Process for producing p-eugenol and / or o-eugenol

Abstract

The present invention relates to a method for preparing p-eugenol and / or o-eugenol, comprising the step (i) of deallylating at least one compound having the formula (I): wherein R 1 and R 2 are different and are selected from hydrogen and allyl (‑CH 2 ‑CH=CH 2 ) group.

Description

Technical Field

[0001] The present invention relates to a process for preparing p-eugenol and / or o-eugenol, comprising the step (i) of deallylating at least one compound having the formula (I):

[0002]

[0003] wherein R1 and R2 are different and are selected from the group consisting of hydrogen and allyl (-CH2-CH=CH2), characterized in that step (i) is carried out in the presence of a solvent or a solvent / water mixture. Background Art

[0004] Eugenol is the main aromatic compound of many essential oils, such as clove essential oil. Eugenol is commonly used in perfumes, but it also has antiseptic, antibacterial, analgesic and antioxidant properties. Eugenol and o-eugenol can also be used as synthetic intermediates: for example, eugenol can be used to prepare vanillin.

[0005] In view of this wide range of utilization, it is necessary to produce eugenol on an industrial scale and to have an optimized preparation process available.

[0006] Eugenol is conventionally a natural source extracted from plants. Extraction can be performed notably by water distillation, microwave-assisted extraction or extraction with supercritical fluids. Eugenol of natural origin is usually in the form of a composition comprising a mixture of p-eugenol and o-eugenol in a 99 / 1 (p / o) ratio.

[0007] Eugenol can also be obtained by a chemical process as described in FR 2 302 991, in which guaiacol is allylated in the presence of allyl chloride and a catalyst.

[0008] CN 105294409 describes an alternative synthesis method using a composite catalyst based on copper and cobalt.

[0009] When using these synthesis methods, several side reactions may occur, notably leading to the formation of O-allylated compounds, notably corresponding to compounds of formula (I). Eugenol purification is therefore complicated.

[0010] The process according to the invention allows the efficient preparation of p-eugenol and / or o-eugenol from said O-allylated compounds. The present invention therefore relates to an efficient and improved process for the preparation of p-eugenol and / or o-eugenol, notably a process for the efficient conversion of O-allylated compounds into p-eugenol and / or o-eugenol on an industrial scale, notably with improved yields. Summary of the invention

[0011] A first subject of the present invention is a novel process for preparing p-eugenol and / or o-eugenol, comprising a step (i) of deallylating at least one compound of formula (I):

[0012]

[0013] wherein R1 and R2 are different and are selected from the group consisting of hydrogen and allyl (-CH2-CH=CH2), characterized in that step (i) is carried out in the presence of a solvent or a solvent / water mixture. DETAILED DESCRIPTION

[0014] In the context of the present invention, and unless stated otherwise, the expression "between ..." includes the limit values. Unless stated otherwise, percentages and ppm are percentages and ppm by mass.

[0015] In the context of the present invention, and unless otherwise specified, the term "ppm" means "parts per million." This unit represents the mass fraction: 1 ppm = 1 mg / kg.

[0016] In the context of the present invention, and unless otherwise stated, the term "eugenol" refers to p-eugenol or 4-allyl-2-methoxyphenol according to formula (IIa):

[0017]

[0018] In the context of the present invention, o-eugenol refers to 2-allyl-6-methoxyphenol according to formula (IIb):

[0019]

[0020] In the context of the present invention, the term "deallylation" refers to a reaction that cleaves a covalent bond between a substrate and an allyl group. Preferably, in the context of the present invention, the deallylation reaction allows a compound of formula (I) to be converted into a compound of formula (II) according to the following scheme:

[0021]

[0022] wherein R1 and R2 have the same meanings as previously described. Preferably, in the context of the present invention, the deallylation reaction allows the cleavage of a covalent bond between a carbon atom and an oxygen atom. Advantageously, in the context of the present invention, the deallylation reaction allows the cleavage of an ether bond without deallylation of an allyl group attached to the substrate via a covalent bond between two carbon atoms.

