Process for preparing carbonyl compounds

Abstract

The present invention relates to the field of organic synthesis and more specifically it concerns a process for the oxidation of a non-allylic alcohol into a carbonyl compound in a presence of zirconium catalyst and a hydrogen acceptor.

Description

[0001] PROCESS FOR PREPARING CARBONYL COMPOUNDS

[0002] Technical field

[0003] The present invention relates to the field of organic synthesis and more specifically it concerns a process for the oxidation of a non-allylic alcohol into a carbonyl compound in the presence of a zirconium catalyst and a hydrogen acceptor.

[0004] Background

[0005] Carbonyl compounds represent skeletons highly desirable which could be used as such or as key intermediates useful to prepare more complex compounds in different fields such as, among others, perfumery, cosmetic, pharmaceutic or agrochemistry. In particular, citronellal or 3,7-dimethyloct-6-enal are valuable compounds known as a perfuming ingredient or could be a key intermediate toward more complex compounds. One access toward carbonyl compounds is the oxidation of the corresponding alcohol, in particular Oppenauer oxidation which could be easily implemented at an industrial scale. Nevertheless, such oxidation is carried out at high temperatures and / or with sub- stoichiometric amount of catalyst. However, today, there is a need to develop a sustainable process while reducing energy consumption and simplifying the implementation of the process.

[0006] The present invention allows the oxidation of a non-allylic alcohol into a carbonyl compound under catalytic conditions and at a lower temperature while affording complete conversion and maintaining a high yield. To the best of our knowledge, the use of a zirconium catalyst in such an oxidation process has never been reported in the prior art.

[0007] Summary of the Invention

[0008] The invention relates to a novel process allowing the preparation of carbonyl compound under mild conditions never reported or suggested in the prior art. So, a first object of the present invention is a process for the oxidation of a non-allylic alcohol into a carbonyl compound wherein said process is carried out in the presence of i) a catalyst of formula

[0009] [Zr(L)(X)r] (I) or [Zr(L’)p(X)n] (I’) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and ii) a hydrogen acceptor.

[0010] A second object of the present invention is a catalytic system comprising or consisting of i) a catalyst of formula

[0011] [Zr(L)(X)r] (I) or [Zr(L’)p(X)n] (I’) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and ii) a hydrogen acceptor.

[0012] Description of the invention

[0013] Surprisingly, it has now been discovered that oxidation of a non-allylic alcohol into a carbonyl compound can be performed in an advantageous manner by means of a catalyst of formula (I) or (I’) and a hydrogen acceptor. These unprecedented conditions allow the generation of a carbonyl compound in very high yield without using a high temperature and a stochiometric or sub-stoichiometric amount of catalyst. The inventions process provides a simple access to carbonyl compounds.

[0014] Therefore, a first object of the present invention is a process for the oxidation of a non-allylic alcohol into a carbonyl compound wherein said process is carried out in the presence of iii) a catalyst of formula

[0015] [Zr(L)(X)r] (I) or [Zr(L’)p(X)n] (I ) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and iv) a hydrogen acceptor. The term “carbonyl compound” is understood as a compound that comprises at least one carbonyl group, preferably two carbonyl groups, even more preferably one carbonyl group. Preferably, the carbonyl group of the carbonyl compound is in the form of an aldehyde or a ketone.

[0016] According to any embodiment of the invention, p is 1 and n is 3. In other words, the catalyst of formula (I’) is of formula

[0017] [Zr(L’)(X)3] (I”) wherein L’ and X have the same meaning as defined above.

[0018] According to any embodiment of the invention, the phenolate is of formula wherein the wavy line indicates the location of the bond between the Zirconium atom and L; q is an integer comprised between 0 and 3, R1, simultaneously or independently, represents at least one substituent of the aromatic ring and is a halogen atom, a cyano group, a nitro group, a Ci-6 alkyl group optionally substituted with one or more halogen atoms, a Ci-6 alkoxy group or a COOR group wherein R is a hydrogen atom or a Ci-6 alkyl group.

[0019] The term “optionally” is understood that a group can or cannot comprise a certain functional group or substituent. The term “one or more” is understood as comprising 1 to 7, preferably 1 to 5 and more preferably 1 to 3 functional groups.

[0020] The terms “alkyl group” “alkenyl group” or “alkoxy group” are understood as comprising linear or branched alkyl, alkenyl or alkoxy groups. The term “alkanediyl group” or “alkenediyl group” are understood as comprising linear, branched, alicylic or cyclic alkanediyl or alkenediyl groups. The terms “alkenyl”; “alkenediyl” and “cycloalkenyl” are understood as comprising 1, 2 or 3 olefinic double bonds, preferably 1 or 2 olefinic double bonds, even more preferably 1 double bond. The term “cycloalkenyl” is understood as comprising a monocyclic or fused, spiro and / or bridged bicyclic or tricyclic cycloalkenyl group, preferably monocyclic cycloalkenyl group. According to any embodiment of the invention, R1may be a halogen atom, a cyano group, a nitro group, a Ci-4 alkoxy group, a Ci-4 alkyl group optionally substituted with one to three halogen atoms or a COOR group wherein R is a hydrogen atom or a Ci-4 alkyl group. Particularly, R1may be a chlorine atom, a fluorine atom, a cyano group, a nitro group, a C1-3 alkoxy group or a C1-3 alkyl group optionally substituted with one to three halogen atoms or a COOR group wherein R is a hydrogen atom or a C1-3 alkyl group. Particularly, R1may be a cyano group, a nitro group, a COOH group or a C1-3 alkyl group optionally substituted with one to three fluorine atoms. Even more particularly, R1may be a cyano group, a nitro group or a methyl group optionally substituted with one to three fluorine atoms.

