catalysts Article Catalytic Epoxidation of 3-Carene and Limonene with Aqueous Hydrogen Peroxide, and Selective Synthesis of α-Pinene Epoxide from Turpentine Vladislav V. Fomenko * , Sergey S. Laev and Nariman F. Salakhutdinov N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry Siberian Branch of RAS, 9 Lavrentiev Avenue, 630090 Novosibirsk, Russia; [email protected] (S.S.L.); [email protected] (N.F.S.) * Correspondence: [email protected]; Tel.: +7-383-330-97-47 Abstract: The epoxidation of turpentine (technical α-pinene), 3-carene, and limonene with aqueous hydrogen peroxide was studied in a new catalytic system employing manganese sulfate, salicylic acid, sodium bicarbonate, and acetonitrile, as a polar solvent. The proposed approach makes it possible to carry out a “chemical separation” of turpentine components, yielding valuable individual derivatives of monoterpenes without the need to isolate individual monoterpene reagents. Specific methods have been developed for the production of α-pinene epoxide, 3-carene epoxide, limonene diepoxide, as well as for two related compounds: 3-carene-5-one and 3-carene-2,5-dione. Keywords: epoxidation; turpentine; α-pinene; α-pinene epoxide; 3-carene; 3-carene epoxide; limonene; Citation: Fomenko, V.V.; Laev, S.S.; limonene diepoxide; aqueous hydrogen peroxide Salakhutdinov, N.F. Catalytic Epoxidation of 3-Carene and Limonene with Aqueous Hydrogen Peroxide, and Selective Synthesis of 1. Introduction α-Pinene Epoxide from Turpentine. Catalysts 2021, 11, 436. https:// An epoxidation reaction is one of the important methods for the functionalization of doi.org/10.3390/catal11040436 terpenes, with established industrial applications. Monoterpenes obtained from widely available and renewable raw plant materials are of particular interest, as they are starting Academic Editors: compounds for the production of valuable synthons. The most easily accessible natural Sébastien Leveneur, Vincenzo Russo, monoterpenes are β-pinene, α-pinene 1, 3-carene 2, and limonene 3. The epoxides of these Pasi Tolvanen, Broggini Gianluigi and terpenes can be used for the synthesis of intermediates used in various fragrance, perfumery Victorio Cadierno and pharmaceutical preparations [1,2], as well as in substances having a sweet taste [3]. Another promising use of α-pinene epoxide 4 is its transformation into pinocarveol and Received: 5 March 2021 3-pinanone [4]. Additionally, 3-carene epoxide 5 can be used to obtain carandiols [5]. One Accepted: 25 March 2021 of the limonene epoxides has recently been used as a source of chirality in the synthesis of Published: 29 March 2021 methylphosphonate oligonucleotides [6]. The epoxidation of β-pinene, α-pinene 1, 3-carene 2, and limonene 3 has been reviewed Publisher’s Note: MDPI stays neutral in the literature [7]. Currently, organic peracids and organic peroxides as double bond with regard to jurisdictional claims in oxidizers are being more often replaced by ordinary aqueous hydrogen peroxide. This published maps and institutional affil- oxidizing agent is readily available, environmentally friendly, and practically waste-free. iations. For sterically hindered α-pinene 1, low reactivity, low conversion, and low yield of epoxide 4 are often observed [7]. Different oxidizing agents may be used: oxygen with additives of cobalt (II) complexes [8,9], air as an oxygen source [10,11], sodium hypochlorite [12], meta-chloroperbenzoic acid [13], and hydrogen peroxide at various concentrations [13–17]. Copyright: © 2021 by the authors. In at least one instance [14], epoxidation of α-pinene 1 was achieved by the action of 30% Licensee MDPI, Basel, Switzerland. hydrogen peroxide (10 equivalents) in the presence of manganese sulfate (0.01 equiv.), This article is an open access article and NaHCO3 in an aqueous solution of dimethylformamide (DMF). The resulting yield distributed under the terms and of epoxide 4 was 54%, but the reaction times were significant and the isolation of the conditions of the Creative Commons product challenging, as it requires a high-boiling solvent. A similar situation is described in Attribution (CC BY) license (https:// another work [16]. Recently [18–23], other methods of epoxidation of α-pinene 1 have been creativecommons.org/licenses/by/ 4.0/). described that rely, in particular, on catalysts immobilized on magnetic particles [21,22]. Catalysts 2021, 11, 436. https://doi.org/10.3390/catal11040436 https://www.mdpi.com/journal/catalysts Catalysts 2021, 11, 436 2 of 8 3-Carene 2 is usually referred to as an olefin that readily participates in the epoxidation reaction [7]. As oxidizing agents, it is possible to use peracetic acid [5,24] or hydrogen per- oxide [5,15,17,25] at various concentrations and at different temperatures. In the oxidation of 3-carene 2 with 35% hydrogen peroxide in the presence of a rhenium catalyst at room temperature [25], the yield of 3-carene epoxide 5 was 75%. However, the required catalyst is expensive and hard to find, and the use of a toxic pyridine is clearly a drawback. The oxidation of limonene 3 with hydrogen peroxide has received a lot of