2,5-dithio-3,4,7,8-tetramethylglycoluril | 198063-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2,5-dithio-3,4,7,8-tetramethylglycoluril
• 英文别名: 3,4,7,8-tetramethyl-2,5-dithioglycoluril
• CAS: 198063-28-4
• 化学式: C₈H₁₄N₄S₂
• 分子量: 230.358
• InChiKey: WUFYKWZIOHRONV-OCAPTIKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.06
• 重原子数：
  14.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  30.54
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2,5-dithio-3,4,7,8-tetramethylglycoluril 在 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 N¹-[2-2H3]acetyl-N⁶-benzoyl-2,5-dithio-3,4,7,8-tetramethylglycoluril
  参考文献：
  名称：

  Kinetics of glycoluril template-directed Claisen condensations — Effect of thionation of the glycoluril

  摘要：

  对一系列N¹-乙酰-N⁶-芳酰-2,5-二硫-3,4,7,8-四甲基甘氨酰胺（9a–9f）在叔丁氧化物促进下进行的类克莱森缩合反应的明显速率常数通过紫外光谱法确定。相对于相应的2,5-二酮化合物（7a–7f），发现整体速率加速为3.5至18倍。对9的Hammett图解和与7的比较显示，关键的C—C键形成步骤，即底物的乙酰基的烯醇体攻击芳酰羰基团，受到硫代替换的加速作用。对于芳酰基中的电子吸引取代基，加速足以使这一步骤不再限速：Hammett ρ值从对电子给予基约为1.5降至对电子吸引基约为0.27。在乙酰基中进行氘取代会略微降低速率，这一结果与底物被去质子化的缓慢但部分可逆的第一步一致。当比较二乙酰基甘氨酰胺（2）和二乙酰基二硫基甘氨酰胺（5）时，发现类似的加速和同位素效应。讨论了这些结果的影响。关键词：甘氨酰胺，克莱森缩合，动力学，机理。

  DOI：

  10.1139/v05-119
• 作为产物：
  描述：

  3,4,7,8-tetramethylglycoluril 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以60%的产率得到2,5-dithio-3,4,7,8-tetramethylglycoluril
  参考文献：
  名称：

  A Facile Preparation of Thioglycolurils from Glycolurils, and Regioselectivity in Thioglycoluril Template-Directed Crossed-Claisen Condensations

  摘要：

  Mono- (5) and dithio (4) analogues of 3,4,7,8-tetramethylglycoluril (2) are readily prepared using Lawesson's reagent (1 equiv or excess, respectively). This novel application of Lawesson's reagent to glycolurils can be extended to N-acylglycolurils. Thus the N-acetyl and N-butanoyl derivatives of 2 are converted into the monoacyl-monothio analogues 8 and 9 in which thionation occurs at the least hindered urea carbonyl, Compared to the parent glycoluril 2, the thio analogues are more readily acylated; initial acylation of 5 occurs exclusively on the NH site adjacent to sulfur to give 13, while 4 is converted to either the monoacetyl (11) or diacetyl (12) derivative by acetic anhydride, depending on temperature. Unlike 2, acylation of 4 can be accomplished with tert-butoxide as base and then acyl halide. Further acetylation of 11 gives 12, while 8 gives the unsymmetrical diacetyl-monothioglycoluril 15 or acetyl butanoyl thioglycoluril 17, and 9 gives the isomeric acetyl butanoyl thioglycoluril 16. Derivative 12 undergoes a crossed Claisen-like condensation between the two acetyl groups to give acetoacetyldithioglycoluril (18), in a manner similar to the diacetyl derivative of the parent glycoluril, while 15 undergoes selective crossed-Claisen condensation, predominantly by deprotonation of the acetyl group adjacent to oxygen (2.2:1 ratio of 19:20), In crossed-Claisen condensations, both isomers of acetylbutanoylmonothioglycoluril rearranged to 3-ketohexanoyl and 2-ethyl-3-ketobutanoyl thioglycolurils (16 to 24 and 25; 17 to 26 and 27, respectively), When the selectivities for deprotonation of the acetyl moiety over the butanoyl moiety, and for deprotonation of the acyl group adjacent to oxygen over that adjacent to sulfur, reinforced each other, highly selective crossed-Claisen condensation was achieved (26:27 6:1), In contrast, when these two selectivities worked in opposition, reversal of the regiochemical outcome occurred (24:25 0.75:1), The results show that thionation provides a more sophisticated and selective template for development of intramolecular crossed-Claisen methodology using the glycoluril template-directed approach.

