3-乙酰基-5-氯噻吩-2-磺酰氯 | 165117-07-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-乙酰基-5-氯噻吩-2-磺酰氯
• 英文名称: 3-acetyl-5-chloro-2-thiophenesulfonyl chloride
• 英文别名: 3-Acetyl-5-chlorothiophene-2-sulfonyl chloride
• CAS: 165117-07-7
• 化学式: C₆H₄Cl₂O₃S₂
• 分子量: 259.134
• InChiKey: WMYGKFRPRGAFDT-UHFFFAOYSA-N

物化性质

• 沸点：
  389.5±42.0 °C(Predicted)
• 密度：
  1.629

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  87.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-乙酰基-5-氯噻吩-2-磺酰氯 在 sodium tetrahydroborate 、 lithium perchlorate 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 4.67h， 生成 1-(2-chloro-4-methyl-7-(2,2,2-trifluoroethyl)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethan-1-one
  参考文献：
  名称：

  烯丙基胺通过电合成立体选择性迁移杂芳基三氟甲基化

  摘要：

  开发了一种电化学引发的烯丙基胺杂芳基三氟甲基化反应。级联反应涉及朗格鲁瓦试剂（CF 3 SO 2 Na）的阳极氧化生成CF 3自由基，然后自由基加成到失活的烯烃、Smiles 型杂芳基迁移和氮自由基的还原。不同于传统的氧化反应模式，SO 2来自 Langlois 试剂和 Smiles 重排的分子可能在反应级联中充当化学还原剂，产生氧化还原中性电合成。该反应表现出优异的区域选择性和立体选择性。它为合成对映体纯的β-杂芳基-γ-三氟甲基胺和生物活性化合物的立体选择性后期改性提供了一种有效的方法。

  DOI：

  10.1039/d2gc00960a
• 作为产物：
  描述：

  2,5-二氯-3-乙酰基噻吩 在 氯 、 溶剂黄146 、 硫脲 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 3-乙酰基-5-氯噻吩-2-磺酰氯
  参考文献：
  名称：

  Enantioselective Synthesis of Brinzolamide (AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The “DCAT Route” to Thiophenesulfonamides

  摘要：

  A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A (13a . HCl) and AL-4862 (13b) from 3-acetyl-2,5-dichlorothiophene ("DCAT", 1) is described, Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6, Bromination of 6 gave bromo ketone 7, which upon reduction with (+)-B-chlorodiisopinocampheylborane and cyclization of the resulting bromohydrin produced S thieno[3,2-e]-1,2-thiazine 8a (96% ee) after chromatography, Treatment of 8a in THF with n-BuLi at -70 degrees C resulted in Li-Cl exchange, Reaction of the thienyllithium with SO2 and hydroxylamine O-sulfonic acid afforded bis-sulfonamide 11a, Protection of 11a as the acetinidate 12a, followed by tosylation and amination, gave R amine 13a, The synthesis of 13b proceeded via primary sulfonamide 16, which was brominated, reduced, and cyclized to give S thieno[3,2-e]-1,2-thiazine 18 (>98% ee). By virtue of the ionizable NH, 18 was separable from reduction byproducts by base extraction. Alkylation of 18 with 3-bromopropyl methyl ether afforded 8b, which was converted as above, via 11b, to AL-4862 (13b), These procedures provided multihundred gram lots of 13a and 13b.

  DOI：

  10.1021/op9802125

文献信息

• [EN] PROCESS FOR PREPARING BRINZOLAMIDE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE BRINZOLAMIDE
  申请人：AZAD PHARMACEUTICAL INGREDIENT

  公开号：WO2010103115A1

  公开（公告）日：2010-09-16

  The present invention refers to the preparation and purification of brinzolamide as well as to novel compounds useful in such processes.

  本发明涉及布林唑胺的制备和纯化，以及在这些过程中有用的新化合物。
• 布林佐胺中间体噻吩磺酰胺的制备方法
  申请人：济南诚汇双达化工有限公司

  公开号：CN104031021B

  公开（公告）日：2016-05-04

  本发明属于医药化工的技术领域，具体涉及一种制备布林佐胺中间体噻吩磺酰胺的方法，适用于工业生产。首先将噻吩苄基硫醚溶于适当的溶剂，再加入冰乙酸和水，控温0～15℃，分批加入三氯异氰脲酸，20-40分钟加完，并于该温度下保温反应直至原料消失，水浴30～50℃，减压浓缩除去溶剂，加入质量浓度为25%乙酸乙酯石油醚溶液，搅拌，过滤，滤液减压蒸干，得到噻吩磺酰氯；控温0～15℃，将用乙酸乙酯稀释过的噻吩磺酰氯滴加到氨水或胺的水溶液中，搅拌反应至原料消失，过滤，水洗，固体烘干，即得噻吩磺酰胺。使用该方法所得的产品收率较高，操作简便，而且成本低廉，反应条件温和，适于大规模生产。
• PROCESS FOR PREPARING BRINZOLAMIDE
  申请人：Azad Pharmaceutical Ingredients AG

  公开号：EP2414343A1

  公开（公告）日：2012-02-08
• [EN] PROCESS FOR THE PREPARATION OF INTERMEDIATES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'INTERMÉDIAIRES
  申请人：INDOCO REMEDIES LTD

  公开号：WO2010103550A2

  公开（公告）日：2010-09-16

  An improved process for the preparation of (5)-3,4-dihydro-6- chloro-4-hydroxy-2-(3- methoxypropyl)-4H-thieno[3,2-e]-l,2-thiazine 1,1 -dioxide of Formula (I) is disclosed.
• Enantioselective Synthesis of Brinzolamide (AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The “DCAT Route” to Thiophenesulfonamides
  作者：Raymond E. Conrow、W. Dennis Dean、Paul W. Zinke、Michael E. Deason、Steven J. Sproull、Anura P. Dantanarayana、Mark T. DuPriest

  DOI：10.1021/op9802125

  日期：1999.3.1

  A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A (13a . HCl) and AL-4862 (13b) from 3-acetyl-2,5-dichlorothiophene ("DCAT", 1) is described, Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6, Bromination of 6 gave bromo ketone 7, which upon reduction with (+)-B-chlorodiisopinocampheylborane and cyclization of the resulting bromohydrin produced S thieno[3,2-e]-1,2-thiazine 8a (96% ee) after chromatography, Treatment of 8a in THF with n-BuLi at -70 degrees C resulted in Li-Cl exchange, Reaction of the thienyllithium with SO2 and hydroxylamine O-sulfonic acid afforded bis-sulfonamide 11a, Protection of 11a as the acetinidate 12a, followed by tosylation and amination, gave R amine 13a, The synthesis of 13b proceeded via primary sulfonamide 16, which was brominated, reduced, and cyclized to give S thieno[3,2-e]-1,2-thiazine 18 (>98% ee). By virtue of the ionizable NH, 18 was separable from reduction byproducts by base extraction. Alkylation of 18 with 3-bromopropyl methyl ether afforded 8b, which was converted as above, via 11b, to AL-4862 (13b), These procedures provided multihundred gram lots of 13a and 13b.