Sinteza i antioksidativna aktivnost hidroksi supstituiranih amida N-benzimidazola

undergraduate thesis

• Title (english): Synthesis and antioxidative activity of hydroxy substituted N-benzimidazole amides
• Author: Karla Korda
• Mentor: Marijana Hranjec (mentor)
• 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: 2021-09-24, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovog rada provedena je sinteza hidroksi supstituiranih amida N-benzimidazola klasičnim reakcijama organske sinteze i sintezom potpomognutom mikrovalovima. Aciklički prekursori 2, 3 i 4 dobiveni su mikrovalovima potpomognutom aminacijom iz 4-klor-3-nitrobenzonitrila 1 s odgovarajućim aminom. U drugom koraku sinteze priređeni su aciklički diamino supstituirani spojevi 5, 6 i 7, redukcijom spojeva 2, 3 i 4 sa SnCl2×2H2O. Glavni prekursori 8, 9 i 10, 2-amino supstituirani benzimidazoli sintetizirani su reakcijom ciklokondenzacije iz prekursora 5, 6 i 7 uz BrCN. Metoksi supstituirani karboksamidi 13, 14 i 16 pripravljeni su kondenzacijskom reakcijom spojeva 8, 9, 10 i 11 i 2,4-dimetoksibenzoil-klorida uz trietilamin. Ciljani spojevi 17, 18 i 19 sintetizirani su uklanjanjem zaštitnih skupina spojeva 13, 14 i 16 u reakciji s BBr3 pri niskoj temperaturi uz uspješno uklanjanje samo jedne zaštitne skupine. U drugom sintetskom putu za sintezu dihidroksi supstituiranih derivata, prekursor 21 pripravljen je reakcijom benziliranja 2,4-dihidroksi benzojeve kiseline 20 s benzil-kloridom, dok je prekursor 22 pripravljen debenziliranjem karboksilne skupine spoja 21 uz NaOH. Produkt 24 priređen je kondenzacijskom reakcijom u prisutnosti trietilamina iz spoja 11 i spoja 23, prethodno priređenog iz spoja 22 halogeniranjem karboksilne skupine pomoću SOCl2. Strukture sintetiziranih spojeva potvrđene su 1H, 13C i 2D NMR spektroskopijom. Antioksidativna aktivnost priređenih spojeva ispitana je metodama DPPH i FRAP.

Abstract (english)

This work presents the synthesis of hydroxy substituted N-benzimidazole amides using conventional reactions of organic chemistry and microwave-supported synthesis. Acyclic precursors 2, 3 and 4 were prepared in microwave-supported amination from 4-chlorine-3-nitrobenzonitrile 1 with corresponding amine. In second step of synthesis, acyclic compounds 5, 6 and 7 were prepared by reduction of compounds 2, 3 and 4 with SnCl2×2H2O. Main precursors 8, 9 and 10, 2-a,inosubstituted benzimidazoles were synthesized by cyclocondensation of compounds 5, 6 and 7 with BrCN. Methoxy substituted derivatives 13, 14 and 16 were prepared in condensation reaction of compounds 8, 9, 10 and 11 and 2,4-dimethoxybenzoyl-chloride with triethylamine. Targeted compounds 17, 18 and 19 were synthesized by removal of protecting groups of compounds 13, 14 and 16 in reaction with BBr3 on a low temperature, with successful removal of only one protecting group. In the second synthetic pathway for the synthesiy of dihydroxy substituted derivatives, precursor 21 was prepared by reaction of benzylation 2,4-dihydroxy benzoic acid 20 with benzyl-chloride, while precursor 22 obtained by debenzylation of carboxyl group of compound 21 with NaOH. Targeted product 24 was prepared in condensation reaction in the presence of triethylamine from compound 11 and compound 23, previously prepared from compound 22 by halogenation of carboxyl group using SOCl2. Structures of synthesized compounds were confirmed with 1H, 13C and 2D NMR spectroscopy. Antioxidative activity of prepared compounds was examined by using DPPH nad FRAP methods.

• Keywords: amidi; aminacija; benzimidazoli; karboksamidi; 1H 13C i 2D NMR spektroskopija; antioksidativna aktivnost
• Keywords (english): amides; amination; benzimidazoles; carboxamides; 1H 13C and 2D NMR spectroscopy; antioxidative activity
• Language: croatian
• URN:NBN: urn:nbn:hr:149:490123
• 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 - Undergraduate 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: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) primijenjene kemije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2023-04-05 12:33:18