TY - JOUR

T1 - Preparation of octahydro-2H-chromen-4-ol with analgesic activity from isopulegol and thiophene-2-carbaldehyde in the presence of acid-modified clays

AU - Sidorenko, A. Yu

AU - Kravtsova, A. V.

AU - Wärnå, J.

AU - Aho, A.

AU - Heinmaa, I.

AU - Il'ina, I. V.

AU - Ardashov, O. V.

AU - Volcho, K. P.

AU - Salakhutdinov, N. F.

AU - Murzin, D. Yu

AU - Agabekov, V. E.

N1 - Publisher Copyright: © 2018 Elsevier B.V.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Prins reaction of (−)-isopulegol with thiophene-2-carbaldehyde to physiologically active substituted octahydro-2H-chromenol (as 4R and 4S diastereomers) was studied in the presence of commercial montmorillonites K-10 and K-30, acid-treated illite and glauconite clays as well as synthetic aluminosilicate AS-36 without of any solvent and in cyclohexane solution. The effect of the reaction temperature, catalyst/reagents ratio, solids drying conditions, and the initial concentrations of reagents on the yield of the desired chromenol and selectivity to diastereomers formation was studied for the first time. The catalysts were characterized by XRF, XRD, MAS NMR, FTIR with pyridine and nitrogen low-temperature sorption methods In the absence of any solvent after 1 h 70.8–99.0% conversion of isopulegol depending on the catalyst was achieved with 78.5–82.0% overall selectivity to octahydro-2H-chromenol. Ratio of 4R/4S diastereomers increased from 3.7 to 4.9 with decrease of the acid sites concentration in the catalyst from 153 to 47 μmol/g. The overall selectivity to chromenol and 4R/4S ratio increased with decreasing the drying temperature of illite clay which indicates preferable formation of 4R isomer in the presence of weak Brønsted acid sites. In cyclohexane as a solvent at same substrate conversion the yield of octahydro-2H-chromenol on illite clay decreases with a decrease in the catalyst/reagents ratio. At 50% isopulegol conversion the 4R/4S ratio increased from 5.7 to 6.8 with a decrease in the initial concentration of reagents from 0.5 to 0.05 mol/l, while the overall selectivity to chromenol decreased from 84.9 to 76.1%. It is established that formation of chromenol and dehydration byproducts (chromenes) occurs both in consecutive and parallel pathways, with only 4R diastereomer undergoing dehydrated. Kinetic modeling was performed to describe quantitatively observed regularities for the first time. Acid-modified illite L-1 clay is a promising catalyst for the synthesis of octahydro-2H-chromenol exhibiting analgesic activity.

AB - Prins reaction of (−)-isopulegol with thiophene-2-carbaldehyde to physiologically active substituted octahydro-2H-chromenol (as 4R and 4S diastereomers) was studied in the presence of commercial montmorillonites K-10 and K-30, acid-treated illite and glauconite clays as well as synthetic aluminosilicate AS-36 without of any solvent and in cyclohexane solution. The effect of the reaction temperature, catalyst/reagents ratio, solids drying conditions, and the initial concentrations of reagents on the yield of the desired chromenol and selectivity to diastereomers formation was studied for the first time. The catalysts were characterized by XRF, XRD, MAS NMR, FTIR with pyridine and nitrogen low-temperature sorption methods In the absence of any solvent after 1 h 70.8–99.0% conversion of isopulegol depending on the catalyst was achieved with 78.5–82.0% overall selectivity to octahydro-2H-chromenol. Ratio of 4R/4S diastereomers increased from 3.7 to 4.9 with decrease of the acid sites concentration in the catalyst from 153 to 47 μmol/g. The overall selectivity to chromenol and 4R/4S ratio increased with decreasing the drying temperature of illite clay which indicates preferable formation of 4R isomer in the presence of weak Brønsted acid sites. In cyclohexane as a solvent at same substrate conversion the yield of octahydro-2H-chromenol on illite clay decreases with a decrease in the catalyst/reagents ratio. At 50% isopulegol conversion the 4R/4S ratio increased from 5.7 to 6.8 with a decrease in the initial concentration of reagents from 0.5 to 0.05 mol/l, while the overall selectivity to chromenol decreased from 84.9 to 76.1%. It is established that formation of chromenol and dehydration byproducts (chromenes) occurs both in consecutive and parallel pathways, with only 4R diastereomer undergoing dehydrated. Kinetic modeling was performed to describe quantitatively observed regularities for the first time. Acid-modified illite L-1 clay is a promising catalyst for the synthesis of octahydro-2H-chromenol exhibiting analgesic activity.

KW - Chromene

KW - Chromenol

KW - Clays

KW - Illite

KW - Isopulegol

KW - Kinetic model

KW - Prins cyclization

KW - Stereoselectivity

KW - NATURAL-PRODUCTS

KW - GLAUCONITE

KW - DISCOVERY

KW - SPECTROSCOPY

KW - VANILLIN

KW - CATALYZED PRINS

KW - MONTMORILLONITE

UR - http://www.scopus.com/inward/record.url?scp=85046709082&partnerID=8YFLogxK

U2 - 10.1016/j.mcat.2018.05.007

DO - 10.1016/j.mcat.2018.05.007

M3 - Article

AN - SCOPUS:85046709082

VL - 453

SP - 139

EP - 148

JO - Molecular Catalysis

JF - Molecular Catalysis

SN - 2468-8231

ER -