Myshko A. New approaches for the synthesis of hybrids bearing coumarins or flavonoids and azoles

The dissertation is devoted to developing coumarins, isoflavones, and aurones molecular hybridization methods using azoles. A method of N-alkylation of azoles with the trapping of thermally generated quinone methides in dimethyl carbonate was developed, which makes possible the use of water-insoluble compounds and does not require high temperatures. The feasibility of using aminomethyl, hydroxymethyl, and methoxymethyl derivatives of 7-hydroxybenzopyrones and 6-hydroxybenzofuranones as ortho-quinone methide precursors for the synthesis of flavonoid-azole and coumarin-azole hybrids was developed. An efficient method of regioselective hydroxybenzylation of 5-aminopyrazoles and 5-aminoisoxazoles using coumarin and flavonoid Mannich bases as precursors of ortho-quinone methides was developed. It was found that alkylation at the C-4 position of 5-aminoazoles was observed under the proposed conditions. It was shown that trapping of thermally generated ortho-quinone methides with coumarin and chromone skeletons by 3-aminopyrazoles and 3-aminoisoxazoles furnished 3-NH-substituted azoles. The conditions for the CH2NH-linked coumarin- and flavonoid-azole hybrids synthesis are proposed. New synthetic approaches for the synthesis of pyrazole-based aurones are proposed. It was established that the reaction of 3-aminopyrazole with 2-(aminomethylene)-1-benzofuran-3(2H)-ones led to the formation of 2-[(1H-pyrazol-3-ylamino)methylene]-1-benzofuran-3(2H)-ones. It was shown for the first time that the reaction of 1-methyl-5-aminoprazoles with 2-[(dimethylamino)methylene]-1-benzofuran-3(2H)-ones is afforded a mixture of (2Z)-2-[(5-amino-1-methyl- 1H-pyrazol-4-yl)methylene]-1-benzofuran-3(2H)-ones (major products) and 1-methyl-1H-[1]benzofuro[3,2-b]pyrazolo[4,3-e]pyridines as minor products, whereas the ratio of products depends on the structure of the enaminone. A method for the synthesis of 2-(5-hydroxy-1H-pyrazol-4-yl)methylene]-1-benzofuran-3(2H)-one derivatives by condensation of benzofuran-3(2H)-ones with 4-[(dimethylamino)methylene] -2,4-dihydro-3H-pyrazol-3-ones was developed.