Diastereoselective synthesis of diisoeugenol in presence of catalyst
Through the [3+2] cycloaddition reaction of sulfonic acid and metal complex catalyst, the problems of low yield and insufficient selectivity of diisoeugenol synthesis were solved, and efficient and environmentally friendly industrial production was achieved.
Patent Information
- Application Number
- CN202380084250.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-12-07
- Filing Date
- 2023-12-07
- Publication Date
- 2025-08-12
AI Technical Summary
In the prior art, when preparing diisoeugenol and its derivatives, there are problems of low yields and insufficient diastereoelectivity, making it difficult to achieve effective production on an industrial scale, and the synthesis process is not environmentally friendly.
Diisoeugenol is synthesized by [3+2] cycloaddition reaction using a catalyst containing sulfonic acid and metal complex, such as AgOTf, AuCl or Cu(OTf)2, etc., and a green solvent such as anisole is used to optimize the reaction conditions to improve yield and selectivity.
The high yield and high diastereoselective synthesis of diisoeugenol and its derivatives is achieved, simplifying the synthesis process, saving energy and reducing purification steps, suitable for industrial applications.
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Figure CN120476100A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the synthesis of an isomer of diisoeugenol or one of its derivatives, and more particularly to a cycloaddition reaction involving isoeugenol or one of its derivatives in the presence of a catalyst.
[0002] In the text of the specification, the following references are indicated as follows: [ ]; they are also listed in a reference table. Background Art
[0003] Isoeugenol, used as a raw material for the synthesis of diisoeugenol, is an isomer of eugenol. Eugenol is a natural phenol that can be obtained from a variety of plants, particularly clove buds, cinnamon bark, holy basil leaves, turmeric, pepper, ginger, oregano, and thyme [1]. Isoeugenol, a positional isomer of eugenol, is one of the main volatile products emitted by petunia hybrida [2]; and isoeugenol can also be isolated from clove oil [3] or lignin [4]. Alternatively, isoeugenol can be synthesized by isomerization of eugenol [5].
[0004] Therefore, in addition to the isolation of isoeugenol from natural sources, the isomerization of eugenol makes it possible to obtain isoeugenol via several synthetic routes, all of which involve isomerization reactions of the C-C double bond. Isoeugenol can be synthesized from eugenol in alkaline medium and / or in the presence of metal catalysts, with the ratio between the various positional isomers obtained being variable depending on the synthetic route considered [6-13].
[0005] Isoeugenol itself is the preferred reactant for the preparation of diisoeugenol, and it is known to prepare diisoeugenol from isoeugenol by catalysis in the presence of strong Bronsted acids such as HCl
[14] , or by using UV irradiation
[15] , or even by electrochemical processes
[16] ; however, these various methods must be carried out under overly stringent conditions (high acid and / or catalyst loading, reflux for hours, etc.) and / or provide too low yields or selectivities.
[0006] In order to obtain the desired products from the same reactants, other reactions were developed, and the first synthetic route for the preparation of diisoeugenol identified as belonging to "green chemistry" was carried out using a composite catalytic system incorporating BF3·OEt2 or FeCl3 or SiO2-OSO3H; using this route involving a [3+2] cycloaddition, no more than 80% of the isomers with the γ-diisoeugenol configuration could be isolated
[17] .
[0007] The last synthetic route proposed above has the advantage of showing the sought diastereoselectivity, given that diisoeugenol has three asymmetric carbons and thus produces six possible diastereomers (or diastereomers), including two diastereomers: α-diisoeugenol and γ-diisoeugenol. The main obtaining of γ-diisoeugenol is a breakthrough in this respect, although the yield is still too low.
[0008] The following figure contains the main molecules discussed in this introduction, including eugenol of formula (I), isoeugenol of formula (II), and diisoeugenol of formula (III), with the three asymmetric carbons identified by asterisks:
[0009]
[0010] Other synthetic routes involving [3+2] cycloadditions have been described, including the use of an Ag(OTf) / AuCl catalytic system to separate the two diastereomers in a 10:1 ratio to favor the α configuration corresponding to the compound of formula (IV); and the γ configuration corresponding to the compound of formula (V)
[18] :
[0011]
[0012] Another synthetic route via [3+2] cyclization involves 0.75 mol% of Fe(OTf)3 in the presence of a chiral ligand, which allows the isolation of more than 99% of diisoeugenol (compound of formula (V)) in the γ configuration
[19] . The starting compound of formula (II) is specified to be a cis / trans mixture considering the olefinic bond.
