Process for preparation of alpha, beta-unsaturated carbonyl compounds

Abstract

The invention relates to the field of organic synthesis, in particular to a method for oxidizing allylic alcohol into an alpha, beta-unsaturated carbonyl compound in the presence of a zirconium catalyst and a hydrogen acceptor.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and more particularly to a method for oxidizing allylic alcohols to α,β-unsaturated carbonyl compounds in the presence of a zirconium catalyst and a hydrogen acceptor. Background Art

[0002] α,β-unsaturated carbonyl compounds represent highly desirable skeletons that can be used directly or as key intermediates for the preparation of more complex compounds, and are applied in fields such as perfumery (cosmetic fragrance), cosmetics, pharmaceuticals, or agrochemistry. In particular, carvone or (E)-4-methyl-dec-3-en-5-one is a valuable compound known as a flavoring ingredient and can also be used as a key intermediate for the preparation of more complex compounds. One method for preparing α,β-unsaturated carbonyl compounds is the oxidation of the corresponding alcohols, especially the Oppenauer oxidation reaction, which is easily implemented on an industrial scale. Nevertheless, this oxidation reaction needs to be carried out at high temperatures. In addition, since the Oppenauer reaction is reversible, it is necessary to gradually add a hydrogen acceptor and then remove the generated alcohol and the unreacted hydrogen acceptor after each addition. However, there is currently a need to develop sustainable processes while reducing energy consumption and simplifying the implementation of the process.

[0003] The present invention allows the oxidation of allylic alcohols to α,β-unsaturated carbonyl compounds under catalytic conditions at lower temperatures, while achieving complete conversion and maintaining high yields. To our knowledge, the use of zirconium catalysts in this oxidation process has not been reported in the prior art. Summary of the Invention

[0004] The present invention relates to a new method that allows the preparation of α,β-unsaturated carbonyl compounds under mild conditions that have never been reported or suggested in the prior art, thereby suppressing the number of batch additions of the hydrogen acceptor and several distillations in the method.

[0005] Therefore, a first object of the present invention is a method for oxidizing allylic alcohols to α,β-unsaturated carbonyl compounds, wherein the method is carried out in the presence of:

[0006] i) a catalyst of the following formula:

[0007] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0008] wherein L is bisphenolate, triphenolate or calixarene having at least 4 phenol units, L’ is phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is bisphenolate, or r is 1 when L is triphenolate, or r is 0 when L is calixarene having at least 4 phenol units; and

[0009] ii) a hydrogen acceptor.

[0010] A second object of the present invention is a catalytic system comprising or consisting of the following substances:

[0011] i) a catalyst of the following formula:

[0012] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0013] wherein L is bisphenolate, triphenolate or calixarene having at least 4 phenol units, L’ is phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is bisphenolate, or r is 1 when L is triphenolate, or r is 0 when L is calixarene having at least 4 phenol units; and

[0014] ii) a hydrogen acceptor. Detailed Embodiments

[0015] Surprisingly, it has now been found that allylic alcohols can be oxidized to α,β-unsaturated carbonyl compounds in an advantageous manner with the aid of the catalysts of formula (I) or (I’) and a hydrogen acceptor. These unprecedented conditions enable the formation of α,β-unsaturated carbonyl compounds in extremely high yields without the need for high temperatures, without the need for batchwise addition of the hydrogen acceptor, and without the need to remove the alcohol formed by distillation before each addition of the hydrogen acceptor. The process of the present invention provides a simple method for obtaining α,β-unsaturated carbonyl compounds.

[0016] Accordingly, a first object of the present invention is a process for oxidizing an allylic alcohol to an α,β-unsaturated carbonyl compound, wherein the process is carried out in the presence of the following substances:

[0017] iii) a catalyst of the following formula:

[0018] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0019] wherein L is a bisphenolate, a triphenolate or a calixarene having at least 4 phenol units, L’ is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units; and

[0020] iv) a hydrogen acceptor.

[0021] The term “α,β-unsaturated carbonyl compound” should be understood as an enal or enone compound.

[0022] According to any embodiment of the present invention, p is 1 and n is 3. In other words, the catalyst of formula (I’) conforms to the following formula:

[0023] [Zr(L’)(X)3](I”)

[0024] wherein L’ and X have the same meanings as defined above.

[0025] According to any embodiment of the present invention, the phenolate conforms to the following formula:

[0026]

[0027] where the wavy line indicates the position of the bond between the zirconium atom and L; q is an integer from 0 to 3, and R 1 simultaneously or independently represents at least one substituent of the aromatic ring and is a halogen atom, a cyano group, a nitro group, a C 1-6 alkyl group, a C 1-6 alkoxy group or a COOR group, wherein R is a hydrogen atom or a C 1-6 alkyl group.

[0028] The term “optionally” should be understood that the group may or may not contain a certain functional group or substituent. The term “one or more” should be understood to include 1 to 7, preferably 1 to 5, more preferably 1 to 3 functional groups.

[0029] The terms “alkyl”, “alkenyl” or “alkoxy” should be understood to include straight-chain or branched-chain alkyl, alkenyl or alkoxy groups. The terms “alkanediyl” or “alkenediyl” should be understood to include straight-chain, branched-chain, alicyclic or cyclic alkanediyl or alkenediyl groups. The terms “alkenyl”, “alkenediyl” and “cycloalkenyl” should be understood to include 1, 2 or 3 olefinic double bonds, preferably 1 or 2 olefinic double bonds, more preferably 1 double bond. The term “cycloalkenyl” should be understood to include monocyclic or fused, spiro and / or bridged bicyclic or tricyclic cycloalkenyl groups, preferably monocyclic cycloalkenyl groups.

[0030] According to any embodiment of the present invention, R 1 may be a halogen atom, a cyano group, a nitro group, a C 1-4 alkoxy group, a C 1-4 alkyl group optionally substituted with 1 to 3 halogen atoms, or a COOR group (wherein R is a hydrogen atom or a C 1-4 alkyl group). In particular, R 1 may be a chlorine atom, a fluorine atom, a cyano group, a nitro group, a C 1-3 alkoxy group, or a C 1-3 alkyl group optionally substituted with 1 to 3 halogen atoms, or a COOR group (wherein R is a hydrogen atom or a C 1-3 alkyl group). In particular, R 1 may be a cyano group, a nitro group, a COOH group, or a C 1-3 alkyl group optionally substituted with 1 to 3 fluorine atoms. Even more particularly, R 1 may be a cyano group, a nitro group or a methyl group optionally substituted with 1 to 3 fluorine atoms.

[0031] According to any embodiment of the present invention, q may be 0 or 1, particularly 1.

[0032] According to any embodiment of the present invention, R 1 may be a substituent ortho to the 1-position on the aromatic ring. In other words, the phenolate radical of formula (I) conforms to the following formula:

[0033]

[0034] where the wavy line indicates the position of the bond between the zirconium atom and L; R 1 ’ is a hydrogen atom or an R 1 group as defined above.

[0035] According to any embodiment of the present invention, the phenolate radical is selected from the group consisting of 2-nitrophenolate, o-cresolate, 2-(trifluoromethyl)phenolate and 2-cyanophenolate.

