Priprava i karakterizacija N-[2-kloro-6-metilfenil]-2-[[6-[4-(2-hidroksietil)-1-piperazinil]-2-metil-4-pirimidinil]amino]-5-tiazolkarboksiamid N-oksida

master's thesis

• Title (english): Preparation and characterisation of N-[2-chloro-6-methylphenyl]-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide N-oxide
• Author: Dženita Šola
• Mentor: Vesna Tomašić (mentor)
• Committee member: Vesna Tomašić (predsjednik povjerenstva)
• Committee member: Vanja Kosar (član povjerenstva)
• Committee member: Mirela Leskovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2017-07-04, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering; Reaction Engineering

Abstract

U ovom radu provedena je sinteza N-[2-kloro-6-metilfenil]-2-[[6-[4-(2-hidroksietil)-1-piperazinil]-2-metil-4-pirimidinil]amino]-5-tiazolkarboksiamid N-oksida oksidacijom N-[2-kloro-6-metilfenil]-2-[[6-[4-(2-hidroksietil)-1-piperazinil]-2-metil-4-pirimidinil]amino]-5-tiazolkarboksiamida vodikovim peroksidom u ledenoj octenoj kiselini, N-metil pirolidonu te u smjesi otapala, tj. N-metil pirolidonu i metanolu. Cilj rada bio je postizanje visoke kromatografske čistoće dobivenog spoja (<99%), te je pritom ispitan utjecaj različitih parametara sinteze na dobivene rezultate. Utvrđeno je da koncentracija vodikovog peroksida utječe na brzinu nastajanja N-oksida. Reakcija je praćena tekućinskom kromatografijom visokog učinka. U završnom dijelu istraživanja sirovi kristali N-[2-kloro-6-metilfenil]-2-[[6-[4-(2-hidroksietil)-1-piperazinil]-2-metil-4-pirimidinil]amino]-5-tiazolkarboksiamid N-oksida suspendirani su u metanolu s ciljem smanjenja koncentracije primarnog otapala. Rezultati kinetičke analize dobiveni u kotlastom reaktoru primjenom integralne metode pokazali su dobro slaganje između eksperimentalnih rezultata i pretpostavljenog jednostavnog kinetičkog modela za reakciju prvog reda. Procijenjene su vrijednosti kinetičkih parametara predloženog modela i pripadajuće vrijednosti korijena srednjeg kvadratnog odstupanja te je izvedena ocjena prihvatljivosti predloženog modela. Kvalitativne i kvantitativne analize uzoraka provedene su primjenom tekućinske kromatografije visokog učinka, volumetrijskom Karl Fischerovom titracijom te plinskom kromatografijom. Zadnji uzorak analiziran je i primjenom nuklearne magnetske rezonancije. Analizom je identificiran N-[2-kloro-6-metilfenil]-2-[[6-[4-(2-hidroksietil)-1-piperazinil]-2-metil-4-pirimidinil]amino]-5-tiazolkarboksiamid N-oksida kromatografske čistoće 99,89% i potvrđena je njegova struktura.

Abstract (english)

The subject of this work is a synthesis of N-[2-chloro-6-methylphenyl]-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide N-oxide by oxidation of N-[2-chloro-6-methylphenyl]-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide with hydrogen peroxide in glacial acetic acid, N-methyl pyrrolidone and mixture of solvents, i.e. N-methyl pyrrolidone and methanol. The aim of the paper was to achieve high chromatographic purity (<99%) of the obtained compound and to examine the influence of different synthesis parameters on the obtained results. It was found that hydrogen peroxide concentration affected the rate of N-oxide synthesis. The effect was monitored by high performance liquid chromatography. In the final part of the investigation crude crystals of N-[2-chloro-6-methylphenyl]-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide N-oxide were suspended in methanol to reduce the concentration of residual solvent. Kinetic analysis results obtained in the batch reactor applying integral method showed good agreement between experimental measurements and proposed simple kinetic model for reaction of the first order. Kinetic parameters and appropriate values of the standard deviations were estimated and validation of the proposed model was carried out. Qualitative and quantitative determinations of samples were conducted by high performance liquid chromatography, volumetric Karl Fischer titration and gas chromatography. The final product, N-[2-chloro-6-methylphenyl]-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide N-oxide, was prepared with high chromatographic purity of 99.89% and its structure was confirmed.

• Keywords: oksidacija; sinteza N-oksida; kromatografska čistoća; kinetika reakcije; integralna metoda
• Keywords (english): oxidation; synthesis of N-oxide; chromatographic purity; reaction kinetics; integral method
• Language: croatian
• URN:NBN: urn:nbn:hr:149:772056
• Study programme: Title: Chemical Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka kemijskog inženjerstva (magistar/magistra inženjer/inženjerka kemijskog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-10-01 14:08:08