L es nouvelles perspectives de l ’ ol ´ eochimie europ ´ eenne Ultrasound-assisted self-metathesis reactions of monounsaturated fatty acids

– An e ﬃ cient protocol for the self-metathesis of oleic acid, using ruthenium catalysts is described. The self-metathesis reaction under ultrasonic activation allows the conversion of monoenic fatty acids such as oleic acid, elaidic acid and erucic acid into diacids and oleﬁns with very short reaction times in the presence of Grubbs ruthenium catalysts. These yields and selectivity towards the desired products are inﬂuenced by the nature of solvents. This study demonstrated that metathesis reaction carried out in DCM or 1-butanol showed promising results, since it produced a variety of products, like n-alkenes and diacids with good yields (45–75%) and high selectivities (75–95%). de l’acide oléique par réaction métathèse utilisant des catalyseurs de ruthénium est décrit dans cet article. La réaction d’homocouplage activée par ultrasons permet d’obtenir avec des temps de réaction très faibles, la conversion d’acides gras insaturés tels que l’acide oléique, l’acide élaïdique et l’acide érucique en diacides et oléﬁnes en présence de catalyseurs au ruthénium de Grubbs. Les rendements et la sélectivité des produits obtenus sont inﬂuencés par la nature du solvant utilisé. Cette étude a démontré que la réaction de métathèse réalisée dans du dichlorométhane ou du 1-butanol donne des résultats prometteurs : elle permet d’obtenir une grande variété d’alcènes et des diacides à longues chaînes avec de bons rendements (45–75 %) et des sélectivités élevées (75–95 %).


Introduction
Vegetable oils high in monounsaturated fatty acids have attained the status of technical oils.Indeed, sunflower cultivation has shifted from traditional food varieties containing 24% oleic acid (OA) to higholeic acid varieties with an OA content of 86 to 87% (Dufaure et al., 1999), with one recently developed variety having an OA content as high as 90 to 92% (Kab, 2000;OLEOVISION;Godard et al., 2013aGodard et al., , 2013b)).The crucifer Crambe abyssinica also appears to be a good source of technical oil as its oil naturally contains 55 to 60% erucic acid, whereas rapeseed oil contains only 40 to 45% erucic acid (Nieschalg and Wolff, 1971).These commercial monounsaturated vegetable oils are now used extensively in chemical processes for manufacturing chemical feedstocks, lubricants, Correspondence: emeline.vedrenne@ensiacet.frdetergents, plastics and polyamides, for example (Van Dyne and Blase, 1990).
Very-high OA oil is considered a pure substance with welldefined chemical and physical characteristics.Its oxidative stability is high due to its very low linoleic acid content (3-10%), and linolenic acid is entirely absent.Its temperature characteristics are also very good, due to its very low saturated fatty acid content (palmitic acid C16: 0.4%, stearic acid C18: 0.2%).
These plants conform well to the concept of oil crop platforms producing technical oils (Carlsson, 2009) but this notion should be extended to monounsaturated fatty acids.In organic synthesis oleic acid (C18:1) and erucic acid (C22:1) are pure chemical substances characterized by exact defined functional groups such as a double bond and a terminal methyl group.They are good candidates for the production of new chemicals, including dibasic acids.For example, the ozonolysis reaction, an oxidative cleavage, converts oleic acid into azelaic acid or erucic acid into brassylic acid with pelargonic acid as a co-product.We recently described an improved oxidative cleavage process, based on the use of catalytic amounts of a peroxo-tungsten complex in the presence of hydrogen peroxide as an oxidant.With OA from a very higholeic acid sunflower oil (VHOSO, 86-87% OA) and commercial erucic acid, these mild and efficient catalytic conditions generated very interesting C9 mono/dibasic acids and dibasic azelaic acid, with excellent yields (Godard et al., 2013a(Godard et al., , 2013b)).
We describe here the continuation of our research into the synthesis of new platform chemicals, and a new process for obtaining long-chain dibasic acids such as 1,18-octadec-9enedioic acid and 1,26-hexacos-13-enedioic acid from oleic, elaidic and erucic acid.The availability of these new unsaturated dibasic acids opens up real possibilities for novel uses in the future.For example, octadec-9-enedioic acid has potential applications in cosmetics due to its inhibition of melanin synthesis, resulting in skin-lightening effects (Wiechers et al., 2005;Bernard and Mahe, 2007;Hansenne and Sore, 2005).Long-chain dibasic acids are also used in numerous industrial applications including the production of synthetic resins, polyesters, polyamides and anticorrosion products (Kroha, 2004).
For academic and industrial purposes, C18 dibasic acid synthesis is based on biopathways involving the ω-oxidation of the terminal methyl group of fatty acids through microbial fermentation (Yang et al., 2011).However, the chemical process is also of potential interest.It does not rely on an oxidative process, but is instead based on redistribution of the olefinic bonds of unsaturated fatty acids via a self-metathesis reaction (Behr et al., 2014;Chikkali and Mecking, 2012;Jenkins et al., 2015;Levin et al., 2015;Meier, 2000;Montero de Espinosa and Meier, 2012;More et al., 2013;Ngo and Foglia, 2009;Nicolaou et al., 2005;Ohlmann et al., 2012;Ozturk et al., 2015;Le Ravalec et al., 2010;Tomasek and Schatz, 2013;Vilela et al., 2012;Vyshnavi et al., 2013;Wels et al., 2013;Winkler and Meier, 2014).For example, Foglia has shown that 1,18-octadec-9-enedioic acid (2) can be obtained with a yield of 71% from oleic acid (1) if it is stirred mechanically at 45 • C for three days in the presence of catalytic amounts of a secondgeneration Grubbs catalyst C1 (Ngo et al., 2006).Octadec-9ene (3) (Scheme 1) was also obtained as a co-product but its yield and use were not discussed in the article.
The main objective of this study was the achievement of self-metathesis reactions for monounsaturated C18:1 and C22:1 fatty acids, in new conditions, such as sonochemical activation in conventional organic solvents or bio-based solvents, to improve the existing processes.