[0036] According to any embodiment of the present invention, the bisphenolate radical conforms to the following formula:

[0037]

[0038] where the wavy line indicates the position of the bond between the zirconium atom and L; m is 0 or 1; R 2 , R 3 , R 4 , R 5 , R 2 ’, R 3 ’, R 4 ’ and R 5When considered individually, each is independently hydrogen, a halogen atom, a nitro group, 2H-benzo[d][1,2,3]triazol-2-yl, C 1-6 alkoxy, C 1-6 thioalkyl or C optionally substituted with one or more of a halogen atom, a hydroxyl group, an amine or C 1-3 alkoxy; or R 1-10 alkyl; or R 2 together with R 3 or R 3 together with R 4 or R 2 ' together with R 3 ' or R 3 ' together with R 4 ' represents an -O-(CH2) y -O-group, where y is 1 or 2, or forms a C6 aryl, C 5-6 cycloalkyl, each of which is optionally substituted with one or more of a halogen atom, a hydroxyl group or C 1-3 alkoxy; and Z is an oxygen or sulfur atom, a (-CH2-)2 group, an -NH- group, a -SO2- group, a -S-S- group, a -CH2-NH-CH2- group or a -C(R 6 )(R 7 )-group, where when R 6 and R 7 are considered individually, each is independently a hydrogen atom or a C6 aryl, C6 heteroaryl or C 1-3 alkyl, each of which is optionally substituted with one to three halogen atoms or C 1-3 alkoxy, and where the heteroatom is one or more of an oxygen or nitrogen atom.

[0039] According to any embodiment of the present invention, R 2 , R 3 , R 4 , R 5 , R 2 ', R 3 ', R 4 ' and R 5 ' are independently of each other, when considered individually, a hydrogen atom, a chlorine atom or C 1-9 alkyl; or R 2 together with R 3 or R 3 together with R 4 or R 2 ' together with R 3 ' or R 3 ' together with R 4 ' forms a C6 aryl.

[0040] According to any embodiment of the present invention, R 2 and R2 ’ may each independently be a hydrogen atom or a C 1-4 alkyl group. In particular, R 2 and R 2 ’ may each independently be a hydrogen atom, a methyl group or a tert-butyl group. In particular, R 2 and R 2 ’ may be a hydrogen atom or a tert-butyl group. More particularly, R 2 and R 2 ’ may be a tert-butyl group.

[0041] According to any embodiment of the present invention, R 3 and R 3 ’ may each independently be a hydrogen atom or a C 1-4 alkyl group. In particular, R 3 and R 3 ’ may each independently be a hydrogen atom or a C 1-3 alkyl group. In particular, R 3 and R 3 ’ may each independently be a hydrogen atom or a C 1-2 alkyl group. In particular, R 3 may each independently be a hydrogen atom or a methyl group. Even more particularly, R 3 and R 3 ’ may be a hydrogen atom.

[0042] According to any embodiment of the present invention, R 4 and R 4 ’ may each independently be a hydrogen atom or a C 1-9 alkyl group. In particular, it may be a hydrogen atom or a C 1-4 alkyl group. In particular, R 4 and R 4 ’ may each independently be a hydrogen atom, a methyl group or a tert-butyl group. More particularly, R 4 and R 4 ’ may be a methyl group or a tert-butyl group.

[0043] According to any embodiment of the present invention, R 5 and R 5 ’ may independently of each other be a hydrogen atom or a C 1-4 alkyl group. In particular, R 5 and R 5 ’ may each independently be a hydrogen atom or a C 1-3 alkyl group. In particular, R 5 and R 5 ’ may each independently be a hydrogen atom or a C 1-2 alkyl group. In particular, R 5 may each independently be a hydrogen atom or a methyl group. More particularly, R 5 and R 5’ may be a hydrogen atom.

[0044] According to any embodiment of the present invention, R 3 together with R 4 may form a C6 aryl when combined.

[0045] According to any embodiment of the present invention, R 3 ’ together with R 4 ’ may form a C6 aryl when combined.

[0046] According to any embodiment of the present invention, m is 1.

[0047] According to any embodiment of the present invention, Z is CR 6 R 7 group.

[0048] According to any embodiment of the present invention, R 6 and R 7 when considered separately may independently of each other be a hydrogen atom or a C 1-2 alkyl. In particular, R 6 and R 7 when considered separately may independently of each other be a hydrogen atom or a methyl group. Even more particularly, R 6 may be a hydrogen atom, while R 7 may be a hydrogen atom or a methyl group.

[0049] According to any embodiment of the present invention, the bisphenolate radical may be selected from the group consisting of: [1,1'-biphenyl]-2,2'-diol, [1,1'-binaphthalene]-2,2'-diol, 6,6'-methylenebis(2,4-di-tert-butylphenol), 6,6'-(ethane-1,1-diyl)bis(2,4-di-tert-butylphenol), 6,6'-methylenebis(2-tert-butyl-4-methylphenol), 6,6'-oxybis(2-tert-butyl-4-methylphenol) and 6,6'-thiobis(2-tert-butyl-4-methylphenol).

[0050] According to any embodiment of the present invention, the triphenolate radical conforms to the following formula:

[0051]

[0052] where the wavy line indicates the position of the bond between the zirconium atom and L; Z, m, R 2 , R 3 , R 4 , R 5 , R 2 ’, R 3 ’, R 4 ’ and R 5 ’ have the same meaning as defined above, and R 2”, R 3 ”, R 4 ” and R 5 ” are respectively R 2 , R 3 , R 4 , R 5 groups.

[0053] According to any embodiment of the present invention, the triphenolate can be selected from the group consisting of: 2,6-bis[(2-hydroxyphenyl)methyl]phenol, 2,6-bis[(2-hydroxy-3,5-dimethylphenyl)methyl]-4-methylphenol, 2,6-bis(3-tert-butyl-5-methyl-2-hydroxybenzyl)-4-methylphenol, 4-chloro-2,6-bis[(2-hydroxy-5-methylphenyl)methyl]phenol, 2,6-bis[(5-chloro-2-hydroxyphenyl)methyl]-4-methylphenol, 2,6-bis[(2-hydroxy-4-methylphenyl)methyl]-3-methylphenol, 4-chloro-2,6-bis[(2-hydroxy-3,5-dimethylphenyl)methyl]phenol, 2,6-bis[1-(2-hydroxyphenyl)ethyl]phenol, (2S)-1-[3,5-bis[[2,6-dihydroxy-4-methoxy-3-methyl-5-(1-oxobutyl)phenyl]methyl]-2,4,6-trihydroxyphenyl]-2-methyl-1-butanone, 2,2'-methylenebis[6-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol].

[0054] According to any embodiment of the present invention, the calixarene can contain 4, 6 or 8 phenol units, especially 4 phenol units. The calixarene having 4 phenol units conforms to the following formula:

[0055]

[0056] where the wavy line indicates the position of the bond between the zirconium atom and L; Z, m, R 3 , R 4 and R 5 have the same meanings as defined above.

[0057] According to any embodiment of the present invention, the calixarene having at least 4 phenol units can be selected from the group consisting of p-tert-butylcalix[4]arene, 25,26,27,28-tetrahydroxycalix[4]arene, calix[6]arene, tert-butylcalix[8]arene, tert-butylcalix[6]arene, calix[8]arene, p-isopropylcalix[4]arene.

