3,5-dibromoisothiazole-4-carbonitrile | 3878-07-7

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 3,5-dibromoisothiazole-4-carbonitrile
• 英文别名: 3,5-dibromo-isothiazole-4-carbonitrile；3,5-Dibrom-4-isothiazolcarbonitril；3,5-Dibrom-4-cyanoisothiazol；3.5-Dibrom-4-cyan-isothiazol；3,5-dibromo-1,2-thiazole-4-carbonitrile
• CAS: 3878-07-7
• 化学式: C₄Br₂N₂S
• 分子量: 267.931
• InChiKey: VTCXYDUMNATXHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-dibromoisothiazole-4-carbonitrile 在 甲酸-d2 、 锌 作用下， 以71%的产率得到3-bromo-5-deuterioisothiazole-4-carbonitrile
  参考文献：
  名称：

  Regioselective hydrodehalogenation of 3,5-dihaloisothiazole-4-carbonitriles: synthesis of 3-haloisothiazole-4-carbonitriles

  摘要：

  3,5-Dibromoisothiazole-4-carbonitrile 1 treated with Zn or In dust (5 equiv) and HCO2H undergoes regioselective hydrodebromination to give 3-bromoisothiazole-4-carbonitrile 3 in 70-74% yield. Similarly, 5-bromo and iodo 3-chloroisothiazole-4-carbonitriles 8 and 9 give 3-chloroisothiazole-4-carbonitrile 4 in 77 and 85% yields, respectively. Also hydrodeamination of 5-amino-3-chloroisothiazole-4-carbonitrile 7 using isoamyl nitrite gives the latter in 95% yield. The dibromoisothiazole 1 reacts with Zn dust in either DCO2D or HCO2D to give 3-bromo-5-deuterioisothiazole-4-carbonitrile 10 in 71 and 58% yields, respectively. The 3-bromoisothiazole 3 reacts with cyclic dialkylamines to give the corresponding 2-(dialkylaminomethylene)-malononitriles and not the expected 3-dialkylaminoisothiazole-4-carbonitriles. Finally, the 3-bromoisothiazole 3 is readily converted into both 3-bromoisothiazole-4-carboxamide 19 and the carboxylic acid 20. All products are fully characterized. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.03.065
• 作为产物：
  描述：

  dimercaptomethylene-malononitrile 在 溴 作用下， 以 四氯化碳 为溶剂， 生成 3,5-dibromoisothiazole-4-carbonitrile
  参考文献：
  名称：

  The Synthesis of Isothiazoles. I. 3,5-Dichloro-4-isothiazolecarbonitrile and Its Derivatives

  摘要：

  DOI：

  10.1021/jo01026a033

文献信息

• New regiospecific isothiazole C–C coupling chemistry
  作者：Irene C. Christoforou、Panayiotis A. Koutentis

  DOI：10.1039/b607442a

  日期：——

  Regioselective palladium catalysed coupling reactions are achieved in good to high yields, starting from either 3,5-dichloro- or 3,5-dibromoisothiazole-4-carbonitriles 1 and 2, providing 3-halo-5-(hetero/aryl, alkenyl and alkynyl)isothiazoles 3, 4, 6–9 from Stille couplings, 3-halo-5-(hetero/arylethynyl)isothiazoles 14–19 from Sonogashira and 5,5′-bi(3-chloroisothiazole-4-carbonitrile) (13) from an Ullmann type coupling. 3,5-Dibromoisothiazole-4-carbonitrile 2 is more reactive than the dichloroisothiazole-4-carbonitrile 1 and effective enough for Stille, Negishi and Sonogashira couplings. 5,5-Bi(3-chloroisothiazole-4-carbonitrile) (13) is prepared by a palladium catalysed Ullmann coupling from 3-chloro-5-iodoisothiazole-4-carbonitrile (11). A variety of 3-substituted isothiazoles (3-substituents = Cl, Br, OMs, OTs and OTf) are less reactive and fail to give successful Suzuki couplings at the isothiazole C-3 position. The 3-iodo-5-phenyl-isothiazole-4-carbonitrile (28), prepared via Sandmeyer iodination, participates successfully in Suzuki, Ullmann type, Stille, Negishi and Sonogashira coupling reactions. All products are fully characterized.

  区域选择性钯催化的偶联反应以良好至高产率实现，从3,5-二氯或3,5-二溴异噻唑-4-腈1和2出发，通过Stille偶联反应得到3-卤代-5-(杂/芳基、烯基和炔基)异噻唑3、4、6–9，通过Sonogashira反应得到3-卤代-5-(杂/芳基炔基)异噻唑14–19，以及通过Ullmann型偶联反应得到5,5'-二(3-氯异噻唑-4-腈)13。3,5-二溴异噻唑-4-腈2比3,5-二氯异噻唑-4-腈1更具反应活性，足以有效进行Stille、Negishi和Sonogashira偶联反应。5,5-二(3-氯异噻唑-4-腈)13通过钯催化的Ullmann偶联反应由3-氯-5-碘异噻唑-4-腈11制备。多种3-取代异噻唑（3-取代基=Cl、Br、OMs、OTs和OTf）反应活性较低，未能成功在异噻唑C-3位置进行Suzuki偶联反应。通过Sandmeyer碘化法制备的3-碘-5-苯基异噻唑-4-腈28成功参与了Suzuki、Ullmann型、Stille、Negishi和Sonogashira偶联反应。所有产物均经过充分表征。
• Regiospecific Suzuki coupling of 3,5-dichloroisothiazole-4-carbonitrile
  作者：Irene C. Christoforou、Panayiotis A. Koutentis、Charles W. Rees