[0021] According to any embodiment of the invention, q may be 0 or 1, particularly 1.

[0022] According to any embodiment of the invention, R1may be, relative to position 1, an ortho substituent of the aromatic ring. In other words, the phenolate of formula (I) is of formula wherein the wavy line indicates the location of the bond between the Zirconium atom and L; R1is a hydrogen atom or a R1group as defined above

[0023] According to any embodiment of the invention, the phenolate is selected from the group consisting of 2-nitrophenolate, ortho-cresolate, 2-(trifluoromethyl)phenolate and 2- cy anophenolate.

[0024] According to any embodiment of the invention, the bisphenolate is of formula wherein the wavy lines indicate the location of the bond between the Zirconium atom and L; m is 0 or 1; R2, R3R4, R5, R2, R3, R4and R5, when taken separately, independently from each other, are a hydrogen, a halogen atom, a nitro group, a 2H- benzo[d][l,2,3]triazol-2-yl group, a Ci-6 alkoxy group, a Ci-6 thioalkyl group or a Ci-io alkyl group optionally substituted with one or more of a halogen atom, hydroxy, amine or Ci-3 alkoxy group; or R2and R3or R3and R4or R2and R3or R3and R4, when taken together represent a -0-(CH2)y-0- group wherein y is 1 or 2 or form a Ce aryl, C5-6 cycloalkyl group, each optionally substituted with one or more of a halogen atom, hydroxy or C1-3 alkoxy group; and Z is an oxygen or sulphur atom, a (-Clfc-h group, a - NH- group, a -SO2- group, a -S-S- group, a -CH2-NH-CH2- group, or a -C(R6)(R7)- group wherein R6and R7, when taken separately, independently from each other, are a hydrogen atom or a Ce aryl, Ce heteroaryl or a C1-3 alkyl group, each optionally substituted by one to three halogen atoms or C1-3 alkoxy groups, and wherein the heteroatom is one or more of an oxygen or nitrogen atom.

[0025] According to any embodiment of the invention, R2, R3R4, R5, R2, R3, R4and R5, when taken separately, independently from each other, may be a hydrogen atom, a chlorine atom or a C1-9 alkyl group; or R2and R3or R3and R4or R2and R3or R3and R4, when taken together form a Ce aryl group.

[0026] According to any embodiment of the invention, R2and R2, independently from each other, may be a hydrogen atom or a C1-4 alkyl group. Particularly, R2and R2, independently from each other, may be a hydrogen atom or a methyl or a tert-butyl group. Particularly, R2and R2may be a hydrogen atom or a tert-butyl group. Even more particularly, R2and R2may be a tert-butyl group.

[0027] According to any embodiment of the invention, R3and R3, independently from each other, may be a hydrogen atom or a C1-4 alkyl group. Particularly, R3and R3, independently from each other, may be a hydrogen atom or a C1-3 alkyl group. Particularly, R3and R3, independently from each other, may be a hydrogen atom or a C1-2 alkyl group. Particularly, R3, independently from each other, may be a hydrogen atom or a methyl group. Even more particularly, R3and R3may be hydrogen atom.

[0028] According to any embodiment of the invention, R4and R4, independently from each other, may be a hydrogen atom or a C1-9 alkyl group. Particularly, may be a hydrogen atom or a C1-4 alkyl group. Particularly, R4and R4, independently from each other, may be a hydrogen atom or a methyl or a tert-butyl group. Even more particularly, R4and R4may be a methyl or a tert-butyl group.

[0029] According to any embodiment of the invention, R5and R5, independently from each other, may be a hydrogen atom or a C1-4 alkyl group. Particularly, R5and R5, independently from each other, may be a hydrogen atom or a C1-3 alkyl group. Particularly, R5and R5, independently from each other, may be a hydrogen atom or a C1-2 alkyl group. Particularly, R5, independently from each other, may be a hydrogen atom or a methyl group. Even more particularly, R5and R5may be hydrogen atom.

[0030] According to any embodiment of the invention, R3and R4, when taken together may form a Ce aryl group.

[0031] According to any embodiment of the invention, R3and R4, when taken together may form a Ce aryl group.

[0032] According to any embodiment of the invention, m is 1.

[0033] According to any embodiment of the invention, Z is a CR6R7group.

[0034] According to any embodiment of the invention, R6and R7, when taken separately, independently from each other, may be a hydrogen atom or a C1-2 alkyl group. Particularly, R6and R7, when taken separately, independently from each other, may be a hydrogen atom or a methyl group. Even more particularly, R6may be hydrogen atom and R7may be a hydrogen atom or a methyl group.