  DOI：

  10.1021/jo9713823

文献信息

• Studies of structure and dynamics in a nominally symmetric twisted amide by NMR and electronic structure calculations
  作者：Alex D Bain、Hao Chen、Paul H.M Harrison

  DOI：10.1139/v06-016

  日期：2006.3.1

  Amides that are twisted around the C—N bond show unusual spectroscopy and reactivity when compared with planar amides. The diacyl derivatives of 3,4,7,8-tetramethyl-2,5-dithioglycoluril are intriguing examples of this class, since the crystal structures show that the two acyl groups are twisted by different amounts on either side of the molecule owing to a combination of steric and electronic effects. However, the ¹H NMR spectra in solution at room temperature exhibit only one acyl resonance, so there must be fast interconversion among pairs of equivalent structures of each compound. We have prepared a number of derivatives with different acyl groups, both on the glycoluril framework as well as on its dithio analogue. The chemical exchange in solution was slowed down sufficiently by cooling to see individual sites for only two compounds: the dithiodipivaloyl and the dithiodiadamantyl derivatives. The barriers were estimated at 41 kJ mol^–1 for the dipivaloyl derivative and 45 kJ mol^–1 for diadamantyl derivative. The results show that rotation around the twisted amide bond is slowed by both the steric size of the acyl group and the presence of the thioureido group vs. the ureido group in the glycoluril core. In the solid-state ¹³C NMR spectra, there is no evidence for any dynamics, even for the diacetyl derivative at ambient temperature. Electronic structure calculations predict a geometry for the dipivaloyl derivative very close to that observed in the crystal structure. These results indicate that the crystal confines, but does not distort the molecule. A mechanism for the exchange is proposed. The relevance of these results to the mechanism of Claisen-like condensations in diacylglycolurils is also discussed.Key words: ¹H and ¹³C NMR, exchange, dynamics, CP/MAS, solids, line shape analysis, amides, twisted amides, atropisomers, glycoluril.

  与平面酰胺相比，围绕 C-N 键扭转的酰胺显示出不同寻常的光谱和反应活性。3,4,7,8-四甲基-2,5-二硫代甘氨酰脲的二酰基衍生物就是这类酰胺的有趣例子，因为晶体结构显示，由于立体效应和电子效应的共同作用，分子两侧的两个酰基发生了不同程度的扭曲。然而，室温下溶液中的 1H NMR 光谱只显示出一种酰基共振，因此每种化合物的对等结构之间一定存在快速的相互转换。我们制备了一些带有不同酰基的衍生物，这些酰基既有在甘氨酰框架上的，也有在其二硫代类似物上的。通过冷却，溶液中的化学交换充分减慢，只有两种化合物可以看到单独的位点：二硫代二特戊酰基和二硫代二金刚烷基衍生物。据估计，二特戊酰衍生物的交换障碍为 41 kJ mol-1，二特二金刚烷基衍生物的交换障碍为 45 kJ mol-1。结果表明，围绕扭曲的酰胺键旋转的速度会因酰基的立体尺寸和羟基脲核心中硫脲基与脲基的存在而减慢。在固态 13C NMR 光谱中，即使是双乙酰衍生物在环境温度下也没有任何动态变化的迹象。电子结构计算预测二戊酰衍生物的几何形状与晶体结构中观察到的非常接近。这些结果表明，晶体限制了分子，但并没有使其变形。提出了一种交换机制。此外，还讨论了这些结果与二酰基甘氨酰脲类克莱森缩合机制的相关性：1H 和 13C NMR、交换、动力学、CP/MAS、固体、线形分析、酰胺、扭曲酰胺、阿托异构体、甘醇二酰胺。
• Biomimetic decarboxylative condensation between malonate and acetate units attached to a glycoluril template
  作者：Hao Chen、Paul H.M. Harrison