  DOI：10.1039/b306005e

  日期：——

  3,5-Dichloroisothiazole-4-carbonitrile 1 reacts with aryl- and methylboronic acids to give in high yields the 3-chloro-5-(aryl and methyl)-isothiazole-4-carbonitrile 2 regiospecifically. The reaction was optimized with respect to base, phase transfer agent and palladium catalyst. Suzuki coupling at C-5 was also achieved in high yield using potassium phenyltrifluoroborate. The regiospecificity of either coupling method is maintained with 3,5-dibromoisothiazole-4-carbonitrile 4 to give exclusively 3-bromo-5-phenylisothiazole-4-carbonitrile 5. Suzuki cross-coupling conditions applied to 3-chloro-5-phenylisothiazole-4-carbonitrile 2a gave 3-phenoxy-5-phenylisothiazole-4-carbonitrile 6, which was prepared independently, and not the 3-phenyl derivative. All isothiazole products were fully characterized.

  3,5-二氯异噻唑-4-甲腈 1 与芳基酸和甲基硼酸反应，可以高产 3-氯-5-（芳基和甲基）异噻唑-4-甲腈 2。该反应在碱、相转移剂和钯催化剂方面进行了优化。使用苯基三氟硼酸钾也在 C-5 处实现了高产率的铃木偶联。在 3,5-二溴异噻唑-4-甲腈 4 中，这两种偶联方法都保持了区域特异性，只得到 3-溴-5-苯基异噻唑-4-甲腈 5。在 3-氯-5-苯基异噻唑-4-甲腈 2a 的铃木交叉偶联条件下，得到了独立制备的 3-苯氧基-5-苯基异噻唑-4-甲腈 6，而不是 3-苯基衍生物。所有异噻唑产品均已完全表征。
• Orally bioavailable Syk inhibitors with activity in a rat PK/PD model
  作者：Gebhard Thoma、Siem Veenstra、Ross Strang、Joachim Blanz、Eric Vangrevelinghe、Jörg Berghausen、Christian C. Lee、Hans-Günter Zerwes

  DOI：10.1016/j.bmcl.2015.08.037

  日期：2015.10

  Design and optimization of benzo- and pyrido-thiazoles/isothiazoles are reported leading to the discovery of the potent, orally bioavailable Syk inhibitor 5, which was found to be active in a rat PK/PD model. Compound 5 showed acceptable overall kinase selectivity. However, in addition to Syk it also inhibited Aurora kinase in enzymatic and cellular settings leading to findings in the micronucleus assay. As a consequence, compound 5 was not further pursued. (C) 2015 Elsevier Ltd. All rights reserved.
• The Synthesis of Isothiazoles. I. 3,5-Dichloro-4-isothiazolecarbonitrile and Its Derivatives
  作者：W. R. Hatchard

  DOI：10.1021/jo01026a033

  日期：1964.3
• Regioselective hydrodehalogenation of 3,5-dihaloisothiazole-4-carbonitriles: synthesis of 3-haloisothiazole-4-carbonitriles
  作者：Heraklidia A. Ioannidou、Panayiotis A. Koutentis

  DOI：10.1016/j.tet.2011.03.065

  日期：2011.5

  3,5-Dibromoisothiazole-4-carbonitrile 1 treated with Zn or In dust (5 equiv) and HCO2H undergoes regioselective hydrodebromination to give 3-bromoisothiazole-4-carbonitrile 3 in 70-74% yield. Similarly, 5-bromo and iodo 3-chloroisothiazole-4-carbonitriles 8 and 9 give 3-chloroisothiazole-4-carbonitrile 4 in 77 and 85% yields, respectively. Also hydrodeamination of 5-amino-3-chloroisothiazole-4-carbonitrile 7 using isoamyl nitrite gives the latter in 95% yield. The dibromoisothiazole 1 reacts with Zn dust in either DCO2D or HCO2D to give 3-bromo-5-deuterioisothiazole-4-carbonitrile 10 in 71 and 58% yields, respectively. The 3-bromoisothiazole 3 reacts with cyclic dialkylamines to give the corresponding 2-(dialkylaminomethylene)-malononitriles and not the expected 3-dialkylaminoisothiazole-4-carbonitriles. Finally, the 3-bromoisothiazole 3 is readily converted into both 3-bromoisothiazole-4-carboxamide 19 and the carboxylic acid 20. All products are fully characterized. (C) 2011 Elsevier Ltd. All rights reserved.