Selective Removal of Chlorinated Impurities from (R)-Carvone Using an Industrial Alkaline Sulfite Process
Keywords:
carvone, dichlorination, impurities, ketones, limonene, terpene.Abstract
Chlorinated impurities present in crude (R)-Carvone, (C10H14O), preferred IUPAC name 2-Methyl-5-(prop-1-en-2-yl) cyclohex-2-en-1-one, resulted in chemical synthesis, represent a significant challenge for its utilization, as they may compromise product stability, safety and applicability in food, fragrance and pharmaceutical formulations. This study presents an industrial validated process, for the selective removal of chlorinated compounds, using an alkaline sulfite system, under moderate reaction conditions. The method employs a biphasic mixture of sodium hydroxide (NaOH), sodium sulfite (Na2SO3), isopropanol (C3H8O) and controlled acetic acid (C2H4O2) addition, in a stirred reactor, equipped with reflux and solvent recovery units, followed by solvent distillation and recycling steps. Process operates at temperatures between 60 and 900C and includes a closed loop recycling stage, which improves reagent utilization and reduces waste generation. The proposed approached enables efficient conversion and removal of chlorinated terpene impurities, while preserving the structural integrity of the targeted ketone. The integration of reaction and purification in a single industrial unit, combined with solvent recovery and neutralization stages, provides a scalable and economically attractive solution for the production of hi purity (R)-Carvone. This work demonstrates a practical and selective dichlorination strategy suitable for large scale terpene processing.
References
Albert T.L., Elena A.D., Tomas B.L., Mojca B.K., Polonca T., Aqueous Chlorination of D-Limonene, Molecules 2022, 27(9), 2988;
Kala R.N.K., Puranik V.G., Gopinathan C., Ramaswamy A.V., Selective oxidation of limonene over sodium salt of cobalt containing sandwich-type polyoxotungstate, Applied Catalysis A: General Volume 256, Issues 1–2, 30 December 2003, Pages 265-273;
Juan B., Alejandro L., Francisco P., Pablo T., Daniel P., Daniel L., Eduardo D., Liquid phase oxidation of limonene catalyzed by palladium supported on hydrotalcites, Applied Catalysis A: General Volume 253, Issue 1, 20 October 2003, Pages 177-189;
Lulu Z., Wanying W., Zixuan W., Weimin S., Haoliang L., Jinchu Y., Zhenzhen H., Gang F., Jingnan R., Yujiao C., Aiqun Y., Jian F., Biotransformation of limonene: pathways, biocatalysts, and applications, Food Bioscience Volume 69, July 2025, 106812;
Trissa J., Halligudi S.B., Oxyfunctionalization of limonene using vanadium complex anchored on functionalized SBA-15, Journal of Molecular Catalysis A: Chemical Volume 229, Issues 1–2, 29 March 2005, Pages 241-247;
Marcela C., Alessandra C., Sibele B.C.P., Maria C.E., Christiane F., Cláudio D., Kátia B.G., Oestreicher E.G., Antunes O.A.C., Catalytic oxidation of limonene, α-pinene and β-pinene by the complex [FeIII(BPMP)Cl(μ-O)FeIIICl3] biomimetic to MMO enzyme, Catalysis Today, Volumes 133–135, April–June 2008, Pages 695-698;
Marcio J.S., Patricia R.D., Luciano Menini, Elena V. Gusevskaya, Cobalt catalyzed autoxidation of monoterpenes in acetic acid and acetonitrile solutions, Journal of Molecular Catalysis A: Chemical Volume 201, Issues 1–2, 1 July 2003, Pages 71-77;
Oliveira P., Machado A., Ramos A.M., Fonseca I., Braz Fernandes F.M. Botelho do Rego, A.M., Vital J., MCM-41 anchored manganese salen complexes as catalysts for limonene oxidation, Microporous and Mesoporous Materials Volume 120, Issue 3, 15 April 2009, Pages 432-440;
