Development of mechanochemical synthesis of amides, ureas and triazoles

Fokus ovog doktorskog rada bio je razjasniti mehanizam mehanokemijske priprave različito supstituiranih amida i urea reakcijom acil-azida i amina, te razjasniti mehanizam Huisgenovih 1,3-cikloadicija kataliziranih bakrovim(I) ionima provedenih u mehanokemijskim uvjetima. Ispitan je utjecaj supstituenata i aditiva na tijek reakcije nukleofilne supstitucije amina i acil-azida korištenjem in situ Ramanove spektroskopije tijekom mljevenja. Iz dobivenih rezultata zaključeno je kako je reakcija nukleofilne supstitucije provedena u mehanokemijskim uvjetima katalizirana bazom, a korak u kojem dolazi do deprotonacije ima ključnu ulogu u ovim reakcijama. U reakcijama provedenim mljevenjem uspješno su izolirani amidni derivati, dok su ureidni derivati dobiveni isključivo reakcijama u otopini. Ispitan je utjecaj bakra i njegovih soli kao katalizatora na iskorištenje Huisgenove 1,3-cikloadicije terminalnih alkina i aril-azida u otopini i mehanokemijskim postupcima. Iz dobivenih rezultata zaključeno je kako reaktivnost p-supstituiranih aril-azida, u obje metode, pada u nizu I>Br>Cl>H. Korištenjem Ramanove spektroskopije in situ ispitan je utjecaj bakra i njegovih soli na nastajanje 1,2,3-triazolnog prstena u mehanokemijskim reakcijama.This work emphasizes the comparation of the mechanochemical and solvent synthesis of amides and ureas carried out without the use of metals as a catalyst, and Huisgen's 1,3-dipolar cycloaddition of azide and terminal alkyne in presence of cooper as a catalyst. Nucleophilic substitution reactions are investigated on the model system of acyl azide and primary amines in the presence of various additives under different reaction conditions using in situ Raman spectroscopy. The nucleophilic substitution reaction under mechanochemical conditions is base catalyzed, akin to catalysis in solution. Mechanochemical reaction as a product provide amide derivatives, while by reactions in solution are obtained only ureas. The mechanism of Huisgen copper-catalyzed mechanochemical reaction and the efficiency of copper catalysts with Cu(0), Cu(I) and Cu(II) oxidation states is clarified by means of in situ Raman spectroscopy. From the obtained results, it was concluded that the reactivity of p-substituted aryl azide, in solution and mechanochemical procedures, follows the sequence I> Br> Cl> H