[0013] Although solutions have been developed for obtaining the desired diastereomers, as described above, the preparation and use of diisoeugenol and its derivatives still face various difficulties. According to the synthetic routes described above, the desired molecules are often difficult to obtain in large enough quantities to envision their manufacture on an industrial scale, and their preparation requires improved yields and / or diastereoselectivities.
[0014] This is all the more worrying because diisoeugenol and its derivatives are molecules of first choice for use as antioxidants, for example in the food industry
[20] . In addition, pharmacological properties of diisoeugenol have been reported, such as cytotoxicity against cancer cells
[21] , anti-inflammatory activity
[22] , antioxidant activity
[22] , anticonvulsant, hypertensive and thromboxane formation inhibitory activity
[23] ; thus, for example, water-soluble derivatives of N-alkyl-N-(2-hydroxyalkyl)aminomethyl groups have been used as active substances for the treatment of liver diseases (Compound VI, R1: h, alkyl, halogen, phenyl; R2: H, phenyl; R3: H, methyl; R4: alkyl, phenyl). O,O'-disubstituted diisoeugenols exhibit spontaneous hypertensive and anticonvulsant effects (Compound VII, n is an integer from 2 to 4; R: one of the optionally substituted groups selected from dialkylamine, piperidine, morpholine, piperazine), which are even more potent than those of papaverine
[24] :
[0015]
[0016] In order to overcome these disadvantages, one of the objects of the present invention is to provide a method for synthesizing diisoeugenol, which can prepare the compound in better yield and greater diastereoselectivity than the methods of the background art. Summary of the Invention
[0017] The present invention relates to a method for preparing compound (X), comprising the following steps:
[0018]
[0019] Among them, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 are independently selected from the group consisting of: hydrogen; hydroxy; alkoxy, preferably methoxy; thioalkyl; amino; and a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from the group consisting of alkyl, alkenyl, alkynyl, aryl and heteroaryl; preferably, R5 is hydrogen; and
[0020] The aliphatic chain optionally comprises at least one of the following atoms or groups: halogen, -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-;
[0021] as well as
[0022] A catalyst comprising at least one compound selected from the group consisting of sulfonic acid and a compound of formula M(OTf) is used. n A metal complex of , wherein M is a metal atom, and n is an integer of 1 to 4, preferably n is an integer of 2 to 4.
[0023] The terms "alkoxy" (or "alkyloxy") and "thioalkyl" refer to an alkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom ("alkoxy") or through a sulfur atom ("thioalkyl"). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, tert-butoxy, neopentoxy, and n-hexoxy. Examples of thioalkyl groups include, but are not limited to, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, and the like.
[0024] As used herein, the term "hydroxy" is intended to refer to a group having an -OH structure.
[0025] The term "amino" refers to a group having the structure -N(R)2, wherein each occurrence of R is independently hydrogen or an aliphatic, heteroaliphatic, aromatic or heteroaromatic group, wherein the R groups taken together can form a heterocyclic group.
[0026] Preferably, and independently for the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 , the alkyl functional group contains 1 to 12 carbon atoms.
[0027] Preferably, and independently for the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 , the alkenyl functional group contains 2 to 12 carbon atoms.
[0028] Preferably, and independently for the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 , the alkynyl functional group contains 2 to 12 carbon atoms.
[0029] The term "aryl" refers to an aromatic group. In some embodiments of the present invention, the term "aryl" refers to a monocyclic or bicyclic carbocyclic ring system having one or two rings that meet Huckel's rules for aromaticity, such carbocyclic ring systems including but not limited to phenyl, naphthyl, tetrahydronaphthyl, indanyl, indenyl and other similar systems. Preferably, and independently for substituents R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 , the aryl functional group contains 6 to 10 carbon atoms.
