Title Sinteza derivata kinazolinona u niskotemperaturnim eutektičkim otapalima primjenom odabranih metoda zelene kemije Title (english) Synthesis of quinazolinone derivatives in deep eutectic solvents using selected green chemistry methods Author Mario Komar Mentor Maja Molnar (mentor)Mentor Tatjana Gazivoda Kraljević (mentor)Committee member Silvana Raić-Malić (predsjednik povjerenstva)Committee member Marijana Hranjec (član povjerenstva)Committee member Vesna Rastija (član povjerenstva)Granter University of Zagreb Defense date and country 2022-11-04, Croatia Scientific / art field, NATURAL SCIENCES Universal decimal classificationUDC ) 54 - Chemistry. Crystallography. Mineralogy Abstract U okviru doktorskog rada sintezirani su 2,3-disupstituirani (1 – 130) i 3-supstituirani derivati kinazolin-4(3H)-ona (131 – 136) u niskotemperaturnim eutektičkim otapalima s ciljem njihove primjene u sintezi heterocikala. Sinteze derivata kinazolin-4(3H)-ona provedene su konvencionalno, potpomognute mikrovalovima i ultrazvukom te mehanokemijskim reakcijama. Niskotemperaturna eutektička otapala za sintezu novih spojeva priređena su miješanjem kolin-klorida (ChCl) i različitih amida, karboksilnih kiselina, ugljikohidrata i alkohola u određenom molarnom omjeru. Optimiranje reakcijskih uvjeta za svaku klasu spojeva provedeno je na odabranoj modelnoj reakciji izborom najpovoljnijeg niskotemperaturnog eutektičkog otapala, volumena otapala, temperature i vremena trajanja reakcije. Pri optimiranju mehanokemijske sinteze ispitan je dodatno i utjecaj količine kuglica. Derivati 2-merkapto-3-supstituiranih kinazolin-4(3H)-ona (1 – 50) sintetizirani su u otapalu ChCl : urea reakcijom antranilne kiseline i alifatskih te aromatskih izotiocijanata konvencionalno s iskorištenjima 19 – 76 %, sintezom potpomognutom mikrovalovima u iskorištenjima 10 – 49 %, sintezom potpomognutom ultrazvukom u iskorištenjima 17 – 64 % i mehanokemijskom sintezom s iskorištenjima 48 – 88 %. 2-metil-3-supstituirani kinazolin-4(3H)-oni (51 – 87) sintetizirani su reakcijom 2-metilbenzoksazin-4-ona i aromatskih amina te hidrazida kumarina i piridin-2,6-dikarbohidrazida u otapalu ChCl : urea konvencionalno s iskorištenjima 17 – 77 %, sintezom potpomognutom mikrovalovima (10 – 41 %), sintezom potpomognutom ultrazvukom (15 – 56 %) i mehanokemijskom sintezom (45 – 87 %). Schiffove baze kinazolin-4(3H)-ona (88 – 130) sintetizirane su u otapalu ChCl : malonska kiselina reakcijom 3-amino-2-metilkinazolin-4(3H)-ona i aromatskih aldehida konvencionalno u iskorištenjima 63 – 97 %, sintezom potpomognutom mikrovalovima (39 – 68 %), sintezom potpomognutom ultrazvukom (40 – 80 %) te mehanokemijskom sintezom u visokim iskorištenjima 79 – 97 %. Trokomponentnim reakcijama antranilnih kiselina, trimetilortoformijata i aromatskih amina u otapalu ChCl : urea detektirani su 3-supstituirani derivati kinazolin-4(3H)-ona (130 – 136) u tragovima. Najbolja iskorištenja reakcija u sintezi 2,3-disupstituiranih derivata kinazolin-4(3H)-ona (1 – 130) dobivena su mehanokemijskom sintezom koju karakteriziraju najkraće vrijeme reakcije i čistoća izoliranih produkata. Zatim slijedi konvencionalna sinteza, sinteza potpomognuta ultrazvukom i s najmanjim iskorištenjem sinteza potpomognuta mikrovalovima. Korištenjem niskotemperaturnih eutektičkih otapala u sintezi smanjen je štetan utjecaj na okoliš organskih otapala i katalizatora, skraćeno je vrijeme trajanja reakcija, jednostavna je izolacija i pročišćavanje produkata te omogućeno recikliranje otapala. Strukture svih sintetiziranih spojeva potvrđene su 1H- i 13C-NMR spektroskopijom te masenom spektrometrijom.