[0035] According to any embodiment of the invention, the bisphenolate may be selected from the group consisting of [l,l'-biphenyl]-2,2'-diol, [l,l'-binaphthalene]-2,2'-diol, 6,6'- methylenebis(2,4-di-tert-butylphenol), 6,6'-(ethane-l,l-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).

[0036] According to any embodiment of the invention, the triphenolate is of formula wherein the wavy lines indicate the location of the bond between the Zirconium atom and L; Z, m, R2, R3R4, R5, R2, R3, R4and R5have the same meaning as defined above and R2”, R3”, R4and R5is respectively a R2, R3R4, R5group.

[0037] According to any embodiment of the invention, the triphenolate may 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- / c / 7-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[l-(2- hydroxyphenyl)ethyl] phenol, (2S)-l-[3,5-bis[[2,6-dihydroxy-4-methoxy-3-methyl-5-(l- oxobutyl)phenyl]methyl]-2,4,6-trihydroxyphenyl]-2-methyl-l-butanone, 2,2'-

[0038] Methylenebis[6-[(2-hydroxy-5-methylphenyl)methyl]-4-methylphenol].

[0039] According to any embodiment of the invention, the calixarene may comprise 4, 6 or 8 phenol units, in particular 4 phenol units. The calixarene with 4 phenol units is of formula wherein the wavy lines indicate the location of the bond between the Zirconium atom and L; Z, m, R3, R4and R5have the same meaning as defined above According to any embodiment of the invention, the calixarene with at least 4 phenol units may be selected from the group consisting of / 7- / c / 7-Butylcalix|4| arene, 25,26,27,28-Tetrahydroxycalix[4]arene, Calix[6]arene, / c77-Butylcalix|8| arene, tert- Butylcalix[6] arene, Calix[8]arene, p-Isopropylcalix[4]arene.

[0040] According to any embodiment of the invention, the anionic ligand, independently from each other, may be a halogen atom, a Mik eton ate, a OOCR8group or a OR9group wherein R8is a Ci-io alkyl group, a benzyl group, a naphtyl group or a phenyl group optionally substituted by a hydroxy group and R9is a Ci-6 alkyl group. The term “ / Miketonate” is understood as a ligand comprising a C(=O)-CH=C(O’) group. Particularly, the / Miketonate is of formula R10-C(=O)-CH=C(O )-R11wherein R10and R11, independently from each other, are a Ci-6 alkyl group, particularly a Ci-4 alkyl group, even more particularly a methyl, propyl, isopropyl or a terbutyl group. Non-limiting example of / Miketonate may include 4-oxopent-2-en-2-olate, 2,2-dimethyl-5-oxohex-3- en-3-olate, 2,6-dimethyl-5-oxohept-3-en-3-olate or 2,2,6,6-tetramethyl-5-oxohept-3-en-3- olate. Particularly, R8may be Ci-s alkyl group, particularly a Ci-6 alkyl group, even more particularly a C1-5 alkyl group. Particularly, R9may be C1-4 alkyl group, particularly a propyl group, a isopropyl group, a butyl group or a tertbutyl group. Particularly, the anionic ligand is selected from the group consisting of acetylacetonate, acetate and pivalate.

[0041] According to a particular embodiment, when p is 0 and n is 4; X is a alkoxide of formula OR9as define above.

[0042] According to any embodiment of the invention, the catalyst is of formula (I). According to any embodiment of the invention, r is 2 and L is a bisphenolate.

[0043] According to any embodiment of the invention, the catalyst of formula (I) may be selected from the group consisting of Zirconium, [2,2'-methylenebis[(4-methyl-6-tert- butyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [2,2'-methylenebis[(4-6-di-tert- butyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [2,2'-methylenebis[(4-6-di- methyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [2,2'-ethylidenenebis[(4-6-di-tert- butyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [2,2'-thiobis[(4-methyl-6-tert- butyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [2,2'-oxobis[(4-methyl-6-tert- butyl)phenolato]]bis(2,4-pentanedionato); Zirconium, [[2,2'-binaphthalene]-l,T-diolato] bis(2,4-pentanedionato); Zirconium, [[2,2'-binaphthalene]-l,T-diolato] bis(propanolate); Zirconium, [[2,2'-biphenyl]-l,l'-diolato] bis(propanolate).

[0044] The catalyst of formula (I) or (I’) can be added into the reaction medium of the invention’s process to form a carbonyl compound in a large range of concentrations. As non-limiting examples, one can cite, as catalyst concentration values those ranging from 0.1 mol% to 10 mol%, relative to the total amount of the non-allylic alcohol. Particularly, the catalyst concentration may be comprised between 0.5 mol% to 5 mol%. It goes without saying that the process works also with more catalyst. However, the optimum concentration of catalyst will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the non-allylic alcohol, on the temperature and on the desired time of reaction.

[0045] The catalyst of formula (I) or (T) can be prepared by several methods starting for example from Zr(acac)4 or Zr(OPr)4. Alternatively, The catalyst of formula (I) or (T) is formed in situ by the reaction between Zr(OPr)4, a phenol or a bisphenol and acetylacetone.

