The present invention relates to the use of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I


whereinR1are identical or different and are each an organic radical having from 1 to 40 carbon atoms, andR2are identical or different and are each an organic radical having from 1 to 40 carbon atoms,

as catalyst in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)—.

The present invention further relates to a process for hydrogenation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)—, to a process for the formation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)— by dehydrogenative coupling of at least one primary alcohol with a second alcoholic OH-group, to a transition metal complex comprising the tetradentate ligand of formula I and to a process for preparing said transition metal complex.

The reduction of carboxylic acid esters to the corresponding alcohols is a fundamental and broadly applied transformation in organic chemistry as well as in industrial applied processes. The most economic approach to reduce an ester functionality to the corresponding alcohols is hydrogenation using molecular hydrogen (H2) in the presence of a catalyst. Also, the dehydrogenative coupling of alcohols to esters is a method to produce esters from alcohols as starting material with molecular hydrogen as the only by-product.

Hydrogenation of Esters:
RaCOORb+2H2→RaCH2OH+HORb

Dehydrogenative Coupling of Alcohols:
RaCH2OH+HORb→RaCOORb+2H2

The ideal catalyst system for these reactions should be robust and easy to prepare, and the catalyst system should not need additives, which require dedicated measures for removal after the reaction. Also, the catalyst should be reusable after the reaction without any elaborate catalyst regeneration step. If additives are necessary, ideally, they are already present being the starting material or reaction product formed during the hydrogenation. This would later allow a simpler workup of the product mixture.

In the prior art, active catalyst systems, which perform the hydrogenation of esters were reported using ruthenium with different multidentate ligands. The catalyst systems, which are disclosed in WO2006106484, US20150202609, WO2013023307, U.S. Pat. No. 8,471,048, US2016/0326199, US2017/0073298, EP1868964/65, Angew. Chem. Int. Ed. 2013, 52, 2538-2542, Angew. Chem. Int. Ed. 2006, 45, 1113-1115, Angew. Chem. Int. Ed. 2007, 46, 7473-7476, Chem. Commun. 1997, 667, J. Mol. Catal. 2011, 346, 70 or Organometallics, 2016, 35, 982-989, require the addition of a base to achieve the hydrogenation. The required base is a drawback of these systems, since it must be removed during work-up.

Other catalyst systems in the prior art avoid the use of a base by using preformed catalysts. WO 2016035080, U.S. Pat. No. 8,524,953 and WO 2012052996 disclose ruthenium complexes with tridentate pincer type ligands. These complexes can be used as catalysts for both above-described reactions without the presence of an additional base. The ruthenium complex bears eithers an anionic BH4-ligand or is deprotonated in a previous synthetic step. A drawback of these catalyst systems is, that they are prepared in four to five step synthesis starting from commercially available starting materials. In addition, the BH4−-anion as well as the deprotonated active catalyst are relatively sensitive towards water and air. These catalysts also protolyze during the reaction by the formed alcohol. Therefore, catalyst recycling of these complexes without adding a new BH4-source or a base has not been achieved so far in the prior art. For an economic process, it is essential, that the catalyst system can be recycled.

The preparation of complexes of ruthenium with polydentate ligands including N(CH2CH2PPh2)3were disclosed in Acta Cient. Venezolana 33, 202-213, 1982.

Proceeding from this prior art, an object of the invention was to provide a robust catalyst system for the above-described hydrogenation of carboxylic esters or the dehydrogenative coupling of alcohols to carboxylic esters in an economically advantageous manner.

This object is achieved by the use of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I


whereinR1are identical or different and are each an organic radical having from 1 to 40 carbon atoms, andR2are identical or different and are each an organic radical having from 1 to 40 carbon atoms,

as catalyst in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)—.