Abstract (english) In the doctoral thesis 2,3-disubstituted (1 – 130) and 3-substituted quinazolin-4(3H)-one derivatives (130 – 136) are synthesized in deep eutectic solvents to investigate their application in the synthesis of heterocycles. Syntheses of quinazolin-4(3H)-one derivatives were performed conventionally, by microwave-assisted and ultrasound-assisted synthesis and mechanochemical reactions as well. Deep eutectic solvents for the synthesis of new compounds were prepared by mixing of choline chloride (ChCl) with various amides, carboxylic acids, carbohydrates and alcohols in a specific molar ratio. The optimization of the reaction conditions for each class of compounds was carried out on the selected model reaction by choosing the most favourable deep eutectic solvents, volume, temperature and reaction time. The influence of the amount of balls in mechanochemical synthesis was also optimized. 2-mercapto-3-substituted quinazolin-4(3H)-one derivatives (1 – 50) were synthesized in ChCl: urea deep eutectic solvent by reaction of anthranilic acids and aliphatic and aromatic isothiocyanates conventionally with yields 19 – 76%, by microwave-assisted synthesis (10 – 49%), by ultrasound-assisted synthesis (17 – 64%) and by mechanochemical synthesis (48 – 88%). 2-methyl-3-substituted quinazolin-4(3H)-one derivatives (51 – 87) were synthesized by the reaction of 2-methylbenzoxazin-4-one and aromatic amines and coumarinyl hydrazides and pyridine-2,6-dicarbohydrazide in ChCl: urea conventionally with yields 17 – 77%, by microwave-assisted synthesis (10 – 47%), by ultrasound-assisted synthesis (15 – 56%) and by mechanochemical synthesis (45 – 87%). Quinazolin-4(3H)-one Schiff bases (88 – 130) were synthesized in ChCl: malonic acid from 3-amino-2-methylquinazolin-4(3H)-ones and aromatic aldehydes conventionally with yields 63 – 97%, by microwave-assisted synthesis (39 – 68%), by ultrasound-assisted synthesis (40 – 80%) and by mechanochemical synthesis with high yields 79 – 97%. 3-substituted quinazolin-4(3H)-one derivatives (130 – 136) were detected in traces obtained by a three-component reaction of anthranilic acids, trimethyl orthoformate and aromatic amines. The best yields of the reactions in the synthesis of 2,3-disubstituted quinazolin-4(3H)-one derivatives (1 – 130) were obtained by mechanochemical synthesis, which is characterized by the shortest reaction time and the purity of the isolated products. Lower yields were obtained with conventional synthesis, ultrasound-assisted synthesis, and the lowest yields were achieved by microwave-assisted synthesis. With the use of deep eutectic solvents in the synthesis, the harmful impact of organic solvents and catalysts on the environment is reduced, the reaction time is shorter, the isolation and purification of products are simple, and the recycling of solvents is enabled. The structures of all synthesized compounds were confirmed by 1H- and 13C-NMR spectroscopy and mass spectrometry.
Keywords
niskotemperaturna eutektička otapala
kinazolin-4(3H)-oni
sinteza potpomognuta mikrovalovima
sinteza potpomognuta ultrazvukom
mehanosinteza
Keywords (english)
deep eutectic solvents
quinazolin-4(3H)-ones
microwave-assisted synthesis
ultrasound-assisted synthesis
mechanosynthesis
Language croatian URN:NBN urn:nbn:hr:149:255868 Promotion 2022 Project Number: UIP-2017-05-6593 Study programme Title: Chemical Engineering and Applied Chemistry - Doctoral course Type of resource Text Extent 165 str. ; 30 cm File origin Born digital Access conditions Open access Terms of use Created on 2022-11-16 12:08:14