[0023] For example, in the context of the present invention, a deallylation reaction of a compound of formula (Ia) allows the formation of a compound of formula (IIa), preferably without the formation of guaiacol or guaiacol allyl ether.

[0024]

[0025] Step (i):

[0026] A first subject of the present invention is a process for preparing p-eugenol and / or o-eugenol, comprising a step (i) of deallylating at least one compound of formula (I):

[0027]

[0028] wherein R1 and R2 are different and are selected from the group consisting of hydrogen and allyl (-CH2-CH=CH2), characterized in that step (i) is carried out in the presence of a solvent or a solvent / water mixture.

[0029] According to a particular aspect, the process according to the invention comprises a step of deallylating the compound of formula (Ia).

[0030]

[0031] The process according to the invention allows the formation of compounds of formula (IIa).

[0032]

[0033] According to another particular aspect, the process according to the invention comprises a step of deallylating the compound of formula (Ib).

[0034]

[0035] The process according to the invention allows the formation of compounds of formula (IIb).

[0036]

[0037] Advantageously, the process according to the invention comprises a step of deallylating a mixture comprising at least one compound of formula (Ia) and one compound of formula (Ib).

[0038] The process according to the invention allows the formation of a mixture comprising at least one compound of formula (IIa) and one compound of formula (IIb).

[0039] Typically, the method according to the invention is carried out on a composition comprising at least 0.1% by weight, preferably at least 0.5% by weight, even more preferably at least 1% by weight, even more preferably at least 2% by weight of a compound of formula (I). Usually, the method according to the invention is carried out on a composition comprising up to 98% by weight, preferably up to 95% by weight, even more preferably up to 90% by weight of a compound of formula (I). The composition used in the deallylation reaction may comprise 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% by weight of a compound of formula (I).

[0040] The method according to the invention can be carried out on a compound of formula (I) alone or as a mixture. Thus, the method according to the invention can be carried out on a composition comprising at least one compound of formula (I). The method according to the invention can be carried out on a composition comprising at least two compounds of formula (I), in particular a compound of formula (Ia) and a compound of formula (Ib).

[0041] The composition may also comprise a compound having formula (III).

[0042]

[0043] The deallylation process according to the invention also allows the formation of guaiacol by deallylating compounds of formula (III).

[0044] The method according to the invention can also be carried out on a composition comprising at least two compounds of formula (I), in particular a compound of formula (Ia) and a compound of formula (Ib), and a compound of formula (III). According to the invention, the method can be carried out on a composition further comprising p-eugenol, o-eugenol and / or guaiacol.

[0045] According to the present invention, step (i) is carried out in the presence of a catalyst. Preferably, the catalyst is a catalyst based on platinum, rhodium, iridium, copper, nickel, aluminum, titanium, iron or palladium; preferably, the catalyst is based on platinum or palladium. Preferably, step (i) is carried out in the presence of Pd / C or Pt / C.

[0046] According to the invention, the amount of catalyst used in step (i) is less than or equal to 30% by weight, preferably less than or equal to 25% by weight, very preferably less than or equal to 20% by weight, relative to the total amount of compounds of formula (I) and optionally of formula (III).

[0047] According to the present invention, the amount of catalyst used in step (i) is greater than or equal to 0.1% by weight relative to the total amount of compounds of formula (I) and optionally of formula (III). Preferably, the amount of catalyst used in step (i) is greater than or equal to 0.5% by weight, preferably greater than or equal to 0.5% by weight, very preferably greater than or equal to 1% by weight, and very preferably greater than or equal to 2% by weight, relative to the total amount of compounds of formula (I) and optionally of formula (III).

[0048] According to the present invention, step (i) is carried out in the presence of a solvent or a water / solvent mixture. Preferably, the solvent is a polar protic solvent. The solvent may be an alcohol, preferably selected from MeOH, EtOH, i-PrOH and BuOH.

