Jaśkowska Jolanta, Drabczyk Anna Karolina, Kułaga Damian, Zaręba Przemysław, Majka Zbigniew, Jodłowski Przemysław
Department of Organic Chemistry and Technology, Faculty of Chemical Engineering and Technology, Cracow University of Technology, ul. 24 Warszawska, 31-155 Cracow, Poland.
Department of Chemical Technology and Environmental Analytics, Faculty of Chemical Engineering and Technology, Cracow University of Technology, ul. 24 Warszawska, Cracow, 31-155, Poland.
Heliyon. 2023 Jul 14;9(7):e18319. doi: 10.1016/j.heliyon.2023.e18319. eCollection 2023 Jul.
In this study, we have developed a new ultrasonic synthesis method of dibenzoepines using olanzapine and quetiapine, which are well-known drugs for the treatment of schizophrenia and bipolar disorder. The method is based on the -alkylation reaction of the piperazine fragment in tricyclic compounds with methyl iodide or 2-(2-chloroethoxy)ethanol as the alkylating agent, respectively. The synthesis reactions were carried out in an ultrasonic bath with solvents such as acetonitrile or dimethylformamide in the presence of potassium or sodium carbonate or sodium hydroxide and metal-free, ecological phase transfer catalyst at a temperature of 40-50 °C. This allowed us to obtain olanzapine in 1 h (Y = 67%), and quetiapine in 3 h (Y = 72%). An ultrasonic reactor (Qsonica Q700) was used in the synthesis of olanzapine and made it possible to shorten the reaction time to 10 min and obtain 90% yield with very high purity. The developed method allows obtaining compounds in mild conditions and in a short time, thanks to which the process is more ecological than others described in the literature.
在本研究中，我们开发了一种利用奥氮平和喹硫平合成二苯并氮䓬类化合物的新型超声合成方法，奥氮平和喹硫平是治疗精神分裂症和双相情感障碍的知名药物。该方法分别基于三环化合物中哌嗪片段与甲基碘或2-(2-氯乙氧基)乙醇作为烷基化剂的N-烷基化反应。合成反应在超声浴中进行，以乙腈或二甲基甲酰胺等为溶剂，在碳酸钾或碳酸钠或氢氧化钠以及无金属的生态相转移催化剂存在下，于40-50℃的温度下进行。这使我们能够在1小时内获得奥氮平（产率Y = 67%），在3小时内获得喹硫平（产率Y = 72%）。在奥氮平的合成中使用了超声反应器（Qsonica Q700），可将反应时间缩短至10分钟，并获得90%的产率且纯度非常高。所开发的方法能够在温和条件下短时间内获得化合物，因此该过程比文献中描述的其他方法更环保。
