4-(4-methylphenylsulfonimidoyl)morpholine | 18513-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-(4-methylphenylsulfonimidoyl)morpholine
• 英文别名: 4-(p-Tolylsulfonimidoyl)morpholine；imino-(4-methylphenyl)-morpholin-4-yl-oxo-λ6-sulfane
• CAS: 18513-08-1
• 化学式: C₁₁H₁₆N₂O₂S
• 分子量: 240.326
• InChiKey: SEWJSIYWTHKTTF-UHFFFAOYSA-N

物化性质

• 沸点：
  364.6±52.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-methylphenylsulfonimidoyl)morpholine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity

  摘要：

  Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 mu g/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 mu g/mL; compound 15 IC50 = 65 mu g/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

  DOI：

  10.1021/acsmedchemlett.9b00285
• 作为产物：
  描述：

  4-<(4-methylphenyl)sulfinyl>morpholine 在 碘苯二乙酸 、 碳酸氢铵 作用下， 以 甲醇 为溶剂， 生成 4-(4-methylphenylsulfonimidoyl)morpholine
  参考文献：
  名称：

  有机硼/碘化物催化的 NH-亚磺酰亚胺/磺酰亚胺的光氧化还原 N 功能化

  摘要：

  氨基喹啉二芳基硼 (AQDAB) 和四丁基碘化铵 (TBAI) 共催化光氧化还原工艺用于NH-亚磺酰亚胺/磺酰亚胺的N功能化已成功开发。该方案可以在没有金属（光）催化剂、外部氧化剂或酸性/碱性添加剂的条件下以良好至优异的产率提供相应的N-磺酰化和N-膦酰化产物。耐受多种官能团，并且首次报道了NH-磺酰亚胺的N-膦酰化产物。

  DOI：

  10.1039/d3cc04351g

文献信息

• Cu-Catalysed Mild Synthesis of <i>N</i> -Imidoyl and <i>N</i> -Oxoimidoyl Sulfonimidamides through the Three-Component Coupling of Sulfonimidamides, Azides, and Alkynes
  作者：Ganesh Chandra Nandi

  DOI：10.1002/ejoc.201701380

  日期：2017.12.8

  Sulfonimidamides have been used as unfamiliar and less reactive imine nucleophiles (S=NH) to obtain N-imidoyl and N-oxoimidoyl sulfonimidamides in a three-component coupling reaction with azides and alkynes under mild conditions.

  磺酰亚胺酰胺已被用作陌生的，反应性较低的亚胺亲核试剂（S = NH），可在温和条件下与叠氮化物和炔烃进行三组分偶联反应，获得N-亚氨基酰基和N-氧亚氨基磺酰基亚酰胺基酰胺。
• Pd-catalyzed C–N coupling of vinylbromides and sulfonimidamides: a facile synthesis of N′-vinylsulfonimidamides
  作者：Ganesh C. Nandi、Sudhakar R. Kota、Prasad B. Wakchaure、Praveen K. Chinthakindi、Thavendran Govender、Hendrick G. Kruger、Tricia Naicker、Per I. Arvidsson

  DOI：10.1039/c5ra10939f

  日期：——

  through a Pd-catalyzed C–N cross coupling between the N′-(imine nitrogen) of N′-deprotected sulfonimidamides and vinyl bromides. The hitherto unreported products were obtained in moderate to excellent yield, and the C–C double bond geometry of the vinylic substrates were retained during the course of reaction. Single crystal X-ray crystallographic analysis confirmed the product structure. Furthermore, we

  N'-乙烯基磺酰亚胺酰胺是通过Pd催化的N'-脱保护的磺酰亚胺酰胺的N '-（亚胺氮）与乙烯基溴之间的C-N交叉偶联而合成的。迄今为止从未报道过的产物以中等至极好的收率获得，并且在反应过程中保留了乙烯基底物的C-C双键几何形状。单晶X射线晶体学分析证实了产物结构。此外，我们证明了形成的N'-乙烯基磺酰亚胺酰胺可以与Pd–C / H 2进行氢化，以提供N'-烷基磺酰亚胺酰胺。
• A convenient synthetic route to sulfonimidamides from sulfonamides
  作者：Yantao Chen、James Gibson

  DOI：10.1039/c4ra14056g

  日期：——

  Sulfonimidamides were prepared in a one-pot transformation from sulfonamides, through nucleophilic substitution of sulfonimidoyl chlorides formed in situ with different amines. This methodology represents a convenient, safe, and easily accessible synthetic route to sulfonimidamides.

  通过用不同的胺原位形成的磺酰亚胺基酰氯进行亲核取代，从磺酰胺以一锅法制得磺酰亚胺酰胺。该方法学代表了一种简便，安全且容易获得的合成亚磺酰胺的途径。
• Cu(OAc)₂-Catalysed Oxidative Dual C-H/N-H Activation of Terminal Alkynes and<i>N</i>-Deprotected Sulfonimidamides: An Easy Access to<i>N</i>-Alkynylated Sulfonimidamides
  作者：Ganesh Chandra Nandi、Sudhakar Rao Kota、Tricia Naicker、Thavendran Govender、Hendrick G. Kruger、Per I. Arvidsson

  DOI：10.1002/ejoc.201500239

  日期：2015.5

  We report a mild and efficient Cu(OAc)2-catalysed protocol for the oxidative C–N cross-coupling of terminal alkynes and N-deprotected sulfonimidamides. The reaction leads to hitherto unknown N-alkynylated sulfonimidamides. Furthermore, we found that the synthesised N-alkynylated sulfonimidamides could undergo silica-gel-mediated hydrolysis to give the corresponding N-acyl-sulfonimidamides, as well

  我们报告了一种温和有效的 Cu(OAc)2 催化方案，用于末端炔烃和 N-脱保护的磺酰亚胺酰胺的氧化 C-N 交叉偶联。该反应导致迄今为止未知的 N-炔基化磺酰亚胺酰胺。此外，我们发现合成的 N-炔基化磺酰亚胺酰胺可以通过硅胶介导的水解得到相应的 N-酰基磺酰亚胺，以及硼烷-二甲硫醚介导的还原反应得到相应的 N-烷基化磺酰亚胺。
• Electrochemical Oxidative Syntheses of NH‐Sulfoximines, NH‐Sulfonimidamides and Dibenzothiazines via Anodically Generated Hypervalent Iodine Intermediates
  作者：Xianqiang Kong、Long Lin、Xiaohui Chen、Yiyi Chen、Wei Wang、Bo Xu

  DOI：10.1002/cssc.202101002

  日期：2021.8.23

  through direct electrochemical oxidative catalysis involving an iodoarene(I)/iodoarene(III) redox couple. In addition, dibenzothiazines can be synthesized from [1,1′-biaryl]-2-sulfides under standard conditions. Notably, only a catalytic amount of iodoarene is required for the generation in situ of an active hypervalent iodine catalyst, which avoids the need for an excess of a hypervalent iodine reagent

  在此，我们报告了一种通过直接电化学氧化催化合成 NH-亚砜亚胺和 NH-磺酰亚胺酰胺的通用方法，该催化涉及碘芳烃 (I)/碘芳烃 (III) 氧化还原对。此外，二苯并噻嗪可以在标准条件下由 [1,1'-联芳基]-2-硫化物合成。值得注意的是，原位生成活性高价碘催化剂只需要催化量的碘芳烃，这避免了相对于常规方法需要过量的高价碘试剂。此外，该协议具有广泛的底物范围和广泛的官能团耐受性，即使在超过 10 g 的规模下，也能以良好到卓越的收率交付目标化合物。