[0046] According to any one of the above embodiments of the invention, hydrogen acceptor is a hydrocarbon comprising at least one carbonyl functional group and having a boiling point equal to or greater than 80°C, preferably equal to or greater than 110°C, even more preferably, equal to or greater than 120°C. Said hydrogen acceptor reacts with generated hydrogen and generates an alcohol. The hydrogen acceptor may be an aldehyde or a ketone, preferably an aldehyde. In particular, the borrowing hydrogen source may be of formula wherein Rarepresents a Ci-io linear alkyl group optionally substituted by a hydroxy group or an aryl group, a C2-10 linear alkenyl group optionally substituted by a hydroxy group or an aryl group, a C3-10 branched or cyclic alkyl or alkenyl group optionally substituted by a hydroxy group or an aryl group, or a phenyl group optionally substituted by one to five C1-3 alkyl or alkoxy groups, hydroxy groups or halogen atoms; Rbrepresents a hydrogen atom or a Ragroup; or Raand Rb, when taken together, represent a C2-10 linear or branched alkanediyl or alkenediyl optionally substituted by a hydroxy group or an aryl group. The hydrogen acceptor of formula (II) is a C4-10 compound.

[0047] The terms “aryl group” or “heteroaryl group” designate the normal meaning in the art; i.e. an aromatic hydrocarbon group such as phenyl, pyridine or naphthyl group optionally substituted. Non-limiting examples of the optional substituent of the aryl group may include C1-3 alkyl or alkoxy group, a hydroxy group or a halogen atom.

[0048] According to any one of the above embodiments, Ramay represent a phenyl group; a C1-10 linear alkyl group, a C2-8 linear alkenyl group or a C3-10 branched or cyclic alkyl group, each optionally substituted by a hydroxy group or aryl group. Preferably, Ramay represent a phenyl group, a C1-10 linear alkyl group optionally substituted by a hydroxy group or a C3-10 branched or cyclic alkyl group optionally substituted by a hydroxy group or a C2-6 linear alkenyl group optionally substituted by a phenyl group. Preferably, Ramay represent a C3-8 linear or branched alkyl group optionally substituted by a hydroxy group or a C2-4 linear alkenyl group optionally substituted by a phenyl group. Even more preferably, Ramay represent a phenyl, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, heptyl or octyl group.

[0049] According to any one of the above embodiments, Rbmay represent a hydrogen atom or a C1-10 linear alkyl group optionally substituted by a hydroxy group or an aryl group or a C3-10 branched or cyclic alkyl group optionally substituted by a hydroxy group or an aryl group. Preferably, Rbmay represent a hydrogen atom, a methyl, an ethyl or a propyl group.

[0050] According to any one of the above embodiments, Raand Rb, when taken together, may represent a C4-8 linear, branched alkanediyl or alkenediyl optionally substituted by a hydroxy group. Preferably, Raand Rb, when taken together, may represent a C4-7 linear, branched alkanediyl or alkenediyl optionally substituted by a hydroxy group. Preferably, Raand Rb, when taken together, may represent a C4-7 linear alkanediyl. Even more preferably, Raand Rb, when taken together, may represent a C4-5 linear alkanediyl.

[0051] Non-limiting examples of suitable hydrogen acceptors may include the compounds selected from the group consisting of benzaldehyde, cinnamaldehyde, cyclohexanone, furfural, camphenolic aldehyde 2-heptanone, 2-octanone, 2-pentanone, acetophenone, 4-methy 1-2 -pentanone, isophorone, 3-methyl-2-butanone, and a mixture thereof.

[0052] The hydrogen acceptor can be added into the reaction medium of the invention’s process to form a carbonyl compound in a large range of concentrations. As non-limiting examples, one can cite, as hydrogen acceptor concentration values those ranging 1 equivalent to 5 equivalents, or even between 1 equivalent to 2 equivalents, relative to the amount of the non-allylic alcohol. It goes without saying that the process works also with more hydrogen acceptor. However, the optimum concentration of hydrogen acceptor will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the non-allylic alcohol, on the temperature and on the desired time of reaction.

[0053] According to any one of the above embodiments, the non-allylic alcohol is a primary non-allylic alcohol or a cycloalkyl non-allylic secondary alcohol.

[0054] According to an embodiment, the non-allylic alcohol is a non-allylic secondary alcohol.

[0055] According to any one of the above embodiments, the non-allylic alcohol is a compound of formula in a form of any one of its stereoisomers or a mixture thereof and wherein, a) Ra represents a hydrogen atom and RP represents a C1-7 alkyl, C3-12 alkenyl, Ce-io cycloalkyl, C6-12 aryl, C1-7 alkyl-oxy-Ci-7 alkyl, C1-7 alkyl-oxy-C7-io aryl, C1-7 alkyl-oxy-Cs-13 alkenyl group, optionally substituted with one or more C1-6 alkoxy group(s), C1-6 alkyl group(s), C6-12 cycloalkyl group(s), or C6-12 aryl group(s) or b) Ra and R taken together represent a C6-12 cycloalkyl group, optionally substituted with one or more C1-6 alkoxy group(s) or C1-6 alkyl group(s), with the proviso that Ra and RP are not forming an allylic alcohol with the -OH group.