Experimental section
Oleic acid (90%) and erucic acid (90%) were purchased from Sigma-Aldrich.Elaidic acid (96%) was purchased from Alfa Aesar.Grubbs ruthenium catalysts C1-C3 and C4-C6 (Scheme 2) were purchased from Sigma-Aldrich and Omega Cat System, respectively.They were stored under N 2 before use.All solvents were obtained from Sigma-Aldrich and used without further purification.The reactions were performed in air.
Product characterization. 1 H NMR and 13 C NMR were carried out on a Bruker Fourier300 spectrometer (300 MHz for 1 H NMR and 75 MHz 13 C NMR), using CDCl 3 or CD 3 OD as the solvent and tetramethylsilane (TMS) as an internal standard.Infrared spectra were recorded on a Perkin-Elmer FTIR spectrometer (KBr discs).Melting points were determined with a Fisher-Johns melting point apparatus.GC analyses were performed after the methylation of fatty acids with trimethylsulfonium hydroxide (TMSH) dissolved in methyl tert-butyl ether (MTBE).Pentadecanoic acid was used as an internal standard.Chromatograms were obtained with a Varian 3900 GC instrument equipped with a fused silica capillary column (50 m × 0.25 mm × 0.25 µm) and a flame ionization detector (FID).The injector temperature was set at 250 • C. The oven temperature profile was: initial temperature 100 • C, held for 2 min, ramp of 8 • C/min to 180 • C, held for 10 min, ramp of 10 • C/min to 250 • C, held for 5 min.Measurements were performed in the splitless and split-split modes (ratio 1:100) using helium as the carrier gas (flow rate 1.2 ml/min).
General procedure for ultrasound-assisted self-metathesis reactions.A 15 ml vial equipped with a magnetic stirrer was charged with a 20 mmol solution of the chosen fatty acid, the ruthenium catalyst (0.02 mmol, 0.1 mol%) and the appropriate solvent.The reaction mixture was exposed to ultrasonic irradiation delivered by a microtip probe connected to a 500 W Sonics Vibracell Ultrasonic machine (W75042) from Fisher Bioblock Scientific operating at 20 kHz at 20% of the maximum power output.The resulting mixture was filtered through a silica gel pad, and washed with solvent.The solvent was removed under reduced pressure, yielding the crude product, which was characterized by GC and purified by chromatography on a silica gel column (cyclohexane/ethyl acetate: 10/0 to 7/3 v/v).

