From Olive Pomace to Squalane: A Green Chemistry Route Using 2-Methyltetrahydrofuran

Abstract

Squalene (SQE) is a key triterpene used in pharmaceuticals, nutraceuticals and cosmetics. Although olive pomace (OP) is a sustainable source of SQE, conventional hexane extraction raises environmental and health concerns. This study investigates the potential of 2-methyltetrahydrofuran (2-MeTHF) as a greener alternative for SQE extraction and catalytic hydrogenation to squalane (SQA); a high-value compound in industrial applications. 2-MeTHF provided 83% SQE recovery from OP, which was further concentrated in deodorizer distillates during refining. SQE hydrogenation in 2-MeTHF significantly improved reaction efficiency at lower temperatures (60 °C, 3 bar H₂, 0.5 mol % Pd/C), enabling full conversion within 1 h. This represents a major advantage over conventional industrial hydrogenation, which requires harsher conditions (200 °C, 4–30 bar H₂) and longer reaction times (6–7 h). In order to assess industrial feasibility, SQE from OP deodorizer distillates (6.8 wt %) was concentrated via saponification and molecular distillation (∼34 wt %), followed by flash chromatography (59 wt % purity, 85% recovery). However, residual impurities caused catalyst poisoning, lowering the SQA yield to 19.8%. This study highlights 2-MeTHF’s potential for industrial-scale SQE valorization via integrated extraction and hydrogenation. Future efforts should focus on improving SQE purification from OP-DDs and enhancing catalyst recyclability.

Introduction

Squalene (SQE) is a linear triterpene that is frequently used in pharmaceuticals, food supplements and cosmetics due to its multiple functions. (1) SQE acts as a biochemical precursor to sterols and terpenoids, which play a central role in the functions of plants, animals and humans. (2)

Originally identified in the early 20th century by Tsujimoto in deep-sea shark liver oils, SQE is known for its anticancer, antioxidant, detoxifier and skin emollient activities. (3) SQE has traditionally been extracted from shark liver oil (40–80% of the total oil), raising conservation concerns due to declining shark populations. (4) SQE of over 98 wt % purity is obtained from shark oil through a single vacuum distillation at 200–230 °C. (5) Alternative sources, such as plant-derived SQE from vegetable oils and refining byproducts, have attracted attention due to their sustainability and potential to meet market demand. (6) Olive oil, with ∼564 mg/100 g of SQE, is the main plant source for SQE extraction. (4)

Recent advancements in synthetic biology have enabled the engineering of microorganisms for enhanced SQE production, offering the potential for large-scale manufacturing. (7) Additionally, phytosqualene can be derived from trans-β-farnesene, which is produced through the fermentation of sugar cane by genetically modified Saccharomyces cerevisiae and then converted to SQA via catalytic dimerization and hydrogenation. (8)

The recovery of SQE from olive pomace (OP) oil has emerged as a viable alternative, particularly when using deodorizer distillates (DDs) obtained during the physical refining of the oil. OP contains approximately 10% oil by dry weight and is typically extracted using hexane. In a previous study, we have demonstrated that 2-methyltetrahydrofuran (2-MeTHF) is a valuable green alternative to hexane for the extraction of OP oil. (9) The main advantages of this solvent are its biodegradability, its fully biobased character and its toxicological profile, which is safer than that of hexane. In addition, its use in industrial systems is economically advantageous compared to other alternatives such as ethanol (EtOH), due to its lower latent heat of vaporization (364 vs 846 kJ/kg) and supercritical CO2, which requires higher capital investment. (10) 2-MeTHF has also already been approved for food production in Europe. (11)

Due to its high acidity, OP oil requires refining and deodorization. OP-DDs have proven to be a rich source of SQE. (6) Bondioli et al., have analyzed various types of OP-DDs and have reported SQE yields ranging from 224 to 452 mg/g DDs. (12) Two processes are typically used to increase SQE concentration; the esterification of fatty acids and separation of high purity (>95%) SQE via vacuum distillation, and the extraction of the unsaponifiable fraction with hexane to recover SQE with a maximum purity of around 80%. (5)

Due to its chemical structure, in particular its high degree of unsaturation, SQE is very unstable and easily oxidized. (13) One of the key transformations of SQE is its catalytic hydrogenation to squalane (SQA). (14) SQA is widely used in nutraceutical and cosmetics ingredients, because of its proven emollient and moisturizing properties. (13) Regardless of its source, SQE must be converted to SQA at over 92% purity and with an iodine value of below 1.00 (preferably <0.10) for cosmetic use. (5)

SQE hydrogenation is traditionally conducted in stirred tank reactors, with high loadings of Ni- and Pd-based catalysts under harsh conditions and/or over extended reaction times. (1) Suboptimal process conditions are typically employed on an industrial scale in a two-step, one-pot process. The first step is carried out at low H2 pressure, followed by a second step at higher H2 pressure and higher temperature to achieve complete reduction. Ni-based catalysts have long been used in hydrogenation processes, mainly due to Ni’s lower cost compared to Pd. (15) However, Ni-catalysts require higher metal loading and temperatures. Recently, various Pd-based catalysts have been used for the hydrogenation of SQE, either with or without solvent, including carbon-nanotube-supported Pd, (1) Pd/C, (16) sol–gel-entrapped SiliaCat Pd(0), (14,17) and Pd/clay. (18)

Figure 1. Integrated industrial process for SQA production from OP using 2-MeTHF as a green solvent.