Preparation of octahydro-2 H -chromen-4-ol with analgesic activity from isopulegol and thiophene-2-carbaldehyde in the presence of acid-modified clays

Acid‐modified Halloysite Nanotubes as a Stereoselective Catalyst for Synthesis of 2H‐Chromene Derivatives by the Reaction of Isopulegol with Aldehydes

“…4 R ‐isomers synthesized with 5‐bromo‐thiophene‐2‐carbaldehyde or acetone displayed a profound anti‐influenza activity, whereas only poor antiviral effect was showed by 4 S ‐diastereomers ,. Quite recently we have demonstrated that an increase in selectivity to thiophenyl‐substituted chromenol with illite clay as a catalyst was observed with an increase in the initial concentrations of reactants, the catalyst to reactants ratio, and a decrease in the reaction temperature . Kinetic modeling was applied to rationalize the observed regularities .…”

“…Quite recently we have demonstrated that an increase in selectivity to thiophenyl‐substituted chromenol with illite clay as a catalyst was observed with an increase in the initial concentrations of reactants, the catalyst to reactants ratio, and a decrease in the reaction temperature . Kinetic modeling was applied to rationalize the observed regularities . Considering high physiological activity of 4 R ‐diastereomers of octahydro‐2 H ‐chromenols, development of novel stereoselective catalysts for their synthesis is a very important task.…”

“…Recently, it has been shown, that in catalytic condensation of a natural allyl alcohol (−)‐isopulegol (I) with aldehydes, substituted octahydro‐2 H ‐chromen‐4‐ol (III) as 4 R ‐ and 4 S ‐diastereomers was formed along with a dehydration product IV (Scheme ). Different catalysts such as I 2 , p ‐toluenesulfonic acid, BF 3 ⋅Et 2 O, zeolites, clays were used in this reaction . A relatively high 4 R /4 S ratio (9.0) with overall yields of 70–88 % were observed in condensation of isopulegol (obtained by cyclization of R ‐citronellal) with aromatic aldehydes at −78 °C using scandium triflate .…”

“…At the same time, selectivity only to the target 4 R diastereomer on HNT (79.0 %) was comparable to that for the sum of isomers on K‐10 and K‐30 catalysts (Table ). According to previously published results, the yield of the 4 R ‐isomer was 69 % on illite clay, 65 % on K‐10 and 33.0 % in the presence of H‐K‐10 clay . Thus, the modified halloysite is an excellent catalyst for synthesis of the 4 R ‐diastereomer of chromenols (79.0 %) exhibiting analgesic activity.…”

“…Thus, the modified halloysite is an excellent catalyst for synthesis of the 4 R ‐diastereomer of chromenols (79.0 %) exhibiting analgesic activity. The second order rate constant k for the clays HNT, K‐10 and K‐30 increases with an increase in the a.s. concentration, whereas for AS‐36 the k value was the lowest, which may be related to the presence of micropores …”