The substituents according to the present invention are, unless restricted further, defined as follows:

The term “organic radical having from 1 to 40 carbon atoms” as used in the present text refers to, for example, C1-C40-alkyl radicals, C1-C10-fluoroalkyl radicals, C1-C12-alkoxy radicals, saturated C3-C20-heterocyclic radicals, C6-C40-aryl radicals, C2-C40-heteroaromatic radicals, C6-C10-fluoroaryl radicals, C6-C10-aryloxy radicals, silyl radicals having from 3 to 24 carbon atoms, C2-C20-alkenyl radicals, C2-C20-alkynyl radicals, C7-C40-arylalkyl radicals or C8-C40-arylalkenyl radicals. An organic radical is in each case derived from an organic compound. Thus, the organic compound methanol can in principle give rise to three different organic radicals having one carbon atom, namely methyl (H3C—), methoxy (H3C—O—) and hydroxymethyl (HOC(H2)—). Therefore, the term “organic radical having from 1 to 40 carbon atoms” comprises besides alkoxy radicals for example also dialkylamino radicals, monoalkylamino radicals or alkylthio radicals.

In the present description, the term radical is used interchangeably with the term group, when defining the variables Rxin the presented formulas.

The term “alkyl” as used in the present text encompasses linear or singly or multiply branched saturated hydrocarbons which can also be cyclic. Preference is given to a C1-C18-alkyl radical such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, cyclopentyl, cyclohexyl, isopropyl, isobutyl, isopentyl, isohexyl, sec-butyl or tert-butyl.

The term “alkenyl” as used in the present text encompasses linear or singly or multiply branched hydrocarbons having one or more C—C double bonds which can be cumulated or alternating.

The term “saturated heterocyclic radical” as used in the present text refers to, for example, monocyclic or polycyclic, substituted or unsubstituted aliphatic or partially unsaturated hydrocarbon radicals in which one or more carbon atoms, CH groups and/or CH2groups have been replaced by heteroatoms which are preferably selected from the group consisting of the elements O, S, N and P. Preferred examples of substituted or unsubstituted saturated heterocyclic radicals are pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydro thienyl and the like, and also methyl-, ethyl-, propyl-, isopropyl- and tert-butyl-substituted derivatives thereof. In the present application the term “heterocycloalkyl radical” is used for those saturated heterocyclic radicals, which are substituted or unsubstituted aliphatic hydrocarbon radicals in which one or more carbon atoms, CH groups and/or CH2groups have been replaced by heteroatoms which are preferably selected from the group consisting of the elements O, S, N and P as described above.

The term “aryl” as used in the present text refers to, for example, aromatic and optionally fused polyaromatic hydrocarbon radicals which may be monosubstituted or polysubstituted by linear or branched C1-C18-alkyl, C1-C18-alkoxy, C2-C10-alkenyl, halogen, in particular fluorine, or functional groups such as COOH, hydroxy, NH2, mercapto or SO3H. Preferred examples of substituted and unsubstituted aryl radicals are, in particular, phenyl, pentafluorophenyl, 4-methylphenyl, 4-ethylphenyl, 4-n-propylphenyl, 4-isopropylphenyl, 4-tert-butylphenyl, 4-methoxyphenyl, 1-naphthyl, 9-anthryl, 9-phenanthryl, 3,5-dimethylphenyl, 3,5-di-tert-butylphenyl or 4-trifluoromethylphenyl.

The term “heteroaromatic radical” as used in the present text refers to, for example, aromatic hydrocarbon radicals in which one or more carbon atoms or CH groups have been replaced by nitrogen, phosphorus, oxygen or sulfur atoms or combinations thereof. These may, like the aryl radicals, optionally be monosubstituted or polysubstituted by linear or branched C1-C18-alkyl, C2-C10-alkenyl, halogen, in particular fluorine, or functional groups such as COOH, hydroxy, NH2, mercapto or SO3H. Preferred examples are furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyrimidinyl, pyrazinyl and the like, and also methyl-, ethyl-, propyl-, isopropyl- and tert-butyl-substituted derivatives thereof.

The term “arylalkyl” as used in the present text refers to, for example, aryl-comprising substituents where the corresponding aryl radical is linked via an alkyl chain to the rest of the molecule. Preferred examples are benzyl, substituted benzyl, phenethyl, substituted phenethyl and related structures.

The terms fluoroalkyl and fluoroaryl mean that at least one hydrogen atom, preferably more than one and ideally all hydrogen atoms, of the corresponding radical have been replaced by fluorine atoms. Examples of preferred fluorine-comprising radicals are trifluoromethyl, 2,2,2-trifluoroethyl, pentafluorophenyl, 4-trifluoromethylphenyl, 4-perfluoro-tert-butylphenyl and related structures.