[0030] The term "heteroaryl" refers to a heteroaromatic group. Preferably, and independently for the substituents R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 , the heteroaryl functional group contains 4 to 10 carbon atoms.
[0031] Compounds (VIII) and (IX) include at least one of the olefin isomers Z and E corresponding to the following compounds (VIIIa); (VIIIb); (IXa) and (IXb), respectively:
[0032]
[0033] In R1, R2, R3, R4, R6, R7, R8, R9 and R 10 The radicals of the compounds (X) according to the invention positioned in ortho position on the aromatic ring may together form a ring preferably comprising 5 to 7 atoms; more particularly, the radicals R1 and R2; R2 and R3; R3 and R4; R6 and R7; R7 and R8; R8 and R9 and / or R9 and R 10 Together they form such a ring; advantageously, the ring is a 5-atom ring comprising the acetal function; preferably, the groups R2 and R3 and the groups R7 and R8 together form such a ring.
[0034] Preferably, the process for preparing compound (X) previously described within the scope of the present invention involves preparing a compound selected from the group consisting of the following compounds (III) and (Xa) to (Xc):
[0035]
[0036] These four compounds (III) and (Xa) to (Xc) advantageously include compounds which can also be described as follows:
[0037] - For compound (Xa), asarone dimer;
[0038] - For compound (Xb), isosafrole dimer;
[0039] - for compound (Xc), anethole; and
[0040] - For compound (III), diisoeugenol.
[0041] Preferably, the compound (X) obtained according to the method of the present invention comprises only at least one of the following two isomers:
[0042]
[0043] Preferably, the process according to the invention is suitable for the preparation of a compound selected from diisoeugenol and derivatives of diisoeugenol and / or involves the preparation of compound (XIII) obtained from compounds (XI) and (XII) according to the following reaction scheme:
[0044]
[0045] wherein the R'1 group is selected from: hydrogen; a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from alkyl, alkenyl, alkynyl, aryl and heteroaryl; preferably, the group R'1 is selected from hydrogen; a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from alkyl, alkenyl and alkynyl; and preferably R'1 is alkyl; and
[0046] The aliphatic chain optionally comprises at least one of the following atoms or groups: halogen, -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-; and preferably, the aliphatic chain optionally comprises at least one of the following atoms or groups: -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-;
[0047] wherein the R'2 group is selected from hydrogen; and -CHR 11 -NR 12 -CH-R 13 -CHR 14 OH group; R 11 is selected from hydrogen, alkyl, halogen and phenyl; R 12 and R 13 are independently selected from hydrogen and alkyl; and R 14 selected from alkyl and phenyl; and
[0048] A catalyst comprising at least one compound selected from the group consisting of sulfonic acid and a compound of formula M(OTf) is used. n A metal complex of , wherein M is a metal atom, and n is an integer of 1 to 4, preferably n is an integer of 2 to 4.
[0049] Compounds (X) and / or (XIII) are advantageously chosen from diisoeugenol and derivatives of diisoeugenol, the expression "derivatives of diisoeugenol" used within the scope of the present invention defining an organic molecule comprising the carbon backbone of diisoeugenol, as represented by compound (III), and in which:
[0050] - the phenol function is protected by an organic group incorporating carbon, hydrogen and optionally oxygen, nitrogen, halogen and / or sulfur atoms; and / or
[0051] - The hydrogen of the aromatic group is replaced by an organic substituent incorporating carbon, hydrogen and optionally oxygen, nitrogen, halogen and / or sulfur atoms.
[0052] The term "catalyst", as used herein before within the scope of the present invention, is to be interpreted with reference to its generally accepted definition in the field of organic chemistry, whose action can only be kinetic, since its presence in the reaction medium cannot modify thermodynamic quantities, namely the enthalpy change and the free enthalpy change; when a reaction can occur in several permissible thermodynamic directions, a suitable catalyst will accelerate only one of these stages in order to achieve selectivity between the various permissible reaction paths. The desired quality of a catalyst corresponds in particular to its ability to accelerate the reaction in the chosen synthetic pathway, while being present in the reaction medium at the lowest possible concentration and at a turnover frequency (TOF) which must be as high as possible; TOF is defined as the turnover number (TON) per unit time. TON corresponds to the number of moles of reactant / substrate that one mole of catalyst can convert before it becomes deactivated.
