cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone | 1071223-07-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone
• CAS: 1071223-07-8
• 化学式: C₂₂H₁₈Cl₂O₂
• 分子量: 385.29
• InChiKey: QUUMPHYEOKHOOW-OTVXOJSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.19
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.14
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以3.4 g的产率得到cis-atovaquone
  参考文献：
  名称：

  A Single-Pot Synthesis of Atovaquone: An Antiparasitic Drug of Choice

  摘要：

  The present article relates to a practical, economically viable, and validated at industrial scale, single-pot synthetic route for preparation of atovaquone, one of the most versatile antiparasitic drugs of choice used for the prophylaxis and treatment of diseases such as pneumocystis, toxoplasmosis, babesiosis, coccidiosis, and malaria. However, owing to the extremely poor yields of synthesis and very high doses of treatment (due to poor bioavailability) the cost of treatment with this drug is not affordable by the patients in need, particularly in the third world countries where these diseases are most prevalent. Unlike most of the reported processes which use 2-chloronaphthoquinone and pure trans-4-chlorophenyl cyclohexane carboxylic acid, our process is based on the decarboxylative alkylation of isomeric mixture of 4-chlorophenyl cyclohexane carboxylic acid with 1,4-naphthoquinone to give 42% overall yield of atovaquone, 10 times higher than from the reported process (4%) from the innovators of this drug.

  DOI：

  10.1021/op500032w
• 作为产物：
  描述：

  对氯碘苯 在 ammonium peroxydisulfate 、 sodium tetrahydroborate 、 adogen 464 、 四碘化二磷 、 水 、 叔丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone
  参考文献：
  名称：

  Synthesis of atovaquone

  摘要：

  A short synthesis of atovaquone 1 is achieved via the radical coupling of the trans-1,4-sbustituted cyclohexyl mono-oxalate 2 and 2-chloronapthoquinone under phase transfer conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(98)01691-8

文献信息

• PROCESS FOR THE EPIMERIZATION OF ATOVAQUONE ISOMER, ATOVAQUONE INTERMEDIATES AND MIXTURE THEREOF
  申请人：Zhu Fuqiang

  公开号：US20110144347A1

  公开（公告）日：2011-06-16

  Provided is a process for the epimerization of the cis isomer of atovaquone, atovaquone intermediates and isomeric mixtures thereof into their corresponding trans-isomers resulting in higher yield of pure atovaquone.

  提供了一种将阿托喹酮的顺式异构体、阿托喹酮中间体及其同分异构体混合物转化为相应的反式异构体的过程，从而得到更高纯度的阿托喹酮。
• [EN] PROCESS FOR THE EPIMERIZATION OF ATOVAQUONE ISOMER, ATOVAQUONE INTERMEDIATES AND MIXTURE THEREOF<br/>[FR] PROCÉDÉ D'ÉPIMÉRISATION D'UN ISOMÈRE D'ATOVAQUONE, D'INTERMÉDIAIRES D'ATOVAQUONE ET DE LEUR MÉLANGE
  申请人：CHEMAGIS LTD

  公开号：WO2010001378A1

  公开（公告）日：2010-01-07

  Provided is a process for the epimerization of the cis isomer of atovaquone, atovaquone intermediates and isomeric mixtures thereof into their corresponding trans-isomers resulting in higher yield of pure atovaquone.

  提供了一种将阿托伐醌的顺式异构体、阿托伐醌中间体及其异构混合物进行顺式异构化的方法，从而获得更高纯度的阿托伐醌产量。
• [EN] PROCESS FOR PREPARATION OF ATOVAQUONE AND THE CONVERSION OF CIS-ISOMER TO TRANS- ISOMER<br/>[FR] PROCÉDÉ DE PRÉPARATION DE L'ATOVAQUONE ET CONVERSION DE L'ISOMÈRE CIS EN ISOMÈRE TRANS
  申请人：CADILA HEALTHCARE LIMITED

  公开号：WO2008122988A1

  公开（公告）日：2008-10-16

  [EN] Substantially pure atovaquone and parocess for the preparation thereof is disclosed.
  [FR] Cette invention a trait à l'atovaquone sensiblement pure et à son procédé de préparation.
• Synthesis of atovaquone
  作者：David R. Williams、Michael P. Clark

  DOI：10.1016/s0040-4039(98)01691-8

  日期：1998.10

  A short synthesis of atovaquone 1 is achieved via the radical coupling of the trans-1,4-sbustituted cyclohexyl mono-oxalate 2 and 2-chloronapthoquinone under phase transfer conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.
• A Single-Pot Synthesis of Atovaquone: An Antiparasitic Drug of Choice
  作者：Suneel Y. Dike、Dharmendra Singh、Byju N. Thankachen、Brajesh Sharma、Pramil K. Mathur、Swapnil Kore、Ashok Kumar

  DOI：10.1021/op500032w

  日期：2014.5.16

  The present article relates to a practical, economically viable, and validated at industrial scale, single-pot synthetic route for preparation of atovaquone, one of the most versatile antiparasitic drugs of choice used for the prophylaxis and treatment of diseases such as pneumocystis, toxoplasmosis, babesiosis, coccidiosis, and malaria. However, owing to the extremely poor yields of synthesis and very high doses of treatment (due to poor bioavailability) the cost of treatment with this drug is not affordable by the patients in need, particularly in the third world countries where these diseases are most prevalent. Unlike most of the reported processes which use 2-chloronaphthoquinone and pure trans-4-chlorophenyl cyclohexane carboxylic acid, our process is based on the decarboxylative alkylation of isomeric mixture of 4-chlorophenyl cyclohexane carboxylic acid with 1,4-naphthoquinone to give 42% overall yield of atovaquone, 10 times higher than from the reported process (4%) from the innovators of this drug.