Catalytic synthesis of bioactive 2H-chromene alcohols from (−)-isopulegol and acetone on sulfonated clays

Abstract

Condensation of (−)-isopulegol with acetone was investigated at 25–40 °C over clay based materials (K10, cloisite Na+ and halloysite nanotubes) modified with sulfonic acid groups by one-pot sulfonation with chlorosulfonic acid or via organosilylation with 2-(4-chlrosulfonylphenyl)-ethyltrimethoxysilane. The target product was the R diastereomer of dimethyl-substituted octahydro-2H-chromen-4-ol with exhibits antiviral activity. The catalysts were characterized by a range of physico-chemical methods. The effect of the initial isopulegol concentrations on the yield of ketone-derived chromenols and the R/S isomers ratio was studied for the first time. The best catalyst was a highly acidic, large pore K10-clay modified by sulfonic acid. Varying the initial concentration of the reagents allows to find a balance between dehydration by-products and a side etherification reaction. A high yield (73%) of the desired chromenols was reached using 0.52 mol/l initial (−)-isopulegol concentration after 240 min at 87% substrate conversion and reaction temperature 25 °C. The yield exceeded that of other previously reported in the open literature catalysts.

Catalytic activity of hierarchical beta zeolites in the Prins cyclization of (−)-isopulegol with acetone

“…Halloysite nanotubes (HNT) pretreated with HCl were discovered to be active catalysts for the Prins reaction with acetone allowing to increase the chromenols yield up to 78% (the R/S ratio 8.4) [13]. Condensation of (−)-isopulegol with acetone over large pore K10-clay modified by sulfonic acid allowed the highest yield (73%) of the desired chromenols among the reported ones in the literature [14]. A very limited scope of the tested catalysts and unclear influence of surface acidity and the porous structure prompt evaluation of the effect of acidity and porosity on the catalyst performance.…”

Catalytic synthesis of terpenoid-derived hexahydro-2H-chromenes with analgesic activity over halloysite nanotubes

“…Note that in a similar reaction of (-)-isopulegol with thiophene-2-carbaldehyde, partial dehydration of the 4R-isomer (with cis arrangement of substituents) was reported, which, according to [38], may be because of its preferable adsorption on the catalyst surface. On the other hand, in the Prins reaction of (-)-isopulegol with acetone, selectivity to 4R-and 4S-isomers increased with an increase in conversion due to backward reaction of the ester of isopulegol with chromenol [21,39].…”

“…As catalysts for the monoterpenoid alcohols condensation with carbonyl compounds, modified clays [16][17][18][19][20][21], zeolites and mesoporous silicates [15,22] SO3H-functionalized carbon nanotubes [23], iodine [24], as well as traditional Lewis and Brønsted acids can be used [25][26][27].…”

Heterogeneous Catalytic Conversion of Citronellal into Isopulegol and Menthol: Literature Review

“…Isopulegol has been reported as a good antioxidant and anti-in ammatory (Ramos et al, 2020) , antihyperlipidemic (Kalaivani and Sankaranarayanan, 2019) , analgesic (Kalaivani and Sankaranarayanan, 2019) , and antitumor agent (Jaafari et al, 2012) . Isopulegol is also the intermediate for the synthesis of the anti-in uenza compound octahydro-2Hchromenes Ilyina et al, 2021 and bioactive 2H-chromene alcohols as an antiviral agent (Laluc et al, 2020). Exclusively, isopulegol, especially (-)-isopulegol, is the starting compound in the production of menthol, which is a compound in high demand throughout the world (Coman et al, 2009;Plößer et al, 2014).…”