[0056] In a particular embodiment, a) Ra represents a hydrogen atom and RP represents a C1-4 alkyl, C7-12 alkenyl, C1-4 alkyl-oxy-Ce-n alkenyl group, Cm alkyl-oxy-Ce aryl group, optionally substituted with one or more C1-4 alkoxy group(s) or C1-4 alkyl group(s), Ce-9 cycloalkyl group, Ce aryl group or b) Ra and RP taken together represent a Ce-7 cycloalkyl group, optionally substituted with one or more C1-4 alkoxy group(s) or C1-4 alkyl group(s), with the proviso that Ra and RP are not forming an allylic alcohol with the -OH group.

[0057] In a particular embodiment, Ra represents a hydrogen atom and RP represents a C1-3 alkyl, C7-12 alkenyl, C1-3 alkyl-oxy-Cs-io alkenyl group, optionally substituted with one or more C1-4 alkoxy group(s) or C1-4 alkyl group(s), Ce-9 cycloalkyl group, with the proviso that Ra and RP are not forming an allylic alcohol with -OH group. In a particular embodiment Ra and RP taken together represent a Ce-7 cycloalkyl group, optionally substituted with one or more C1-4 alkoxy group(s) or C1-4 alkyl group(s), with the proviso that Ra and R are not forming an allylic alcohol with -OH group.

[0058] The terms “alkyl group”, “alkenyl group” or “alkoxy group” are understood as comprising linear or branched alkyl, alkenyl or alkoxy groups.

[0059] The term “alkenyl” is understood as comprising 1, 2 or 3 olefinic double bonds, preferably 1 or 2 olefinic double bonds, even more preferably 1 double bond.

[0060] The term “cycloalkyl” is understood as comprising a monocyclic or fused, spiro and / or bridged bicyclic or tricyclic cycloalkyl group, preferably a monocyclic cycloalkyl group, and optionally further comprising at least one C1-C4 alkyl group.

[0061] The term “aryl group” designates the normal meaning in the art; i.e. an aromatic hydrocarbon group such as phenyl, pyridine or naphthyl group optionally substituted. Non-limiting examples of the optional substituent of the aryl group may include a C1-4 alkyl or alkoxy group, a hydroxy group or a halogen atom.

[0062] The term “alkyl-oxy-alkyl” is understood as comprising 1, 2, or 3 ether bonds, preferably 1 or 2 ether bonds, even more preferably 1 ether bond, and at least 2 alkyl groups.

[0063] The term “alkyl-oxy-aryl” is understood as comprising 1, 2, or 3 ether bonds, preferably 1 or 2 ether bonds, even more preferably 1 ether bond and at least one alkyl group and at least one aryl group.

[0064] The term “alkyl-oxy-alkenyl” is understood as comprising 1, 2, or 3 ether bonds, preferably 1 or 2 ether bonds, even more preferably 1 ether bond and at least one alkyl group and at least one alkenyl group.

[0065] According to an embodiment, the non-allylic alcohol is chosen from the group consisting of consisting of citronellol, 3,9-dimethyldec-8-en-l-ol, 3-methylbutan-l-ol, (E / Z)-dec-8-en-l-ol, (E / Z)-non-7-en-l-ol, 2-phenylpropan-l-ol, 2-phenoxyethan-l-ol, 3- phenylpropan-l-ol, 2-(6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethan-l-ol, 2-((3,9- dimethyldpec-8-en-l-yl)oxy)ethan-l-ol, 2-(4-methylphenyl) ethan-l-ol, 2-phenylethan-l- ol, 2-(2-methylphenyl)ethan-l-ol, 2-(3-methylphenyl)ethan-l-ol, 2-(4- methylphenyl)ethan-l-ol, 2-(2-ethylphenyl)ethan-l-ol, 2-(3-ethylphenyl)ethan-l-ol, 2-(4- ethylphenyl)ethan-l-ol, 2-(2-propylphenyl)ethan-l-ol, 2-(3-propylphenyl)ethan-l-ol, 2- (4-propylphenyl)ethan-l -ol, 2-(2-isopropylphenyl)ethan-l -ol, 2-(3- isopropylphenyl)ethan-l-ol, 2-(4-isopropylphenyl)ethan-l-ol, (2S,5R)-2-(tert-butyl)-5- methylcyclohexan-l-ol, 9-decen-l-ol, 9-dodecen-l-ol and 1,7,7- trimethylbicyclo[2.2.1]heptan-2-ol. According to an embodiment, the non-allylic alcohol is citronellol.

[0066] According to any one of the above embodiments, the carbonyl compound is a in a form of any one of its stereoisomers or a mixture thereof and wherein Ra and RP have the same meaning as defined above.

[0067] In a particular embodiment, the carbonyl compound is not an enal or an enone compound.

[0068] The definitions for Ra and R of a non-allylic alcohol compound of formula (III) apply mutatis mutandis to the carbonyl compound of formula (IV).