[0053] The present inventors have unexpectedly demonstrated that diisoeugenol and its derivatives can be synthesized from readily available chemicals using a simple catalytic process, which saves energy, avoids lengthy purification steps, and achieves better yields relative to conventional syntheses.
[0054] The catalyst may be a silver catalyst such as AgOTf other than AgOTf combined with a promoter comprising gold Au, particularly a silver catalyst other than AgOTf combined with a 1:1 molar amount of AuCl or AuBr3.
[0055] Preferably, within the scope of the process according to the invention, the M atoms are metal atoms other than Ag atoms, combined with a promoter comprising the element Au.
[0056] Preferably, within the scope of the method according to the present invention, the M atom is a metal atom other than at least one of the elements selected from Ag and Fe, and preferably M is selected from: a metal atom of an alkali metal; a metal atom of an alkaline earth metal such as Mg; a metal atom of a metal selected from d-block metals such as Ti, Cu and Zn; and a metal atom of a metal selected from f-block metals such as La.
[0057] Preferably, the formula M(OTf) described within the scope of the process according to the invention n The metal complex is selected from the following complexes: Ti(OTf) 4 , Zr(OTf) 4 and Hf(OTf) 4 . Preferably, it is Ti(OTf) 4 .
[0058] Preferably, the formula M(OTf) described within the scope of the process according to the invention nThe metal complex of is Cu(OTf) 2. The inventors have fortuitously demonstrated that copper catalysts are prime candidates for obtaining excellent results in terms of chemoselectivity in favor of the α and γ diastereomers of diisoeugenol corresponding to compounds (IV) and (V), as explained in the preamble to this specification.
[0059] Preferably, the sulfonic acid is selected from TfOH (trifluoromethanesulfonic acid) and / or MesOH (methanesulfonic acid), preferably MesOH; since MesOH is considered a compound classified as a green chemical molecule, it is more in line with the sustainable development trend. In fact, methanesulfonic acid, the simplest alkanesulfonic acid, is a strong organic acid that is widely known for its outstanding chemical and physical properties
[25] . MesOH is often called "green acid" because it is easily biodegradable and has lower toxicity and corrosiveness than inorganic acids
[26] .
[0060] Preferably, the R'1 group is a methyl group or an alkyl group chosen from linear alkyl groups containing from 2 to 4 carbon atoms; said C2-C4 alkyl group is substituted by a group chosen from dialkylamines, piperidine, morpholine and piperazine, optionally containing an alkyl group or an aromatic group, preferably a phenyl group, on at least one of its heteroatoms.
[0061] Preferably, the R'1 group is methyl and the R'2 group is hydrogen.
[0062] More preferably, the reaction mixture comprises a mixture of diastereomers of diisoeugenol: α-diisoeugenol (ie, compound (IV)) and γ-diisoeugenol (ie, compound (V)):
[0063]
[0064] More advantageously, the molar ratio of compounds (IV) and (V) obtained is X:Y such that X>70; Y<30.
[0065] Preferably, α-diisoeugenol is obtained in a content greater than or equal to 85% relative to the total diastereomers of diisoeugenol obtained in the reaction mixture.
[0066] Preferably, the reaction solvent is selected from at least one solvent of toluene, anisole, THF, MeTHF and ethyl acetate; preferably, the solvent is selected from anisole, MeTHF and ethyl acetate. Advantageously, the solvent is anisole because it enables the method according to the present invention to be used for industrial purposes.
[0067] Preferably, the catalyst used in the process according to the invention is used in an amount less than or equal to 1.5% by mole relative to the total moles of all reactants.
