ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate | 54449-02-4

• 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: ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
• 英文别名: 4-chloromethyl-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidin-2(1H)-one；4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester；Ethyl 4-(chloromethyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；ethyl 4-(chloromethyl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 54449-02-4
• 化学式: C₉H₁₃ClN₂O₃
• mdl: MFCD18785484
• 分子量: 232.667
• InChiKey: LNXYTDACAVHJLJ-UHFFFAOYSA-N

物化性质

• 熔点：
  175-176 °C(Solv: ethanol (64-17-5))
• 沸点：
  334.1±42.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 sodium hydride 作用下， 以 乙腈 为溶剂， 反应 7.5h， 以78%的产率得到(+/-)-diethyl 9-methyl-5-methylene-3,11-dioxo-2,3,4,5,6a,7,10,11-octahydro-1,6-methanol[1,3]diazepino[1,7-e][1,3,5]triazocine-6,8(1H)-dicarboxylate
  参考文献：
  名称：

  嘧啶酮衍生物的空前碱基促进的级联转化为新型三环双二氮杂酮

  摘要：

  在强碱（NaH，DBU，KOH）的存在下，将4-氯甲基-6-甲基-2-氧-2-1,2,3,4-四氢嘧啶-5-羧酸乙酯4转化为新型三环化合物，二乙基9-甲基-5-亚甲基-3,11-二氧代-2,3,4,5,6a，7,10,11-八氢-1,6-甲基[1,3]二氮杂[1,7- e ] [1,3,5] triazocine-6,8（1 H）-dicarboxylate ，5，是级联反应的结果。

  DOI：

  10.1016/j.tetlet.2008.04.136
• 作为产物：
  描述：

  3-ureido-crotonic acid ethyl ester 、 1,2-二氯乙氧基乙烷 以65%的产率得到
  参考文献：
  名称：

  BULLOCK E.; CARTER R. A.; COCHRANE R. M.; GREGORY B.; SHIELDS D. C., CAN. J. CHEM. , 1977, 55, NO 5, 895-905

  摘要：

  DOI：

文献信息

• Preparation of 7-Alkyl-2,3,6,7-tetrahydro-4-alkyl-2-oxo- 1<i>H</i>-1,3-diazepine-5-carboxylates by Ring Expansion-Nucleophilic Addition
  作者：David A. Claremon、Seth A. Rosenthal

  DOI：10.1055/s-1986-31740

  日期：——

  The preparation of ethyl 7-alkyl-2,3,6,7-tetrahydro-4-alkyl-2-oxo-1H-1,3-diazepine-5-carboxylates 2 by a one pot ring expansion-nucleophilic addition of ethyl 4-chloromethyl-1,2,3,4-tetraydro-6-alkyl-2-oxopyrimidine-5-carboxylates 1 is described.

  本发明描述了通过 4-氯甲基-1,2,3,4-四氢-6-烷基-2-氧代-1H-1,3-二氮杂卓-5-羧酸乙酯 1 的一锅扩环-亲核加成制备 7-烷基-2,3,6,7-四氢-4-烷基-2-氧代-1H-1,3-二氮杂卓-5-羧酸乙酯 2 的过程。
• Some ring expansion–ring contraction reactions of ethyl 4-chloromethyl-1,2,3,4-tetrahydro-6-methyl-2-oxopyrimidine-5-carboxylate
  作者：John Ashby、D. Griffiths

  DOI：10.1039/c39740000607

  日期：——

  Reaction of the title chloromethylpyrimidine with potassium hydrosulphide yields a sulphur-bridged 1,3-diazepin-2-one; in contrast, reaction with various amines give rise to α-aminopyrrolines and controlled reaction with hydroxide an α-hydroxypyrroline.

  标题氯甲基嘧啶与氢硫化钾反应，得到硫桥连的1，3-二氮杂-2--2-酮。相反，与各种胺的反应产生α-氨基吡咯啉，与氢氧化物的受控反应为α-羟基吡咯啉。
• Nucleophile-Mediated Ring Expansion of 5-Acyl-substituted 4-Mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones in the Synthesis of 7-Membered Analogues of Biginelli Compounds and Related Heterocycles
  作者：Anastasia A. Fesenko、Mikhail S. Grigoriev、Anatoly D. Shutalev

  DOI：10.1021/acs.joc.7b01348

  日期：2017.8.4

  state and solutions were established using X-ray diffraction and NMR spectroscopy. A plausible mechanism of tetrahydropyrimidine ring expansion based on DFT calculation at B3LYP/6-31+G(d,p) level and NMR monitoring experiments was discussed. The ring contraction reaction of methoxy- or phenylthio-diazepinones under acidic conditions resulted in the corresponding 3-functionalized 1-carbamoyl-1H-pyrroles