[0069] According to an embodiment, non-limiting examples of suitable carbonyl compounds may include the compounds selected from the group consisting of citronellal, 3,9-dimethyldec-8-enal, 3-methylbutanal, (E / Z)-dec-8-enal, (E / Z)-non-7-enal, 2- phenylpropanal, 2-phenoxyethanal, 3-phenylpropanal, 2-(6,6- dimethylbicyclo[3.1. l]heptan-2-yl)acetaldehyde, 2-((3,9-dimethyldec-8-en-l- yl)oxy)acetaldehyde, 2-(p-tolyl)acetaldehyde, 2-phenylacetaldehyde, 2-(2-methylphenyl) acetaldehyde, 2-(3 -methylphenyl) acetaldehyde, 2-(4-methylphenyl) acetaldehyde, 2-(2- ethylphenyl) acetaldehyde, 2-(3 -ethylphenyl) acetaldehyde, 2-(4-ethylphenyl) acetaldehyde, 2-(2-propylphenyl) acetaldehyde, 2-(3-propylphenyl) acetaldehyde, 2-(4- propylphenyl) acetaldehyde, 2-(2-isopropylphenyl) acetaldehyde, 2-(3-isopropylphenyl) acetaldehyde, 2-(4-isopropylphenyl) acetaldehyde, (2S,5R)-2-(tert-butyl)-5- methylcyclohexan-l-one, 9-decen-l-al; 9-dodecen-l-al and 1,7,7- trimethylbicyclo[2.2.1]heptan-2-one.

[0070] According to an embodiment, the carbonyl compound is citronellal.

[0071] For the sake of clarity, by the expression “any one of its stereoisomers or a mixture thereof”, or the similar, it is meant the normal meaning understood by a person skilled in the art, i.e. that the compounds cited in the invention can be a pure enantiomer or a mixture of enantiomers. In other words, the compounds cited in the invention may possess at least one stereocenter which can have two different stereochemistries (e.g. R or S). Said compounds may even be in the form of a pure enantiomer or in the form of a mixture of enantiomers. The compounds cited in the invention may even be in the form of a pure diastereoisomer or in the form of a mixture of diastereoisomer when said compounds possess more than one stereocenter. Said compounds can be in a racemic form or scalemic form. Therefore, said compounds can be one stereoisomer or in the form of a composition of matter comprising, or consisting of, various stereoisomers.

[0072] According to any one of the invention’s embodiments, the invention’s process for the oxidation of a non-allylic alcohol into a carbonyl compound is carried out at a temperature comprised between 50°C and 190°C. In particular, the temperature is in the range between 90°C and 110°C. Of course, a person skilled in the art is also able to select the preferred temperature as a function of the melting and boiling point of the starting and final products as well as the desired time of reaction or conversion.

[0073] In a particular embodiment the invention’s process for the oxidation of a non- allylic alcohol into a carbonyl compound is carried out under reactive distillation conditions. Thereby, it is understood that the process is carried out in a chemical reactor which is also the still.

[0074] The reactive distillation can be run in batch mode or by continuous addition of one or both reagents to the catalytic system. Thereby, the addition of the portion wise hydrogen acceptor addition and several distillations along the process is avoided.

[0075] The invention’s process for the oxidation of a non-allylic alcohol into a carbonyl compound can be carried out in the presence or absence of a solvent. When a solvent is required or used for practical reasons, then any solvent current in such reaction type can be used for the purposes of the invention. Non-limiting examples include Ce-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 solvent such as acetonitrile, esteral solvents such as ethyl acetate or ethereal solvents such as tetrahydrofuran, diethylether, methyl tetrahydrofuran or mixtures thereof. The choice of the solvent is function of the nature of the substrate and / or catalyst and the person skilled in the art is well able to select the solvent most suitable in each case to optimize the reaction.

[0076] The invention’s process for the oxidation of a non-allylic alcohol into a carbonyl compound may carried out under batch or continuous conditions. The invention’s process for the oxidation of a non-allylic alcohol into a carbonyl compound may be performed under atmospheric pressure.

[0077] Another object of the present invention is the use of a catalytic system comprising or consisting of i) a catalyst of formula

[0078] [Zr(L)(X)r] (I) or [Zr(L’)P(X)n] (I ) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and ii) a hydrogen acceptor. in the process for the oxidation of a non-allylic alcohol into a carbonyl compound.

[0079] The definitions and embodiments described herein-above for the process for the oxidation of non-allylic alcohol into a carbonyl compound apply mutatis mutandis to the use according to the present invention.

[0080] Typical manners to execute the invention’s process are reported herein below in the examples.

[0081] Examples

[0082] The invention will now be described in further detail by way of the following examples, wherein the abbreviations have the usual meaning in the art, the temperatures are indicated in degrees centigrade (°C). The preparation of precatalysts and ligands solutions were carried out under an inert atmosphere (Argon) using standard Schlenk techniques. The solvents were dried by conventional procedures and distilled under an argon atmosphere. NMR spectra were recorded at 20 °C on Bruker AV 300, AV 400, or AV 500 MHz spectrometers. Chemical shifts are reported in ppm relative to solvent signals (chloroform, 5H = 7.26 ppm, 5c = 77.0 ppm). The signal assignment was ensured by recording COSY, -NOESY,13C,JH-HSQC and -HMBC experiments. The NMR of all prepared compounds are in accordance with NMR reported in the literature.

[0083] Example 1 Catalytic oxidation of citronellol using complex [Zr(6,6'-methylenebis(2-(tert-butyl)-4- methylphenol)(acac)2] and cinnamaldehyde as a hydrogen acceptor.

[0084] A mixture of citronellol (800g), [Zr(6,6'-methylenebis(2-(tert-butyl)-4- methylphenol)(acac)2] (lmol.%) and cinnamaldehyde (800g, 1.2eq) was heated up to 90°C-100°C in a 3L flask equipped with a 4 Sulzer elements column under 2 mbar pressure. Under these reactive distillation conditions, 692g of a product containing a 78 / 22 mixture of citronellal and unreacted citronellol were collected. The distillation afforded citronellal in 84% yields based on reacted citronellol.

[0085] Example 2

[0086] Catalytic oxidation of further primary alcohols

[0087] To a flask placed under nitrogen atmosphere and equipped with a magnetic stirring bar, a temperature probe and a 2 Sulzer elements column, were added under nitrogen flow 2,2’ - bisphenol (1 equiv. / Zr), a portion of the primary alcohol (130 mmol, 0.135 equiv.) and Zr(OPr)4 [70 wt.% solution in propanol, 2 mol% of the primary alcohol]. After 30 minutes stirring at room temperature, dibenzyltoluene (Marlotherm) (150g) and freshly distilled cinnamaldehyde (1.6 eq, based on the primary alcohol) used as the hydrogen acceptor were added to the reaction mixture under nitrogen flow. The reaction mixture was heated at 100°C under vacuum when needed. The remaining part (0.865 eq.) of primary alcohol placed under nitrogen atmosphere was then introduced into the reaction mixture in 6h. The resulting aldehyde was collected by distillation. The results are depicted in Table 1

[0088] Table 1

[0089] 1Yields are determined upon unreacted alcohol recovery.

[0090] Example 3 Catalytic oxidation of secondary alcohols

[0091] To a 50mL Schlenk tube placed under nitrogen atmosphere and equipped with a magnetic stirring bar were added under nitrogen flow the secondary alcohol (60 mmol, 1 equiv.), Zr(OPr)4 (0.6mmol, lmol%), 2,2’ -bisphenol (0.6 mmol, lmol%) and cinnamaldehyde as the hydrogen acceptor (90mmol, 1.5equiv.). The reaction mixture was then allowed to stir under required temperature and monitored by GC analysis to afford results reported in table 2.

[0092] Table 2

Claims

Claims1. A process for the oxidation of non-allylic alcohol into a carbonyl compound wherein said process is carried out in the presence of i) a catalyst of formula[Zr(L)(X)r] (I) or [Zr(L’)P(X)n] (I’) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and ii) a hydrogen acceptor.

2. The process according to claim 1, wherein the phenolate is of formulawherein the wavy line indicates the location of the bond between the Zirconium atom and L; R1is a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Ci-6 alkoxy group, a Ci-6 alkyl group optionally substituted with one or more halogen atoms or a COOR group wherein R is a hydrogen atom or a Ci-6 alkyl group.

3. The process according to any one of claims 1 and 2, wherein the phenolate is selected from the group consisting of 2-nitrophenolate, ortho-cresolate, 2- (trifluoromethyl)phenolate and 2-cyanophenolate.

4. The process according to claim 1, wherein the bisphenolate is of formulawherein the wavy lines indicate the location of the bond between the Zirconium atom and L; m is 0 or 1; R2, R3R4, R5, R2, R3, R4and R5, when taken separately, independently from each other, are a hydrogen, a halogen atom, a nitro group, a 2H- benzo[d][l,2,3]triazol-2-yl group, a Ci-6 alkoxy group, a Ci-6 thioalkyl group or a Ci-io alkyl group optionally substituted with one or more of a halogen atom, hydroxy, amine or C1-3 alkoxy group; or R2and R3or R3and R4or R2and R3or R3and R4, when taken together represent a -0-(CH2)y-0- group wherein y is 1 or 2 or form a Ce aryl, C5-6 cycloalkyl group, each optionally substituted with one or more of a halogen atom, hydroxy or C1-3 alkoxy group; and Z is an oxygen or sulphur atom, a (-Clfc-h group, a -NH- group, a -SO2- group, a -S-S- group, a - CH2-NH-CH2- group, or a -C(R6)(R7)- group wherein R6and R7, when taken separately, independently from each other, are a hydrogen atom or a Ce aryl, Ce heteroaryl or a C1-3 alkyl group, each optionally substituted by one to three halogen atoms or C1-3 alkoxy groups, and wherein the heteroatom is one or more of an oxygen or nitrogen atom.

5. The process according to any one of claims 1 and 4, wherein the bisphenolate is selected from the group consisting of [l,l'-biphenyl]-2,2'-diol, [l,l'-binaphthalene]-2,2'- diol, 6,6'-methylenebis(2,4-di-tert-butylphenol), 6,6'-(ethane-l,l-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 process according to any one of claims 1 to 5, wherein the anionic ligand, independently from each other, is a halogen atom, a / >-diketonate. a OOCR8group or a OR9group wherein R8is a C1-10 alkyl group, a benzyl group, a naphtyl group or a phenylgroup optionally substituted with a hydroxy group, and R9is a Ci-6 alkyl group.

