病、恐慌和强迫症。还提供了这些化合物的药用盐、立体异构体、溶剂合物和前药。还揭示了含有化合物与药用载体组合的组合物，以及与使用有关的方法，用于在需要的温血动物中抑制PDE10。
• NEIGHBORING GROUP PARTICIPATION IN CARBENE CHEMISTRY. EFFECT OF NEIGHBORING CARBOXYLATE GROUP ON ARYLCARBENE REACTIVITY
  作者：Hideo Tomioka、Kazuo Tabayashi、Yasuji Izawa

  DOI：10.1246/cl.1985.1103

  日期：1985.8.5

  The carbene generated by photolysis of sodium α-diazoacetate in a binary mixture of methanol and 2-methyl-2-butene showed 3 000 times enhanced reactivity toward methanol relative to the alkene compared to that derived from the corresponding ester or acid. The results are interpreted as indicating that the neighboring carboxylate group interacts with electron-deficient center of carbene.

  α-重氮乙酸钠在甲醇和 2-甲基-2-丁烯的二元混合物中光解产生的卡宾，与相应的酯或酸相比，对甲醇的反应性比烯烃高 3000 倍。结果被解释为表明相邻的羧酸根基团与卡宾的缺电子中心相互作用。