| Abstract [eng] |
Pyrazole is a five-membered heterocyclic compound that contains two adjacent nitrogen atoms. One of the nitrogen atoms in the pyrazole ring is pyridine-like, whereas the second nitrogen atom is considered pyrrolic. There is a large number of 1-phenyl-1H-pyrazole derivatives that are useful in pharmacy because they possess antibacterial, anti-inflammatory, antifungal, anticancer, anthelmintic activities. However, small-molecule 1-phenyl-1H-pyrazole derivatives that could be suitable for photodynamic therapy have not been described in the scientific literature to date. The aim of this master‘s final degree project was to synthesize new 1-phenyl- and 1-(4-methoxyphenyl)-1H-pyrazole derivatives with methoxyethoxy or methoxy substituents in the 3-position of the pyrazole ring from commercially available compounds (4-methoxyphenyl)hydrazine hydrochloride and 1-phenyl-3-hydroxy-1H-pyrazole. 1-(4-methoxyphenyl)-3-hydroxy-1H-pyrazole was obtained from (4-methoxyphenyl)hydrazine hydrochloride in two steps. Subsequent alkylation, Vilsmeier-Haack formylation and Wittig reactions gave rise to 4-ethenyl-3-alkoxy-1-phenyl- and 4-ethenyl-3-alkoxy-1-(4-methoxyphenyl)-1H-pyrazoles from aforementioned 3-hydroxy-1H-pyrazoles. Also, it was determined that 3-(2-chloroethoxy)-1H-pyrazole-4-carbaldehydes form as side products upon cleavage of methoxy group in 3-(2-methoxyethoxy)-1H-pyrazoles when Vilsmeier-Haack formylation is conducted at 70 °C. Lastly, 4-ethenyl-1H-pyrazoles were coupled with known compound 5-iodo-3,3-dimethyl-2-phenyl-3H-indole under palladium-catalysed Heck reaction conditions to yield four new 5-[(E)-2-(3-alkoxy-1-phenyl-1H-pyrazol-4-yl)ethenyl]- and 5-{(E)-2-[3-alkoxy-1-(4-methoxyphenyl)-1H-pyrazol-4-yl]ethenyl}-3,3-dimethyl-2-phenyl-3H-indoles. The structures of all new compounds were elucidated by 1D, 2D NMR, FT-IR, HRMS data. Upon investigation of the optical properties of 5-[(E)-2-(3-alkoxy-1-phenyl-1H-pyrazol-4-yl)ethenyl]- and 5-{(E)-2-[3-alkoxy-1-(4-methoxyphenyl)-1H-pyrazol-4-yl]ethenyl}-3,3-dimethyl-2-phenyl-3H-indoles dissolved in dilute tetrahydrofuran solutions, it was observed that the fluorescence quantum yields of the compounds are in the range of 71-80%, and they also possess large Stokes shifts (101-105 nm). The target fluorescent pyrazole-indole derivatives will be sent to Palacký university (Czech Republic) for investigation of their photodynamic activity. |