[0049] According to the invention, step (i) can be carried out in the presence of a water / solvent mixture; preferably, the solvent / water weight ratio is between 10 / 1 and 1 / 1, preferably between 8 / 1 and 3 / 1 and very preferably between 6 / 1 and 4 / 1.

[0050] According to the invention, step (i) is carried out in the presence of a base; preferably, the pKa in water is greater than or equal to 8, preferably greater than or equal to 9, very preferably greater than or equal to 10. The base may be selected from the group consisting of KOH, NaOH, K2CO3, Na2CO3, Ba(OH)2, Ca(OH)2, CsOH and LiOH or a compound of formula NR3OH, wherein R is a linear or branched alkyl chain containing from 1 to 6 carbon atoms. According to a particular aspect, step (i) is carried out in the presence of a strong base. Typically, step (i) is carried out in the presence of KOH, NaOH, Ba(OH)2 or Ca(OH)2.

[0051] According to the present invention, the content of alkali in step (i) is greater than or equal to 5% by weight, preferably greater than or equal to 8% by weight, relative to the amount of solvent used. According to the present invention, the amount of alkali in step (i) is less than or equal to 15% by weight, preferably less than or equal to 10% by weight, relative to the amount of solvent used.

[0052] According to the present invention, step (i) may be carried out at a temperature greater than or equal to 20° C., preferably greater than or equal to 30° C., preferably greater than or equal to 40° C., very preferably greater than or equal to 50° C. According to the present invention, step (i) may be carried out at a temperature less than or equal to 100° C., preferably less than or equal to 85° C., very preferably less than or equal to 70° C. Typically, step (i) may be carried out at 65° C. Typically, heating is maintained for a period ranging from 2 hours to 24 hours.

[0053] According to the present invention, step (i) is usually carried out at atmospheric pressure. Step (i) can also be carried out in an autoclave; preferably, the reaction is carried out at a pressure greater than or equal to atmospheric pressure, preferably greater than or equal to 2 bar, very preferably greater than or equal to 5 bar. Preferably, the reaction is carried out at a pressure less than or equal to 50 bar, preferably less than or equal to 20 bar, very preferably less than or equal to 10 bar.

[0054] Typically, the conversion of the compound of formula (I) into the compound of formula (II) is greater than or equal to 60%, preferably greater than or equal to 75%, very preferably greater than or equal to 85% and even more preferably greater than or equal to 95%.

[0055] According to a particular aspect, the process according to the invention is carried out on a composition comprising at least one compound of formula (I) obtained from a process for the allylation of guaiacol in the presence of an allylic halide or an allylic alcohol.

[0056] Allylation of guaiacol

[0057] The method for allylation of guaiacol in the presence of an allyl halide can be carried out under conditions as described in FR 2 302991 or in CN 105294409. According to another aspect, the method for allylation of guaiacol in the presence of an allyl alcohol can be carried out under conditions as described in J. Mol. Cat. A: Chemical, 2006, 244, 124-138.

[0058] In a particular aspect of the invention, guaiacol is reacted with an allyl halide, preferably allyl chloride, as described in FR 2 302 991.

[0059] This reaction allows the formation of at least one compound of formula (I), notably compounds of formula (Ia), (Ib) and (III). This reaction also allows the formation of p-eugenol or o-eugenol.

[0060] Specifically, the alkylation reaction is carried out in the presence of an aqueous solution of an alkali metal or alkaline earth metal hydroxide such as NaOH or KOH. In addition, the reaction can be carried out in the presence of a catalyst, notably a copper-based catalyst such as CuCl, CuCl2.2H2O, Cu(NO3)2 or Cu(OAc)2.2H2O. The reaction can also be carried out in the presence of a composite catalyst based on copper and cobalt, as described in patent application CN 105294409.

