Substituted 2H-pyran-2-ones are systems with a wide spectrum of pharmacological activity, therefore they are used as a substance in many modern drugs, which determines the relevance of creating complex systems based on them, including polycyclic O-, S-heterosystems. In recent years, Lawesson's reagent has been explored for the synthesis of both open-chain P,S-containing derivatives and P,S-heterocyclic systems, with potential biological activity.The character of the interaction between arylmethylene-2H-pyran-2-ones and Lawesson's reagent depends on the structure and position of the substituent in the aromatic ring of the substrate and on the polarity of the reaction medium. Three main pathways were shown to be realized for this group of compounds. In the absence of a substituent in the ring, the reaction proceeds as a classical thionation followed by S-heterocyclization. In the presence of the most electron-withdrawing nitro group at the metaposition of the substituent, the enol form of the substrate is stabilized, which promotes the formation of a new pyran ring. For the substrate with a chlorine atom at the paraposition of the cycle, according to the result of the decomposition of UV spectra by the chemometric method of independent components (MILCA) of the benzannulated analog, the content of the keto tautomeric form in nonpolar solvents is higher compared to that for the meta-NO₂ group, which explains the presence of both O- and S-heterocyclization products in the reaction mixture.