Results and discussion
Based on the work published by Foglia, we first carried out a self-metathesis reaction on oleic acid (1) in the presence of catalytic amounts of a second-generation Grubbs catalyst C1 D507, page 2 of 6 M.K. Elmkaddem et al.: OCL 2016, 23(5) D507 Schema 1. Self-metathesis of oleic acid (1).Schema 2. Catalysts used (C1-C6) for the self-metathesis reactions.
[d] Yields were determined after purification by flash chromatography on silica gel.
A viscous precipitate formed during these reactions.We assumed that this was due to molecular interactions between the ruthenium-based carbene complex and oleic acid, and concluded that some catalyst may have stuck to the wall of the reaction vial, thus limiting reaction yields.An ultrasound probe was used to ensure effective mixing (Gulajski et al., 2008;Jakobs and Sijbesma, 2012;Piermattei et al., 2009;Sacco et al., 2015;Sari et al., 2013).With sonication and in the absence of solvent, higher rates of oleic acid conversion were observed after only 5 h of reaction (Tab. 1, entry 1 vs. Tab.2, entry 1).However the yields of compounds ( 2) and (3) D507, page 3 of 6 Dossier M.K. Elmkaddem et al.: OCL 2016, 23(5) D507 Schema 3. Self-metathesis reactions of elaidic acid (4) and erucic acid (5).
A kinetic study was then conducted to optimize the reaction time.The OA consumption and the appearance of (2) and (3) were monitored by GC.Maximal conversion was achieved in one hour, so subsequent assays were carried out with this reaction time.
Different solvents were then screened.Alcohols with various chain lengths were tested (Tab.3, entries 2-6).A general trend was found towards alcohols with longer chains giving the best conversion rates and yields.This was probably due to the higher solubility of oleic acid in less polar solvents (Hoerr and Harwood, 1952).The use of iso-hexane resulted in similar yields of the desired compounds (Tab.3, entries 7).We also tested chlorinated solvents.The use of chloroform and dichloromethane (Tab.3, entries 8-9) did not significantly improve the results, indicating that the self-metathesis of oleic acid can be achieved in green solvents, such as 1-butanol, with the same reactivity as in conventional metathesis solvents.
We broadened the scope of the reaction, by considering the self-metathesis reactions of elaidic (4) and erucic (5) acids (Scheme 3).In the presence of 0.1 mol% catalyst, these fatty acids gave rise to the desired alkenes and diacids after one hour of sonication in 1-butanol or dichloromethane.The same products, (2) and (3) were obtained whether we started from elaidic acid or oleic acid (Tab.4, entries 1-4).However, elaidic acid gave a lower conversion rate and yield, because the cis double bond of oleic acid was more reactive than the trans isomer of elaidic acid in metathesis conditions (Chatterjee et al., 2003).In particular, a diacid with a 26-carbon chain was obtained with a yield of 58% yield, through the self-metathesis of erucic acid (Tab.4, entries 5-6), demonstrating the great potential of this process for generating verylong chain alkenes and diacids from renewable resources.

Conclusion
In summary, we describe here a new process for the selfmetathesis of fatty acids, based on the use of sonication to activate this ruthenium-catalyzed reaction, which can be performed with very short reaction times in a green solvent.These mild, efficient and greener reaction conditions give good yields of the desired long-chain diacids, along with longchain olefins.These interesting alkenes should be considered not only as by-products, but also as new biosourced platform molecules with potential uses in lubricant applications, for example.