[0058] According to any embodiment of the present invention, the anionic ligand can be, independently of each other, a halogen atom, a β-diketonate, an OOCR 8 group or an OR 9a group, where R 8 is C 1-10 alkyl, benzyl, naphthyl or phenyl optionally substituted with a hydroxyl group, R 9 is C 1-6 alkyl. The term "β-diketonato" is understood to include ligands containing a C(=O)-CH=C(O - ) group. In particular, β-diketonato conforms to the formula R 10 -C(=O)-CH=C(O - )-R 11 , where R 10 and R 11 are each independently C 1-6 alkyl, especially C 1-4 alkyl, even more particularly methyl, propyl, isopropyl or tert-butyl. Non-limiting examples of β-diketonato may include 4-oxopent-2-enoato, 2,2-dimethyl-5-oxohex-3-enoato, 2,6-dimethyl-5-oxohept-3-enoato or 2,2,6,6-tetramethyl-5-oxohept-3-enoato. In particular, R 8 can be C 1-8 alkyl, especially C 1-6 alkyl, even more particularly C 1-5 alkyl. In particular, R 9 can be C 1-4 alkyl, especially propyl, isopropyl, butyl or tert-butyl. In particular, the anionic ligand is selected from the group consisting of acetylacetonato, acetate and pivalate.

[0059] According to a particular embodiment, when p is 0 and n is 4, X is an alkoxide of the formula OR 9 as defined above.

[0060] According to any embodiment of the present invention, the catalyst conforms to formula (I).

[0061] According to any embodiment of the present invention, r is 2 and L is bisphenolato.

[0062] According to any embodiment of the present invention, the catalyst of formula (I) can be selected from the group consisting of: bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenolato]]; bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-6-di-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-methylenebis[(4-6-dimethyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-ethylenebis[(4-6-di-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-thiobis[(4-methyl-6-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [2,2'-oxybis[(4-methyl-6-tert-butyl)phenol]]; bis(2,4-pentanedionato)zirconium [[2,2'-binaphthalene]-1,1'-diolate]; bis(propanolate)zirconium [[2,2'-binaphthalene]-1,1'-diolate]; bis(propanolate)zirconium [[2,2'-biphenyl]-1,1'-diolate].

[0063] The catalyst of formula (I) or formula (I') can be added to the reaction medium of the method of the present invention to form α,β-unsaturated carbonyl compounds in a wide range of concentrations. As a non-limiting example, a catalyst concentration in the range of 0.1 mol% to 10 mol% relative to the total amount of allylic alcohol can be cited. In particular, the catalyst concentration can be 0.5 mol% to 5 mol%. It goes without saying that the method is also applicable to more catalysts. However, as is known to those skilled in the art, the optimal concentration of the catalyst will depend on the nature of the catalyst, the nature of the allylic alcohol, the reaction temperature, and the required reaction time.

[0064] The catalyst of formula (I) or formula (I') can be prepared by various methods, for example starting from Zr(acac)4 or Zr(OPr)4. Alternatively, the catalyst of formula (I) or formula (I') can be formed in situ by the reaction between Zr(OPr)4, phenol or bisphenol and acetylacetone.

[0065] According to any of the above embodiments of the present invention, the hydrogen acceptor is a hydrocarbon containing at least one carbonyl functional group and having a boiling point equal to or higher than 80 °C, preferably equal to or higher than 110 °C, more preferably equal to or higher than 120 °C. The hydrogen acceptor reacts with the generated hydrogen and generates an alcohol. The hydrogen acceptor can be an aldehyde or a ketone. In particular, the borrowing hydrogen source can conform to the following formula:

[0066]

[0067] wherein R arepresents a C optionally substituted with a hydroxyl group or an aryl group 1-10 straight-chain alkyl, a C optionally substituted with a hydroxyl group or an aryl group 2-10 straight-chain alkenyl, a C optionally substituted with a hydroxyl group or an aryl group 3-10 branched or cyclic alkyl or alkenyl, or a phenyl group optionally substituted with 1-5 C 1-3 alkyl or alkoxy groups, hydroxyl groups or halogen atoms; R b represents a hydrogen atom or an R a group; or R a together with R b represents a C optionally substituted with a hydroxyl group or an aryl group 2-10 straight-chain or branched alkanediyl or alkenediyl. The hydrogen acceptor of formula (II) is a C 4-10 compound.

[0068] The terms "aryl" or "heteroaryl" have their conventional meanings in the art, i.e., aromatic hydrocarbon groups optionally having substituents, such as phenyl, pyridine or naphthyl. Non-limiting examples of optional substituents of aryl include C 1-3 alkyl or alkoxy groups, hydroxyl groups or halogen atoms.

[0069] According to any of the above embodiments, R a can represent phenyl, C 1-10 straight-chain alkyl or C 3-10 branched or cyclic alkyl, each of which is optionally substituted with a hydroxyl group. Preferably, R a can represent phenyl, a C optionally substituted with a hydroxyl group 1-10 straight-chain alkyl or a C optionally substituted with a hydroxyl group 3-10 branched or cyclic alkyl. Preferably, R a can represent a C optionally substituted with a hydroxyl group 3-8 straight-chain or branched alkyl. More preferably, R a can represent phenyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl, octyl.

[0070] According to any of the above embodiments, R b can represent a hydrogen atom, a C optionally substituted with a hydroxyl group or an aryl group 1-10 straight-chain alkyl, or a C optionally substituted with a hydroxyl group or an aryl group 3-10 branched or cyclic alkyl. Preferably, R b can represent a hydrogen atom, methyl, ethyl or propyl.

[0071] According to any of the above embodiments, R a together with R b can represent a C optionally substituted with a hydroxyl group 4-8 straight-chain, branched alkanediyl or alkenediyl. Preferably, R a together with Rb When combined, can represent optionally substituted hydroxy-C 4-7 Straight-chain, branched-chain alkanediyl or alkenediyl. Preferably, R a And R b When combined, can represent C 4-7 Straight-chain alkanediyl. More preferably, R a And R b When combined, can represent C 4-5 Straight-chain alkanediyl.

[0072] Non-limiting examples of suitable hydrogen acceptors can include compounds selected from the group consisting of benzaldehyde, cyclohexanone, 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methyl-2-pentanone, isophorone, 3-methyl-2-butanone, and mixtures thereof.

[0073] The hydrogen acceptor can be added to the reaction medium of the method of the present invention to form α,β-unsaturated carbonyl compounds over a wide concentration range. As non-limiting examples, concentration values of the hydrogen acceptor in the range of 1 equivalent to 5 equivalents, and even 1 equivalent to 2 equivalents, relative to the amount of the allylic alcohol, can be cited. Needless to say, the method is also applicable to more hydrogen acceptors. However, it is known to those skilled in the art that the optimal concentration of the hydrogen acceptor will depend on the nature of the hydrogen acceptor, the nature of the allylic alcohol, the reaction temperature, and the desired reaction time.

[0074] According to any of the above embodiments, the allylic alcohol is a compound of the following formula:

[0075]

[0076] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R c Is a hydrogen atom or C 1-10 Alkyl or C 2-10 Alkenyl, R d Is a hydrogen atom or C 1-3 Alkyl, R e Is a hydrogen atom or C 1-5 Alkyl, R f Is a hydrogen atom or methyl; or R c And R e When combined, represent C 2-16 Alkanediyl or C 3-16 Alkenediyl; or R d And R e When combined, represent C 2-16 Alkanediyl; or R c And R d When combined, represent C 2-16 Alkanediyl or C 3-16a divalent group; and the α,β-unsaturated carbonyl compound is a compound of the following formula:

[0077]

[0078] The compound is in the form of any one of its stereoisomers or a mixture thereof, and wherein R c , R d and R e have the same meanings as defined above.

