2,2,4,4-tetramethyl-3-thioxocyclobutanone | 10181-59-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫代羰基化合物
• 英文名称: 2,2,4,4-tetramethyl-3-thioxocyclobutanone
• 英文别名: 2,2,4,4-tetramethyl-3-thiocyclobutanone；2,2,4,4-tetramethyl-3-thioxocyclobutan-1-one；2,2,4,4-Tetramethyl-3-sulfanylidenecyclobutan-1-one
• CAS: 10181-59-6
• 化学式: C₈H₁₂OS
• 分子量: 156.249
• InChiKey: SVRXPTCPQFXZSF-UHFFFAOYSA-N

物化性质

• 熔点：
  54-55 °C
• 沸点：
  211.1±50.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  49.2
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  2,2,4,4-tetramethyl-3-thioxocyclobutanone 以 乙醚 为溶剂， 反应 5.0h， 生成 1,1,3,3-tetramethyl-2-oxo-5-thiaspiro<3.4>octane-8-carbonitrile
  参考文献：
  名称：

  Can polymerization trap intermediates in 1,3-dipolar cycloadditions?

  摘要：

  2,2,4,4-Tetramethyl-3-thioxocyclobutanone S-methylide (TTCM) is a nucleophilic 1,3-dipole which is known to undergo two-step cycloadditions to very electron poor olefins. When this 1,3-dipole is generated from its precursor, the 1,3,4-thiadiazoline 7, in acrylonitrile or acrylic esters at 45-degrees-C, only cycloaddition and no polymerization is observed, suggesting a concerted cycloaddition. Small amounts of polymers were observed alongside the cycloadducts with nitroethylene, methacrylonitrile, and methacrylates. Most cycloadducts were produced as regioisomeric mixtures. The reaction of TTCM with benzylidenemalononitrile, a nonpolymerizable olefin, is nonconcerted and furnished in THF and 1 vol % methanol or 3 vol % water a 7-membered lactim methyl ether or lactam formed by interception of a ketene imine. The observed polymerizations are radical in nature and are proposed to be initiated by a minor contribution of a diradical intermediate to the cycloaddition reaction.

  DOI：

  10.1021/ja00027a035
• 作为产物：
  描述：

  四甲基环丁烷-1,3-二酮 在 吡啶 、 tetraphosphorus decasulfide 作用下， 生成 2,2,4,4-tetramethyl-3-thioxocyclobutanone
  参考文献：
  名称：

  亚磺酰氯和亚磺酰氯与3-苯基-1-氮杂双环[1.1.0]丁烷的加成反应

  摘要：

  3-苯基-1-氮杂双环[1.1.0]丁烷与α-氯亚磺酰氯和亚磺酰氯的反应分别得到相应的亚磺酰胺和亚磺酰胺，它们具有氮杂环丁烷环。提出发生涉及中间碳正离子的两步机理，该中间碳正离子是通过在N原子上添加亲电试剂并裂解N（1）C（3）键而形成的。9b和10b的结构通过X射线晶体学确定。

  DOI：

  10.1002/hlca.200890154
• 作为试剂：
  描述：

  2-(乙酰氨基)-4-甲基吡啶 在 potassium permanganate 、 2,2,4,4-tetramethyl-3-thioxocyclobutanone 、 氢溴酸 、 N,N'-羰基二咪唑 、 亚硝酸异戊酯 作用下， 以 水 为溶剂， 生成 N-{4-[4-(4-fluorophenyl)-1-methyl-2-methylsulfanyl-1H-imidazol-5-yl]pyridin-2-yl}acetamide
  参考文献：
  名称：

  Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases

  摘要：

  The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38 alpha MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38 alpha MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

  DOI：

  10.1021/acs.jmedchem.6b01647

文献信息

• 1,3-Dipole mit zentralem S-Atom aus der Umsetzung von Aziden mit Thiocarbonyl-Verbindungen: Eine unerwartete MeS-Wanderung im Abfangprodukt eines ?Thiocarbonyl-aminids? mit Dithiobenzoes�ure-methylester
  作者：Grzegorz Mlosto?、Jaroslaw Roma?ski、Anthony Linden、Heinz Heimgartner

  DOI：10.1002/hlca.19950780609

  日期：1995.9.20

  1,3-Dipoles with a Central S-Atom from the Reaction of Azides and Thiocarbonyl Compounds: An Unexpected MeS Migration in the Trapping Product of a ‘Thiocarbonyl-aminide’ with Methyl Dithiobenzoate

  叠氮化物与硫代羰基化合物反应产生的具有中心S原子的1,3-偶极子：“硫代羰基氨基化物”与二硫代苯甲酸甲酯的捕集产物中发生意外的MeS迁移
• Formal Insertion of Thioketenes into Donor–Acceptor Cyclopropanes by Lewis Acid Catalysis
  作者：André U. Augustin、Marius Busse、Peter G. Jones、Daniel B. Werz

