Primjena zelenih eutektičkih otapala u sintezi novih N-heterocikličkih derivata 1,1'-disupstituiranih ferocena

undergraduate thesis

• Title (english): Application of deep eutectic solvents in the synthesis of new N-heterocycle 1,1'-disubstituted ferrocene conjugates
• Author: Leon Sačer
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Andrijana Meščić Macan (član povjerenstva)
• Committee member: Danijela Ašperger (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2021-09-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Proteklih godina, sve se više koriste načela „zelene“ kemije u sintezi novih biološki aktivnih spojeva. Značajnu važnost u zelenoj kemiji imaju zelena eutektička otapala te mehanokemijska sinteza jer smanjuju uporabu toksičnih hlapljivih organskih otapala. U ovom radu opisana je sinteza novih 1,1'-disupstituiranih ferocenskih derivata purina, purinskih bioizostera i 5-supstituiranih pirimidina (13−23), kao spojeva s potencijalnim antitumorskim djelovanjem. U tu svrhu pripravljen je 1,1'-bis(azidometil)ferocen (1) iz
1,1'-ferocendimetanola. Nadalje, pripravljeni su N-propargilirani derivati purina i purinskih bioizostera (2−8) te 5-supstituiranih pirimidina (9−12). Reakcijom 1,3-dipolarne cikloadicije 1,1'-bis(azidometil)ferocena i odgovarajućih terminalnih alkina (2−12) dobiveno je jedanaest različitih ferocenskih derivata purina, indola, 7-deazapurina (13−19) i pirimidina (20−23). Reakcija 1,3-dipolarne cikloadicije katalizirane bakrom provedena je na četiri različita načina: (i) u metanolu uz bakrov (II) acetat kao katalizator, (ii) u zelenim eutektičkim otapalima D-sorbitol/urea/NH4Cl, (iii) u kolin-klorid/glicerolu uz bakrov (I) jodid kao katalizator i
(iv) mehanokemijski uz bakrov (II) acetat kao katalizator. Kao najefikasnija metoda provođenja reakcije 1,3-dipolarne cikloadicije za navedene spojeve pokazala se mehanokemijska sinteza. Strukture spojeva potvrđene su 1H i 13C NMR spektroskopijom, a biološka ispitivanja novosintetiziranih spojeva (13−23) su u tijeku.

Abstract (english)

In recent years, the principles of ˝green˝ chemistry have been more frequently used in the synthesis of new biologically active compounds. Deep eutectic solvents and mechanochemical synthesis are of significant importance in green chemistry because they decrease the use of toxic volatile organic solvents. The aim of this work was the synthesis of 1,1'-disubstituted ferrocene derivatives of purines, purine bioisosteres and 5-substituted pyrimidines, as compounds with potential antitumor activity. For this purpose,
1,1'-bis(azidomethyl)ferrocene (1) was prepared from 1,1'-ferrocendimethanol. Furthermore, propargylated derivatives of purines and purine bioisosteres (2−8) as well as 5-substituted pyrimidines (9−12) were prepared. Eleven ferrocene derivatives of purine, indole, 7-deazapurine (13−19) and 5-substituted pyrimidine (20−23) were obtained by the reaction of 1,3-dipolar cycloaddition of 1,1'-bis(azidomethyl)ferrocene and the corresponding terminal alkynes (2−12). The copper-catalyzed 1,3-dipolar cycloaddition reaction was performed in four different procedures: (i) in methanol with copper (II) acetate as a catalyst, (ii) in green eutectic solvents D-sorbitol/urea/NH4Cl and (iii) in choline chloride/glycerol with copper (I) iodide as a catalyst and (iv) mechanochemically with copper (II) acetate as a catalyst. Mechanochemical synthesis has been shown to be the most effective method for the
1,3-dipolar cycloaddition reaction of these compounds. The structures of the compounds were confirmed by 1H and 13C NMR spectroscopy, and biological studies of compounds (13−23) are ongoing.

• Keywords: „zelena“ kemija; eutektička otapala; mehanokemijska sinteza; ferocen; bioizosteri purina; pirimidini; 1 2 3-triazoli; Huisgenova 1 3-dipolarna cikloadicija
• Keywords (english): ˝green˝ chemistry; deep eutectic solvents; mechanochemical synthesis; ferrocene; purine bioisosteres; pyrimidines; 1 2 3-triazoles; Huisgen 1 3-dipolar cycloaddition
• Language: croatian
• URN:NBN: urn:nbn:hr:149:273500
• 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: 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: 2023-04-20 11:16:44