ethyl 3,3-bis(methylthio)-2-methylacrylate | 153683-41-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基硫酯
• 英文名称: ethyl 3,3-bis(methylthio)-2-methylacrylate
• 英文别名: ethyl-2-cyano-3,3-bismethylthioacrylate；Ethyl 2-methyl-3,3-bis(methylsulfanyl)prop-2-enoate
• CAS: 153683-41-1
• 化学式: C₈H₁₄O₂S₂
• 分子量: 206.33
• InChiKey: KPKYOCGAWPMPIX-UHFFFAOYSA-N

物化性质

• 沸点：
  305.8±37.0 °C(Predicted)
• 密度：
  1.113±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  76.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3,3-bis(methylthio)-2-methylacrylate 在 氢氧化钾 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 苯 为溶剂， 反应 6.0h， 生成 3,3-bis(methylthio)-2-methylacryloyl chloride
  参考文献：
  名称：

  Synthesis and Anti-HIV-1 Activity of a Series of 1-Alkoxy-5-alkyl-6-(arylthio)uracils

  摘要：

  A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing st catalytic amount of p-TsOH produced 1-alkaxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-l activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 mu M; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 mu M). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.

  DOI：

  10.1021/jm9607921
• 作为产物：
  描述：

  2-溴丙酸乙酯 、 alkaline earth salt of/the/ methylsulfuric acid 在 碘 、 potassium carbonate 、 锌 作用下， 以 丁酮 为溶剂， 反应 6.75h， 生成 ethyl 3,3-bis(methylthio)-2-methylacrylate
  参考文献：
  名称：

  硫代羰基化合物的Reformatsky反应：新的CC键形成反应

  摘要：

  Reformatsky regants被证明可以通过消除硫或烷硫基形成的亲碳性额外生成物，在三硫代碳酸酯，黄原酸酯，硫酮和二硫代酯上轻松形成CC键。

  DOI：

  10.1016/0040-4039(93)85065-5

文献信息

• Synthesis and pharmacological investigation of novel 2-substituted-3-carboxamido-4H-pyrimidobenzothiazole derivatives as a new class of H1-antihistaminic agent
  作者：Sunil V. Gupta、Kamalkishor G. Baheti、Saurabh B. Ganorkar、Deepak Dekhane、Shivaji Pawar、S. N. Thore

  DOI：10.1007/s00044-012-0100-4

  日期：2013.3

  maleate was used as a standard drug. The active derivatives (8d–8g and 9d–9g) were found to have IC50 values comparable to reference standard chlorpheniramine maleate. The sedative potential of both series (8a–g and 9a–g) is less than the reference drug. Hence, it could serve as prototype molecules for further development as a new class of H1-antihistaminic agents.

  为了开发潜在的H 1-抗组胺药，一系列新型的2-取代-3-羧酰胺基-4-氧代-4 H-嘧啶基[ 2,1- b ] [1,3]苯并噻唑（8a–g）合成了2-取代的3-羧酰胺基-8-氯-4-氧代-4 H-嘧啶[ 2,1- b ] [1,3]苯并噻唑（9a–g），并对其体外H 1-抗组胺药进行了评估活动对豚鼠回肠的制备。发现化合物的IC 50值在微摩尔范围内。马来酸氯苯那敏用作标准药物。发现活性衍生物（8d–8g和9d–9g）具有IC 50值可与参考标准马来酸氯苯那敏相媲美。两个系列（8a–g和9a–g）的镇静潜力均低于参考药物。因此，它可以作为原型分子作为新的H 1-抗组胺药进一步开发。
• A convenient approach to the synthesis of 6-substituted 1,5-dialkyluracils and -2-thiouracils
  作者：Dae-Kee Kim、Young-Woo Kim、Jongsik Gam、Jinsoo Lim、Key H Kim

  DOI：10.1016/0040-4039(95)01238-d

  日期：1995.8

  A general and convenient approach to the synthesis of 6-substituted 1,5-dialkyluracils and 2-thiouracils via 1,5-dialkyl-6-(methylsulfonyl) uracils 1 and 1,5-dialkyl-6-(methylsulfinyl)-2-thiouracils 2, respectively, has been described. The compounds 1 and 2 were synthesized from ethyl 2-alkyl-3,3-di(methylthio)acrylates 3 in live steps in good yields.
• Reformatsky reaction on thiocarbonyl compounds: New CC bond forming reaction
  作者：M. Chandrasekharam、Laxminaraya Bhat、Hiriyakkanavar Ila、Hiriyakkanavar Junjappa

  DOI：10.1016/0040-4039(93)85065-5

  日期：1993.10

  Reformatsky regants are shown to undergo facile CC bond formation on trithiocarbonates, xanthates, thione and dithioesters, through carbophilic additional yielding products formed by elimination of either sulphur or alkylthio group.

  Reformatsky regants被证明可以通过消除硫或烷硫基形成的亲碳性额外生成物，在三硫代碳酸酯，黄原酸酯，硫酮和二硫代酯上轻松形成CC键。
• Synthesis and Anti-HIV-1 Activity of a Series of 1-Alkoxy-5-alkyl-6-(arylthio)uracils
  作者：Dae-Kee Kim、Jongsik Gam、Young-Woo Kim、Jinsoo Lim、Hun-Taek Kim、Key H. Kim

  DOI：10.1021/jm9607921

  日期：1997.7.1

  A series of 1-alkoxy-5-alkyl-6-(arylthio)uracils was synthesized and tested for their ability to inhibit HIV-1 replication. Treatment of 2-alkyl-3,3-bis(methylthio)acryloyl chlorides (5a-e) with AgOCN in benzene followed by reaction of the resulting isocyanates 6a-e with an appropriate alkoxyamine gave N-alkoxy-N'-((2-alkyl-3,3-bis(methylthio (10a-z) in good to excellent yields. Cyclization of 10a-z in AcOH containing st catalytic amount of p-TsOH produced 1-alkaxy-5-alkyl-6-(methylthio)uracils (11a-z). Oxidation of 11a-z with 3-chloroperoxybenzoic acid in CH2Cl2 resulted in high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils (12a-x and 12z) and 1-(benzyloxy)-6-(methylsulfinyl)thymine (12y), which were subsequently reacted with an appropriate arenethiol in ethanolic NaOH solution to afford 1-alkoxy-5-alkyl-6-(arylthio)uracils (14-49). Substitution at the 3- and 5-positions of the C-6-(phenylthio) ring by two methyl groups significantly increased its original anti-HIV-l activity (EC50: 6-((3,5-dimethylphenyl)thio)-5-isopropyl-1-propoxyuracil (18), 0.064 mu M; 6-((3,5-dimethylphenyl)thio)-1-(3-hydroxypropoxy)-5-isopropyluracil (23), 0.19 mu M). Among the various alkoxy substituents at the N-1, the propoxy group was the most beneficial for improving the anti-HIV-1 activity. The 1-propoxy derivative 18 proved to be the most potent inhibitor of HIV-1 replication, followed by the 1-(3-hydroxypropoxy) derivative 23. Introduction of an isopropyl group at C-5 of the uracil base also remarkably enhanced the activity. When compound 18 was incubated with a rat liver homogenate preparation, no metabolite was observed, thus confirming the metabolic stability of the N-O bond in these 1-alkoxyuracils.