3-oxo-5-phenyltetrahydrothiophen-2-ethylcarboxylate | 80278-80-4

• 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: 3-oxo-5-phenyltetrahydrothiophen-2-ethylcarboxylate
• 英文别名: ethyl 5-phenylthiolan-3-on-2-carboxylate；2-etoxycarbonyl-5-phenylthiolan-3-one；3-oxo-5-phenyl-tetrahydro-thiophene-2-carboxylic acid ethyl ester；3-Oxo-5-phenyl-tetrahydro-thiophen-2-carbonsaeure-aethylester；Ethyl 3-oxo-5-phenylthiolane-2-carboxylate
• CAS: 80278-80-4
• 化学式: C₁₃H₁₄O₃S
• 分子量: 250.318
• InChiKey: AQALVMULAIIVTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-oxo-5-phenyltetrahydrothiophen-2-ethylcarboxylate 在 哌啶 、 氢氧化钾 、 硫酸 、 溶剂黄146 作用下， 以 乙醇 、 水 、 溶剂黄146 、 苯 为溶剂， 反应 11.0h， 生成 Methyl 2-(5-phenylthiophen-3-yl)acetate
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents

  摘要：

  5-(Phenylthiophene)-3-carboxylic acid (2a), a metabolite of esonarimod (1), which was developed as a new antirheumatic drug, was considered as a lead compound for new antirheumatic drugs. A new series of 2a derivatives were synthesized and their characteristic pharmacological effects, that is their antagonistic effect toward interleukin (IL)-1 in mice and the suppressive effect against adjuvant-induced arthritis (AIA) in rats, were evaluated and compared with those of 1. The structure-activity relationships indicated that [5-(4-bromophenyl)- thiophen-3-yl]acetic acid (5d), methyl [5-(4-chlorophenyl)-thiophen-3-yl]acetate acid (5d), and methyl [5-(4-bromophenyl)-thiophen-3-yl]acetate (5i) suppressed AIA more potently than 1 and all of the other synthesized compounds. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.08.009
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 乙醚 、 sodium ethanolate 作用下， 生成 3-oxo-5-phenyltetrahydrothiophen-2-ethylcarboxylate
  参考文献：
  名称：

  2-Phenylthiolane¹ Derivatives

  摘要：

  DOI：

  10.1021/ja01239a041

文献信息

• A study of the tautomerism of 2- and 4-ethoxycarbonylthiolan-3-ones implicating stereochemical effects of ring-substitution
  作者：F. Duus

  DOI：10.1016/s0040-4020(01)98968-9

  日期：1981.1

  an-3-ones are generally more enolized (40–74%) than the 2-ethoxycarbonylthiolan-3-ones (6–34%), and both series of compounds generally are less enolized than six-membered ring analogues. The extent of enolization of the title compounds is highly influenced by the nature and position of the ring-substitutents. Provable differencies in population of diastereomeric ketone forms related to the same, common

  已经合成了一系列的2-和4-乙氧基羰基噻喃-3-酮，并通过1 H NMR和IR光谱进行了研究。在四氯甲烷溶液中互变异构平衡的条件下，与2-乙氧基羰基噻喃-3-酮（6-34％）相比，4-乙氧基羰基噻喃-3-酮通常被更烯化（40–74％），并且这两个系列的化合物通常都更少。比六元环类似物烯醇化。标题化合物的烯醇化程度高度受环取代基的性质和位置影响。根据立体化学鉴定，讨论了与相同，常见的烯醇形式有关的非对映体酮形式的可证明的差异。
• 13C and1H NMR study of structure and structural dynamics of tautomeric 2-ethoxycarbonylthiolane-3-thiones
  作者：Fritz Duus

