HPLC-mass spectrometric analysis of a three-component reaction involving 4-hydroxy-2(1H) – quinolone and various aminoazoles
Abstract
Modern rational design of structures of organic compounds requires high efficiency due to the need to simultaneously increase the molecular complexity and minimize the number of stages of synthetic proce-dures. These problems become even more significant when designing various polyazaheterocyclic structures, including those with the pyrimidine skeleton, which is one of the most common fragments in the structures of natural and synthetic biologically active compounds. Therefore, the problems associated with the search for new selective synthetic approaches to the construction of pyrimidine heterocyclic systems, the study of the mechanisms of their formation, reactivity and further directed functionalization, and the choice of available reagents for their synthesis are relevant.
Currently, the production of new heterocyclic compounds by multicomponent methods is considered as the most promising, from the point of view of creating combinatorial libraries for high-performance bio-logical screening, which allows in vitro simultaneous testing of thousands of compounds for various types of bioactivity. The main direction of solving these problems is the modernization of synthetic procedures through the introduction of multi-component and cascade process methodologies.
In addition, the main problem in the study of three-component cascade reactions using various poly-nucleophilic matrices is to determine the sequence of processes leading to the target products. To implementthis task, we need information about the structure of intermediate compounds, the possibility of individuali-zation of which by traditional preparative methods is very difficult.
The route of three-component interaction of aminoazoles with 4-hydroxy-2(1H)-quinolonone and dimethyl acetal N,N-dimethylformamide was studied by HPLC combined with mass spectrometry. It is shown that the expected azolopyrimido [5,4-c]quinoline-6(7H) - ones are formed only in a minor amount, and the main product of this interaction is 3,3’ - biquinoline-2,2’,4,4’(1,H, 1'H, 3H, 3'H) is a tetron formed by oxidative dimerization of 4-hydroxy-2(1H) - quinolonone under the action of air oxygen. When dimethyla-cetal N,N-dimethylformamide was replaced with triethyl orthoformate, only 3,3’-biquinoline was isolated-2,2’,4,4’(1,H,1'H, 3H, 3'H) is a tetron. The study of the composition of the mother liquor showed a difficult-to-separate mixture, in which the initial reagents 3,3’-biquinoline were present in residual amounts-2,2’,4,4’(1,H, 1'H, 3H, 3'H) - tetron, as well as the target azolopyrimido[5,4-c]quinoline-6(7H) - one.
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