[0079] According to any one of the above embodiments, R f is a hydrogen atom.

[0080] According to any one of the above embodiments, the allylic alcohol is a compound of the following formula:

[0081]

[0082] The compound is in the form of any one of its stereoisomers or a mixture thereof, and wherein R c is a hydrogen atom or a C 1-10 alkyl group or a C 2-10 alkenyl group, R d is a hydrogen atom or a C 1-3 alkyl group, R e is a hydrogen atom or a C 1-5 alkyl group; or R c and R e together represent a C 2-16 alkanediyl group or a C 3-16 alkenediyl group; or R d and R e together represent a C 2-16 alkanediyl group; or R c and R d together represent a C 2-16 alkanediyl group or a C 3-16 alkenediyl group; and the α,β-unsaturated carbonyl compound is a compound of the following formula:

[0083]

[0084] The compound is in the form of any one of its stereoisomers or a mixture thereof, and wherein R c , R d and R e have the same meanings as defined above.

[0085] According to any one of the above embodiments, the allylic alcohol is a compound of the following formula:

[0086]

[0087] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R c is C 1-10 alkyl, R d is a hydrogen atom or C 1-3 alkyl, R e is C 1-3 alkyl; or R c together with R e represents C 2-16 alkanediyl; or R d together with R e represents C 2-16 alkanediyl; or R c together with R d represents C 2-16 alkanediyl; and the α,β-unsaturated carbonyl compound is a compound of the following formula:

[0088]

[0089] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R c , R d and R e have the same meanings as defined above.

[0090] The terms "alkanediyl" or "alkenediyl" should be understood to include straight-chain, branched-chain, cyclic or cycloaliphatic alkanediyl or alkenediyl.

[0091] For the sake of clarity, by the expression "any of its stereoisomers or mixtures thereof" or a similar expression, it means the normal meaning understood by those skilled in the art, that is, the compounds cited in the present invention can be pure enantiomers or mixtures of multiple enantiomers. In other words, the compounds cited in the present invention can have at least one stereocenter, and this stereocenter can have two different stereochemistries (e.g., R or S), for example, the R 1 group can contain at least one stereocenter. The compound can even be in the form of a pure enantiomer or a mixture of multiple enantiomers. When the compound has more than one stereocenter, the compounds cited in the present invention can even be in the form of pure diastereomers or mixtures of multiple diastereomers. The compound can be in racemic form or non-racemic (scalemic, proportionally optically active) form. Therefore, the compound can be a stereoisomer or in the form of a substance composition containing various stereoisomers or composed of various stereoisomers.

[0092] The wavy line indicates that the double bond can be in the form of its E or Z isomer, or a mixture thereof; for example, the present invention encompasses a substance composition comprising one or more compounds of formula (III) or one or more compounds of formula (IV) having the same chemical structure but different double bond configurations.

[0093] According to any of the above embodiments, R c can be a hydrogen atom, C 1-8 alkyl or C 2-8 alkenyl. In particular, R c can be a hydrogen atom, C 1-6 alkyl or C 2-6 alkenyl. In particular, R c can be a hydrogen atom, C 1-4 alkyl or C 4-6 alkenyl. In particular, R c can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R c can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R c can be a hydrogen atom, C 1-3 alkyl or C 4-6 alkenyl. In particular, R c can be a hydrogen atom, C 1-2 alkyl or C6 alkenyl. Even more particularly, R c can be a hydrogen atom, methyl, ethyl, hex-3-en-1-yl or 4-methylpent-3-en-1-yl.

[0094] According to any of the above embodiments, R e can be a hydrogen atom or C 1-5 alkyl. In particular, R e can be a hydrogen atom, C 1-3 alkyl or pentyl. In particular, R e can be a hydrogen atom or methyl, ethyl or pentyl. In particular, R e can be a hydrogen atom or pentyl. Even more particularly, R e can be a hydrogen atom or a straight-chain pentyl.

[0095] According to any of the above embodiments, R d can be a hydrogen atom or C 1-2 alkyl. In particular, R d can be a hydrogen atom or methyl. Even more particularly, R d can be methyl.

[0096] According to any of the above embodiments, R c is the same as R dTogether represent C 2-12 alkanediyl or C 3-12 alkenediyl. In particular, R c and R d together represent C 2-10 alkanediyl or C 3-10 alkenediyl. In particular, R c and R d together represent C 2-8 alkanediyl or C 3-8 alkenediyl. In particular, R c and R d together represent C 4-8 alkanediyl or C 4-8 alkenediyl. In particular, R c and R d together represent C 6-8 alkanediyl or C 6-8 alkenediyl. In particular, R c and R d together form C 5-6 cycloalkenyl, which may optionally be substituted with C 1-4 alkyl or alkenyl. Even more particularly, R c and R d together represent 2-isopropenyl-1,4-butadienyl or a group of formula (a):

[0097]

[0098] The compound is in the form of any one of its stereoisomers or a mixture thereof.

[0099] According to any of the above embodiments, R d and R e together represent C 2-12 alkanediyl. In particular, R d and R e together represent C 2-10 alkanediyl. In particular, R d and R e together represent C 2-8 alkanediyl. In particular, R d and R e together represent C 4-8 alkanediyl. In particular, R d and R e together represent C 6-8 alkanediyl. Even more particularly, R d and R e together represent a 2-group of formula (a):

[0100]

[0101] The compound is in the form of any of its stereoisomers or mixtures thereof.

[0102] According to any of the above embodiments, R c together with Re represents C 2-12 alkanediyl or C 3-12 alkenediyl. In particular, R c together with Re represents C 2-10 alkanediyl or C 3-10 alkenediyl. In particular, R c together with Re represents C 2-8 alkanediyl or C 3-8 alkenediyl. In particular, R c together with Re represents C 4-8 alkanediyl or C 4-8 alkenediyl. In particular, R c together with Re represents C 5-8 alkanediyl or C 5-8 alkenediyl. In particular, R c together with Re represents C 5-7 alkanediyl or C 5-7 alkenediyl. In particular, R c together with R e represents C6 alkanediyl or C6 alkenediyl. Even more particularly, R c together with R e represents 2-isopropenyl-1,3-propanediyl, a group of formula (b) or a group of formula (c):

[0103]

[0104] The compound is in the form of any of its stereoisomers or mixtures thereof.

[0105] According to any of the above embodiments, R c together with R e represents C 2-12 alkanediyl, and R d is a hydrogen atom or C 1-3 alkyl. In particular, R c together with R e represents C 2-8 alkanediyl, and R d is a hydrogen atom or C 1-3 alkyl. In particular, R c together with R e represents C 2-6 alkanediyl, and R d is a hydrogen atom or C 1-3 alkyl. In particular, Rc together with R e represents C 2-4 alkanediyl, and R d is a hydrogen atom or C 1-3 alkyl. In particular, R c together with R e represents C 2-4 alkanediyl, and R d is a hydrogen atom or C 1-2 alkyl. In particular, R c together with R e represents C 2-3 alkanediyl, and R d is a hydrogen atom or C 1-2 alkyl. Even more particularly, R c together with R e represents C3 alkanediyl, and R d is methyl.

