Mytiuk A. Synthesis of functionalized annelated pyridines by [3+3]-heterocyclization of α-unsubstituted aminoheterocycles as CCN-binucleophiles

The thesis for the scientific degree of Candidate of Sciences by specialty 02.00.03 – organic chemistry. Taras Shevchenko National University of Kyiv of MES of Ukraine, Kyiv, 2019. The dissertation is devoted to developing methods for the synthesis of functionalized (hetero)annelated pyridines by the reaction of [3+3]-heterocyclization of synthetic equivalents of functionalized malonic dialdehyde and α-unsubstituted aminoheterocycles as CCN-bisnucleophiles. It was shown that hetaryl[3,4-b]pyridine-5-carboxylic acids can be obtained by a two-step conversion involving the reactions of readily available 1,3-biselectrophilic 1,3-dimethyl-5-formyluracil with electron-enriched aminoheterocycles (aminoazoles, aminothiophenes and aminouracils) and subsequent hydrolysis of the obtained products. The mechanism of formation of the recycled product is offered which is confirmed by carrying out the corresponding reactions with the deuterated formiluracil. It has been illustrated that the reaction of 2-dimethylaminomethylene-1,3-bis-(dimethylimino)propane diperchlorate with various five-membered aminoheterocycles is a convenient method for the synthesis of compounds containing fused fragments of 3-formylpyridine or 5-formylpyrimidine. The reaction occurs by boiling in acetic acid and leads to the corresponding formylheterocycles with good to high yields. A limitation of this condensation reaction is the sensitivity of the starting compounds to acidic reaction conditions. A method for obtaining new types of building blocks based on heteroannelated pyridines containing a cyano group was developed and optimized. In the process, the temperature and HCl concentration were selected to avoid the decomposition of heterocycles that are unstable under harsh acidic conditions. The softer transformation conditions (i.e., the solvent's selection and its amount, the reaction time and reagent ratio) were optimized.