Martin L.M.A., Yates M., Diaz M., Saez R.E., Gonzalez G.L., Renewable fine chemicals from rice and citric subproducts: Ecomaterials, Applied Catalysis B: Environmental Volume 106, Issues 3–4, 11 August 2011, Pages 488-493;
Isabel C.M.S.S., José A.F.G., Tiago A.G.D., Mário M.Q.S., Graça P.M.S.N., José A.S.C, Ana M.V.C., Catalytic homogeneous oxidation of monoterpenes and cyclooctene with hydrogen peroxide in the presence of sandwich-type tungstophosphates [M4(H2O)2(PW9O34)2] n−, M = CoII, MnII and FeIII, Journal of Molecular Catalysis A: Chemical, Volume 426, Part B, January 2017, Pages 593-599;
Diana L.G., Lina M.G., Aída L.V., Catalytic oxidative dehydrogenation of carveol to carvone over the phthalocyanine complex FePcCl16 immobilized on the mesoporous silica SBA-15, Applied Catalysis A: General, Volume 541, 5 July 2017, Pages 15-24;
Agnieszka W., Edyta M., Jacek M., Zvi C. K., Beata M., Oxidation of limonene over molybdenum dioxide-containing nanoporous carbon catalysts as a simple effective method for the utilization of waste orange peels, Reaction Kinetics, Mechanisms and Catalysis (2018) 125:843–858;
Alicja G, Agnieszka W, Limonene oxidation over Ti-MCM-41 and Ti-MWW catalysts with t-butyl hydroperoxide as the oxidant, Reac Kinet Mech Cat (2018) 124:523–543;
Virginia M.V., Analía L.C., Deicy B., Karim S., Griselda A.E., Sandra G.C., Limonene oxyfunctionalization over Cu-modified silicates employing hydrogen peroxide and t-Butyl hydroperoxide: Reaction pathway analysis, Molecular Catalysis Volume 481, February 2020, 110234;
Virginia M.V., Griselda A.E., Analía L.C., Sandra G.C., Catalytic performance of V-MCM-41 nanocomposites in liquid phase limonene oxidation: Vanadium leaching mitigation, Microporous and Mesoporous Materials, Volume 311, February 2021, 110678;
Jaime A.B., Juan M.G., Aída L.V., Comparison by Life-Cycle Assessment of Alternative Processes for Carvone and Verbenone Production, Molecules 2022, 27(17), 5479;
Jiangyong L., Hui T., Panming J., Bing L., Oxygen-vacancy defect engineering to boost the aerobic oxidation of limonene over Co3O4 nanocubes, Applied Catalysis B: Environmental, Volume 334, 5 October 2023, 122828
Jaime A.B., Juan M. G. Aída L.V, Comparison by Life-Cycle Assessment of Alternative Processes for Carvone and Verbenone Production, Molecules 2022, 27(17), 5479;
Albert T.L., Elena A.D, Tomas B.L., Mojca B.K., Polonca T., Aqueous Chlorination of D-Limonene, Molecules 2022, 27(9), 2988;
Hayat M.M., Nishant K., Amandeep S., Abhay S., Priyanka P., Prince A.M. Isolation, Purification and Characterization of L-Carvone from Mentha longifolia Using Fractional Distillation and Quantified by Gas Chromatography, Pharmacogn. Res., 2024; 16(1):156-160;
BenchChem Technical Support Team, Purification of (-) Carvone from Crude Spearmint Oil, BenchChem, Compound Name: (-)-Carvone, CAS No.: 6485-40-1, Cat. No.: B1668593;
Jalil M.S., Mohammad T.E., Mahdi A., Steps to achieve carvone-rich spearmint (Mentha spicata L.) essential oil: a case study on the use of different distillation methods, Frontiers in Plant Science, Volume 14 – 2023;
Rupali S.P., Bhalchandra M.B., One-pot hydroformylation/hydrogenation of bio-renewable (R)-carvone in a recyclable Rh-catalyzed aqueous biphasic medium: Targeting dual remote sites with a single catalyst, Molecular Catalysis, Volume 580, 1 June 2025, 115102;
Dami P.S., Ellen R., Timothy J.B., Synthesis of (R)-(–)-Carvone Derivatives, De Gruyter Brill, Z. Naturforsch. 2010, 65b, 1381 – 1383.