[0106] According to any of the above embodiments of the present invention, the allylic alcohol is carveol, (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol, 4-methyl-3-decen-5-ol, 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-ol i.e. iso-carveol, (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol, 1-octen-3-ol, 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol, 3,7,7-trimethylbicyclo[4.1.0]hept-3-en-2-ol, geraniol, nerol, 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol, (2E,6Z)-nona-2,6-dien-1-ol, 3-methyl-2-buten-1-ol, 6-isopropyl-3-methylcyclohex-2-en-1-ol, 5-isopropyl-2-methylcyclohex-2-en-1-ol, (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol. In particular, the allylic alcohol is carveol.

[0107] According to any of the above embodiments of the present invention, the α,β-unsaturated carbonyl compound is carvone, 6,6-dimethylbicyclo[3.1.1]hept-2-en-2-carbaldehyde, 4-methyldec-3-en-5-one, 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-one, 4-prop-1-en-2-ylcyclohexene-1-carbaldehyde, 1-octen-3-one, 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-one, 3,7,7-trimethylbicyclo[4.1.0]hept-3-en-2-one, (2E)-3,7-dimethylocta-2,6-dienal, (2Z)-3,7-dimethylocta-2,6-dienal, 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one, (2E,6Z)-non-2,6-dienal, 5-isopropyl-2-methylcyclohex-2-en-1-one, 6-isopropyl-3-methylcyclohex-2-en-1-one or 3-methylbut-2-enal. In particular, the α,β-unsaturated carbonyl compound is carvone.

[0108] According to any of the embodiments of the present invention, the method for oxidizing allylic alcohol to α,β-unsaturated carbonyl compound of the present invention is carried out at a temperature of 50 °C to 190 °C. In particular, the temperature ranges from 100 °C to 140 °C. Of course, those skilled in the art can also select the preferred temperature according to the melting and boiling points of the starting product and the final product and the required reaction or conversion time.

[0109] The method for oxidizing allylic alcohol to α,β-unsaturated carbonyl compound of the present invention can be carried out with or without a solvent. When a solvent is required or used for practical reasons, any solvent existing in such reactions can be used in the present invention. Non-limiting examples include C 6-12 aromatic solvents such as xylene, toluene, 1,3-diisopropylbenzene, cumene or pseudocumene, or mixtures thereof, hydrocarbon solvents such as cyclohexane, heptane, or mixtures thereof; nitrile solvents such as acetonitrile; ester solvents such as ethyl acetate; ether solvents such as tetrahydrofuran, diethyl ether, methyltetrahydrofuran, or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or the catalyst, and those skilled in the art can select the most suitable solvent according to the specific situation to optimize the reaction.

[0110] The method for oxidizing allylic alcohol to α,β-unsaturated carbonyl compound of the present invention can be carried out under batch or continuous conditions.

[0111] The method for oxidizing allylic alcohol to α,β-unsaturated carbonyl compound of the present invention can be carried out at atmospheric pressure.

[0112] According to any of the above embodiments, allylic alcohol can be prepared by rearranging an epoxide to allylic alcohol. In other words, the method of the present invention comprises the following steps:

[0113] i) Rearrange the epoxide to an allylic alcohol;

[0114] ii) Oxidize the allylic alcohol obtained in step i) to an α,β-unsaturated carbonyl compound as defined above.

[0115] According to a specific embodiment of the present invention, the rearrangement of the epoxide to an allylic alcohol and the oxidation of the allylic alcohol to an α,β-unsaturated carbonyl compound can be carried out in one pot. The term "one pot" should be understood as the two steps being carried out continuously in a single reaction system. In this case, the hydrogen acceptor and the zirconium catalyst are added after the first step is completed. The zirconium catalyst can also be generated in situ after the first step is completed.

[0116] According to a specific embodiment of the present invention, the rearrangement of the epoxide to an allylic alcohol is carried out in the presence of: a catalyst of the formula Zn(aa)2, where aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate, or a catalyst of the formula Zn(carboxylate)2; and an aminophenol.

[0117] According to any of the above embodiments, the α-amino acid is selected from the group consisting of proline, valine, lysine, D-proline, D-valine, D-lysine, L-proline, L-valine, L-lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof, and the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, and mixtures thereof.

[0118] According to any embodiment of the present invention, the β-aminocarboxylate is anthranilate.

[0119] According to any of the above embodiments, the catalyst of the formula Zn(carboxylate)2 is selected from the group consisting of Zn(2-ethylhexenoate)2, Zn(OAc)2, Zn(benzoate)2, Zn(naphthoate)2, Zn(laurate)2, Zn(stearate)2, Zn(palmitate)2, Zn(2-octyldodecanoate)2; and the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, and mixtures thereof.

[0120] According to any of the above embodiments, the epoxide is a compound of the following formula:

[0121]

[0122] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R c 、R d and Re has the same meaning as defined above.

[0123] According to any of the above embodiments, the epoxide is a compound of the following formula:

[0124]

[0125] The compound is in the form of any of its stereoisomers or mixtures thereof, and wherein R c , R d and R e has the same meaning as defined above.

[0126] According to any of the above embodiments of the present invention, non-limiting examples of the epoxide are 1,2-limonene oxide, 3,8,8-trimethyl-4-oxatricyclo[5.1.0.0 3,5 octane, 4,8,8-trimethyltricyclo[5.1.0.0 2,4 octane, 2-isopropyl-5-methyl-7-oxabicyclo[4.1.0]heptane, 4-isopropyl-1-methyl-7-oxabicyclo[4.1.0]heptane, alpha-pinene oxide, beta-pinene oxide, 2,2,6-trimethyl-1-oxaspiro[2.5]oct-5-ene, 2,2,6-trimethylspiro[2.5]oct-4-ene, caryophyllene oxide. In particular, the epoxide can be 1,2-limonene oxide.

[0127] A catalyst of the formula Zn(aa)2 or Zn(carboxylate)2 can be added to the reaction medium of the method of the present invention to form allylic alcohols in a wide range of concentrations. As non-limiting examples, catalyst concentration values in the range of 0.1 mol% to 10 mol% relative to the total amount of epoxide can be cited. In particular, the catalyst concentration can be 0.25 mol% to 5 mol%. Needless to say, the method is also applicable to more catalysts. However, it is known to those skilled in the art that the optimal concentration of the catalyst will depend on the nature of the catalyst, the nature of the epoxide, the reaction temperature, and the required reaction time.

[0128] According to any of the embodiments of the present invention, the aminophenol is selected from the group consisting of 2-aminophenol, 2-aminomethylphenol, 2-amino-4-chlorophenol, 2-amino-3-methylphenol, 2-amino-5-chlorophenol, 2-amino-4-nitrophenol, 2-amino-5-nitrophenol, 2-amino-3-nitrophenol, 2-amino-4-methoxyphenol, 2-amino-4-tert-butylphenol, and mixtures thereof.

[0129] Aminophenol can be added to the reaction medium of the method of the present invention to form allylic alcohols over a wide concentration range. As non-limiting examples, aminophenol concentrations in the range of 1 mol% to 5 mol%, and even 1 mol% to 3 mol%, relative to the amount of epoxide, can be cited. Needless to say, the method is also applicable to more aminophenols. However, it is known to those skilled in the art that the optimal concentration of aminophenol will depend on the nature of the aminophenol, the nature of the epoxide, the nature of the catalyst, the reaction temperature, and the desired reaction time.

