ОПТИМИЗАЦИЯ ПРОЦЕССА СИНТЕЗА 6-НИТРО-3,4-ДИГИДРОХИНАЗОЛИН-4-ОНА
Аннотация
Разработана методика синтеза субстанции 6-нитро-3,4-дигидрохиназолин-4-она. Количественное определение целевого продукта проводились спектрофотометрическим методом на приборе СФ-46. В качестве растворителя использован раствор 0,1 моль/л НСl. Измерение оптической плотности стандартного и испытуемого образца проведен при длине волны 254 нм. Изучены условия синтеза 6-нитро-3,4-дигидрохиназолин-4-она. Структура полученного продукта исследована методами ИК, масс-, 1Н, 13С ЯМР спектроскопии, а также установлено строение синтезированного соединения. Выявлены основные факторы, влияющие на процесс получения 6-нитро-3,4-дигидрохиназолин-4-она, проведена оптимизация процесса методом математического планирования эксперимента, составлена математическая модель, рассчитано регрессионное уравнение. Проведено крутое восхождение по поверхности отклика и найдены оптимальные условия процесса: температура, время, количественное соотношение исходных веществ. Установлено, что основным фактором, влияющим на процесс нитрования 3,4-дигидрохиназолин-4-она, является температура 40 ºС и продолжительность реакции 4,5 ч. Отметим, что при более высокой температуре по данным анализа, происходит образование значительного количества динитропроиз-водного в качестве побочного продукта реакции.
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Литература
Ziyadullaev M.E., Saidov S.S., Karimov R.K., Abdurazakov A.Sh. Synthesis of 6-nitroquinazolin-4-one based on anthranilic acid. Proceedings of the international conference «Modern innovation: chemistry and chemical technology of acetylene compounds. Petroleum chemistry. Catalysis» Tashkent. 2018. P. 196.
Kuznetsov D.N., Kobrakov K.I., Ruchkina A.G., Stankevich G.S. Biologically active synthetic organic dyes. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. [Russ. J. Chem. & Chem. Tech.]. 2017. V. 60. N 1. P. 433 (in Russian). DOI: 10.6060/tcct.2017601.5423.
Solodunova E.A., Novikov M.S., Ozerov A.A. Features of the synthesis of 6-bromo-2-methylquinazolin-4 (3H) -one. Volg. Nauch. Med. Zhurn. 2015. N 3. P. 36-38 (in Russian).
Abdurazakov A.Sh., Elmurodov B.J., Dustmukhamedov T.T., Shakhidoyatov Kh.M. The perchlorates of 6-nitro-9-aryliden-deoxyvasicinones potentially active compounds. 7th International Symposium on the Chemistry of Natural Compounds. Tashkent. 2007. P. 174.
Ziyadullaev M.E. 3,4-dihydroquinazolin-4-one production process. The program and theses of the scientific-practical conference of young scientists dedicated to the 110th anniversary of academician S.Yu. Yunusov «Actu-al problems of chemistry of natural compounds» Tashkent. 2019. P. 78.
Nahed F.A. Synthesis and biological evaluation of some nitrogen containing heterocycles. J. Nat. Sci. 2011. 9(7). P. 190-201.
Mohamed S.M., Kamel M.M., Kassem M.M., Emad N.A., Nofal M.S., Ahmed F.M. Novel 6,8-dibromo-4(3H)-quinazolinone derivaties of promising anti-inflammatory and analgesic properties. Acta Pol. Pharm. (Engl. Transl.). 2010. V. 67. N 2. P. 159-171.
Vashi R.T., Patel. S.B. Synthesis, biological evaluation of some nitrogen containing heterocycles. E-J. Chem. 2009. V. 6. P. 445-451. DOI: 10.1155/2009/624150.
Hassanzadeh F., Jafari E., Hakimelahi G.H., Rahmani Khajouei M., Jalai M., Khodarahmi G.A. Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives. Res. Pharm. Sci. 2012. V. 7. N. 2. 87–94.
Xingwen G. Synthesis and antiviral bioactivities of 2-aryl- or 2-methyl -3-(substituted-benzylamino)-4(3H)-quinazolinone derivaties. Molecules. 2007. V. 12. P. 2621-2642.
