2-carbomethoxy-4-cyano-4-(p-tolyl)cyclohexanone | 65619-00-3

• 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: 2-carbomethoxy-4-cyano-4-(p-tolyl)cyclohexanone
• 英文别名: methyl 5-cyano-5-(4-methylphenyl)-2-oxocyclohexane-1-carboxylate
• CAS: 65619-00-3
• 化学式: C₁₆H₁₇NO₃
• 分子量: 271.316
• InChiKey: BPIAXJUVIKSBTH-UHFFFAOYSA-N

物化性质

• 沸点：
  443.6±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-carbomethoxy-4-cyano-4-(p-tolyl)cyclohexanone 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 硫酸 、 叠氮磷酸二苯酯 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇 、 溶剂黄146 、 苯 为溶剂， 反应 54.0h， 生成 4-methylamino-4-(p-tolyl)cyclohexanone, ethylene ketal
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014
• 作为产物：
  描述：

  4-Cyano-4-(p-tolyl)-pimelinsaeuredimethylester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以99%的产率得到2-carbomethoxy-4-cyano-4-(p-tolyl)cyclohexanone
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014
• 作为试剂：
  描述：

  methyl 5-cyano-5-(4-chlorophenyl)-2-oxocyclohexanecarboxylate 在 硫酸 作用下， 以 溶剂黄146 、 2-carbomethoxy-4-cyano-4-(p-tolyl)cyclohexanone 为溶剂， 以74%的产率得到4-氰基-4-(4-甲基苯基)环己酮
  参考文献：
  名称：

  4-Amino-4-phenylcyclohexanone ketal compositions and process of use

  摘要：

  一类新的4-氨基-4-芳基环己酮，它们的缩醛和酸盐已经合成，并发现对于缓解动物的疼痛很有用。它们的镇痛活性似乎是很高的，并且一些还表现出对镇痛引起的心血管、呼吸和行为抑制有用的麻醉拮抗活性。其中几种显示出混合的镇痛和麻醉拮抗活性。该类化合物的首选化合物是4-(间羟基苯基)-4-二甲氨基环己酮乙二醚缩醛，以及4-(间羟基苯基)-4-(正丁基甲基氨基)环己酮乙二醚缩醛，作为游离碱和其盐酸盐形式。描述了合成和中间体的过程。披露了单位剂量形式和治疗方法。

  公开号：

  US04065573A1

文献信息

• 4-Pyrrolidino-cyclohexanone ketals
  申请人：The Upjohn Company

  公开号：US04180584A1

  公开（公告）日：1979-12-25

  A class of new 4-amino-4-arylcyclohexanones, their ketals, and acid addition salts have been synthesized and found to be useful for relieving pain in animals. Their analgesic activity appears to be of high order, and in addition some exhibit narcotic antagonist activity that is useful in modifying the cardiovascular, respiratory, and behavioral depression caused by other analgesics. Several show mixed analgesic and narcotic antagonist activity. Preferred compounds of the class are 4-(m-hydroxyphenyl)-4-dimethylaminocyclohexanone ethylene ketal, and 4-(m-hydroxyphenyl)-4-(n-butylmethylamino)cyclohexanone ethylene ketal as free bases and as their hydrochloride salts. Processes for snythesis and intermediates are described. Unit dosage forms and therapeutic treatments are disclosed.

  一类新的4-氨基-4-芳基环己酮、它们的缩酮和酸加成盐已被合成并发现对缓解动物疼痛有用。它们的镇痛活性似乎是高级别的，另外一些表现出麻醉拮抗活性，有助于改变其他镇痛剂引起的心血管、呼吸和行为抑制。几种显示出混合的镇痛和麻醉拮抗活性。该类化合物的首选物是4-（间羟基苯基）-4-二甲氨基环己酮乙二醇缩酮和4-（间羟基苯基）-4-（正丁基甲基氨基）环己酮乙二醇缩酮，作为自由碱和它们的盐酸盐。描述了合成和中间体的过程。揭示了单元剂量形式和治疗方法。
• LEDNICER D.; VOIGTLANDER P. F.; EMMERT D. E., J. MED. CHEM., 1980, 23, NO 4, 424-430
  作者：LEDNICER D.、 VOIGTLANDER P. F.、 EMMERT D. E.

  DOI：——

  日期：——
• US4065573A
  申请人：——

  公开号：US4065573A

  公开（公告）日：1977-12-27
• US4180584A
  申请人：——

  公开号：US4180584A

  公开（公告）日：1979-12-25
• US4460604A
  申请人：——

  公开号：US4460604A

  公开（公告）日：1984-07-17