Yadav Geeta D, Aalam Mohd J, Chaudhary Pooja, Singh Surendra
Department of Chemistry, University of Delhi, Delhi 110007, India.
Curr Org Synth. 2019;16(5):776-786. doi: 10.2174/1570179415666181113154232.
DABCO salts were evaluated as catalysts for the Biginelli reaction between 4- methoxybenzaldehyde, urea and ethyl acetoacetate under solvent-free conditions. 1,4-Diazabicyclo [2.2.2] octane triflate was found to be a simple, inexpensive, highly efficient catalyst for Biginelli reaction for a variety aromatic aldehyde with urea and ethyl acetoacetate at 80°C afforded corresponding 3,4-dihydropyrimidinones in 50-99% yields after 30-120 minutes. 1,3-Cyclohexadione was used in place of ethyl acetoacetate in the absence of urea this methodology is giving hexahydro xanthene derivatives in good to excellent yields after 3-4 hours.
DABCO salt 4 (5 mol%), 4-methoxybenzaldehyde (0.73 mmol) and urea (0.73 mmol) were stirred for 10 minutes at 80°C, then ethyl acetoacetate (1.5 equiv.) was added and reaction mixture was stirred at 80°C for specified time. The resulting solution was stirred continuously and progress of the reaction was followed by TLC. The crude reaction mixture was purified by flash column chromatography on silica gel (hexane/ethyl acetate (1:2)) to give pure desired product.
Reaction conditions of the Biginelli reaction were optimized using 4-methoxybenzaldehyde (0.73 mmol), urea (0.73 mmol), and ethyl acetoacetate (5 equiv.) as model substrates catalyzed by 1,4-Diazabicyclo [2.2.2] octane triflate (5 mol%) in a different solvents, screening of different catalysts and different temperatures. Neat condition was found to be the best for the Biginelli condensation and corresponding 3,4- dihydropyrimidinones was obtained in good to excellent yields. When the reaction was carried out with benzaldehyde derivatives and cyclohexane-1,3-dione in place of ethyl acetoacetate in the absence of urea, solely corresponding hexahydro xanthene derivatives were obtained in 61-91% yields.
In conclusion, we have applied salts of 1,4-Diaza-bicyclo [2.2.2] octane as catalysts in the Biginelli condensation and corresponding 3,4-dihydropyrimidinones were obtained in 50- 99% yields under solvent free conditions. This methodology is having advantages like simple work-up; low loading of catalyst and reaction was performed at moderate temperature under solvent-free conditions.
评估三乙烯二胺盐在无溶剂条件下作为4-甲氧基苯甲醛、尿素和乙酰乙酸乙酯之间Biginelli反应的催化剂。发现1,4-二氮杂双环[2.2.2]辛烷三氟甲磺酸盐是一种简单、廉价、高效的催化剂，用于80℃下多种芳香醛与尿素和乙酰乙酸乙酯的Biginelli反应，30 - 120分钟后可得到产率为50 - 99%的相应3,4-二氢嘧啶酮。在无尿素的情况下，用1,3-环己二酮代替乙酰乙酸乙酯，该方法在3 - 4小时后可得到产率良好至优异的六氢呫吨衍生物。
将三乙烯二胺盐4（5 mol%）、4-甲氧基苯甲醛（0.7 mmol）和尿素（0.7 mmol）在80℃搅拌10分钟，然后加入乙酰乙酸乙酯（1.5当量），反应混合物在80℃搅拌指定时间。所得溶液持续搅拌，通过薄层层析监测反应进程。粗反应混合物通过硅胶快速柱层析（己烷/乙酸乙酯（1:2））纯化，得到纯目标产物。
以4-甲氧基苯甲醛（0.7 mmol）、尿素（0.7 mmol）和乙酰乙酸乙酯（5当量）为模型底物，在不同溶剂中，筛选不同催化剂和不同温度，对1,4-二氮杂双环[2.2.2]辛烷三氟甲磺酸盐（5 mol%）催化的Biginelli反应条件进行了优化。发现无溶剂条件最适合Biginelli缩合反应，可得到产率良好至优异的相应3,4-二氢嘧啶酮。当反应在无尿素的情况下，用苯甲醛衍生物和环己烷-1,3-二酮代替乙酰乙酸乙酯进行时，仅得到产率为及61 - 91%的相应六氢呫吨衍生物。
总之，我们将1,4-二氮杂双环[2.2.2]辛烷盐用作Biginelli缩合反应的催化剂，在无溶剂条件下可得到产率为50 - 99%的相应3,4-二氢嘧啶酮。该方法具有后处理简单、催化剂用量低以及反应在无溶剂条件下于适中温度进行等优点。