  DOI：10.1139/v02-059

  日期：2002.6.1

  Compound 10 (3,4,7,8-tetramethyl-2,5-dithioglycoluril) was converted in two steps to 12a, which contains a malonate and acetate unit attached to N1 and N6, respectively. These two groups are held in proximity in a manner analogous to the loaded ketosynthase domain of polyketide and fatty acid synthases. After cleavage of the methyl ester by pig liver esterase (PLE), a polar intermediate assigned to acid 15 was separated. This material undergoes conversion to acetoacetylglycoluril 18 upon attempted isolation. The overall conversion thus resembles the decarboxylative condensation catalyzed by ketosynthase. Furthermore, isotope labeling and product studies support a mechanism in which decarboxylation of 15 precedes an intramolecular Claisen-like condensation, as it is believed to occur for the ketosynthase enzymic case. The system thus provides a functional chemical model of the key carbon–carbon bond-forming step in fatty acid and polyketide biosynthesis.Key words: biomimetic, decarboxylation, polyketide, esterase, Claisen condensation.

  化合物10（3,4,7,8-四甲基-2,5-二硫代糠脲）经过两步反应转化为12a，其中一个马隆酸基和一个乙酸基分别连接在N1和N6上。这两个基团以类似于多酮和脂肪酸合成酶的负载酮合酶结构域的方式靠近。在猪肝酯酶（PLE）水解甲酯后，分离出一个被指定为酸15的极性中间体。在试图分离时，该物质会转化为乙酰乙酰基糠脲18。因此，总的转化过程类似于由酮合酶催化的脱羧缩合反应。此外，同位素标记和产物研究支持一种机制，即15的脱羧作用先于类似于克莱森缩合的分子内反应，这与酮合酶酶催化的情况类似。因此，该系统为脂肪酸和多酮生物合成中关键的碳-碳键形成步骤提供了一个功能性的化学模型。关键词：仿生、脱羧、多酮、酯酶、克莱森缩合。
• Twisted Amides:  Synthesis and Structure of 1,6-Dipivaloyl-3,4,7,8- tetramethyl-2,5-dithioglycoluril
  作者：Petar A. Duspara、Chérif F. Matta、Stephen I. Jenkins、Paul H. M. Harrison

  DOI：10.1021/ol000349r

  日期：2001.2.1

  [structure: see text] The 1,6-dipivaloyl derivative of 3,4,7,8-tetramethyl-2,5-dithioglycoluril (6) was prepared and the crystal structure determined by X-ray diffraction; 6 is a twisted amide in which severe ring strain and nonbonded interactions compel both pivaloyl groups to twist dramatically out of the ring plane. The amide oxygen atoms point in opposite directions with respect to the mean plane

  [结构：见正文]制备了3,4,7,8-四甲基-2,5-二硫基甘脲（1）的1,6-二戊酰衍生物，并通过X射线衍射确定晶体结构。图6是扭曲的酰胺，其中严重的环应变和未键合的相互作用迫使两个新戊酰基均显着地扭曲离开环平面。酰胺氧原子相对于通过甘脲核的平均平面指向相反的方向，桥头甲基被迫脱离对称的syn几何构型（η= 30.5度）。还通过单晶X射线衍射测定了7的结构，即在6的合成期间产生的重排产物。