[0068] The invention is further described in the following detailed description using an experimental section that details some embodiments using examples that are given by way of illustration only and should not be considered limiting, and the accompanying drawings briefly described in the following section. BRIEF DESCRIPTION OF THE DRAWINGS
[0069] Figure 1 Depicts from Figure 2 and Figure 3 The attribution of the data extracted from the shown spectra;
[0070] Figure 2 Describes the 1 H{ 1 H}COSY NMR spectrum (CDCl3, 400 MHz); and
[0071] Figure 3 Describes the 13 C{ 1 H}HSQC NMR spectrum (CDCl3, 100MHz{400MHz}). DETAILED DESCRIPTION
[0072] Experimental part
[0073] A—Compound Synthesis
[0074] Materials and methods All reactions were carried out under an inert atmosphere using argon. All solvents used were synthetic grade. Isoeugenol (cis / trans, 98+%) was prepared from Sold and must be kept refrigerated; from Alfa Anisole (99%), acetonitrile (99%) and methanesulfonic acid (98+%) were obtained for sale. Ethyl acetate (99%) and acetone (99%) were obtained from Chemicals. Available from Copper trifluoromethanesulfonate (98%) was purchased for sale. Trifluoromethanesulfonic acid was obtained from Fluorochem TM Sold and must be kept refrigerated.
[0075] Within the scope of the present invention, the weight percentages expressed in wt. % define the weight percentage of the ingredients used in the preparation and are relative to the total weight of the object under consideration: mixture, material (composite, etc.), film, etc.
[0076] 1 H and 13 C NMR
[0077] exist Recorded on Advance III 400MHz spectrometer 1H and 13 C spectra were calibrated using the chemical shifts of residual resonances of the solvent.
[0078] synthesis
[0079] Part 1: Synthesis performed
[0080] Example 1 :
[0081] Representative scheme for 1000 equivalents of isoeugenol
[0082] The catalyst (8.3·10 -3 mmol) and solvent (4.129 g, 4.15 mL, 8.3 mmol) were added to a Schlenk tube. Isoeugenol (1.26 mL, 8.3 mmol) was then added to the reaction medium using a syringe. The reaction system was stirred in an oil bath at the specified temperature until complete conversion.
[0083]
[0084]
[0085] The results are presented in Table 1.
[0086] [Table 1]
[0087] Example 2
[0088] Synthesis of diisoeugenol (1-ethyl-5-hydroxy-3-(4-hydroxy-5-methoxyphenyl)- 6-methoxy-2-methylindane).
[0089] In a glove box, copper trifluoromethanesulfonate (3.6 mg, 0.01 mmol) and 0.35 mL of anhydrous toluene were loaded into an oven-dried Schlenk tube. Outside the glove box, under argon, isoeugenol (0.15 ml, 160 mg, 1 mmol) was added to the reaction mixture via a syringe. The reaction medium was vigorously stirred at room temperature for 5 minutes. Exothermic reaction and precipitation were observed during the reaction. At the end of the reaction, dichloromethane was added and filtered through a small amount of diatomaceous earth column (yield 95%). A light yellow powder (=85:15) was obtained; mp = 178°C-180°C. The reaction was carried out on a gram scale.
[0090] NMR spectra and peak assignments are shown in Figure 1 、 Figure 2 and Figure 3 middle.
[0091] Example 3
[0092] The protocol and reaction scheme are the same as those shown in Example 1.
[0093]
[0094] TON (turnover number) is the number of moles of reaction product obtained per mole of catalyst used. TOF (turnover frequency) is the TON per time unit. The value for input 1 is calculated according to reference 19, the value for input 2 is calculated according to reference 18, and the values for inputs 6 through 8 are calculated according to reference 17.
[0095] Iron derivatives (inputs 1 and 8), boron derivatives (input 7), and silver derivatives (input 2) were able to convert isoeugenol but had weak catalytic activity (TOF < 10 h in each case). -1 In contrast, the [3+2] cycloaddition of isoeugenol using catalysts such as Cu(OTf)2, HOTf, and MesOH is more efficient (80 <TOF<2300h -1 ), and ensured excellent catalytic yield, which was different from the heterogeneous catalyst SiO2-OSO3H.
