3,4,7,8-tetramethylglycoluril | 146496-85-7

• 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: 3,4,7,8-tetramethylglycoluril
• CAS: 146496-85-7
• 化学式: C₈H₁₄N₄O₂
• 分子量: 198.225
• InChiKey: VAVWMGOZIGAEOE-OCAPTIKFSA-N

物化性质

• 熔点：
  228 °C
• 沸点：
  494.6±45.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.27
• 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：
  64.68
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3,4,7,8-tetramethylglycoluril 在 lithium tert-butoxide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 20.0h， 生成 (3aS,6aR)-3,3a,4,6a-tetramethyl-6-(3-oxobutanoyl)-1H-imidazo[4,5-d]imidazole-2,5-dione
  参考文献：
  名称：

  甘脲†是分子内克莱森型缩合反应的有效分子模板

  摘要：

  易于制备的3,4,7,8-四甲基甘脲1用作模板，以促进连接至N -1和N -6位置的两个酰基之间有效的分子内Claisen样缩合。因此，两个连续的1的酰化反应会以高收率得到对称或不对称的二酰基甘氨酰9-18。用叔醇锂处理9-18可以在温和的条件下以高收率获得N-（β-酮酰基）甘脲19-27。限速去质子化主要发生在两个酰基的最少取代基上，然后发生快速的分子内克莱森型缩合。还原19和26中的酮基，然后消除水，得到烷基-2-烯丙基甘脲6和7；共轭氢化物加成（然后将L- Selectride生成链烷酰基甘脲糖醇5。化合物5-7经过N-酰化反应后再进行分子内缩合。因此，可以通过酰化-缩合-官能团转化的重复序列在1上构建线性链。N 1-烷基-2-烯丙基-N 6-烷酰基甘露糖醇14-17在用L处理后也能提供高选择性的缩合产物-Selectride，实现了在碱基促进的重排中观察到的区域选择性的净逆转的方法

  DOI：

  10.1039/a706855g
• 作为产物：
  描述：

  1-acetyl-3,4,7,8-tetramethylglycoluril 在 sodium tetrahydroborate 、 正丁基锂 、 2-甲基-2-丁醇 、 potassium tert-butylate 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 为溶剂， 反应 9.67h， 生成 3,4,7,8-tetramethylglycoluril
  参考文献：
  名称：

  Synthesis of the fatty acid of pramanicin

  摘要：

  天然产物十四碳烯酸-4,5-环氧化物(2)，也是抗生素普拉曼霉素(1)的组分之一，通过一种以甘氨酰脲为模板的方向性方法制备了其外消旋形式。在模板上，通过分子内缩合反应模拟了到1的生物合成途径，将乙酸基单位顺序加入癸酸分子中。从模板上割离生长的反式、反式-四十二碳二烯酰链并环氧化，得到2。这个反应序列说明了这种仿生方法在天然产物的全合成中的适用性。关键词：普拉曼霉素、仿生、甘氨酰脲、模板。

  DOI：

  10.1139/v97-106

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。
• Repetitive template-directed acyl transfer to mimic steps in the biosynthesis of polyketides and fatty acids
  作者：Sengen Sun、Paul Harrison

  DOI：10.1039/c39940002235

  日期：——

  Efficient condensations between two acyl groups attached to a tetramethylglycoluril template provide a repetitive sequence for efficient construction of fatty acids and polyketide-like natural products in a biomimetic fashion.

  附着在四甲基甘氨酰模板上的两个酰基之间的高效缩合提供了一种重复序列，从而以生物仿生的方式高效地构建脂肪酸和类聚酮天然产物。
• Efficient claisen-type condensation between acyl units bound to a molecular template
  作者：Sengen Sun、Paul Harrison

  DOI：10.1016/0040-4039(93)88025-e

  日期：1992.12

  Acylation of 3,4,7,8-tetramethylglycoluril1 (1) provides the monoacyl derivative 3 which can be acylated further with LDA and acyl chlorides. The resulting symmetric or asymmetric diacyl derivatives 4 undergo efficient base-catalyzed acyl transfer to provide 2-(acylacyl)glycolurils 5,6. Thus, 1 acts as a template to allow facile condensations between acyl units.
• A Facile Preparation of Thioglycolurils from Glycolurils, and Regioselectivity in Thioglycoluril Template-Directed Crossed-Claisen Condensations
  作者：Christopher N. Cow、Paul H. M. Harrison

  DOI：10.1021/jo9713823

  日期：1997.12.1

  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.