attention in the literature [7]. However, it should be noted that monoepoxidations, at the double bond in the ring and in the side chain, require difficult-to-find and expensive catalysts: molybdenum [26] and vanadium [27], respectively. Monoepoxidation of limonene has also been described [23,28–32]. The use of 60% hydrogen peroxide and of a conventional catalyst—chromatography grade aluminum oxide—leads to the formation of a mixture of both mono derivatives of limonene and its diepoxide—the reaction requiring the creation of an inert atmosphere [33]. Our interest was drawn to the epoxidation of limonene 3 by the action of 35% aqueous hydrogen peroxide in the presence of methyltrioxorenium [1]. To obtain a 90% content of limonene diepoxide 8 in the reaction mixture, we employed a 3.4-fold molar amount of hydrogen peroxide and 1 molar percent of the catalyst was used; the reaction was carried out for 40 h at 0 ◦C;. In our previous communication [34], we studied the epoxidation of β-pinene with hydrogen peroxide in a reaction mixture containing water, sodium bicarbonate, and man- ganese salts. Methanol, DMF, and acetonitrile were used as the required polar organic solvents, and it was found that the reaction was accelerated by the addition of salicylic acid. Optimum epoxidation was obtained in the presence of acetonitrile, sodium bicarbonate, manganese sulfate, and salicylic acid during oxidation with 35%–38% aqueous hydrogen peroxide at 18–22 ◦C. A quantitative tandem 1H NMR-GLC method was also developed in order to determine the content of β-pinene and its labile epoxide. In this work, we ex- tended the application of our catalytic system to other monoterpenes: α-pinene 1, 3-carene 2, and limonene 3. We also developed methods for the preparation of epoxides of these monoterpenes, and selectively obtained α-pinene 4 epoxide from turpentine. 2. Results and Discussion Our objective was to develop a simple, economical, and technologically sound method to produce α-pinene epoxide 4. To this aim, we epoxidized turpentine (technical α-pinene 1), which contained ~ 75% of the main substance, according to the combined data obtained by GLC and gas chromatography-mass spectrometry [34]. The cost of the technical product is about two orders of magnitude lower than that of commercial α-pinene 1. The strategy to achieve this result consisted of setting up a gradual interaction of technical α-pinene 1 with 36% aqueous hydrogen peroxide in aqueous acetonitrile in the presence of a cat- alytic system, which included manganese sulfate, bicarbonate sodium and salicylic acid (Scheme1 ). Hydrogen peroxide was used in a tenfold molar amount, and manganese sulfate was used in an amount of 2 percent molar amount relative to the loaded substrate. The products of interest—α-pinene epoxide 4, unreacted α-pinene 1, side monoterpenes and their oxidation products—were recovered from the reaction mixture using methylene chloride. After concentrating the extract, α-pinene epoxide 4 was isolated by vacuum distillation in 30% yield. The epoxidation system has a typical selectivity for epoxidation with peracids, so the usual selectivity is observed for α-pinene, namely 2,3-epoxy-cis-pinan 4 is formed. A fraction with a high content of α-pinene 1 was also isolated, which was then subjected to reoxidation using the above procedure. The composition of the reaction mixtures and the structures of the obtained compounds were determined by 1H NMR, GLC and gas chromatography-mass spectrometry, and by comparing the spectra with those described earlier in the literature [35]. Catalysts 2021, 11, x FOR PEER REVIEW 3 of 8 Catalysts 2021, 11, x FOR PEER REVIEW 3 of 8 determined by 1H NMR, GLC and gas chromatography-mass spectrometry, and by com- Catalysts 2021, 11, 436 paring the spectra with those described earlier in the literature [35]. 3 of 8 determined by 1H NMR, GLC and gas chromatography-mass spectrometry, and by com- paring the spectra with those described earlier in the literature [35]. Scheme 1. Preparation of α-pinene epoxide 4 by epoxidation of α-pinene 1 of turpentine. Scheme 1.1. Preparation of αα-pinene-pinene epoxideepoxide 44 byby epoxidationepoxidation ofof αα-pinene-pinene 11 ofof turpentine.turpentine. In addition to its simplicity, the proposed method for producing epoxide 4 offers two advantages: (i), the epoxidation of α-pinene 1 is achieved by the action of simple, cheap, InIn additionaddition toto its simplicity, thethe proposedproposed methodmethod forfor producingproducing epoxideepoxide 44 offersoffers twotwo and commercially available reagents, and (ii), inexpensive technical α-pinene is used as advantages: (i), the epoxidation of α-pinene 1 is achieved by the actionaction ofof simple,simple, cheap,cheap, the starting compound. Although, in our work, we did not use the distillation residue and commerciallycommercially availableavailable reagents,reagents, andand (ii),(ii), inexpensiveinexpensive technicaltechnical αα-pinene-pinene isis usedused asas containing valuable products of the transformation of β-pinene, 3-carene, and limonene; thethe startingstarting compound.compound.