The transition metal catalyst TMC1 can comprise besides the tetradentate ligand of formula I one or more additional ligands, such as an anion selected from the group consisting of hydride, alkoxides, aryloxides, carboxylates and acyl, or a neutral ligand selected from the group consisting of carbon monoxide, triaryl phosphines, amines, N-heterocyclic carbenes and isonitriles. Preferably the transition metal catalyst TMC1 further comprises a carbon monoxide ligand.

In one embodiment of the present invention, the inventive use is characterized in that the transition metal catalyst TMC1 further comprises a carbon monoxide ligand.

In one embodiment of the present invention, the inventive use is characterized in that the transition metal catalyst TMC1 is a transition metal complex of formula


whereinM is a transition metal selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC,R1are identical or different and are each an organic radical having from 1 to 40 carbon atoms,R2are identical or different and are each an organic radical having from 1 to 40 carbon atoms, andR3is hydrogen or an organic radical having from 1 to 40 carbon atoms which is bound via a carbon atom to the oxygen atom, preferably R3is an organic radical having from 1 to 40 carbon atoms which is bound via a carbon atom to the oxygen atom,or R3together with R1or R3together with R2, together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms.

The transition metal M of transition metal catalyst TMC1 and of the transition metal complex of formula II is selected from metals of groups 7, 8, 9 and 10, preferably selected from metals of groups 8, 9 and 10, of the periodic table of elements according to IUPAC, preferably selected from the metal consisting of iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium and platinum, in particular ruthenium.

In one embodiment of the present invention, the inventive use is characterized in that the transition metal M is ruthenium.

While in formula I and accordingly in formula II, the three radicals R1are identical or different, preferably identical, and the three radicals R2are identical or different, preferably identical, two radicals R1and R2, which are both attached to the same phosphorus atom, are again identical or different, preferably identical. The six radicals R1and R2in formula I and accordingly in formula II might represent up to 6 different radicals. Preferably all six radicals R1and R2are identical.

In one embodiment of the present invention, the inventive use is characterized in that R1and R2are identical.

In one embodiment of the present invention, the inventive use is characterized in thatR1are identical or different, preferably identical, and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, preferably a C6to C40aryl radical or a C2to C40heteroaromatic radical, which can be substituted at any position with a radical which is an organic radical having from 1 to 40 carbon atoms, a halogen, preferably F, Cl or Br, in particular F, or COOH, hydroxy, NH2, mercapto or SO3H, andR2are identical or different, preferably identical, and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, preferably a C6to C40aryl radical or a C2to C40heteroaromatic radical, which can be substituted at any position with a radical which is an organic radical having from 1 to 40 carbon atoms, a halogen, preferably F, Cl or Br, in particular F, or COOH, hydroxy, NH2, mercapto or SO3H.

Preferably R1and R2are identical and are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-hexyl, 1-octyl-iso-butyl, adamantyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, cyclohexyl, cyclopentyl, tert.-butyl, p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-tolyl, p-methoxy-phenyl, p-trifluoromethyl-phenyl, 4-biphenyl, naphthyl or phenyl, in particular phenyl.

The radical R3in formula II is hydrogen or an organic radical having from 1 to 40 carbon atoms which is bound via a carbon atom to the oxygen atom. Preferably the radical R3in formula II is an organic radical having from 1 to 40 carbon atoms which is bound via a carbon atom to the oxygen atom. More preferably the anion−OR3represents an alcoholate or a carboxylate ion.

In one embodiment of the present invention, the inventive use is characterized in thatR3is a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical, a C to C40arylalkyl radical or a C2to C40heteroaromatic radical, or R3is C(═O)R4, wherein R4is hydrogen, a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical, a C7to C40arylalkyl radical or a C2to C40heteroaromatic radical.

Preferably R3is a C1to C6alkyl radical such as methyl, ethyl, isopropyl, cyclohexyl, cyclopentyl, tert.-butyl, or a substituted or unsubstituted C6to C1aryl radical such as p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-toly, naphthyl, phenyl, or a substituted or unsubstituted C to C1, arylalkyl radical such as benzyl, a C1to C15alkanoyl radical, such as formyl, acetyl, propionyl, or substituted or unsubstituted benzoyl.

