Microwave-Assisted Synthesis of Sulfurated Heterocycles with Herbicidal Activity: Reaction of 2-Alkynylbenzoic Acids with Lawesson's Reagent

Abstract

The reactivity of 2-alkynylbenzoic acids toward Lawesson's reagent (LR) under microwave irradiation (300 W, 100 °C, CH₂ Cl₂ ) was assessed. It was found that, depending on reaction conditions, either a dithionation- or a monothionation-cycloisomerization process takes place with formation of important sulfurated heterocycles. In particular, using 1 equivalent of LR for 1 h, dithionation occurred, with formation of benzo[c]thiophene-1(3H)-thiones or 1H-isothiochromene-1-thiones, while with 0.5 equiv. of LR for 10-30 min, monothionated products were selectively obtained (benzo[c]thiophen-1(3H)-ones or 1H-isothiochromen-1-ones). The regiochemical output of the process strongly depended on the substitution pattern of the starting 2-alkynylbenzoic acid derivatives. These compounds were also assayed as potential herbicides by assessing their phytotoxic activity on seedling growth and development of the model species Arabidopsis thaliana. All compounds, to different extents, influenced the morpho-physiological parameters that were monitored; in particular, the fresh weight (FW) was significantly affected, with ED₅₀ values ranging from 4.81-63.7 μM.

Keywords: Lawesson's reagent; cycloisomerization; herbicides; heterocycles; microwave-assisted synthesis; thionation.