[0061] Typically, the amount of catalyst is greater than or equal to 0.01% by weight, preferably greater than or equal to 0.02% by weight, more preferably greater than or equal to 0.05% by weight and very preferably greater than or equal to 0.1% by weight relative to the amount of guaiacol. Typically, the amount of catalyst is less than or equal to 10% by weight, preferably less than or equal to 5% by weight, more preferably less than or equal to 2% by weight and very preferably greater than or equal to 1% by weight relative to the amount of guaiacol.

[0062] Typically, the reaction temperature is greater than or equal to 5° C., preferably greater than or equal to 10° C., more preferably greater than or equal to 15° C. and very preferably greater than or equal to 25° C. Typically, the reaction temperature is less than or equal to 95° C., preferably less than or equal to 80° C., more preferably less than or equal to 65° C. and very preferably less than or equal to 50° C.

[0063] The reaction is generally carried out in the presence of ammonium salts or ammonia, as described in FR 2 302 991. Ammonia can form a copper-amine type complex with the catalyst.

[0064] Typically, in the first stage, the guaiacol salt is formed in aqueous solution. The catalyst is added to the reaction mixture, followed by aqueous ammonia solution, and finally the allyl halide is added to the reaction mixture.

[0065] According to the invention, the allylation reaction may be a step before step (i). Advantageously, when the method for preparing p-eugenol and / or o-eugenol according to the invention (and comprising step (i) as described above) is carried out on a composition obtained by the allylation reaction of guaiacol, only compounds of formula (I) and / or (III) are converted into compounds of formula (II) and / or guaiacol, respectively. Thus, at the end of the method according to the invention, the composition of the mixture comprises p-eugenol and / or o-eugenol and / or guaiacol. Thus, purification is facilitated. Guaiacol may also be recycled.

[0066] Typically, at the end of the allylation reaction, a two-phase mixture is obtained: an aqueous phase and an organic phase. Advantageously, the pH of the composition obtained from the allylation reaction of guaiacol can be adjusted; preferably, the pH is less than or equal to 8.5, preferably less than or equal to 8.

[0067] According to a particular aspect, the composition obtained by the allylation reaction of guaiacol can be the organic phase obtained at the end of the allylation reaction, with an optionally adjusted pH. Typically, the composition comprises at least one compound selected from the group consisting of a compound of formula (Ia), a compound of formula (Ib), a compound of formula (III), guaiacol, p-eugenol and o-eugenol. The composition is subjected to step (i) as described above.

[0068] At the end of step (i), the composition obtained comprises at least one compound chosen from p-eugenol, o-eugenol and guaiacol.

[0069] According to one embodiment, the guaiacol is distilled off. The guaiacol can be recycled to the guaiacol allylation reaction. The o-eugenol and p-eugenol compounds can then be separated by distillation. Optionally, the distillation can be carried out in the presence of at least one antioxidant such as vitamin E, BHA, BHT, TBHQ or TBC.

[0070] According to a particular aspect, the composition obtained by the allylation reaction of guaiacol can be the organic phase obtained at the end of the allylation reaction, with an optionally adjusted pH. Typically, the composition comprises at least one compound selected from the group consisting of a compound of formula (Ia), a compound of formula (Ib), a compound of formula (III), guaiacol, p-eugenol and o-eugenol. The composition is subjected to step (i) as described above.

[0071] At the end of step (i), the composition obtained comprises at least one compound chosen from p-eugenol, o-eugenol and guaiacol.

[0072] According to another embodiment, guaiacol is distilled out. Guaiacol can be recycled to the guaiacol allylation reaction. The o-eugenol and p-eugenol compounds can then be separated by selective salification. The o-eugenol and p-eugenol compounds are diluted in a solvent that is not acidic in nature and is capable of reacting with K2CO3; preferably, the solvent has a pKa of less than or equal to 8.5, preferably less than or equal to 8 in water. Preferably, the solvent is a hydrocarbon solvent of the cyclic or non-cyclic alkane family. Preferably, the hydrocarbon solvent of the alkane family is an alkane containing from 5 to 15 carbon atoms; preferably, the hydrocarbon solvent of the alkane family is selected from the group consisting of pentane, hexane, heptane, octane, nonane and cyclohexane. K2CO3 is added to the solution. The mixture is then filtered. The o-eugenol is preferably recovered from the filtrate by evaporating the solvent. The p-eugenol is obtained in the filter cake in the form of a salt and can be recovered by acidification.