In one embodiment the present invention relates to the use of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I


whereinR1are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, andR2are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, and,

wherein the transition metal M is ruthenium and wherein the transition metal catalyst TMC1 further comprises a carbon monoxide ligand,

as catalyst in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)—.

In another embodiment of the present invention, the inventive use is characterized in that the transition metal catalyst TMC1 is a transition metal complex of formula II


wherein M, R1and R2are defined as described above andR3is a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocy-cloalkyl radical, a C6to C40aryl radical, a C to C40arylalkyl radical or a C2to C40heteroaromatic radical, or R3is C(═O)R4, wherein R4is hydrogen, a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical, a C to C40arylalkyl radical or a C2to C40heteroaromatic radical, which in each case is bound via a carbon atom to the oxygen atom,or R3together with R1or R3together with R2, together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms.

The above-described transition metal catalyst TMC1, which comprises the tetradentate ligand of formula I, can be used in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— in the presence of additional bases or without additional bases. An advantage of above-described transition metal catalyst TMC1 compared with transition metal catalyst of the literature is the fact that TMC1 can be used in the above-mentioned processes without the need of additional bases, such as alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and alkali metal or alkaline earth metal alcoholates. Furthermore, a base-free catalyst enables the hydrogenation of base-labile substrates (possibly chiral α-substituted esters).

In one embodiment of the present invention, the inventive use is characterized in that no base selected from the group consisting of alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and alkali metal or alkaline earth metal alcoholates is combined with the transition metal catalyst TMC1.

The amount of the transition metal catalyst TMC1, which is applied for practicing the inventive use can be varied in a wide range. Preferably, the amount of transition metal catalyst TMC1, which is used in the hydrogenation of esters as well as the dehydrogenative coupling of alcohols, is in the range from 0.1 to 5000 ppm (parts per weight), more preferably in the range from 1 to 2000 ppm, in particular in the range from 50 to 1000 ppm, in each case based on the total weight of the liquid reaction mixture.

In one embodiment of the present invention, the inventive use is characterized in that the catalyzed reactions take place in a homogenous liquid reaction phase. That means, that the hydrogenation of carboxylic acid esters and the formation of carboxylic acid esters starting from at least one primary alcohol by dehydrogenative coupling are preferably homogenous processes.

A further aspect of the invention relates to a process for hydrogenation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)— to the corresponding compound or compounds each comprising at least one alcoholic hydroxy group,

comprising the process step:a) treating said compound, which comprises at least one carboxylic acid ester functional group —O—C(═O)—, with molecular hydrogen H2in the presence of a catalytic amount of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I, wherein TMC1 M and the tetradentate ligand of formula I are defined as described above, including preferred embodiments of said transition metal catalyst TMC1 and its components.

In the sense of the invention, the term compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— refers to carboxylic acid esters.

In the sense of the invention, examples of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)—, are: monocarboxylic acid esters such as ethyl acetate, n-hexyl hexanoate, isopropyl benzoate or benzyl stearate; cyclic monocarboxylic acid esters, also called lactones, such as γ-butyrolactone, δ-valerolactone, ε-caprolactone or sclareolide; dicarboxylic acid esters such as diethyl malonate, dimethyl terephthalate, ethylene glycol diacetate or 1,4-diacetoxybutane; cyclic dicarboxylic acid esters like lactide or glycolide; tricarboxylic acid esters such as triethyl citrate or triacylglycerides of fatty acids; or oligo- or polycarboxylic acid esters such as polybutylene terephthalate (PBT), polyethylene terephthalate (PET), polyethylene naphthalate or polylactide.

In the sense of the invention, the compound or compounds each comprising at least one alcoholic hydroxy group refer to alcohols or phenols. The part of the ester originating from the carboxylic acid is hydrogenated to a primary alcohol (—CH2—OH) while the part of the ester originating from alcohol or phenol produces the respective alcohol or phenol.

