鲁拉西杂质1 | 223586-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 鲁拉西杂质1
• 英文名称: 3,3'-(1,4-piperazinyl)-1,2-benzisothiazole
• 英文别名: N,N'-Bis-(benzothiazol-3-yl)piperazine；3-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]-1,2-benzothiazole
• CAS: 223586-82-1
• 化学式: C₁₈H₁₆N₄S₂
• 分子量: 352.484
• InChiKey: UGYNLCWENVIDFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  88.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  哌嗪 、 2,2-二硫代双(苯甲腈) 以 二甲基亚砜 、 异丙醇 为溶剂， 反应 48.0h， 以61%的产率得到3-(1-哌嗪基)苯并异噻唑盐酸盐
  参考文献：
  名称：

  New Disulfide Route to 3-(1-Piperazinyl)-1,2-benzisothiazole. Nucleus for Atypical Antipsychotic Drugs

  摘要：

  A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new "atypical antipsychotic" drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120-140 degrees C for 3-24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(1-piperazinyl)-1,2-benzisothiazole in 75-80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(1-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone.

  DOI：

  10.1021/op980210k

文献信息

• New Disulfide Route to 3-(1-Piperazinyl)-1,2-benzisothiazole. Nucleus for Atypical Antipsychotic Drugs
  作者：Stanley W. Walinsky、Darrell E. Fox、John F. Lambert、Terry G. Sinay

  DOI：10.1021/op980210k

  日期：1999.3.1

  A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-1,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new "atypical antipsychotic" drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120-140 degrees C for 3-24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(1-piperazinyl)-1,2-benzisothiazole in 75-80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(1-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone.