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февраль, 2025 г.
ORGANIC CHEMISTRY
OPTIMAL SYNTHESIS OF QUINAZOLIN-4- ONE
Gulbaxar Baymuratova
Independent Researcher at the Tashkent Chemical-Technological Research Institute,
Uzbekistan, Tashkent E-mail: _ [email protected]
ОПТИМАЛЬНЫЙ СИНТЕЗ ХИНАЗОЛИН-4-ОНА
Баймуратова Гулбахар Орынбаевна
исследователь
Ташкентского химико-технологического научно-исследовательского института,
Республика Узбекистан, г. Ташкент
ABSTRACT
The optimal synthesis of quinazolin-4-one is a critical area of research due to its significant biological activity, including antibacterial, antifungal, and anticancer properties. This study focuses on developing an efficient and environmentally friendly method for synthesizing quinazolin-4-one derivatives. The synthesis involves the cyclization of anthranilic acid and formamide in the presence of a Lewis acid catalyst, such as ZnCL, under controlled temperature and solvent conditions. Using DMSO as a solvent and maintaining a reaction temperature of 110°C results in high yields and selectivity. This method offers a greener approach by reducing the need for harsh reagents and minimizing energy consumption. The optimal reaction conditions were determined by evaluating the effects of temperature, catalyst concentration, and solvent choice on the reaction outcome. The developed method provides a promising pathway for the large-scale synthesis of quinazolin-4-one derivatives with potential applications in pharmaceuticals and agrochemicals.
АННОТАЦИЯ
Оптимальный синтез квиназолино-4-она является важной областью исследований из-за его значительной биологической активности, включая антибактериальные, противогрибковые и противораковые свойства. Это исследование направлено на разработку эффективного и экологически чистого метода синтеза производных квина-золино-4-она. Синтез включает циклизацию антраниловой кислоты и формамида в присутствии катализатора Льюиса, такого как ZnCL, при контролируемой температуре и условиях растворителя. Использование DMSO в качестве растворителя и поддержание температуры реакции на уровне 110°C приводит к высоким выходам и селективности. Этот метод предлагает более экологичный подход, уменьшая необходимость в агрессивных реактивах и снижая потребление энергии. Оптимальные условия реакции были определены путем оценки воздействия температуры, концентрации катализатора и выбора растворителя на результат реакции. Разработанный метод предоставляет перспективный путь для массового синтеза производных квиназолино-4-она с возможными применениями в фармацевтике и агрохимии.
Keywords: Quinazolin-4-one, synthesis, cyclization, anthranilic acid, formamide, ZnCL, DMSO, catalyst, high yield, selectivity, environmentally friendly, reaction conditions, pharmaceutical applications, agrochemical applications.
Ключевые слова: Хинозолино-4-он, синтез, циклизация, антраниловая кислота, формамид, ZnCL, DMSO, катализатор, высокий выход, селективность, экологически чистый, условия реакции, фармацевтические применения, агрохимические применения.
Introduction
The many biological and pharmacological characteristics of quinazolin-4-one and its derivatives, including their antibacterial, anticancer, and anti-inflammatory effects, have drawn a lot of attention. One of the most important steps in creating novel medications and useful materials is the synthesis of these substances. Maximiz-
ing yields, guaranteeing selectivity, and reducing environmental impact all depend on achieving ideal reaction conditions [1, p. 788, 2, p. 258, 3.p.5, 4.p. 256, 5. p, 5].
The main goals of this study are to investigate selective methylation processes in various solvents and optimize the synthesis of quinazolin-4-one since it affects the reactivity, selectivity, and stability of intermediates, the solvent plays a crucial role in reaction processes. We hope to learn more about the impact of solvents on chemical transformations and determine
Библиографическое описание: Baymuratova G. OPTIMAL SYNTHESIS OF QUINAZOLIN-4-ONE // Universum: химия и биология : электрон. научн. журн. 2025. 2(128). URL: https://7universum.com/ru/nature/archive/item/19207
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the most effective medium for these reactions by researching different solvents. By investigating environmentally friendly solvents and refining reaction conditions, this work advances sustainable chemistry [6, p. 10, 7, p. 1, 8.p.452, 9.p. 6524, 10. p, 452, 11.p. 6524, 12. p, 65, 13. p, 389].
Methods and results
The scientific community is currently facing a difficult problem in determining the best synthesis techniques for heterocyclic compounds, especially quinazolin-4-one and its homologs. Due to their antibacterial, antifungal, and anthelmintic qualities, quinazolin-4-one derivatives are of great interest to the pharmaceutical industry. Low yields, poor selectivity, and the use of solvents that are harmful to the environment are issues that arise during their synthesis, though.