In one embodiment of the present invention, the inventive process for hydrogenation of a compound comprising at least one carboxylic acid ester functional group —O—C(═O)— is characterized in that the compound comprising at least one carboxylic acid ester functional group —O—C(═O)— is a compound of formula III


whereinR5is an organic radical having from 1 to 40 carbon atoms, which is bound via a carbon atom to the oxygen atom, andR6is hydrogen or an organic radical having from 1 to 40 carbon atoms, which is bound via a carbon atom to the carbonyl groupor R5and R6together with the atoms connecting them form a divalent organic group having from 1 to 40 carbon atoms.

As explained above, the compound of formula III might comprise one or more additional carboxylic acid ester functional groups, which is/are part of R5and/or of R6. Preferably, R5is a C1to C40alkyl radical, a C2to C40alkenyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, and R6is hydrogen, a C1to C40alkyl radical, a C2to C40alkenyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, wherein R5and R6can be substituted at any position with a radical which is an organic radical having from 1 to 40 carbon atoms, an ester function, a halogen, in particular F, C or Br, COOH, hydroxy, NH2, mercapto or SO3H.

In one embodiment R5in formula III is a C1to C40alkyl radical, preferably methyl, ethyl, propyl, isopropyl or butyl.

In one embodiment R6in formula III is substituted by one or more additional groups —C(═O)OR5, preferably one additional group —C(═O)OR5. Examples of such diesters of formula III derived from dicarboxylic acids, such as terephthalic acid, phthalic acids, maleic acid, adipic acid or succinic acid, are preferably di esters, wherein R5is in particular methyl, ethyl, propyl, isopropyl, butyl or iso-butyl, for example dimethyl terephthalate (terephthalic acid dimethyl ester).

In one embodiment R5and R6together with the atoms connecting them form a divalent organic group having from 1 to 40 carbon atoms. Examples of cyclic monoesters of formula III are lactones such as γ-butyrolactone, δ-valerolactone, ε-caprolactone or sclareolide. Examples of cyclic di-esters of formula III are glycolide, the cyclic di-ester of glycolic acid, or lactide, the cyclic di-ester of lactic acid.

In one embodiment of the present invention, the inventive process for hydrogenation of a compound comprising at least one ester functional group is characterized in that an alcohol or a carboxylic acid, preferably an alcohol, is added to the reaction mixture, which comprises the compound comprising at least one ester functional group and the transition metal catalyst TMC1 before starting the hydrogenation reaction of process step a). The added alcohol can be varied in a wide range. Preferably the added alcohol can be defined as R3—OH, R5—OH or R6—CH2—OH, wherein R3, R5and R6are defined as described above. The addition of an alcohol, which is the same as one of the alcohols formed in the ester hydrogenation, simplifies the workup of the final product mixture of the hydrogenation reaction. The added alcohol or carboxylic acid, preferably the alcohol, serves as activator of the transition metal catalyst TMC1.

The amount of alcohol or carboxylic acid added to the reaction mixture, preferably alcohol, can be varied in a wide range. Preferably the amount of alcohol or carboxylic acid added, preferably alcohol, ranges from 0.001 to 90 wt.-%, more preferably from 0.01 to 10 wt.-%, in particular from 0.01 to 5 wt.-%, in each case based on the total weight of the liquid reaction mixture.

As already mentioned above, the transition metal catalyst TMC1 can be used in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— in the presence of additional bases or without additional bases, such as alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and alkali metal or alkaline earth metal alcoholates. Even though, the addition of said bases improves the activity of transition metal catalyst TMC1 but the performance of the transition metal catalyst TMC1 is still satisfying even without adding a base. Avoiding the addition of said bases to the reaction mixture of process step a) prevents extra work during isolation of the desired product and also base labile substrates (e.g. esters of α-chiral carboxylic acids) can be used.

In one embodiment of the present invention, the inventive process for hydrogenation of a compound comprising at least one carboxylic acid ester functional group is characterized in that no base selected from the group consisting of alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and alkali metal or alkaline earth metal alcoholates is added to the reaction mixture of process step a).

The inventive process for hydrogenation of a compound comprising at least one ester functional group works in a broad temperature range. Preferably the ester hydrogenation takes place at a temperature in the range from 20 to 250° C. More preferably, the process according to the invention is carried out at temperatures in the range from 70 to 200° C., in particular in the range from 80 to 150° C.