[0130] According to any embodiment of the present invention, the method of the present invention for rearranging epoxides to allylic alcohols is carried out at a temperature in the range of 50 °C to 190 °C. In particular, the temperature is in the range of 100 °C to 190 °C. In particular, the temperature is in the range of 100 °C to 185 °C. In particular, the temperature is in the range of 160 °C to 190 °C. Even more particularly, the temperature is in the range of 170 °C to 190 °C. Of course, those skilled in the art can also select the preferred temperature according to the melting and boiling points of the starting and final products and the required reaction or conversion time.

[0131] The method of the present invention for rearranging epoxides to allylic alcohols can be carried out with or without a solvent. When a solvent is required or used for practical reasons, any solvent existing in such reactions can be used for the purposes of the present invention. Non-limiting examples include C 6-12 aromatic solvents such as xylene, toluene, 1,3 - diisopropylbenzene, cumene or pseudocumene, or mixtures thereof, and hydrocarbon solvents such as cyclohexane, heptane, or mixtures thereof. The choice of solvent depends on the nature of the substrate and / or the catalyst, and those skilled in the art can select the most suitable solvent according to the specific situation to optimize the reaction.

[0132] The method of the present invention for rearranging epoxides to allylic alcohols can be carried out under batch or continuous conditions.

[0133] The method of the present invention for rearranging epoxides to allylic alcohols can be carried out at atmospheric pressure.

[0134] Another object of the present invention is a catalytic system comprising or consisting of the following substances:

[0135] i) A catalyst of the following formula:

[0136] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0137] wherein L is a bisphenolate, a triphenolate or a calixarene having at least 4 phenol units, L’ is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units; and

[0138] ii) a hydrogen acceptor.

[0139] According to any embodiment of the present invention, the catalytic system as defined above is suitable for the method of oxidizing allylic alcohols to α,β-unsaturated carbonyl compounds as defined above.

[0140] Another object of the present invention is the use of a catalytic system in the method of oxidizing allylic alcohols to α,β-unsaturated carbonyl compounds, the catalytic system comprising or consisting of the following substances:

[0141] i) a catalyst of the following formula:

[0142] [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’)

[0143] wherein L is a bisphenolate, a triphenolate or a calixarene having at least 4 phenol units, L’ is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units; and

[0144] ii) a hydrogen acceptor.

[0145] The typical manner of implementing the method of the present invention is reported in the following examples.

[0146] Examples

[0147] The present invention will now be described in more detail by the following examples, where the abbreviations have their conventional meanings in the art and the temperature is expressed in degrees Celsius (°C). The preparation of the pre-catalyst and ligand solutions was carried out using standard Schlenk techniques under an inert atmosphere (argon). The solvents were dried by conventional methods and distilled under an argon atmosphere. The NMR spectra were recorded at 20 °C on a Bruker AV 300, AV 400 or AV 500 MHz spectrometer. The chemical shifts are reported in ppm relative to the solvent signals (chloroform, δ H = 7.26 ppm, δ C = 77.0 ppm). By recording 1 H, 1H-COSY, -NOESY, 13 C, 1 H-HSQC and -HMBC experiments were performed to ensure signal assignment. The NMR of all prepared compounds was consistent with the NMR reported in the literature.

[0148] Example 1

[0149] Catalytic oxidation of carveol using the complex [Zr(L)(acac)2] or [Zr(L’)(acac)3] (acac = acetylacetonate) is carried out

[0150] A mixture of carveol (Aldrich, ca. 1:1 mixture of isomers), [Zr(L)(acac)2] or [Zr(L’)(acac)3] (1 mol %), and cyclohexanone (1.5 equiv) was heated to 130 °C in a glass reactor equipped with a stirrer, thermometer, and condenser. The reaction mixture was heated at 130 °C for 4 h to complete the conversion of carveol to carvone. The results obtained using different L or L’ ligands in Table 2 are shown in Table 1.

[0151] Table 1: Oxidation of carveol using the complexes [Zr(L)(acac)2] or [Zr(L’)(acac)3]

[0152]

[0153] Table 2: Structures of the bisphenoxide or phenoxide used

[0154]

[0155] a) The wavy line indicates the position of the bond between the zirconium atom and L or L’

[0156] Example 2

[0157] R-(-)-carvone is prepared by a one-pot sequential rearrangement of R-(+)-1,2-epoxy limonene using Zn(L-prolinate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium

[0158] In a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator and condenser, a mixture of R-(+)-1,2-epoxymenthene (R-LMO), Zn(L-prolinato)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) was heated at 185 °C for 9 h. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and 1.1 equivalents of cyclohexanone relative to the initial R-LMO were added. The reaction mixture was heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation in a yield of 99% based on the weighed amount of the intermediate carveol and 82% based on the initial R-LMO. The substance was purified by conventional methods to give R-(-)-carvone with a purity > 99 GC%.

[0159] and cyclohexanone as a hydrogen acceptor

[0160] Example 3 R-(-)-carvone is prepared by a one-pot sequential rearrangement of R-(+)-1,2-epoxy limonene using Zn(L-prolinate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol

[0161] In a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator and condenser, a mixture of R-(+)-1,2-epoxymenthene (R-LMO), Zn(L-prolinato)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) was heated at 185 °C for 9 h. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and 1.1 equivalents of benzaldehyde relative to the initial R-LMO were added. The reaction mixture was heated at 130 °C for 4 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation in a yield of 96% based on the weighed amount of the intermediate carveol and 79% based on the initial R-LMO. The substance was purified by conventional methods to give R-(-)-carvone with a purity > 99 GC%.

[0162] in the presence of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium

[0163] and benzaldehyde as a hydrogen acceptor Example 4 R-(-)-carvone is prepared by a one-pot sequential rearrangement of R-(+)-1,2-epoxy

[0164] In a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator and a condenser, a mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(L-prolinato)2 (0.25 mol.%), and 2-aminophenol (4 equivalents / Zn) was heated at 185 °C for 9 hours. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and benzaldehyde in an amount of 1.1 equivalents relative to the initial R-LMO were added. The reaction mixture was heated at 100 °C for 2 hours and then at 130 °C for another 2 hours to complete the conversion of carveol to carvone. Carvone was obtained by distillation in a yield of 99% based on the weighed amount of the intermediate carveol and 82% based on the initial R-LMO. The substance was purified by conventional methods to obtain R-(-)-carvone with a purity > 99 GC%.

[0165] limonene using Zn(L-prolinate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol

[0166] in the presence of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and benzaldehyde as a hydrogen acceptor Example 5

[0167] In a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator and a condenser, a mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol.%), and 2-aminophenol (3 equivalents / Zn) was heated at 185 °C for 15 hours. After the rearrangement step was completed, the reaction mixture was cooled to room temperature. 1 mol.% of zirconium bis(2,4-pentanedionate) of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] and benzaldehyde in an amount of 1.1 equivalents relative to the initial R-LMO were added. The reaction mixture was heated at 100 °C for 2 hours and then at 130 °C for another 2 hours to complete the conversion of carveol to carvone. Carvone was obtained by distillation in a yield of 99% based on the weighed amount of the intermediate carveol and 83% based on the initial R-LMO. The substance was purified by conventional methods to obtain R-(-)-carvone with a purity > 99 GC%.

