Sinteza i strukturna karakterizacija novih derivata benztiazola s potencijalnim antitripanosomskim djelovanjem

master's thesis

• Title (english): Synthesis and structural characterization of novel benzothiazole derivatives with potential anti-trypanosomal activity
• Author: Mateja Novak
• Mentor: Tatjana Gazivoda Kraljević (mentor)
• Committee member: Tatjana Gazivoda Kraljević (predsjednik povjerenstva)
• Committee member: Silvana Raić-Malić (član povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu opisana je sinteza novih derivata benztiazola te njihova strukturna karakterizacija 1H i 13C-NMR te UV/VIS spektroskopijom. 6-aminobenztiazol (2) pripravljen je redukcijom 6-nitrobenztiazola (1) s SnCl2 te je preveden reakcijom diazotacije u 6-cijanobenztiazol (3). Reakcijom 4-haloanilina s KSCN i Br2 sintetizirani su 6-klor- (4) i 6-fluorbenztiazol-2-amin (5) koji potom reakcijom s vodenom otopinom NaOH daju 2-amino-5-halotiofenole (6 i 7). 2-aminotiofenol (8) priređen je reakcijom 2-aminobenztiazola s KOH u etilenglikolu. O-supstituirani derivati benzaldehida (9-12) sintetizirani su reakcijom 4-hidroksibenzaldehida s odgovarajućim haloalkilirajućim reagensima uz K2CO3 kao bazu. 4-O-propargilbenzaldehid (13) je bakrom kataliziranom klik reakcijom s odgovarajućim azidima (TMSN3 i N-azidoetilmorfolin) preveden u 1,2,3- triazolne derivate benzaldehida (16 i 17). Reakcijom 4-hidroksibenzaldehida s odgovarajućim tiofenolima (6-8) pripravljeni su 2-(4-hidroksifenil)benztiazolni derivati 21-23 koji su zatim O-alkiliranjem prevedeni u 2-(4-alkoksifenil)benztiazolne derivate (24-32), a propargiliranjem uz NaH kao bazu u O-propargilirane derivate benztiazola (33-35). Huisgenovom 1,3-dipolarnom cikloadicijom terminalnih alkina 33-35 i etilmorfolinskog azida (16) kataliziranom bakrom i potpomognutom mikrovalnim zračenjem priređeni su 1,2,3- triazolni derivati benztiazola 36-38. Strukture svih novopripravljenih spojeva potvrđene su 1H i 13C-NMR spektroskopijom.

Abstract (english)

This work presents the synthesis of novel benzothiazole derivatives and their structural characterization by 1H and 13C-NMR and UV/VIS spectroscopy. 6-aminobenzothiazole (2) was prepared by reduction reaction of 6-nitrobenzothiazole (1) with SnCl2 and was converted by diazotisation reaction to 6-cyanobenzothiazole (3). The reaction of 4-haloaniline with KSCN and Br2 gave 6-chloro- (4) and 6-fluorobenzothiazol-2-amine (5), which were then converted with an aqueous NaOH solution to 2-amino-5-halothiophenols (6 and 7). 2-Aminothiophenol (8) was obtained by reaction of 2-aminobenzothiazole with KOH in ethylene glycol. O-substituted benzaldehyde derivatives (9-12) were synthesized by reaction of 4-hydroxybenzaldehyde with the corresponding haloalkylating reagents with K2CO3 as base. 4-O-propargylbenzaldehyde (13) with corresponding azides (TMSN3 and N-azidoethylmorpholine) in copper-catalyzed reaction were converted to 1,2,3-triazole benzaldehyde derivatives (16 and 17). Reaction of 4-hydroxybenzaldehyde with the corresponding thiophenols (6-8) gave 2-(4-hydroxyphenyl) benzothiazole derivatives 21-23 which were then by O-alkylation reaction gave 2-(4-alkoxyphenyl)benzothiazole derivatives (24-32), and by propargylation reaction with NaH as a base gave O-propargylated benzothiazole derivatives (33-35). 1,2,3-triazole derivatives of benzothiazole 36-38 were synthesized by copper catalysed Huysgen 1,3-dipolar cycloaddition reaction of terminal alkynes 33-35 and ethylmorpholine azide (16) under microwave irradiation. The structures of all newly prepared compounds were confirmed by 1H and 13C-NMR spectroscopy.

• Keywords: benztiazol; 1 2 3- triazol; klik reakcija; Huisgenova 1 3-dipolarna cikloadicija
• Keywords (english): benzothiazole; 1 2 3-triazole; click reaction; Huysgenov 1 3-dipolar cycloaddition
• Language: croatian
• URN:NBN: urn:nbn:hr:149:230170
• Project: Number: IP-2018-01-4682; Title: Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja; Acronym: PurBioCaPa; Leader: Silvana Raić-Malić; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-10-01
• Created on: 2022-02-26 11:52:27