As explained above, for the reduction of each carboxylic acid ester functional group two equivalents of molecular hydrogen (2 H2) are consumed. During the inventive process for hydrogenation the hydrogen pressure can be varied in a wide range. Preferably, the ester hydrogenation takes place at hydrogen pressures in the range from 0.1 to 50 MPa, more preferably at hydrogen pressures in the range from 1 to 20 MPa, in particular in the range from 3 to 15 MPa.

The inventive process for hydrogenation of a compound comprising at least one ester functional group can be carried out in the customary devices and/or reactors known to the person skilled in the art for liquid-gas reactions in which the catalyst is present in the liquid phase. For the inventive process, it is in principle possible to use all reactors which are fundamentally suitable for gas-liquid reactions under the stated temperatures and the stated pressures. Suitable standard reactors for gas-liquid and for liquid-liquid reaction systems are discussed for example in K. Henkel, “Reactor Types and Their Industrial Applications”, Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH Verlag GmbH & Co. KGaA, chapter 3.3: “Reactors for gas-liquid reactions”, to which reference is hereby made. Examples which may be mentioned are stirred tank reactors, tubular reactors or bubble column reactors. The supply of ester, catalyst, solvent and optionally an alcohol as activator can take place here simultaneously or separately from one another. The reaction here can be carried out discontinuously in batch mode or continuously, semi-continuously with recycle or without recycle. The average residence time in the reaction space can be varied in a wide range, preferably in the range from 15 minutes to 100 h, more preferably in the range from 1 h to 50 h.

The inventive process for hydrogenation of a compound comprising at least one ester functional group can be carried out in the absence of any solvent but also in the presence of a solvent. Suitable solvents are selected from aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, esters, ethers, water and mixtures thereof. Preferred solvents arealiphatic hydrocarbons such as pentane, hexane, heptane, octane or cyclohexane;aromatic hydrocarbons such as benzene, toluene, xylenes, ethylbenzene, mesitylene or benzotrifluoride;alcohols such as methanol, ethanol, propanol or isopropanol;ethers such as dioxane, tetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether, diisopropyl ether or diethylene glycol dimethyl ether and water.

If desired, mixtures of two or more of the afore-mentioned solvents can also be used.

Preference is given to using aliphatic hydrocarbons, aromatic hydrocarbons, ethers and mixtures thereof as solvents.

In one embodiment of the present invention, the inventive process for hydrogenation of a compound comprising at least one ester functional group is characterized in that process step a) is carried out in the presence of a solvent selected from aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, esters, ethers, water and mixtures thereof.

The work-up of the reaction mixture obtained after finishing process step a), in particular the isolation of the formed alcohols, in particular R6CH2OH and R5OH can be realized case dependent, for example by filtration, an aqueous extractive work-up or by distillation as separation method, for example distillation under reduced pressure. Preferably the work up is performed by distillation and the catalyst remains in the residue of the distillation to allow recycling.

A further aspect of the invention relates to a process for the formation of a compound of formula III comprising at least one carboxylic acid ester functional group —O—C(═O)



by dehydrogenative coupling of at least one primary alcohol of formula IV comprising at least one hydroxy methylene group



with a second primary alcohol of formula IV, or

intramolecularly, if present, with a second alcoholic OH group of the primary alcohol of formula IV, or

with an alcohol of formula V comprising at least one alcoholic hydroxyl group


whereinR5is an organic radical having from 1 to 40 carbon atoms, which is bound via a carbon atom to the hydroxy group,R6is hydrogen or an organic radical having from 1 to 40 carbon atoms, which is bound via a carbon atom to the carbonyl group,R7is hydrogen or an organic radical having from 1 to 40 carbon atoms, which is bound via a carbon atom to the hydroxy methylene group,or R5and R6together with the atoms connecting them form a divalent organic group having from 1 to 40 carbon atoms,

comprising the process step:b) treating said primary alcohol of formula IV alone or in a mixture with said alcohol of formula V with a catalytic amount of a transition metal catalyst TMC1, which comprises a transition metal M selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC and a tetradentate ligand of formula I, wherein TMC1, M and the tetradentate ligand of formula I are defined as described above, including preferred embodiments of said transition metal catalyst TMC1 and its components.

