Transformación de monoterpenos usando rutas catalíticas one-pot con materiales heterogéneos

Abstract

ABSTRACT : The valorization of biomass offers a sustainable approach to producing high-value-added chemicals. In particular, monoterpenes such as α- and β-pinene can be extracted from various types of pine trees, and limonene can be obtained from agro-industrial waste like fruit peels. These substrates contain highly reactive double bonds, which can be transformed into valuable chemicals through catalytic routes such as epoxidation. Subsequent reactions can yield epoxide isomers, including myrtanal, myrtenol, and perillyl alcohol from β-pinene epoxide, as well as dihydrocarvone (cis + trans) and carveol from limonene-1,2-epoxide. These products have numerous applications in medicinal chemistry due to their anti-inflammatory and anxiolytic-like effects, in-vitro inhibitory activity, and as intermediates in organic synthesis for the flavor and fragrance industry. This thesis focuses on achieving two catalytic transformations of monoterpenes using the onepot concept. The challenge of discovering new methodologies to synthesize these molecules has significantly motivated research efforts toward optimizing novel catalytic transformations. An attractive target is conducting one-pot reactions, where all consecutive and simultaneous transformations occur in a single reactor. This approach offers substantial advantages, including reduced operation time, maximized energy efficiency, simplified overall processes, and minimized material loss from multiple reaction and purification units. Despite the challenges in controlling multistep reactions and finding compatible reaction conditions, which limit the broad applicability of one-pot catalytic routes, this thesis addresses these issues. It begins by examining independent catalytic routes (epoxidation and isomerization) and subsequently explores one-pot routes. The primary challenge in the latter lies in identifying compatible reaction conditions. The oxidation of monoterpenes over heterogeneous catalysts is one of the most important organic transformations, occurring through two competitive pathways: double bond epoxidation and allylic oxidation. The predominance of each route depends on the substrate´s nature, the oxidizing agent, reaction conditions, and the physicochemical properties of the catalysts. Additionally, the isomerization of monoterpene epoxides significantly depends on the acidity type of the catalyst (Lewis or Brønsted), the solvent type (polarity, donor number), and the architecture of the catalyst. Therefore, it is necessary to methodologically investigate the two independent pathways (epoxidation and epoxide isomerization) and then combine the insights to achieve the one-pot route. The first part of this thesis (Chapter 2 and Chapter 3) explores heterogeneous catalysts for the epoxidation of R-(+)-limonene. Two catalytic systems were evaluated: commercial magnesium oxide (Chapter 2) and catalysts based on metal-modified hierarchical zeolite Y (Chapter 3). For MgO, the epoxidation was conducted in a Payne reaction system using H2O2 and acetonitrile as an activator, achieving high yields of limonene epoxide (80%) and diepoxide (96%) under optimized conditions (50 ºC, 30 min for epoxide, and 2 h for diepoxide). Particularly, limonene diepoxide has recently emerged for use in biomedical applications. Characterization of both fresh and spent MgO catalyst revealed their suitability over four cycles. Mechanistic insights included the description of peroxyacetimidic acid as an intermediate oxidant and modeling using reversible and Eley-Rideal models. For the zeolite Y catalyst, detailed characterization highlighted the superiority of Sn-modified dealuminated zeolite Y, showing a high turnover frequency (TOF) of 96 h-1. This catalyst exhibited optimal properties such as a low Brønsted to Lewis acidity ratio (0.1), significant mesoporosity (43%), and a specific surface area of 465 m2 g-1. Operational conditions yielding high limonene conversion (97%) and selectivity to monoepoxides (up to 96%) included 70 ºC, H2O2:limonene molar ratio = 7, and acetonitrile as a solvent. The hydration of internal epoxides to limonene diol was favored under specific conditions, with H2O2 efficiency reaching 85%. A plausible reaction pathway for the epoxide formation was proposed over the dealuminated zeolite. The second part (Chapter 4 and Chapter 5) focuses on mesoporous catalysts derived from dendritic ZSM-5 zeolites for the isomerization of monoterpene epoxides, specifically α-pinene epoxide, β-pinene epoxide, and limonene-1,2-epoxide (LE). Among these, dendritic ZSM-5 synthesized with a crystallization time of 4 days exhibited exceptional catalytic activity, achieving a turnover frequency (TOF) of 4.4 min-1 for LE isomerization. Detailed characterization underscored its favorable properties, including a low Brønsted to Lewis acidity ratio (1.4), substantial mesopore/external surface area (360 m2 g-1), and a narrow mesopore size distribution. These attributed facilitated significant yields of campholenic aldehyde (72.4%, 70 ºC, 5 min), myrtanal (47.7%, 50 ºC, 5 min), and dihydrocarvone (63%, 70 ºC, 2 h). The investigation delved into the kinetics and mechanisms governing LE isomerization using the highly active dendritic zeolite. The catalyst demonstrated superior efficiency in producing dihydrocarvone diastereoisomers. Ethyl acetate emerged as an optimal green solvent, promoting selective dihydrocarvone formation. Kinetic modeling, augmented by statistical analysis of a reaction network, elucidated activation energies for cis-dihydrocarvone and trans-dihydrocarvone formation, supported by DFT calculations. Notably, carbocation formation (ΔEact = 234 kJ mol-1) was identified as the rate-determining step, highlighting the catalyst’s efficacy in facilitating LE conversion under mild conditions. The last part of the thesis (Chapter 6) investigates metal-modified mesoporous catalysts supported on MCM-41 and SBA-15, in conjunction with MgO, for the one-pot tandem transformation of β-pinene. This process involves epoxidation with H2O2 followed by isomerization to produce myrtanal as major product. Metals (Sn, Fe, Cu, and Co) were incorporated via wetness impregnation, and the resulting catalysts were characterized using several techniques. Among the catalysts, Fe/SBA-15 achieved the highest myrtanal yield (63%) with a H2O2 efficiency of 60%. This catalyst demonstrated a total acidity of 138 μmol g-1, a surface area of 496 m2 g-1, and a pore volume of 0.96 cm3 g-1. While Sn-based catalysts also showed high selectivity for myrtanal, Cu-based catalysts performed poorly, and Co catalysts were ineffective due to H2O2 decomposition. Lewis acidity and acid site density were used as descriptors for catalytic performance. The most active catalysts exhibited excellent reusability and no detectable Fe leaching. A plausible reaction pathway for the β-pinene to myrtanal transformation was proposed based on the material characterization and the catalytic results.