1,2-Di-(3-methyl-5-isoxazolyl)aethan | 41027-39-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,2-Di-(3-methyl-5-isoxazolyl)aethan
• 英文别名: 3,3'-dimethyl-5,5'-ethane-1,2-diyl-bis-isoxazole；3-Methyl-5-[2-(3-methyl-1,2-oxazol-5-yl)ethyl]-1,2-oxazole
• CAS: 41027-39-8
• 化学式: C₁₀H₁₂N₂O₂
• 分子量: 192.217
• InChiKey: XSMWERIWHLTSDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 硫酸 作用下， 反应 2.0h， 生成 1,2-Di-(3-methyl-5-isoxazolyl)aethan
  参考文献：
  名称：

  An Efficient, Scaleable Procedure for the Conversion of Esters to Isoxazoles

  摘要：

  已开发出一种简明的区域选择性合成异噁唑的路线，该方法基于酯与金属化亚胺的缩合。中间体连氨酰胺与羟胺反应顺利，经过脱水后，生成取代的异噁唑。该方法已用于ABT-418的多千克规模制备，ABT-418是一种新型的胆碱能通道激活剂。

  DOI：

  10.1055/s-1997-1211

文献信息

• Lithiation of five-membered heteroaromatic compounds. The methyl substituted 1,2-azoles, oxadiazoles, and thiadiazoles
  作者：R. G. Micetich

  DOI：10.1139/v70-334

  日期：1970.7.1

  The lithiation of various methyl substituted isoxazoles, isothiazoles, pyrazoles, oxadiazoles, and thiadiazoles using n-butyllithium has been studied. Three types of reactions, namely, lateral lithiation, ring cleavage, and addition of butyllithium to the ring, have been found. 3,5-Dimethylisoxazole, 3-phenyl-5-methylisoxazole, 3,4-dimethyl-1,2,5-oxadiazole, 2,5-dimethyl-1,3,4-thiadiazole, 3-phenyl-5-methyl-1,2,4-oxadiazole, and 3,5-dimethyl-1,2,4-thiadiazole all undergo lateral lithiation to give the respective acetic acids after carboxylation. 1-Methyl-3,5-disubstituted pyrazoles form the 1-lithiomethyl derivatives, while 1-phenyl-3,5-disubstituted pyrazoles are converted to the 1-ortholithiophenyl-3,5-disubstituted pyrazoles. 4-Methylisothiazole is lithiated mainly at C-5, but also suffers ring cleavage to form 1-n-butylthio-2-cyanoprop-1-ene. Heteroaromatic compounds containing an N—S bond, such as 3,4-dimeth yl-1,2,5-thiadiazole, 4-methyl-5-phenyl-1,2,3-thiadiazole, and 3,5-dimethylisothiazole, undergo nucleophilic attack at sulfur with resulting ring cleavage. 3,5-Dimethylisothiazole produces 2-n-butylthiopent-2-en-4-one. 3-Methyl-5-phenyl-1,2,4-oxadiazole gave 3-methyl-5-phenyl-5-n-butyl-1,2,4-dihydroöxadiazole by addition to the azomethine bond. The results of these lithiations are discussed. 3-Methyl-5-lithiomethylisoxazole was converted to various derivatives. Nuclear magnetic resonance spectral analysis was used to establish the identity of the products.

  各种甲基取代异噁唑、异硫唑、吡唑、噁二唑和噻二唑的锂化反应已经被研究。发现了三种类型的反应，即侧链锂化、环裂解和丁基锂加入环中。3,5-二甲基异噁唑、3-苯基-5-甲基异噁唑、3,4-二甲基-1,2,5-噁二唑、2,5-二甲基-1,3,4-噻二唑、3-苯基-5-甲基-1,2,4-噁二唑和3,5-二甲基-1,2,4-噻二唑都经历侧链锂化，在羧化后生成相应的乙酸。1-甲基-3,5-二取代吡唑形成1-锂甲基衍生物，而1-苯基-3,5-二取代吡唑转化为1-邻锂苯基-3,5-二取代吡唑。4-甲基异硫唑主要在C-5处发生锂化，但也发生环裂解形成1-正丁硫基-2-氰基丙-1-烯。含有N—S键的杂环化合物，如3,4-二甲基-1,2,5-噻二唑、4-甲基-5-苯基-1,2,3-噻二唑和3,5-二甲基异硫唑，在硫原子上发生亲核攻击，导致环裂解。3,5-二甲基异硫唑产生2-正丁硫代戊-2-烯-4-酮。3-甲基-5-苯基-1,2,4-噁二唑通过加成到偶氮亚胺键生成3-甲基-5-苯基-5-正丁基-1,2,4-二氢噁二唑。讨论了这些锂化的结果。3-甲基-5-锂甲基异噁唑被转化为各种衍生物。核磁共振光谱分析用于确定产物的身份。