  DOI：10.1021/acs.orglett.7b03961

  日期：2018.2.2

  Donor–acceptor cyclopropanes were reacted under Lewis acid catalysis with 3-thioxocyclobutanones as surrogates for disubstituted thioketenes. A broad scope of 2-substituted tetrahydrothiophenes with a semicyclic double bond was obtained under mild conditions with high functional group tolerance and in excellent yield. A sequence of a formal [3 + 2]-cycloaddition followed by the subsequent release of

  供体-受体环丙烷在路易斯酸催化下与3-硫代氧代环丁酮作为双取代硫代乙烯酮的代用品反应。在温和的条件下，具有高官能团耐受性和优异的收率，获得了具有半环双键的2-取代四氢噻吩。推测有一个正式的[3 + 2]-环加成序列，然后随后释放出二取代的乙烯酮作为该机理。
• Cycloadditions of adamantanethione S-methylide to heteromultiple bonds
  作者：Grzegorz Mloston、Rolf Huisgen、Kurt Polborn

  DOI：10.1016/s0040-4020(99)00664-x

  日期：1999.9

  Adamantanethione S-methylide (5) is an easily accessible thiocarbonyl S-ylide. Generated by N2 elimination from the cycloadduct of adamantanethione and diazomethane, the nucleophilic 1,3-dipole 5 reacts in situ with thiocarbonyl compounds furnishing 1,3-dithiolanes. 5 and carbon disulfide afford 1:1 and 2:1 cycloadducts. The structures are assessed by NMR spectra, a X-ray analysis, and C-S hydrogenolyses

  金刚烷硫酮S-亚甲基（5）是易于获得的硫代羰基S-内酯。通过从金刚烷硫酮和重氮甲烷的环加合物中消除N 2生成，亲核性1,3-偶极5与硫代羰基化合物原位反应，从而提供1,3-二硫杂环戊烷。5和二硫化碳可提供1：1和2：1的环加合物。通过NMR光谱，X射线分析和CS氢解来评估结构。CS组是一个亲切的亲电子试剂。区域异构体加合物的比率表明，电子效应有利于4'，5'-取代的1,3-二硫杂环戊烷，而空间效应则支持2'，4'-取代的系统。亲电羰基化合物和5区域特异性地提供2，4-二取代的1，3-氧杂硫杂环戊烷。亚胺与5相比似乎是弱的偶极亲和性。
• Imidazole compounds having an antiinflammatory effect
  申请人：MERCKLE GMBH

  公开号：EP1894925A1

  公开（公告）日：2008-03-05

  The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the invention have an immunomodulating and/or cytokine release-inhibiting effect and are therefore suitable for the treatment of disorders associated with an impairment of the immune system.

  这项发明涉及公式I的2-磺酰基或2-磺酰基取代的咪唑衍生物， 其中基团R1、R2、R3和R4具有描述中指示的含义。该发明的化合物具有免疫调节和/或细胞因子释放抑制作用，因此适用于治疗与免疫系统功能障碍相关的疾病。
• Reactions of a sterically hindered tetrasubstituted thiocarbonyl ylide with acceptor-substituted ethylenes; regioselectivity and stereochemistry
  作者：Grzegorz Mloston、Rolf Huisgen、Henry Giera

  DOI：10.1016/s0040-4020(02)00384-8

  日期：2002.5

  The 1,3-cycloadditions of the tetra-substituted thiocarbonyl ylide 8, set free by N2 extrusion from thiadiazoline 7, with methyl acrylate and acrylonitrile furnish 3′-and 4′-substituted thiolanes, probably by a concerted pathway. In the reactions of 8 with dimethyl 2,3-dicyanofumarate (27) and dimethyl 2,3-dicyanomaleate (28), zwitterionic intermediates, which are capable of conformational rotation

  通过从噻二唑啉7中的N 2挤出而释放的四取代的硫代羰基内酯8的1，3-环加成物可能与丙烯酸甲酯和丙烯腈一起提供3′-和4′-取代的硫杂环戊烷，可能是通过协同途径。在8与2,3-二氰基富马酸二甲酯（27）和2,3-二氰基苹果酸二甲酯（28）的反应中，能够构象旋转的两性离子中间体位于两个不可逆反应的分支点：环化成硫氰酸根23 / 24和片段化至环丙烷31 / 32加硫酮12。两种反应都伴随着一些立体化学纯度的损失。对于环丙烷形成两种机制进行了讨论：分子内亲核取代在抗-zwitterions 29日/ 30或无辅助heterolysis导致叔-carbenium两性离子作为另外的中间。