Sinteza biološki značajnih hibrida dušikovih heterocikla i derivata 1,2,3-triazola

master's thesis

• Title (english): Synthesis of biologically interesting hybrids of nitrogen heterocycles and 1,2,3-triazole derivatives
• Author: Danijel Glavač
• Mentor: Silvana Raić-Malić (mentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Dragana Mutavdžić Pavlović (član povjerenstva)
• Committee member: Andrijana Meščić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2015-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry; Organic Chemistry

Abstract

Cilj ovog rada bila je sinteza novih biološki aktivnih hibrida benzimidazola, pirimidina, 7-deazapurina i 1,2,3-triazola, kao odabranih dušikovih heterocikla. Regioselektivnom 1,3-dipolarnom cikloadicijom azida i alkina uz katalizatore Cu(0), 1M CuSO4 uspješno su sintetizirani ciljani 1,4-disupstituirani 1,2,3-triazolni derivati benzimidazola (1-5), pirimidina (9-17) i 6-klor-7-deazapurina (22). „Click“ reakcije su se odvijale primjenom mikrovalova u smjesi vode i organskih otapala pa možemo zaključiti da su primijenjene sintetske metode prihvatljive za okoliš.
Hibridi benzimidazola i 1,2,3-triazola (1-5) pripravljeni su reakcijom kumarinskog azida, aromatskih azida i alkinilnih derivata benzimidazola. N-1,N-3-disupstituirani (9, 11, 13 i 15) i N-1-monosupstituirani (10, 12 i 14) pirimidinski derivati 1,2,3-triazola sintetizirani su reakcijom dipropargilnog derivata pirimidina i aromatskih azida. Potom je provedena Sonogarshira-ina reakcija N-1 triazolnih derivata 5-joduracila (16) i alkina pomoću paladija kao katalizatora, CuI kao ko-katalizator i N,N-dizopropiletilamina kojom su sintetizirani biciklički 6-supstituirani (18b i 19b) i 5,6-disupstituirani furo[2,3-d]pirimidinski (18a i 19a) derivati.
„Click“ reakcijom 7-(2-azidoetil)-4-klor-7H-pirolo[2,3-d]pirimidina (21) i 4-kloro-N-(prop-2-inil)benzensulfonamida dobiven je ciljani 1,2,3-triazolni derivat 6-klor-7-deazapurina 22.
Strukture svih novopriređenih spojeva potvrđene su spektroskopijom 1H- i 13C-NMR. Antiproliferativna ispitivanja novih spojeva na zloćudne stanice tumora su u tijeku.

Abstract (english)

The aim of this work was the synthesis of new biologically active hybrids of benzimidazole, pyrimidine, 7-deazapurine and 1,2,3-triazole, as selected nitrogen heterocycles. Regioselective 1,3-dipolar cycloaddition of azide and alkyne with Cu(0), 1 M CuSO4 as catalysts were synthesized successfully targeted 1,4-disubstituted 1,2,3-triazole benzimidazole (1-5), pyrimidine (9-17) and 6-chloro-7-deazapurine (22) derivatives. "Click" reactions were conducted by using microwaves in a mixture of water and organic solvents, so we can conclude that the applied synthetic methods were acceptable for the environment.
Hybrids of benzimidazole and 1,2,3-triazole (1-5) were prepared by reaction of the coumarin azide, aromatic azide with alkynyl derivatives of benzimidazole. N-1,N-3-disubstituted (9, 11, 13 and 15) and N-1-monosubstituted (10, 12 and 14) pyrimidine derivative of 1,2,3-triazole were synthesized by reaction of a pyrimidine derivatives and aromatic azides. Sonogashira coupling of N-triazole derivative of 5-iodouracil (16) and alkynes using a palladium catalyst, CuI as a co-catalyst and N,N-diisopropylethylamine afforded bicyclic 6-substituted (18b and 19b) and 5,6-disubstituted furo[2,3-d]pyrimidine (18a and 19a) derivatives.
"Click" reaction of 7-(2-azidoethyl)-4-chloro-7H-pyrolo[2,3-d]pyrimidine (21) and 4-chloro-N-(prop-2-ynyl)benzenesulfonamide was obtained as a target 1,2,3-triazole derivative of 6-chloro-7-deazapurine 22. The structures of all compounds were confirmed by 1H and 13C NMR spectroscopy. Antiproliferative evaluations of new compounds on malignant tumor cells are in progress.

• Keywords: 1 2 3-triazol; benzimidazol; pirimidin; "click“ kemija; Huisgenova cikloadicija
• Keywords (english): 1 2 3-triazole; benzimidazole; pyrimidine; "click“ reaction; Huisgen cycloaddition; Sonogashira coupling
• Language: croatian
• URN:NBN: urn:nbn:hr:149:940403
• 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: Open access
• Created on: 2016-12-16 13:32:29