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

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

9. The process according to any one of claims 1 to 8, wherein the non-allylic alcohol is of formulawherein, a) Ra represents a hydrogen atom and RP represents a C1-7 alkyl, C3-11 alkenyl, Ce-io cycloalkyl, C6-12 aryl, C1-7 alkyl-oxy-Ci-7 alkyl, C1-7 alkyl-oxy-C7-io aryl, C1-7 alkyl-oxy-Cs-13 alkenyl group, optionally substituted with one or more C1-6 alkoxy group(s), C1-6 alkyl group(s), C6-12 cycloalkyl group(s), or C6-12 aryl group(s), or b) Ra and R taken together represent a C6-12 cycloalkyl group, optionally substituted with one or more C1-6 alkoxy group(s) or C1-6 alkyl group(s), with the proviso that Ra and RP are not forming an allylic alcohol with the -OH group.

10. The process according to any one of claims 1 to 9, wherein the alcohol is chosen in the group consisting of citronellol, 3,9-dimethyldec-8-en-l-ol, 3-methylbutan-l-ol, (E / Z)- dec-8-en-l-ol, (E / Z)-non-7-en-l-ol, 2-phenylpropan-l-ol, 2-phenoxyethan-l-ol, 3- phenylpropan-l-ol, 2-(6,6-dimethylbicyclo[3.1.1]heptan-2-yl)ethan-l-ol, 2-((3,9- dimethyldec-8-en-l-yl)oxy)ethan-l-ol, 2-(4-methylphenyl) ethan-l-ol, 2-phenylethan-l- ol, 2-(2-methylphenyl)ethan-l-ol, 2-(3-methylphenyl)ethan-l-ol, 2-(4- methylphenyl)ethan-l-ol, 2-(2-ethylphenyl)ethan-l-ol, 2-(3-ethylphenyl)ethan-l-ol, 2-(4-ethylphenyl)ethan-l-ol, 2-(2-propylphenyl)ethan-l-ol, 2-(3-propylphenyl)ethan-l-ol, 2- (4-propylphenyl)ethan-l -ol, 2-(2-isopropylphenyl)ethan-l -ol, 2-(3- isopropylphenyl)ethan-l-ol, 2-(4-isopropylphenyl)ethan-l-ol, (2S,5R)-2-(tert-butyl)-5- methylcyclohexan-l-ol, 9-decen-l-ol, 9-dodecen-l-ol and 1,7,7- trimethylbicyclo[2.2.1]heptan-2-ol, preferably citronellol.

11. Use of a catalytic system comprising or consisting of i) a catalyst of formula[Zr(L)(X)r] (I) or [Zr(L’)p(X)n] (I’) wherein L is a bisphenolate, a triphenolate or a calixarene with 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 with at least 4 phenol units; and ii) a hydrogen acceptor for preparing a carbonyl compound from a non-allylic alcohol compound.

12. Use of a catalytic system according to claim 11, wherein the non-allylic alcohol iswherein, a) Ra represents a hydrogen atom and RP represents a C1-7 alkyl, C3-12 alkenyl, Ce-io cycloalkyl, C6-12 aryl, C1-7 alkyl-oxy-Ci-7 alkyl, C1-7 alkyl-oxy-C7-io aryl, C1-7 alkyl-oxy-C3-i3 alkenyl group, optionally substituted with one or more C1-6 alkoxy group(s), C1-6 alkyl group(s), C6-12 cycloalkyl group(s), or C6-12 aryl group(s) or b) Ra and R taken together represent a C6-12 cycloalkyl group, optionally substituted with one or more C1-6 alkoxy group(s) or C1-6 alkyl group(s), with the proviso that Ra and RP are not forming an allylic alcohol with the -OH group.

13. Use of a catalytic system according to any one of claims 11 to 12, wherein the alcohol compound is chosen from the group consisting of citronellol, 3,9-dimethyldec-8- en-l-ol, 3-methylbutan-l-ol, (E / Z)-dec-8-en-l-ol, (E / Z)-non-7-en-l-ol, 2-phenylpropan-1-ol, 2-phenoxyethan-l-ol, 3-phenylpropan-l-ol, 2-(6,6-dimethylbicyclo[3.1.1]heptan-2- yl)ethan-l-ol, 2-((3,9-dimethyldec-8-en-l-yl)oxy)ethan-l-ol, 2-(4-methylphenyl) ethan-1- ol, 2-phenylethan-l-ol, 2-(2-methylphenyl)ethan-l-ol, 2-(3-methylphenyl)ethan-l-ol, 2- (4-methylphenyl)ethan-l-ol, 2-(2-ethylphenyl)ethan-l-ol, 2-(3-ethylphenyl)ethan-l-ol, 2- (4-ethylphenyl)ethan-l -ol, 2-(2-propylphenyl)ethan-l-ol, 2-(3-propylphenyl)ethan-l -ol,2-(4-propylphenyl)ethan-l-ol, 2-(2-isopropylphenyl)ethan-l-ol, 2-(3- isopropylphenyl)ethan-l-ol, 2-(4-isopropylphenyl)ethan-l-ol, (2S,5R)-2-(tert-butyl)-5- methylcyclohexan-l-ol, 9-decen-l-ol, 9-dodecen-l-ol and 1,7,7- trimethylbicyclo[2.2.1]heptan-2-ol, wherein the alcohol is preferably citronellol.

Images