Sinteza i biološka ispitivanja konjugata benzotiazola i tiouree

undergraduate thesis

• Title (english): Synthesis and biological evaluation of benzothiazole and thiourea conjugates
• Author: Josipa Šajnović
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Silvija Maračić (član povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-09-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U ovom radu provedena je sinteza derivata benzotiazola i tiouree s potencijalnom citostatskom aktivnošću. Ciljane N-aciltiouree (2a–f, 4a–i, 5a–i) pripravljene su one-pot metodom iz acil-klorida, preko acil-tiocijanatnog intermedijera te njihovom adicijom na 2-aminobenzotiazolne i 2-(4-aminofenil)benzotiazolne heterocikle. Za sintezu su korišteni 2-aminobenzotiazoli i 2-(4-aminofenil)benzotiazoli sa supstituentom u položaju 6. Derivati 2-aminobenzotiazola (1a–f) potrebni za sintezu N-aciltiourea dobiveni su reakcijom odgovarajuće supstituiranog anilina s kalijevim tiocijanatom i bromom u ledenoj octenoj kiselini, dok je 2-(4-aminofenil)benzotiazol (3) pripravljen reakcijom kondenzacije 2-aminotiofenola s 4-aminobenzojevom kiselinom u polifosfornoj kiselini (PPA) pri 220°C. N-aciltiouree su izolirane i pročišćene metodama prekristalizacije i kolonske kromatografije.
U sintezi acil-tiourea 2-aminobenzotiazola (2a–f) nastali su odgovarajući amidi (2a*–f*), kao nusprodukti, dok su u sintezi acil-tiourea 2-(4-aminofenil)benzotiazola (4a–i) te
6-metil-2-(4-aminofenil)benzotiazola (5a–i) dobiveni samo željeni produkti.
Derivati acil-tiouree i 2-aminobenzotiazola (2a–f) dobiveni su u manjim iskorištenjima
(4 – 59 %) u odnosu na derivate acil-tiouree i 2-(4-aminofenil)benzotiazola (4a–i)
(52 – 88 %) te acil-tiouree i 6-metil-2-(4-aminofenil)benzotiazola (5a–i) (22 – 89 %). Strukture svih priređenih spojeva potvrđene su spektroskopijom 1H i 13C NMR.

Abstract (english)

In this paper, the synthesis of benzothiazole and thiourea derivatives with potential cytostatic activity is performed. Targeted N-acylthioureas (2a–f, 4a - i, 5a–i) were prepared by one-pot method from acyl chloride, via acyl thiocyanate intermediate and their addition to 2-aminobenzothiazole and 2-(4-aminophenyl)benzothiazole heterocycles. 2-Aminobenzothiazoles and 2-(4-aminophenyl)benzothiazoles substitued in position 6 were used for the synthesis. The 2-aminobenzothiazole (1a–f) derivatives required for the synthesis of N-acylthiourea were obtained by reaction of the appropriately substituted aniline with potassium thiocyanate in acetic acid, while 2-(4-aminophenyl)benzothiazole (3) was prepared by condensation of 2-aminothiophenol with 4-aminobenzoic acid in polyphosphoric acid (PPA) at 220°C. N-Acylthioureas were isolated and purified by recrystallization and column chromatography. In the synthesis of 2-aminobenzothiazole derivatives of acyl thioureas (2a–f) the corresponding amides (2a*–f*) were formed as by-products, while the synthesis of 2-(4-aminophenyl)benzothiazole derivatives of acyl thioureas (4a–i) and 6-methyl-2-(4-aminophenyl)benzothiazole derivatives of acyl thioureas (5a–i) gave only the desired products. 2-Aminobenzothiazole acyl-thioureas (2a–f) were obtained in lower yields (4 - 59%) compared to 2-(4-aminophenyl)benzothiazole acyl-thioureas (5a - i) (52 – 88%) and 6-methyl-2-(4-aminophenyl)benzothiazole acyl thioureas (6a–i) (22 – 89%). The structures of all compounds were confirmed by 1H and 13C NMR spectroscopy.

• Keywords: antitumorska aktivnost; 2-arilbenzotiazol; benzotiazol; N-aciltiourea; tiourea
• Keywords (english): antitumor activity; 2-arylbenzothiazole; benzothiazole; N-acylthiourea; thiourea
• Language: croatian
• URN:NBN: urn:nbn:hr:149:748295
• Project: Number: KK.01.1.1.04.0013; Title: Inovativna rješenja u katalitičkim proizvodnim procesima za potrebe farmaceutske industrije; Title: Innovative solutions in catalytic processes in the pharmaceutical industry; Acronym: CAT PHARMA; Leader: Srećko Kirin; Jurisdiction: eu; Funder: EC; Funding stream: EFRR
• 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: 2023-04-24 07:58:11