1-acetyl-3,4,7,8-tetramethylglycoluril | 146496-86-8

• 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: 1-acetyl-3,4,7,8-tetramethylglycoluril
• 英文别名: (3aS,6aR)-6-acetyl-3,3a,4,6a-tetramethyl-1H-imidazo[4,5-d]imidazole-2,5-dione
• CAS: 146496-86-8
• 化学式: C₁₀H₁₆N₄O₃
• 分子量: 240.262
• InChiKey: JEHDRVIBBYRDFH-ZJUUUORDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  73
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-acetyl-3,4,7,8-tetramethylglycoluril 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以47%的产率得到(3aR,6aR)-6-acetyl-3,3a,4,6a-tetramethyl-2-sulfanylidene-1H-imidazo[4,5-d]imidazol-5-one
  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：

  3,4,7,8-tetramethylglycoluril 、 乙酰氯 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 以89%的产率得到1-acetyl-3,4,7,8-tetramethylglycoluril
  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

文献信息

• Kinetics of glycoluril template-directed Claisen condensations and mechanistic implications
  作者：Mohammad Rahimizadeh、Karen Kam、Stephen I Jenkins、Robert S McDonald、Paul HM Harrison

  DOI：10.1139/v02-071

  日期：2002.5.1

  Eight N-acetyl-N-aroyl-glycolurils were prepared and found to undergo efficient tert-butoxide-promoted Claisen-like condensation between the two acyl moieties. The kinetics for formation of each of the N-(aroylacetyl)gly coluril products were monitored by UV spectroscopy. The reaction exhibited pseudo-first-order kinetics in substrate in the presence of excess base. For the parent benzoyl compound the observed first-order rate constant (k_obs) was linearly dependent on the concentration of the base, tert-butoxide. A Hammett plot of the resulting apparent second-order rate constants (k_app) vs. σ for each of the eight aroyl derivatives was linear and had a positive ρ value 1.04 ± 0.04), demonstrating that the substituent on the aromatic ring exerts a significant effect upon the condensation reaction. The corresponding plot for three [D₃]acetyl analogues was also linear, but the slope was reduced by 20% relative to the protonated compounds. The isotope effect (k^H_app/k^D_app) thus increased from 1.4 (benzoyl) to 2.6 (p-nitrobenzoyl). The results are consistent with a three-step mechanism in which both deprotonation of the acetyl entity and the ensuing nucleophilic attack of the resulting enolate on the benzoyl group are partially rate-determining steps. The tetrahedral intermediate thus produced rapidly collapses to the product. For the [D₃]acetyl benzoyl derivative, exchange of substrate deuterium with solvent hydrogen due to reprotonation of the enolate intermediate occurs at a rate that is similar to that of condensation, but the enolate partitions towards the product when electron withdrawing groups are present in the aroyl ring. Thus, despite the presence of a large excess of co-solvent tert-butanol, the efficiency with which the enolate undergoes condensation remains high. The clean kinetics observed allows further exploration of the details of this intramolecular Claisen-like condensation process.Key words: Claisen condensation, glycoluril, kinetics, Hammett, mechanism.