  DOI：10.1002/mrc.1260270810

  日期：1989.8

  2-Ethoxycarbonylthiolane-3-thione (1) and its 5-methyl, 5-phenyl, 5,5-dimethyl and 4,5-dimethyl derivatives (2–5) were studied in solution by 13C and 1H NMR spectroscopy, using solvents of various polarity. Compounds 1–4 exist entirely in the tautomeric (Z)-enethiol form, i.e. they are in fact 2-ethoxycarbonyl-3-mercapto-4,5-dihydrothiophenes (1C-4C), apparently irrespective of their molecular surroundings. Compound 5 exists predominantly as the pair of enantiomeric (and hence NMR-indistinguishable) 2-ethoxycarbonyl-3-mercapto-4,5-dimethyl-4,5-dihydrothiophenes having a trans location of their ring-methyl groups, i.e. 5C(4R, 5R) and 5C(4S, 5S). The diastereomeric counterparts 5C(4R, 5S)/5C(4S, 5R) are observable as minor constituents, co-existing with the former in a double two-step equilibrium system, involving tautomeric 2-ethoxycarbonyl-3-mercapto-4,5-dimethyl-2,5-dihydrothiophenes as intermediates. The 13C chemical shifts of C-4 and C-5 of the unsubstituted and mono- and di-methyl-substituted 4,5-dihydrothiophenes (1C, 2C, 4C, 5C) are describable in terms of additive methyl-substituent shielding. The observed solvent-induced displacement of the mercapto proton chemical shift is interpreted in terms of the solvent's ability to effect pertubation of the intramolecular S—H ⃛O hydrogen bonding. Vicinal couplings between ring protons at C-4 and C-5 are influenced by substitution at C-4 and C-5, and also by the nature (polarity) of the solvent used. The measured coupling constants have been rationalized in terms of the conformational mobility of the 4,5-dihydrothiophene framework. A methyl group at C-5 has little significance for conformational preference. A phenyl group at C-5 preferentially occupies the near-equatorial position. The conformational equilibrium of the trans-4,5-dimethyl-4,5-dihydrothiophenes 5C(4R, 5R)/5C(4S, 5S) apparently depends on the solvent's polarity, a more polar solvent favouring the conformer having near-diaxial methyl groups.

  使用不同极性的溶剂，通过 13C 和 1H NMR 光谱研究了溶液中的 2-乙氧羰基巯基-3-硫酮（1）及其 5-甲基、5-苯基、5,5-二甲基和 4,5- 二甲基衍生物（2-5）。化合物 1-4 完全以同分异构体 (Z)-enethiol 形式存在，即它们实际上是 2-乙氧羰基-3-巯基-4,5-二氢噻吩（1C-4C），显然与它们的分子环境无关。化合物 5 主要是一对对映体（因此 NMR 无法区分），即 5C(4R,5R)和 5C(4S,5S)。非对映异构体 5C(4R，5S)/5C(4S，5R) 是可观察到的次要成分，与前者共存于一个双两步平衡体系中，中间产物包括同分异构体 2-乙氧羰基-3-巯基-4,5-二甲基-2,5-二氢噻吩。 未取代的以及一甲基和二甲基取代的 4,5- 二氢噻吩（1C、2C、4C、5C）的 C-4 和 C-5 的 13C 化学位移可以用甲基取代基的加成屏蔽来描述。 观察到的溶剂诱导的巯基质子化学位移位移是通过溶剂对分子内 S-H ⃛O 氢键的扰动来解释的。 C-4 和 C-5 处环状质子之间的毗连偶联受 C-4 和 C-5 处的取代以及所用溶剂的性质（极性）的影响。根据 4,5-二氢噻吩框架的构象流动性，测得的耦合常数是合理的。位于 C-5 的甲基对构象偏好的影响很小。位于 C-5 的苯基优先占据近赤道位置。反式-4,5-二甲基-4,5-二氢噻吩 5C(4R,5R)/5C(4S,5S)的构象平衡显然取决于溶剂的极性，极性较强的溶剂有利于具有近轴甲基的构象。
• Synthesis and Antiviral Study of Dihydrothieno and Thianopyrimidine Diones Acyclic Nucleosides As Potential Anti-HIV Agents
  作者：Jacques Renault、Daniel Laduree、Max Robba

  DOI：10.1080/15257779408011884

  日期：1994.6

  Acyclic nucleosides were prepared by alkylation of dihydrothieno and thianopyrimidines diones following Vorbruggen and Niedballa's method.((1))None of these HEPT analogues showed significant activity against Human Immunodeficiency Virus-1 (HIV-1).
• DUUS F., TETRAHEDRON, 1981, 37, NO 15, 2633-2640
  作者：DUUS F.

  DOI：——

  日期：——
• Synthesis and structure–activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents
  作者：Toshiya Noguchi、Masahiro Hasegawa、Kazuyuki Tomisawa、Morihiro Mitsukuchi

  DOI：10.1016/j.bmc.2003.08.009

  日期：2003.11

  5-(Phenylthiophene)-3-carboxylic acid (2a), a metabolite of esonarimod (1), which was developed as a new antirheumatic drug, was considered as a lead compound for new antirheumatic drugs. A new series of 2a derivatives were synthesized and their characteristic pharmacological effects, that is their antagonistic effect toward interleukin (IL)-1 in mice and the suppressive effect against adjuvant-induced arthritis (AIA) in rats, were evaluated and compared with those of 1. The structure-activity relationships indicated that [5-(4-bromophenyl)- thiophen-3-yl]acetic acid (5d), methyl [5-(4-chlorophenyl)-thiophen-3-yl]acetate acid (5d), and methyl [5-(4-bromophenyl)-thiophen-3-yl]acetate (5i) suppressed AIA more potently than 1 and all of the other synthesized compounds. (C) 2003 Elsevier Ltd. All rights reserved.