Sinteza i spektroskopska karakterizacija novih konjugata benzimidazola i benzotiazola kao biološki aktivnih agensa

master's thesis

• Title (english): Synthesis and spectroscopic characterization of novel benzimidazole and benzothiazole conjugates as biologically active agents
• Author: Lucija Žonja
• Mentor: Marijana Hranjec (mentor)
• Mentor: Kristina Starčević (komentor)
• Committee member: Marijana Hranjec (predsjednik povjerenstva)
• Committee member: Dragana Vuk (član povjerenstva)
• Committee member: Kristina Starčević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-22, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovog rada provedena je sinteza i spektroskopska karakterizacija novih amidino supstituiranih 1,2-fenilendiamina 8-9 i kloridnih soli benzimidazola 15-28 i benzotiazola 32- 36. Ciljani spojevi priređeni su klasičnim reakcijama organske sinteze te mikrovalovima potpomognutom sintezom. Glavni prekursori za sintezu amidino supstituiranih derivata benzimidazola 15-28, amidino supstituirani 1,2-fenilendiamini 8-9, priređeni su Pinnerovom reakcijom u kiselom mediju iz 4-amino-3-nitrobenzonitrila 4 i katalitičkom hidrogenacijom potpomogutom mikrovalovima uz 10%-tni Pd/C. Ciljani spojevi 15-26 sintetizirani su kondenzacijom priređenih prekursora 8-9 s odgovarajućim aldehidima 10-13 u apsolutnom etanolu uz korištenje p-benzokinona kao oksidansa. Također, ispitana je sintetska metoda priprave amidino supstituiranih kloridnih soli benzimidazola 27 i 28, pomoću otopina odgovarajućih aldehida 10-11 i amidina 9 u DMSO-u uz Na2S2O5, koja nije dala željene produkte. Pomoću dviju sintetskih metoda ispitana je mogućnost priprave amidino supstituiranih kloridnih soli benzotiazola 32-36. Prema metodi A, u otopinu odgovarajućeg zwitter iona 29-31 u ledenoj octenoj kiselini dodan je odgovarajući aldehid 10-11 i reakcijska se smjesa miješala pod dušikom, a nastala slobodna baza suspendirana je u etanolu i ekvimolarnoj količini 36%-tne HCl. Prema metodi B, u otopinu odgovarajućeg zwitter iona 30 u glicerolu dodan je odgovarajući aldehid 11 i ekvimolarna količina 36%-tne HCl. Navedenim sintetskim metoda nisu izolirani željeni produkti. Strukture priređenih produkata potvrđene su 1H i 13C NMR spektroskopijom. Tijek Pinnerove reakcije praćen je IR spektroskopijom. Kako bi se ispitala mogućnost primjene spojeva kao bioloških aktivnih agensa, ispitana im je antioksidativna aktivnost korištenjem DPPH, FRAP i ABTS metode. N,N-dietilamino supstituirani derivati s oba ciklička amidinska supstituenta 24 i 25 pokazuju bolju antioksidativnu aktivnost u usporedbi sa standardom BHT prema ABTS metodi.

Abstract (english)

This work presents the synthesis and spectroscopic characterization of novel amidino substituted 1,2-phenylenediamines 8-9 and hydrochloride salts of benzimidazoles 15-28 and benzothiazoles 32-36. Target compounds were prepared by conventional reactions of organic syntheses as well as by microwave assisted reactions. The main precursors for the synthesis of amidino substituted benzimidazoles 15-28, amidino substituted 1,2-phenylenediamines 8-9, were prepared by Pinner reaction in acid medium starting from 4-amino-3-nitrobenzonitrile 4 and microwave-assisted catalytic hydrogenation with 10% Pd/C. Target compounds 15-26 were synthesized by condensation of the prepared precursors 8-9 with the corresponding aldehydes 10-13 using p-beznoquinone as an oxidant. Also, the synthetic method of preparation of amidino-substituted benzimidazole hydrochlorides 27 and 28 was investigated, using solutions of the corresponding aldehydes 10-11 and amidine 9 in DMSO with Na2S2O5, which did not give the desired products. The possibility of preparing amidino-substituted benzothiazole hydrochlorides 32-36 was investigated by two methods. According to method A, in a solution of the corresponding zwitter ion 29-31 in glacial acetic acid was added the corresponding aldehyde 10-11 and the reaction mixture was stirred under nitrogen to form a free base which was suspended in ethanol and an equimolar amount of 36% HCl. According to method B, in a solution of the corresponding zwitter ion 30 in glycerol was added the corresponding aldehyde 11 and an equimolar amount of 36% HCl. The desired products were not isolated by above synthetic methods. The structures of prepared products were confirmed by 1H and 13C NMR spectroscopy. The Pinner reaction was monitored by IR spectroscopy. In order to investigate the possibility of using the compounds as biologically active agents, the antioxidative activity was determined by DPPH, FRAP and ABTS method. N,N-diethylamino substituted derivatives 24-25 with both cyclic amidino supstituents showed improved activity in comparison to BHT standard.

• Keywords: amidini; antioksidativna aktivnost; benzimidazoli; benzotiazoli; NMR spektroskopija
• Keywords (english): amidines; antioxidative activity; benzimidazoles; benzothiazoles; NMR spectroscopy
• Language: croatian
• URN:NBN: urn:nbn:hr:149:261591
• Project: Number: IP-2018-01-4379; Title: Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa; Acronym: AntioxPot; Leader: Marijana Hranjec; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2022-04-21 13:15:38