Arora R., Kapoor A., Gill N.S., Rana A.C. Quinazolinone: an overview. Int. Res. J. Pharm. 2011. V. 2. P. 22-28.
Corbett J.W., Rodgers J.D. Discovery of second-generation quinazolinone non-nucleoside reverse tran-scriptase inhibitors of HIV-1. Prog. Med. Chem. 2002. V. 40. P. 63 -105.
Veerachamy Alagarsamy, Kunchu Kavitha, Mani Rupesh Kumar, Viswas Raja Solomon, Jaya Kumar, Dinakaran Sathesh Kumar, Hemant Kumar Sharma. Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-ones as a new class of H1-antihistaminic agents. Acta Pharm. Int. 2009. V. 59. P. 97–106. DOI: 10.2478/v10007-009-0003-1.
Shveiygeymer G.A. Synthesis of heterocyclic compounds based on is ate anhydrides (2H-3,1-benzoxazine-2,4-dione). Chem. Heterocycle. Comp. 2001. N 4. P. 435-441 (in Russian).
Elmurodov B.J., Bozorov X.A., Abdurazakhov A.SH., Turdibaev J.E., Nasrullayev A.O., Makhmadiyarova Ch.E., Shakhidoyatov Kh.M. Chemical design of quinosaline alkaloids and their analogues. Symposium of the nonprofit partnership of the institutes of the Russian Academy of Sciences “Orchemed”: “Development of medicinal and physiologically active compounds based on natural substances”. Sankt-Petersburg. 2010. P. 346 (in Russian).
Abdurazakhov A.SH., Elmurodov B.J., Dustmukhamedov T.T., Shakhidoyatov Kh.M. The new derivatives of alkaloid deoxyvasicinones potentially antibacterial active compounds. 50 Years of the Phytochemical Society of Europe. Cambridge. 2007. P. 122.
Sahu S.H., Afzal A.M., Banerjee A.S., Acharrya S., Behera S.S. Synthesis, characterization and biological ac-tivity of 2-methyl-3-aminoquinazolin-4(3h)-ones schiff bases. J. Braz. Chem. Soc. 2008. V. 5. P. 963-969.
Shashikant V. Bhandari, Bhavana J. Deshmane, Sudarshan C. Dangare, Suraj T. Gore, Vankekesh T. Raparti, Chetan V. Khachane, Aniket P. Sarkate. Anticovulsant activities of some novel 3-[5-substituted 1,3,4-thiadiazole-yl]-2-styryl quinazoline-4(3h)-ones Pharmacologyonline. 2008. N 2. P. 604-613.
Karimov R.K., Zukhurova G.V., Xvan А.М., Sadikov Т., Abdurazakhov A.Sh. Optimization of the process of obtaining the pharmacopeial substance of azinox. Zhurn. Farm. 2016. N 4. P. 82-85 (in Russian).
Ziyadullaev M.E., Karimov R.K., Saidov S.S., Zukhurova G.V., Abdurazakhov A.Sh. 3,4-Dihydroquinazoline substance obtaining process optimization. Zhurn. Farm. 2018. N 4. P. 64-68 (in Russian).
Saidov S.S., Ziyadullaev M.E., Abdurazakhov A.Sh., Karimov R.K., Saidova G.E., Sagdullaev Sh.Sh. 2-Acetyl-aminobenzimidazole substance obtaining process optimization. Universum J. Tech. Sci. 2019. N 4. P. 56-59. DOI: 10.32743/UniTech.2019.61.4 (in Russian).
Adler Yu.P., Markova E.V., Granovskiy Yu.V. Planning an experiment while searching for optimal conditions. M.: Nauka. 1971. 282 р. (in Russian).
Ziyadullaev M.E., Zakirova R.P., Karimov R.K., Abdurazakhov A.Sh. The biological activity of hydrocarbons in the quinazoline series «Materials of the international conference». Tashkent. 2019. P. 21.
Ismailov V.M., Ibragimova G.G., Sadykhova N.D., Nagiyev F.N., Gasimov R.A., Yusubov N.N. Acylation of the hydroquinone ethers and products of their conversion. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. [Russ. J. Chem. & Chem. Tech.]. 2019. v. 62. N 6. P. 29-35 (in Russian). DOI: 10.6060/ivkkt201962fp.5875.