Finding innovative, effective, and ecologically friendly processes for their synthesis is therefore becoming more and more important. The synthesis process may be enhanced by creating new techniques and refining catalysts, solvents, and reaction conditions. The efficient use of quinazolin-4-one and its homologs in industrial and medicinal applications will be made possible by the development of synthesis techniques.
A 96% yield of quinazolin-4-one was successfully synthesized at 140°C by researchers at The Institute
of the Chemistry of Plant Substances named after acad.S.Yu.Yunusov of the AS RUz. The requirement for high temperatures and the use of an oil bath are disadvantages of this technique, though. This complicates the procedure and raises energy consumption, which might lower overall efficiency and ecological safety.
We propose a cyclization reaction of anthranilic acid and formamide in a Wudda mixture at 110°C, using DMSO as the solvent and ZnCL as the catalyst. This method is designed to ensure high selectivity and efficiency while minimizing energy consumption.
0.01 mol of anthranilic acid, the proper proportions of formamide, and ZnCL catalyst are introduced to a 250 ml three-necked round-bottom flask containing a Wudda mixture that is submerged in an oil bath. The flask has a reflux condenser, thermometer, and magnetic stirrer. 50 mL of DMSO solvent is added. To guarantee good selectivity and yield, the mixture is heated for three hours under reflux while the temperature and time are continuously monitored. The reactions were carried out in the ratios of 1:1, 1:2, 1:3, 1:4, and 1:5.
The reaction with a 1:2 ratio yielded quinazolin-4-one with an 82% yield. The melting point was 218°C, and the Rf value was 0.63.
aCOOH
NH2 +
A-82%
B-74 %
Figure 1. Methods for the synthesis of quinazolin-4-one in different solvents
ZnCl2 was used as a catalyst and DMF as a solvent in the same process. Consequently, a rise in yield, product formation rate, and reaction efficiency was seen. ZnCl2 increased the chemical reactivity, whereas DMF stabilized the reaction medium. Although the synthesis efficiency was much increased under these circumstances, the yield was only 76% when compared to the process mentioned before.
AlCl3 served as a catalyst for the reactions, which were conducted in DMSO solvent. Consequently, a greater product yield and an improvement in reaction efficiency were seen. AlCl3 supplied catalytic activity, and DMSO enhanced the chemical solubility as a solvent. The product yield under these circumstances was
78%, which aided in identifying the ideal synthesis parameters.
Due to its potent Lewis acid characteristics, AlCl3 acted as a catalyst in the reactions, promoting the cyclization process. The reaction proceeded well because the solvent DMF was a great medium for dissolving re-actants and stabilizing intermediates. The quinazolin-4-one synthesis's yield and selectivity were greatly increased by this catalyst and solvent combination, demonstrating how well it promoted the intended chemical changes. The product yield under these circumstances was 74%, which aided in identifying the ideal synthesis parameters.
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Discussion
A high degree of selectivity, which is essential for preventing undesirable side reactions, was attained by the use of ZnCL as a catalyst and DMSO as a solvent. The cyclization reaction was aided by the solvent polarity and aprotic properties as well as the catalytic activity of ZnCL, guaranteeing the quinazoline ring formation under moderate circumstances. Temperature and timing controls were used to monitor the response and guarantee the consistency of the product's quality. The requirement for precise temperature control, since fluctuations may impact the reaction yield and selectivity, is one possible drawback of this approach. Additional reaction condition adjustment, such as modifying the ratio of formamide to anthranilic acid or investigating other catalysts, may result in even greater yields or more ecologically friendly reaction configurations.
Overall, this process provides a dependable and effective way to synthesize quinazolin-4-one, which has a wide range of potential uses in agrochemical and pharmaceutical fields because of its adaptable chemical structure and biological activity.
Conclusion
In this method, quinazolin-4-one synthesis was successfully carried out by reacting anthranilic acid with formamide and ZnCL catalyst in the presence of DMSO solvent. The reaction was conducted in a Wudda mixture setup at 110°C for 2 hours under reflux conditions. The process provided good selectivity and yield, with temperature and time control being essential for optimal results. This method offers an efficient approach for synthesizing quinazolin-4-one, demonstrating the effectiveness of ZnCL as a catalyst and DMSO as a solvent, which contributed to the high selectivity and yield of the desired product.
The 'H NMR spectrum of quinazolin-4-one (Xinazolin-4-one) typically shows the following key features. A doublet or multiplet around 7.5-8.5 ppm, corresponding to the aromatic protons on the benzene ring (C-H). The signals may split depending on the substitution pattern on the aromatic ring. A broad singlet around 8.5-9.5 ppm, corresponding to the proton of the amide (NH) group in quinazolin-4-one. Additional aromatic protons may appear as multiplets within the aromatic region depending on the specific substitution pattern.
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