[0168] R-(-)-carvone is prepared by a one-pot sequential rearrangement of R-(+)-1,2-epoxy

[0169] limonene using Zn(2-ethylhexanoate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol in the presence of [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium and benzaldehyde as a hydrogen acceptor

[0170] A mixture of R-(+)-1,2-epoxy-limonene (R-LMO), Zn(2-ethylhexanoate)2 (0.5 mol.%), and 2-aminophenol (3 equivalents / Zn) was heated at 185 °C for 15 h in a glass reactor equipped with a stirrer, thermometer, Dean-Stark water separator, and condenser. After completion of the rearrangement step, the reaction mixture was cooled to 30 °C. 1 mol.% of Zr(OPr)4 (70% propanol solution), 6,6'-methylenebis(2-(tert-butyl)-4-methylphenol), and 2.2 equivalents of acetylacetone were added, and the reaction mixture was stirred for 1 h. Then, benzaldehyde (1.1 equivalents relative to the initial R-LMO) was added. The reaction mixture was heated at 100 °C for 2 h and then at 130 °C for another 2 h to complete the conversion of carveol to carvone. Carvone was obtained by distillation in 99% yield based on the amount of intermediate carveol weighed and 83% yield based on the initial R-LMO. The substance was purified by conventional methods to obtain R-(-)-carvone with a purity > 99 GC%.

[0171] Example 6

[0172] R-(-)-carvone is prepared by a one-pot sequential rearrangement of R-(+)-1,2-epoxy

[0173] A mixture of (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol (10 g, 65.7 mmol), bis(2,4-pentanedionato)[2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]zirconium (1 mol.%), and benzaldehyde (1.1 equivalents) was heated at 130 °C for 2 h in a Schlenk reactor equipped with a magnetic stirrer, thermometer, and condenser until the conversion reached 79%. After distilling the residue, the desired product 6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbaldehyde was obtained in 91% yield.

[0174] limonene using Zn(2-ethylhexanoate)2 as a catalyst, and Oppenauer oxidation of R-(-)-carveol

[0175] in the presence of in-situ generated [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]bis(2,4-pentanedionato)zirconium

[0176] A mixture of (E)-4-methyldec-3-en-5-ol (5 g, 29.4 mmol), bis(2,4-pentanedionato)[2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]zirconium (1 mol.%), and benzaldehyde (1.1 equivalents) was heated at 130 °C for 2 h in a Schlenk reactor equipped with a magnetic stirrer, thermometer, and condenser until the conversion reached 92%. After distilling the residue, the corresponding ketone, (E)-4-methyldec-3-en-5-one, was obtained in 98% yield.

[0177] and benzaldehyde as a hydrogen acceptor

[0178] Example 7

[0179] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-ol (2 g, 13.1 mmol), zirconium bis(2,4-pentanedionato)bis[(4-methyl-6-tert-butyl)phenol] (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 82%. After distilling the residue, 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-one was obtained in 91% yield.

[0180] Catalytic oxidation of (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methanol is carried out

[0181] using the conditions of the present invention

[0182] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol (4 g, 25.9 mmol), zirconium bis(2,4-pentanedionato)bis[(4-methyl-6-tert-butyl)phenol] (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 80%. After distilling the residue, 4-(prop-1-en-2-yl)cyclohex-1-en-1-carbaldehyde was obtained in 95% yield.

[0183] Example 8

[0184] Catalytic oxidation of (E)-4-methyldec-3-en-5-ol is carried out

[0185] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of 1-octen-3-ol (4 g, 31.2 mmol), zirconium bis(2,4-pentanedionato)bis[(4-methyl-6-tert-butyl)phenol] (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 38%. After distilling the residue, 1-octen-3-one was obtained in 97% yield.

[0186] using the conditions of the present invention Example 9 Catalytic oxidation of 6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-3-ol is carried out using the conditions of the present invention Example 10 Catalytic oxidation of (4-(prop-1-en-2-yl)cyclohex-1-en-1-yl)methanol is carried out using the conditions of the present invention Example 11 Catalytic oxidation of 1-octen-3-ol is carried out using the conditions of the present invention Example 12

[0187] Catalytic oxidation of 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol under the conditions of the present invention

[0188] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of 4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-ol (2 g, 13.1 mmol), bis(2,4-pentanedionato)[2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]zirconium (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 82%, and the selectivity for 7,7-trimethylbicyclo[4.1.0]hept-4-en-3-one was 70%.

[0189] Example 13

[0190] Catalytic oxidation of geraniol under the conditions of the present invention

[0191] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of geraniol (4 g, 25.9 mmol), bis(2,4-pentanedionato)[2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]zirconium (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 68%, and the selectivity for (2E)-3,7-dimethylocta-2,6-dienal was 87%.

[0192] Example 14

[0193] Catalytic oxidation of nerol under the conditions of the present invention

[0194] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of nerol (4 g, 25.9 mmol), bis(2,4-pentanedionato)[2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]]zirconium (1 mol.%), and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 58%, and the selectivity for (2Z)-3,7-dimethylocta-2,6-dienal was 85%.

[0195] Example 15

[0196] Catalytic oxidation of 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol under the conditions of the present invention

[0197] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol (5 g, 32.8 mmol), zirconium bis(2,4-pentanedionato) [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] (1 mol.%) and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 99%, and the selectivity for 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one was 98%.

[0198] Example 16

[0199] Catalytic oxidation of (2E,6Z)-nona-2,6-dien-1-ol under the conditions of the present invention

[0200] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of (2E,6Z)-nona-2,6-dien-1-ol (4 g, 28.5 mmol), zirconium bis(2,4-pentanedionato) [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] (1 mol.%) and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 65%, and the selectivity for (2E,6Z)-nona-2,6-dienal was 90%.

[0201] Example 17

[0202] Catalytic oxidation of 3-methylbut-2-en-1-ol under the conditions of the present invention

[0203] In a Schlenk reactor equipped with a magnetic stirrer, a thermometer and a condenser, a mixture of 3-methylbut-2-en-1-ol (i.e., isoprenol) (4 g, 46.4 mmol), zirconium bis(2,4-pentanedionato) [2,2'-methylenebis[(4-methyl-6-tert-butyl)phenol]] (1 mol.%) and benzaldehyde (1.1 equiv) was heated at 130 °C for 2 h until the conversion reached 45%, and the selectivity for 3-methylbut-2-enal (i.e., isoprenaldehyde) was 95%.

[0204] Example 18

[0205] Under the conditions of the present invention and comparative conditions, R-(−)-carvone was prepared by one-pot continuous rearrangement of R-(+)-limonene oxide and Oppenauer oxidation of R-(−)-carveol

[0206] In a glass reactor equipped with a stirrer, a thermometer, a Dean-Stark water separator and a condenser, a mixture of limonene 1,2-oxide (LMO, 60% cis isomer and 40% trans isomer, 400 g), a catalyst and 2-aminophenol (2-AP) (the equivalents of 2-AP relative to Zn are shown in Table 3) was heated to the temperature specified in Table 3. This temperature was maintained until the conversion of R-LMO > 96%. After cooling, the oxidation catalyst was added together with a hydrogen acceptor (the amounts used are shown in Table 3). In some embodiments, the hydrogen acceptor was added in batches after selectively removing the excess hydrogen acceptor (HA) and its corresponding alcohol. It should be clarified that if 2 / 2 is reported in the time column, it means that half of the total amount of HA was added first, and then after heating for 2 hours at the reported temperature, the unreacted HA and its corresponding alcohol were removed by distillation, and then the operation was repeated; for example, 2 / 2 / 2 means that HA was added every 2 hours, a total of 3 times. Then the crude carvone was purified by distillation to obtain carvone with a purity > 98%. The yields are reported in the column of carvone separation yields. The excess HA and its corresponding alcohol can also be distilled separately or together. If possible, their total yields ((the number of moles of excess HA + the number of moles of alcohol) / the number of moles of the initial total HA) are also reported.

