2024

A. Yu Sidorenko; Yu M. Kurban; I. V. Il'ina; N. S. Li-Zhulanov; O. S. Patrusheva; V. V. Goltsova; M. P. Bei; A. Aho; J. Wärnå; I. Heinmaa; T. F. Kouznetsova; K. P. Volcho; N. F. Salakhutdinov; D. Yu Murzin; V. E. Agabekov

<p>While synthesis of hydroxymethyl derivatives of common terpenes by a reaction with formaldehyde (FA) has been commercialized, no open data are available on the preparation of such α-pinene derivatives. Here, an approach for the renewable (–)-α-pinene catalytic utilization by its condensation with FA into a novel terpenoid 8-acetoxy-6-hydroxymethyllimonene is proposed. Both common homogeneous acids and aluminosilicates (halloysite nanotubes pretreated with H₃PO₄ and HCl, montmorillonite K-10, zeolite H-Beta-25) have been investigated. The solids were characterized by SEM, EDX, ²⁷Al and ²⁹Si MAS NMR, as well as FTIR with pyridine and N₂ adsorption–desorption methods. Traditional Lewis and Brønsted acids (ZnCl₂, FeCl₃, H₃PO₄ etc.) catalyzed the desired condensation although selectivity did not exceed 24 % in the case of phosphoric acid due to the side reactions, including opening of the α-pinene cyclobutane ring, as well as skeletal rearrangements of its bicyclic structure. On aluminosilicates with a weak to moderate Lewis and Brønsted acidity (45–104 µmol/g), the products of a direct substrate protonation (up to 52.8 %) were predominantly formed. In the presence of strongly acidic H-Beta-25 (301 µmol/g) and phosphoric acid, selectivity to α-pinene addition products with formaldehyde (32.3–35.3 %) and substrate direct protonation (30.0–36.8 %) were comparable. However, with H₃PO₄ the content of borneol derivatives formed via the Wagner-Meerwein rearrangement was the smallest (13.5 %) giving subsequently the largest selectivity to the desired 8-acetoxy-6-hydroxymethyllimonene. Higher selectivity to the target product was observed at lower reaction temperature and a larger formaldehyde amount. The reaction mechanism has been proposed and elucidated using kinetic and quantum chemical approaches. The developed kinetic model adequately describes the experimental results. The DFT calculations showed that in the presence of H₃PO₄ there are no significant differences between the energy of the intermediates formed due to formaldehyde addition to α-pinene or its direct protonation. Synthesis of 8-acetoxy-6-hydroxymethyllimonene was performed on 22 g scale. This compound can be considered as a chiral platform for further utilization, including synthesis of heterocyclic compounds.</p>