[0073] According to a particular aspect, the composition obtained by the allylation reaction of guaiacol can be the organic phase obtained at the end of the allylation reaction, with an optionally adjusted pH. Typically, the composition comprises at least one compound selected from the group consisting of a compound of formula (Ia), a compound of formula (Ib), a compound of formula (III), guaiacol, p-eugenol and o-eugenol. The composition is subjected to step (i) as described above.

[0074] At the end of step (i), the composition obtained comprises at least one compound chosen from p-eugenol, o-eugenol and guaiacol.

[0075] The o-eugenol and p-eugenol compounds can then be separated by selective salification. Optionally, the deallylated solvent can be evaporated in advance. The o-eugenol and p-eugenol compounds are diluted in a solvent that is not acidic in nature and is capable of reacting with K2CO3; preferably, the solvent has a pKa of less than or equal to 8.5, preferably less than or equal to 8 in water. Preferably, the solvent is a hydrocarbon solvent from the cyclic or non-cyclic alkane family. Preferably, the hydrocarbon solvent from the alkane family is an alkane containing from 5 to 15 carbon atoms; preferably, the hydrocarbon solvent from the alkane family is selected from the group consisting of pentane, hexane, heptane, octane, nonane and cyclohexane. K2CO3 is added to the solution. The mixture is then filtered. The o-eugenol is preferably recovered from the filtrate by evaporating the solvent. The filter cake contains at least one compound selected from p-eugenol and guaiacol in salified form and can be recovered by acidification. After acidification, guaiacol and p-eugenol can be separated by distillation.

[0076] According to another specific aspect, the organic phase obtained at the end of the allylation reaction can be subjected to a selective salification pretreatment. In particular, the organic phase is diluted in a solvent that does not have an acidic property and that is capable of reacting with K2CO3; preferably, the solvent has a pKa of less than or equal to 8.5, preferably less than or equal to 8 in water. Preferably, the solvent is a hydrocarbon solvent of a cyclic or non-cyclic alkane family. Preferably, the hydrocarbon solvent of the alkane family is an alkane containing from 5 to 15 carbon atoms; preferably, the hydrocarbon solvent of the alkane family is selected from the group consisting of pentane, hexane, heptane, octane, nonane and cyclohexane. K2CO3 is added to the solution. The mixture is then filtered, and step (i) can be performed on the filtrate. The solvent is usually distilled off in advance. The filtrate comprises at least one compound selected from a compound of formula (Ia), a compound of formula (Ib), a compound of formula (III) and o-eugenol. Typically, after distilling off the solvent, the content of p-eugenol and guaiacol in the filtrate is less than or equal to 1% by weight relative to the total weight of the filtrate.

[0077] At the end of step (i), the composition comprises at least one compound selected from p-eugenol, o-eugenol and guaiacol. Guaiacol can be distilled off and recycled to the guaiacol allylation reaction. The o-eugenol and p-eugenol compounds can then be separated by distillation. Optionally, the distillation can be carried out in the presence of at least one antioxidant such as vitamin E, BHA, BHT, TBHQ or TBC.

[0078] Therefore, according to the present invention, the total yield of synthesizing p-eugenol and / or o-eugenol comprises:

[0079] - a step of allylation of guaiacol,

[0080] - Step (i) of the deallylation according to the invention can be improved by recycling guaiacol.

[0081] Examples

[0082] Example 1 : The compound of formula (Ia) (250 mg, 1.22 mmol) was dissolved in KOH (10% by weight in methanol, 25 mL). Pd / C (10% by weight, 50 mg) was added. The mixture was heated at 65° C. for 3 hours.

[0083] The conversion rate of the compound of formula (Ia) to p-eugenol was 95%.