  烷基2-氧代-2,3,6,7-四氢-1 H -1,3-二氮杂-5-羧酸盐和5-酰基-2,3,6,7-四氢-1的一般六步方法基于5-官能化的4-甲磺酰氧基甲基-1,2,3,4-四氢嘧啶-2-酮的亲核试剂介导的扩环反应，已经开发了H -1,3-二氮杂-2-酮。后者的合成涉及容易获得的N -[（2-苯甲酰氧基-1-甲苯基）乙基]脲中的甲苯磺酰基被β-氧酸酯或1,3-二酮的烯醇钠亲核取代，然后将其脱水或杂环化脱水得到的产物，除去苯甲酰基保护，并将羟甲基转化为甲磺酰氧基甲基。所得四氢-1 H的构型使用X射线衍射和NMR光谱确定了固态和溶液形式的-1,3-二氮杂-2-酮。讨论了基于D3在B3LYP / 6-31 + G（d，p）水平上的DFT计算和NMR监测实验得出的四氢嘧啶环扩环的合理机理。甲氧基或苯硫基二氮杂庚酮在酸性条件下的环收缩反应产生相应的3-官能化的1-氨基甲酰基-1 H-吡咯。
• Synthesis and Acylation of 4-Chloroalkyl-3,4-dihydropyrimidin-2(1H)- ones
  作者：Maksim A. Kolosov、Olesia G. Kulyk、Muataz Al-Ogaili、Valeriy D. Orlov

  DOI：10.5560/znb.2012-0182

  日期：2012.9.1

  4-Chloroalkyl-3,4-dihydropyrimidin-2(1H)-ones are useful multifunctional 3,4-dihydropyrimidine building blocks with low molecular weight and sufficient solubility, which may be modified selectively by substituents in different positions. Here we propose a simple one-pot protocol for the synthesis of these compounds, which is based on the use of common reagents viz. urea, chloroaliphatic aldehydes and 3-ketoesters. Acylation of 4-chloroalkyl-3,4-dihydropyrimidin-2(1H)-ones by carboxylic acid anhydrides leads to 3-acyl derivatives

  4-氯烷基-3,4-二氢嘧啶-2(1H)-酮是有用的多功能 3,4-二氢嘧啶结构单元，分子量低，溶解性好，可通过不同位置的取代基进行选择性修饰。在此，我们提出了一种简单的单锅合成这些化合物的方案，该方案基于常用试剂的使用，即尿素、氯脂醛和 3-酮酯。羧酸酐对 4-氯烷基-3,4-二氢嘧啶-2(1H)-酮的酰化作用可产生 3-酰基衍生物
• The dramatic effect of thiophenol on the reaction pathway of ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with thiophenolates: ring expansion versus nucleophilic substitution
  作者：Anastasia A. Fesenko、Ludmila A. Trafimova、Dmitry A. Cheshkov、Anatoly D. Shutalev

  DOI：10.1016/j.tetlet.2010.07.098

  日期：2010.9

  result of ring expansion and/or nucleophilic substitution. The reaction pathway was affected strongly by the basicity–nucleophilicity of the reaction media. The results obtained were confirmed by reactions of 4-mesyloxymethyl-6-methyl-5-tosyltetrahydropyrimidin-2-one with PhSNa/PhSH and ethyl 4-chloromethyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate with NaCN/HCN or NaCH(COOEt)2/CH2(COOEt)2

  4-甲基-2-氧代-7-苯硫基-2,3,6,7-四氢-1 H -1,3-二氮杂-5-羧酸酯和/或6-甲基-2-氧代-4-（在4-氯甲基-6-甲基-2-氧-2-，1,2,3,4-四氢嘧啶-5-羧酸乙酯与PhSNa的反应中获得苯硫基甲基）-1,1,2,3,4-四氢嘧啶-5-羧酸酯环的扩展和/或亲核取代的结果，取决于试剂比率，反应时间或温度，有无PhSH的PhSK或PhSK。反应途径受到反应介质的碱性-亲核性的强烈影响。通过4-甲氧基氧甲基-6-甲基-5-甲苯磺酰基四氢嘧啶-2-酮与PhSNa / PhSH和乙基4-氯甲基-6-甲基-2-氧代-1,2,3,4-四氢嘧啶的反应证实了所获得的结果用NaCN / HCN或NaCH（COOEt）2 -5-羧酸盐/ CH 2（COOEt）2。