[0207] Table 3: Rearranging limonene 1,2-oxide to carveol in one-pot using the conditions of the present invention and comparative conditions, and then performing oxidation and Oppenauer oxidation to obtain R-(-)-carvone

[0208]

[0209] 1) Conditions reported in WO2003004448

[0210] 2) Conditions reported in WO2021151790

[0211] 3) Conditions reported in WO2003004448; except for the oxidation temperature

[0212] 4) Conditions of the present invention

[0213] 5) 2,2'-Methylenebis[(4-methyl-6-tert-butyl)phenol]

[0214] 6) Limonene 1,2-oxide

[0215] Contrary to the prior art conditions, the conditions of the present invention can separate carvone in high yield while efficiently recovering the hydrogen acceptor or the corresponding alcohol. When the hydrogen acceptor is benzaldehyde, the resulting reduction product is benzyl alcohol, a valuable ingredient that can be used as a flavoring ingredient.

Claims

1. A method for oxidizing allylic alcohols to α,β-unsaturated carbonyl compounds, wherein the method is carried out in the presence of the following substances: i) A catalyst of the following formula: [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’) wherein L is a bisphenolate, a triphenolate or a calixarene having at least 4 phenol units, L’ is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units; and ii) A hydrogen acceptor.

2. The method according to claim 1, wherein the phenolate conforms to the following formula: where the wavy line indicates the position of the bond between the zirconium atom and L; R 1 ’ is a hydrogen atom, a halogen atom, a cyano group, a nitro group, C 1-6 alkoxy, C optionally substituted with one or more halogen atoms 1-6 alkyl, or a COOR group, where R is a hydrogen atom or C 1-6 alkyl.

3. The method according to claim 2, wherein the phenolate is selected from the group consisting of 2-nitrophenolate, o-cresolate, 2-(trifluoromethyl)phenolate and 2-cyanophenolate.

4. The method according to claim 1, wherein the bisphenolate conforms to the following formula: wherein the wavy line indicates the position of the bond between the zirconium atom and L; m is 0 or 1; R 2 、R 3 、R 4 、R 5 、R 2 ’, R 3 ’, R 4 ’ and R 5 ’ are, when considered individually, independently of one another, hydrogen, a halogen atom, a nitro group, 2H-benzo[d][1,2,3]triazol-2-yl, C 1-6 alkoxy, C 1-6 thioalkyl or C 1-3 alkyl optionally substituted with one or more halogen atoms, hydroxyl groups, amines or C 1-10 alkoxy; or R 2 and R 3 or R 3 and R 4 or R 2 ’ and R 3 ’ or R 3 ’ and R 4 ’ together represent an -O-(CH2) y -O- group, where y is 1 or 2, or form a C6 aryl, C 5-6 cycloalkyl, each of which is optionally substituted with one or more halogen atoms, hydroxyl groups or C 1-3 alkoxy; and Z is an oxygen or sulfur atom, a (-CH2-)2 group, an -NH- group, a -SO2- group, an -S-S- group, a -CH2-NH-CH2- group or a -C(R 6 )(R 7 )- group, where when R 6 and R 7 are, when considered individually, independently of one another, a hydrogen atom or a C6 aryl, C6 heteroaryl or C 1-3 alkyl, each of which is optionally substituted with one to three halogen atoms or C 1-3 alkoxy, and wherein the heteroatom is one or more of an oxygen or nitrogen atom.

5. The method according to claim 4, wherein the bisphenolate is selected from the group consisting of [1,1'-biphenyl]-2,2'-diol, [1,1'-binaphthalene]-2,2'-diol, 6,6'-methylenebis(2,4-di-tert-butylphenol), 6,6'-(ethane-1,1-diyl)bis(2,4-di-tert-butylphenol), 6,6'-methylenebis(2-tert-butyl-4-methylphenol), 6,6'-oxybis(2-tert-butyl-4-methylphenol) and 6,6'-thiobis(2-tert-butyl-4-methylphenol).

6. The method according to any one of claims 1 to 5, wherein the anionic ligands are, independently of one another, halogen atoms, β-diketonate, OOCR 8 groups or OR 9 groups, where R 8 is C 1-10 alkyl, benzyl, naphthyl or phenyl optionally substituted by hydroxyl, and R 9 is C 1-6 alkyl.

7. The method according to any one of claims 1 to 6, wherein the hydrogen acceptor is a hydrocarbon containing at least one carbonyl functional group and having a boiling point equal to or greater than 80 °C, preferably greater than 120 °C.

8. The method according to any one of claims 1 to 7, wherein the hydrogen acceptor is selected from the group consisting of benzaldehyde, cyclohexanone, octalynone, 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methyl-2-pentanone, 3-methyl-2-butanone, isophorone and mixtures thereof.

9. The method according to any one of claims 1 to 8, wherein the allylic alcohol is carveol and the α,β-unsaturated carbonyl compound is carvone.

10. The method according to any one of claims 1 to 9, wherein the method comprises the following steps: i) Rearranging an epoxide to an allylic alcohol; ii) Oxidizing the allylic alcohol obtained in step i) to the α,β-unsaturated carbonyl compound as defined in any one of claims 1 to 9.

11. The method according to claim 10, wherein the rearrangement of the epoxide to an allylic alcohol is carried out in the presence of a catalyst of the formula Zn(aa)2, wherein aa is an α-aminocarboxylate having at least 3 carbon atoms, or a β-aminocarboxylate; and an aminophenol.

12. The method according to claim 11, wherein the α-amino acid is selected from the group consisting of proline, valine, lysine, D-proline, D-valine, D-lysine, L-proline, L-valine, L-lysine, 2-phenylglycine, phenylalanine, 2-amino-2-methylpropanoic acid, and mixtures thereof, and the aminophenol is selected from the group consisting of 2-aminophenol, 2-(aminomethyl)phenol, and mixtures thereof.

13. The method according to claim 10, wherein the rearrangement of the epoxide to the allylic alcohol is carried out in the presence of a catalyst of the formula Zn(carboxylate)2 and an aminophenol.

14. The method according to any one of claims 10 to 13, wherein the epoxide is limonene 1,2-oxide.

15. A catalytic system comprising or consisting of: i) a catalyst of the following formula: [Zr(L)(X) r (I) or [Zr(L’) p (X) n (I’) wherein L is a bisphenolate, a triphenolate, or a calixarene having at least 4 phenol units, L' is a phenolate, X is an anionic ligand, p is 1 when n is 3, or p is 2 when n is 2, or p is 0 when n is 4, and r is 2 when L is a bisphenolate, or r is 1 when L is a triphenolate, or r is 0 when L is a calixarene having at least 4 phenol units; and ii) a hydrogen acceptor.

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