[0084] No formation of guaiacol was observed.

[0085] Example 2 The reaction mixture (253 mg) obtained by the allylation reaction described in patent application FR 2 302 991, comprising the compound of formula (Ia), the compound of formula (Ib), the compound of formula (III), p-eugenol, o-eugenol and guaiacol, is dissolved in KOH (10% by weight in methanol, 25 mL). Pd / C (10% by weight, 13 mg) is added. After 3 hours of reaction at 65° C., the reaction mixture is analyzed and comprises p-eugenol, o-eugenol and guaiacol.

Claims

1. A method for preparing p-eugenol and / or o-eugenol, comprising the step (i) of deallylating at least one compound of formula (I) to obtain a compound of formula (II): wherein R1 and R2 are different and are selected from the group consisting of hydrogen and allyl (-CH2-CH=CH2), characterized in that, Step (i) is carried out in the presence of a solvent or a solvent / water mixture; Step (i) is carried out in the presence of a Pd / C based catalyst; and Step (i) is carried out in the presence of a base.

2. The method for preparing p-eugenol and / or o-eugenol according to claim 1, comprising: a step of deallylating a mixture comprising at least one compound of formula (Ia) and one compound of formula (Ib) 3. The method for preparing p-eugenol and / or o-eugenol according to claim 1 or 2, wherein: Step (i) further comprises forming guaiacol by deallylating a compound having formula (III):

4. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: The content of catalyst during step (i) is between 0.1 and 30% by weight relative to the total amount of compound of formula (I) and optionally compound of formula (II).

5. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: Step (i) is carried out in the presence of a water / solvent mixture.

6. The method for preparing p-eugenol and / or o-eugenol according to claim 5, characterized in that: The solvent / water weight ratio is between 10 / 1 and 1 / 1.

7. The method for preparing p-eugenol and / or o-eugenol according to claim 5, characterized in that: The solvent / water weight ratio is between 8 / 1 and 3 / 1.

8. The method for preparing p-eugenol and / or o-eugenol according to claim 5, characterized in that: The solvent / water weight ratio is between 6 / 1 and 4 / 1.

9. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: The base has a pKa greater than or equal to 8 in water.

10. The method for preparing p-eugenol and / or o-eugenol according to claim 9, characterized in that: The base has a pKa greater than or equal to 9 in water.

11. The method for preparing p-eugenol and / or o-eugenol according to claim 9, characterized in that: The base has a pKa greater than or equal to 10 in water.

12. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: The base is selected from the group consisting of KOH, NaOH, K2CO3, Na2CO3, Ba(OH)2, Ca(OH)2, CsOH and LiOH or a compound having the formula NR3OH, wherein R is a linear or branched alkyl chain containing from 1 to 6 carbon atoms.

13. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: Step (i) is carried out at a temperature greater than or equal to 20°C.

14. The method for preparing p-eugenol and / or o-eugenol according to claim 13, characterized in that: Step (i) is carried out at a temperature greater than or equal to 30°C.

15. The method for preparing p-eugenol and / or o-eugenol according to claim 13, characterized in that: Step (i) is carried out at a temperature greater than or equal to 40°C.

16. The method for preparing p-eugenol and / or o-eugenol according to claim 13, characterized in that: Step (i) is carried out at a temperature greater than or equal to 50°C.

17. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, characterized in that: The compound of formula (I) is derived from a process for allylation of guaiacol in the presence of an allylic halide or an allylic alcohol.

18. The method for preparing p-eugenol and / or o-eugenol according to any one of claims 1 to 2, comprising: After step (i), at least one step of isolating the guaiacol, p-eugenol and / or o-eugenol is carried out.

19. A method for preparing p-eugenol and / or o-eugenol, the method comprising: - a step of allylating guaiacol in the presence of an allyl halide to prepare at least one compound of formula (I) as defined in claims 1 to 18, - a step (i) of deallylating the at least one compound of formula (I), - a step of isolating the guaiacol, p-eugenol and / or o-eugenol.

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