Универзитет у Крагујевцу, Природно-математички факултет
Abstract
Poslednjih godina jonske tečnosti privlače veliku pažnju, kako nauke tako i
industrije. Početak njihove primene neki nazivaju “zelenom“ hemijskom revolucijom. U prilog tome svedoči neprekidan porast broja do sada objavljenih radova i patenata iz ove oblasti (više od 10000 radova i više od 2000 patenata). Ova nova grupa jedinjenja može uticati na smanjenje upotrebe toksičnih i zagađujućih organskih rastvarača zbog njihovih jedinstvenih fizičko-hemijskih karakteristika i mogućnosti da se primene u različitim sintezama. Termini kao što su stopljene soli, nevodene jonske tečnosti I tečne organske soli se, takođe, koriste da bi se opisala ova jonizovana jedinjenja koja su tečna na sobnoj temperaturi, suprotno neorganskim solima koje se tope na izuzetno
visokim temperaturama. Zbog svih ovih osobina koje pokazuje ova interesantna grupa
jedinjenja, u okviru ove disertacije izvršena je sinteza i karakterizacija nekih novih jonskih tečnosti na bazi derivata etanolamina.
Za većinu organskih reakcija koje su tradicionalno katalizovane uobičajenim
kiselinama i bazama, mogu se kao katalizatori upotrebiti i odgovarajuće jonske
tečnosti. Aldolna kondenzacija, Knevenagelova, Majklova, Manihova, Henrijeva, Dils-Alderova i Fridel-Kraftsova reakcija su samo neke od njih.
U okviru ove disertacije ispitana je katalitička uloga nekih etanolaminskih
jonskih tečnosti u Manihovoj reakciji, kao i njihov uticaj na stereohemiju dobijenih proizvoda. Metodama funkcionala gustine ispitan je mehanizam odvijanja ove reakcije. Jedan od najvećih izazova organske hemije je svakako stvaranje S–S veze. Međutim, ugljenik je stabilan i atomi ugljenika ne reaguju lako jedan sa drugim. Sinteza jednostavnih organskih jedinjenja više nije problematična, ali pri sintezama složenijih molekula dolazi do stvaranja velikog broja nusproizvoda. Razvojem paladijum-katalizovanih reakcija rešen je taj problem. U ovim reakcijama atomi ugljenika se vezuju za paladijum, nakon čega dolazi do pokretanja hemijske rekcije. Hekova, Negišijeva, Suzukijeva, Stilova i Sonogaširina reakcija su naročito poznate paladijum-katalizovane reakcije koje se izvode u jonskim tečnostima. Pokazalo se da su ovakve reakcije vrlo efikasne i da ne dolazi do taloženja elementarnog paladijuma, odnosno gubitka katalizatora.
U svetlu ovih činjenica, u okviru ove disertacije testiran je uticaj nekih
etanolaminskih jonskih tečnosti na tok reakcija Hekovog tipa i ispitivan mehanizam
formiranja prekatalitički aktivne Pd(II)-vrste, neophodne za njihovo odvijanje.
Pokazalo se da su upotrebljene jonske tečnosti odličan reakcioni medijum, i da su
efikasni ligandi za formiranje Pd(II), odnosno Pd(0), kompleksa kao katalizatora.
Na osnovu literaturnih podataka moglo se zaključiti da su se neki od Pd(II)-
kompleksa pokazali kao dobri antimikrobni agensi, ali da njihova antitumorska
aktivnost nije naročito izražena. Takođe, poznato je da kompleksi paladijuma(II)
katalizuju selektivnu hidrolizu amidne veze u peptidima i proteinima, pri vrlo blagim reakcionim uslovima. Prema tome, oni se mogu smatrati i obećavajućim agensima za selektivnu hidrolizu peptidne veze, odnosno mogu se koristiti kao efikasne metalopeptidaze. Imajući ovo u vidu, testirana je katalitička uloga dietanolamonijum-tetrahlorido-paladat(II)-kompleksa ([HDEA]2[PdCl4]) u hidrolitičkim reakcijama sa N-acetilovanim derivatima L-histidil-glicina (AcHis-Gly) i L-metionil-glicina (AcMet-Gly). Takođe, ispitivana je i antimikrobna aktivnost nekih jonskih tečnosti i Rd(II)-kompleksa dobijenih iz njih.For last two decades ionic liquids attract great attention from both science and industry. The beginning of their application is marked as new “green” chemical revolution. This is demonstrated by the continually growing number of publications and patents (currently > 10000 and > 2000, respectively). This new class of compounds can reduce the usage of toxic and polluting organic solvents, due to their unique physico-chemical properties, and their ability to
be applied in different synthesis. Terms such as molten salts, non-aqueous ionic liquids and liquid organic salts are used to describe these ionized compounds which are liquid at room temperature, opposite to inorganic salts which melts at extremely high temperature, aslo. Due to all these properties of which poseses this interesting group of compounds, synthesis and
characterization of some new ionic liquids derivatives of ethanolamine was performed in this thesis. Many organic reactions, which are traditionally catalyzed by conventional acids and bases, can be catalyzed by corresponding ionic liquids, also. Reactions such as Aldol condensation, Knoevenagel, Michael, Mannich, Henry, Diels-Ader, Friedel-Crafts reaction, are just some of them.
In this dissertation, catalytic role of some ethanolamine ionic liquids is investigated, as well as their impact on the stereoselectivity of the Mannich reaction products. The mechanism of the Mannich reaction was examined using Density Functional Theory (DFT). One of the biggest challenges in organic chemistry is certainly formation of C–C bonds.
Carbon atoms are stable, and do not react easily with one another. The synthesis of simple organic compounds has not been problematic, but the synthesis of more complex molecules leads to the formation of a large number of by-products. The development of palladium-catalyzed reactions solved this problem. In these reactions, carbon atoms meet on palladium, after which the chemical reaction begins. Heck, Negishi, Suzuki, Stille and Sonogashira reactions are well
known palladium-catalyzed reactions, which are carried out in the presence of ionic liquids. It has been shown that these reactions are very efficient, and appearance of precipitated elemental palladium was not observed, i.e. there was not loss in catalyst activity. In light of this, the effect of some ethanolamine ionic liquids on the Heck type reactions was tested. Also, the mechanism of formation of Pd(II) species necessary for performing these reactions was elucidated. Used ionic liquids were excellent reaction medium and efficient
ligands for formation of Pd(II), as well as Pd(0), complexes as catalyst.
On the basis of literature data it could be concluded that some Pd(II) complexes act as good antimicrobial agents, but their antitumor activity is not particularly pronounced. Also, it is known that palladium(II) complexes catalyze selective hydrolysis of the amide bonds in peptides and proteins, under very mild conditions. Therefore, they can be considered as promising agents
for the selective hydrolysis of peptide bond, and can be used as effective metallopeptidases. Bearing this in mind, catalytic role of diethanolammonium-tetrachloridopalladate(II) complex ([HDEA]2[PdCl4]) was tested in the hydrolytic reaction with N-acetylated derivatives of Lhistidil-
glycine (AcHis-Gly) and L-metionil-glycine (AcMet-Gly). The antimicrobial activity of some ionic liquids and Pd(II)-complexes, obtained from them, was examined, also