[0096] References
[0097] The following table lists references previously cited in this article:
[0098] [Table 2]
[0099]
Claims
1. A method for preparing compound (X), comprising the following steps: Among them, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 are independently selected from the group consisting of: hydrogen; hydroxy; alkoxy, preferably methoxy; thioalkyl; amino; and a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from the group consisting of alkyl, alkenyl, alkynyl, aryl and heteroaryl; preferably, R5 is hydrogen; and The aliphatic chain optionally comprises at least one of the following atoms or groups: halogen; -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-; and A catalyst comprising at least one compound selected from the group consisting of sulfonic acid and a compound of formula M(OTf) is used. n A metal complex of , wherein M is a metal atom, and n is an integer of 1 to 4, preferably n is an integer of 2 to 4.
2. The process according to claim 1, wherein compound (XIII) is obtained from compounds (XI) and (XII) according to the following reaction scheme: wherein the R'1 group is selected from: hydrogen; a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from alkyl, alkenyl, alkynyl, aryl and heteroaryl; preferably, the group R'1 is selected from hydrogen; a linear, branched, cyclic or acyclic aliphatic chain comprising at least one functional group selected from alkyl, alkenyl and alkynyl; and preferably R'1 is alkyl; and The aliphatic chain optionally comprises at least one of the following atoms or groups: halogen, -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-; and preferably, the aliphatic chain optionally comprises at least one of the following atoms or groups: -O-; -N-; -S-; -CO-; ester-CO-O-; amide-CO-N-; thioester-CO-S-; carbonate-O-CO-O-; carbamate-O-CO-N-; wherein the R'2 group is selected from hydrogen; and -CHR 11 -NR 12 -CH-R 13 -CHR 14 OH group; R 11 is selected from hydrogen, alkyl, halogen and phenyl; R 12 and R 13 are independently selected from hydrogen and alkyl; and R 14 selected from alkyl and phenyl; and The catalyst comprising at least one compound selected from the following components is used: the component selected from sulfonic acid and the compound of formula M(OTf) n A metal complex of , wherein M is a metal atom, and n is an integer of 1 to 4, preferably n is an integer of 2 to 4.
3. The process according to claim 1 , wherein within the scope of the process according to the invention, M is a metal atom other than an Ag atom, combined with a promoter comprising the element Au, and preferably M is selected from: a metal atom of an alkali metal; a metal atom of an alkaline earth metal such as Mg; a metal atom of a metal selected from the group consisting of d-block metals such as Ti, Cu and Zn; and a metal atom of a metal selected from the group consisting of f-block metals such as La.
4. The method according to claim 1 , wherein the formula M(OTf) n The metal complex is Cu(OTf)2.
5. The method according to one of claims 1 to 4, wherein the sulfonic acid is selected from at least one acid of TfOH and MesOH, preferably MesOH.
6. The method according to claim 2 , wherein the R′1 group is a methyl group or an alkyl group selected from linear alkyl groups containing 2 to 4 carbon atoms; the C2-C4 alkyl group is substituted by a group selected from dialkylamines, piperidine, morpholine and piperazine, optionally containing an alkyl group or an aromatic group, preferably a phenyl group, on at least one of its heteroatoms.
7. The method according to one of claims 2 to 5, wherein the R'1 group is a methyl group and the R'2 group is hydrogen.
8. The process of claim 7, wherein the reaction mixture comprises a mixture of diastereomers of diisoeugenol, namely α-diisoeugenol or compound (IV) and γ-diisoeugenol or compound (V):
9. The process according to claim 8, wherein the molar ratio of the compounds (IV) and (V) obtained is X:Y such that X>70; Y<30.
10. The process according to claim 8, wherein α-diisoeugenol is obtained in a content greater than or equal to 85% relative to the total diastereomers of diisoeugenol obtained in the reaction mixture.
11. The process according to one of claims 1 to 10, wherein the reaction solvent is at least one solvent selected from toluene, anisole, THF, MeTHF and ethyl acetate. 12 . The process according to claim 1 , wherein the catalyst is used in an amount less than or equal to 1.5%, calculated as a molar percentage relative to the total moles of all reactants.