1-(6-Acetyl-3,3a,4,6a-tetramethyl-2,5-dithioxo-hexahydro-imidazo[4,5-d]imidazol-1-yl)-ethanone | 198063-34-2

• 分子结构分类: 有机化合物
• 英文名称: 1-(6-Acetyl-3,3a,4,6a-tetramethyl-2,5-dithioxo-hexahydro-imidazo[4,5-d]imidazol-1-yl)-ethanone
• CAS: 198063-34-2
• 化学式: C₁₂H₁₈N₄O₂S₂
• 分子量: 314.433
• InChiKey: FVHOQFRYJWRIAD-TXEJJXNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.58
• 重原子数：
  20.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  47.1
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1-(6-Acetyl-3,3a,4,6a-tetramethyl-2,5-dithioxo-hexahydro-imidazo[4,5-d]imidazol-1-yl)-ethanone 在 lithium tert-amoxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以62%的产率得到1-((3aS,6aR)-3,3a,4,6a-Tetramethyl-2,5-dithioxo-hexahydro-imidazo[4,5-d]imidazol-1-yl)-butane-1,3-dione
  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
• 作为产物：
  描述：

  2,5-dithio-3,4,7,8-tetramethylglycoluril 在 正丁基锂 、 potassium tert-butylate 作用下， 反应 4.67h， 生成 1-(6-Acetyl-3,3a,4,6a-tetramethyl-2,5-dithioxo-hexahydro-imidazo[4,5-d]imidazol-1-yl)-ethanone
  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

• Kinetics of glycoluril template-directed Claisen condensations — Effect of thionation of the glycoluril
  作者：Karen Kam、Mohammad Rahimizadeh、Robert S McDonald、Paul HM Harrison、Hao Chen、Stephen I Jenkins、Adrienne Pedrech

  DOI：10.1139/v05-119

  日期：2005.9.1

  Apparent rate constants for the tert-butoxide promoted Claisen-like condensation of a series of N¹-acetyl-N⁶-aroyl-2,5-dithio-3,4,7,8-tetramethylglycolurils (9a–9f) to give N¹-(3′-aroyl-3′-oxopropionyl)-2,5-dithio-3,4,7,8-tetramethylglycolurils (10a–10f) were determined by UV spectroscopy. Overall rate accelerations of 3.5- to 18-fold were found relative to the corresponding reactions of the 2,5-dioxo compounds (7a–7f). Analysis of the Hammett plot for 9 and comparison with that for 7 shows that the key C—C bond-forming step, where the enolate of the acetyl group of the substrate attacks the aroyl carbonyl group, is accelerated by the thio substitution. For electron-withdrawing substituents in the aroyl group, the acceleration is sufficient to make this step nonrate limiting: the Hammett ρ value drops from approx. 1.5 for electron-donating groups to 0.27 for electron-withdrawing groups. Deuterium substitution in the acetyl group reduces the rate slightly, a result consistent with a slow but partially reversible first step in which substrate is deprotonated. A similar acceleration and isotope effect are found when diacetyl glycoluril (2) and diacetyl dithio glycoluril (5) are compared. The implications of these results are discussed.Key words: glycoluril, Claisen condensation, kinetics, mechanism.

  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。