  制备了八种N-乙酰-N-芳酰基-甘氨酰脲，并发现它们在叔丁醇盐促进下，在两个酰基之间进行高效的克莱森样缩合反应。通过紫外光谱监测了每种N-(芳酰乙酰)甘氨酰脲产物形成的动力学。在过量碱存在的情况下，反应在底物中表现出伪一阶动力学。对于母体苯甲酰化合物，观察到的一阶速率常数(k_obs)与碱叔丁醇的浓度呈线性关系。得到的八种芳酰衍生物的表观二阶速率常数(k_app)与σ的汉密特图呈线性关系，并具有正的ρ值1.04 ± 0.04，表明芳香环上的取代基对缩合反应产生显著影响。三种[D₃]乙酰类似物的对应图也是线性的，但与质子化合物相比，斜率降低了20%。因此，同位素效应(k^H_app/k^D_app)从1.4（苯甲酰）增加到2.6（对硝基苯甲酰）。结果与一个三步机制一致，其中乙酰实体的去质子化和随后产生的烯醇负离子对苯甲酰基的亲核攻击是部分决速步骤。因此产生的四面体中间体迅速崩解为产物。对于[D₃]乙酰苯甲酰衍生物，由于烯醇中间体的重质子化，底物氘与溶剂氢的交换速率与缩合的速率相似，但当芳酰环中存在电子吸引基时，烯醇负离子倾向于朝向产物。因此，尽管存在大量的共溶剂叔丁醇，烯醇负离子进行缩合的效率仍然很高。观察到的干净动力学允许进一步探索这种分子内克莱森样缩合过程的细节。关键词：克莱森缩合、甘氨酰脲、动力学、汉密特、机制。
• Synthesis of the fatty acid of pramanicin
  作者：Christopher Cow、David Valentini、Paul Harrison

  DOI：10.1139/v97-106

  日期：1997.6.1

  The natural product tetradec-2-enoic acid-4,5-epoxide (2), which is also a component of the antibiotic pramanicin (1), was prepared in racemic form by a glycoluril-template directed approach. Two sequential additions of acetate units to decanoic acid are effected by intramolecular condensations on the template, mimicking the proposed biosynthetic pathway to 1. Cleavage of the grown trans,trans-tetradeca-2,4-dienoyl chain from the template and epoxidation yields 2. The reaction sequence illustrates the applicability of this biomimetic approach to total synthesis of natural products. Keywords: pramanicin, biomimetic, glycoluril, template.

  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。
• Regioselectivity of glycoluril-directed Claisen condensations — A kinetic and mechanistic study of substituent effects in the nucleophilic acyl group
  作者：Mei Chen、Katie Won、Robert S McDonald、Paul H.M Harrison

  DOI：10.1139/v06-147

  日期：2006.9.1

  The Claisen-like condensation of a series of 1-arylacetyl-6-acetyl-3,4,7,8-tetramethylglycolurils (Ar = Ph, p-OMeC₆H₄, and p-ClC₆H₄) was studied in preparative experiments and by analysis of kinetic data. The reactions proceeded in virtually quantitative yield and were highly regioselective: the corresponding N-(2′-aryl-3′-ketobutanoyl)-3,4,7,8-tetramethylglycolurils were obtained in all cases, with none of the 4′-aryl regioisomers being detected. Clean bimolecular kinetics were observed for each conversion using UV spectroscopy. Reaction rates followed the order Ar = p-OMeC₆H₄ < Ph < p-ClC₆H₄. The results are explained by a mechanism in which the deprotonation of the substrates is rate-limiting; thus, deprotonation of the arylacetyl groups is favoured. The ensuing enolate reacts rapidly in the C–C bond-forming step.Key words: glycoluril, biomimetic, Claisen condensation, regioselectivity, kinetics, mechanism, substituent effects.

  通过制备实验和动力学数据分析，研究了一系列 1-芳基乙酰基-6-乙酰基-3,4,7,8-四甲基甘氨酰脲（Ar = Ph、p-OMeC6H4 和 p-ClC6H4）的类似克莱森缩合反应。反应以几乎定量的产率进行，并且具有高度的区域选择性：在所有情况下都能得到相应的 N-（2′-芳基-3′-酮丁酰基）-3,4,7,8-四甲基甘氨酰脲，没有检测到任何 4′-芳基区域异构体。利用紫外光谱法观察到了每种转化物的清洁双分子动力学。反应速率遵循 Ar = p-OMeC6H4 < Ph < p-ClC6H4 的顺序。这些结果可以用一种机制来解释，在这种机制中，底物的去质子化是限速的；因此，芳基乙酰基的去质子化是有利的。随后的烯醇在 C-C 键形成步骤中迅速发生反应。关键词：甘醇醚、仿生、克莱森缩合、区域选择性、动力学、机理、取代基效应。
• 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.