6-amino-4-benzyl-5-cyano-1-o-tolyl-2(1H)-pyrimidinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-amino-4-benzyl-5-cyano-1-o-tolyl-2(1H)-pyrimidinone
• 英文别名: 6-Amino-4-benzyl-1-(2-methylphenyl)-2-oxopyrimidine-5-carbonitrile；6-amino-4-benzyl-1-(2-methylphenyl)-2-oxopyrimidine-5-carbonitrile
• 化学式: C₁₉H₁₆N₄O
• 分子量: 316.362
• InChiKey: RPUNTZCZQGNBNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl (1,1-dicyano-3-phenylprop-1-en-2-yl)carbamate 、 邻甲苯胺 以 氯苯 为溶剂， 以92%的产率得到6-amino-4-benzyl-5-cyano-1-o-tolyl-2(1H)-pyrimidinone
  参考文献：
  名称：

  Atropisomerization in N-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

  摘要：

  Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)-pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 5a-5f and two 6-amino-5-cyano-4-p-tolyl-1-substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-o-tolyl-4-p-tolyl-2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)-pyrimidinone (5e) were found to be 120.4 and 125.1 kJ.mol(-1) (n-BuOH, 117 degrees C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ.mol(-1) (EtOH, 78 degrees C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in N-aryl-2(1H)-pyrimidinethiones.

  DOI：

  10.1021/jo402149f

文献信息

• Atropisomerization in <i>N</i>-aryl-2(1<i>H</i>)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond
  作者：Ennaji Najahi、Nicolas Vanthuyne、Françoise Nepveu、Marion Jean、Ibon Alkorta、José Elguero、Christian Roussel

  DOI：10.1021/jo402149f

  日期：2013.12.20

  Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)-pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 5a-5f and two 6-amino-5-cyano-4-p-tolyl-1-substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-o-tolyl-4-p-tolyl-2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)-pyrimidinone (5e) were found to be 120.4 and 125.1 kJ.mol(-1) (n-BuOH, 117 degrees C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ.mol(-1) (EtOH, 78 degrees C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in N-aryl-2(1H)-pyrimidinethiones.