N-chloroacetyl-p-toluenesulfinamide | 847980-35-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-chloroacetyl-p-toluenesulfinamide
• 英文别名: Acetamide, 2-chloro-N-[(4-methylphenyl)sulfinyl]-；2-chloro-N-(4-methylphenyl)sulfinylacetamide
• CAS: 847980-35-2
• 化学式: C₉H₁₀ClNO₂S
• 分子量: 231.703
• InChiKey: CIHNIJUXBRWIBP-UHFFFAOYSA-N

物化性质

• 熔点：
  119-121 °C
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-chloroacetyl-p-toluenesulfinamide 在 正丁基锂 、 N,N-双(2-羟乙基)-2-氨基乙磺酸 、 subtilisin E 、 subtilisin Carlsberg 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 30.0h， 生成 对甲苯亚磺酸
  参考文献：
  名称：

  Unexpected Subtilisin-Catalyzed Hydrolysis of a Sulfinamide Bond in Preference to a Carboxamide Bond in N-Acyl Sulfinamides

  摘要：

  Subtilisin Carlsberg-catalyzed hydrolysis of N-chloroacetyl p-toluenesulfinamide favored cleavage of the sulfinamide (S(O)-N) bond with a minor amount ( approximately 25%) of the expected carboxamide (C(O)-N) bond. The sulfinamide hydrolysis was enantioselective (E approximately 17) and yielded remaining starting material enriched in the R-enantiomer and achiral product, sulfinic acid and chloroacetamide, as confirmed by mass spectra and NMR. In contrast, the related subtilisin BPN' and E favored the carboxamide hydrolysis. Hydrolysis of the pseudo-symmetrical N-p-toluoyl p-toluenesulfinamide, which contains a sulfinamide and a carboxamide in similar steric and electronic environments, gave only sulfinamide cleavage (>10:1) for subtilisin Carlsberg, showing that sulfinamide cleavage is the preferred path even when a similar carboxamide is available.

  DOI：

  10.1021/ja0506105
• 作为产物：
  描述：

  4-甲基苯亚磺酰胺 、 氯乙酸酐 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以50%的产率得到N-chloroacetyl-p-toluenesulfinamide
  参考文献：
  名称：

  Subtilisin-Catalyzed Resolution of N-Acyl Arylsulfinamides

  摘要：

  We report the first biocatalytic route to sulfinamides (R-S(O)-NH2), whose sulfur stereocenter makes them important chiral auxiliaries for the asymmetric synthesis of amines. Subtilisin E did not catalyze hydrolysis of N-acetyl or N-butanoyl arylsulfinamides, but did catalyze a highly enantioselective (E > 150 favoring the (R)-enantiomer) hydrolysis of N-chloroacetyl and N-clihydrocinnamoyl arylsulfinamides. Gram-scale resolutions using subtilisin E overexpressed in Bacillus subtilis yielded, after recrystallization, three synthetically useful auxiliaries: (R)-p-toluenesulfinamide (42% yield, 95% ee), (R)-p-chlorobenzenesulfinamide (30% yield, 97% ee), and (R)-2,4,6-trimethylbenzenesulfinamide (30% yield, 99% ee). Molecular modeling suggests that the N-chloroacetyl and N-dihydrocinnamoyl groups mimic a phenylalanine moiety and thus bind the sulfinamide to the active site. Molecular modeling further suggests that enantioselectivity stems from a favorable hydrophobic interaction between the aryl group of the fast-reacting (R)-arylsulfinamide and the S-1' leaving group pocket in subtilisin E.

  DOI：

  10.1021/ja045397b

文献信息

• Subtilisin-Catalyzed Resolution of <i>N</i>-Acyl Arylsulfinamides
  作者：Christopher K. Savile、Vladimir P. Magloire、Romas J. Kazlauskas

  DOI：10.1021/ja045397b

  日期：2005.2.1

  We report the first biocatalytic route to sulfinamides (R-S(O)-NH2), whose sulfur stereocenter makes them important chiral auxiliaries for the asymmetric synthesis of amines. Subtilisin E did not catalyze hydrolysis of N-acetyl or N-butanoyl arylsulfinamides, but did catalyze a highly enantioselective (E > 150 favoring the (R)-enantiomer) hydrolysis of N-chloroacetyl and N-clihydrocinnamoyl arylsulfinamides. Gram-scale resolutions using subtilisin E overexpressed in Bacillus subtilis yielded, after recrystallization, three synthetically useful auxiliaries: (R)-p-toluenesulfinamide (42% yield, 95% ee), (R)-p-chlorobenzenesulfinamide (30% yield, 97% ee), and (R)-2,4,6-trimethylbenzenesulfinamide (30% yield, 99% ee). Molecular modeling suggests that the N-chloroacetyl and N-dihydrocinnamoyl groups mimic a phenylalanine moiety and thus bind the sulfinamide to the active site. Molecular modeling further suggests that enantioselectivity stems from a favorable hydrophobic interaction between the aryl group of the fast-reacting (R)-arylsulfinamide and the S-1' leaving group pocket in subtilisin E.
• Unexpected Subtilisin-Catalyzed Hydrolysis of a Sulfinamide Bond in Preference to a Carboxamide Bond in <i>N</i>-Acyl Sulfinamides
  作者：Paul F. Mugford、Vladimir P. Magloire、Romas J. Kazlauskas

  DOI：10.1021/ja0506105

  日期：2005.5.1

  Subtilisin Carlsberg-catalyzed hydrolysis of N-chloroacetyl p-toluenesulfinamide favored cleavage of the sulfinamide (S(O)-N) bond with a minor amount ( approximately 25%) of the expected carboxamide (C(O)-N) bond. The sulfinamide hydrolysis was enantioselective (E approximately 17) and yielded remaining starting material enriched in the R-enantiomer and achiral product, sulfinic acid and chloroacetamide, as confirmed by mass spectra and NMR. In contrast, the related subtilisin BPN' and E favored the carboxamide hydrolysis. Hydrolysis of the pseudo-symmetrical N-p-toluoyl p-toluenesulfinamide, which contains a sulfinamide and a carboxamide in similar steric and electronic environments, gave only sulfinamide cleavage (>10:1) for subtilisin Carlsberg, showing that sulfinamide cleavage is the preferred path even when a similar carboxamide is available.