In principle, the compound of formula III together with its variables R5and R6and consequently also the compound of formula V with its variable R5are defined as described above in the case of the process for hydrogenation of the compound of formula III comprising at least one carboxylic acid ester functional group —O—C(═O)—. As described above, the compound of formula III can be a monocarboxylic acid ester including a lactone, a dicarboxylic acid ester including a dilactone, tricarboxylic acid ester or even a, oligo- or polycarboxylic acid ester. Preferably, the compound of formula III formed in the dehydrogenative coupling process is a monocarboxylic acid ester.

Whereas the complete hydrogenation of all carboxylic acid ester groups of a single ester of formula III results in the formation of a limited number of alcohols, the dehydrogenative coupling of at least one primary alcohol of formula IV comprising at least one hydroxy methylene group with at least one alcohol of formula V comprising at least one alcoholic hydroxyl group is limited in view of the preferred formation of a single ester of formula III. A single primary alcohol, such as n-pentanol can form only one monoester, while two different primary alcohols, such as a 1:1 mixture of n-pentanol and n-hexanol, can form four different esters.

In one embodiment of the present invention, the inventive process for the formation of a compound of formula III comprising at least one, preferably only one carboxylic acid ester functional group —O—C(═O)— is characterized in that two molecules of the primary alcohol of formula IV, preferably comprising only one alcoholic OH group, react with each other.

In one embodiment R5in formula III is a C1to C40alkyl radical, preferably a C1to C18, n-alkylradical, more preferably methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-octyl, n-decyl, n-dodecyl, n-tetradecyl, n-hexadecyl or n-octadecylanol.

In one embodiment of the present invention, the inventive process for dehydrogenative coupling is characterized in that the alcohol of formula V is identical with the primary alcohol of formula IV and the primary alcohol of formula IV is selected from the group of alcohols consisting of methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-octanol, 1-decanol, 1-dodecanol, 1-tetradecanol, 1-hexadecanol and 1-octadecanol.

As already mentioned above, the transition metal catalyst TMC1 can be used in processes for formation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— starting from at least one primary alcohol and/or hydrogenation of compounds comprising at least one carboxylic acid ester functional group —O—C(═O)— in the presence of additional bases or without additional bases, such as alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and alkali metal or alkaline earth metal alcoholates. Even though, the addition of said bases improves the activity of transition metal catalyst TMC1, but the performance of the transition metal catalyst TMC1 is still satisfying even without adding a base. Avoiding the addition of said bases to the reaction mixture of process step a) prevents extra work during isolation of the desired product and also base labile substrates (e.g. esters of α-chiral carboxylic acids) can be used.

In one embodiment of the present invention, the inventive process for dehydrogenative coupling of at least one primary alcohol of formula IV with at least one alcohol of formula V to at least one ester of formula III is characterized in that no base selected from the group consisting of alkali metal or alkaline earth metal carbonates, alkali metal or alkaline earth metal hydroxides and al kali metal or alkaline earth metal alcoholates is added to the reaction mixture of process step b).

The inventive process for dehydrogenative coupling as described above works in a broad temperature range. Preferably the dehydrogenative coupling of alcohols takes place at a temperature in the range from 20 to 250° C. More preferably, the process according to the invention is carried out at temperatures in the range from 70 to 200° C., in particular in the range from 80 to 180° C.

During the dehydrogenative coupling as describe above for each formed carboxylic acid ester functional group two equivalents of molecular hydrogen (2 H2) are produced. In order to complete the dehydrogenative coupling, the formed molecular hydrogen (H2) is preferably removed from the reaction mixture, in order to avoid the reverse reaction, that is the hydrogenation of the carboxylic acid ester functional group. This is performed either by stripping out with the boiling unreacted alcohol or by introducing a stripping gas such as nitrogen, carbon dioxide or argon.

During the dehydrogenative coupling the overall pressure, of which the partial pressure of molecular hydrogen is only one component, can be varied in a wide range. Preferably the dehydrogenative coupling of alcohols takes place at overall pressures in the range from 0.001 to 10 MPa. More preferably, the process according to the invention is carried out at overall pressures in the range from 0.001 to 1 MPa, in particular in the range from 0.001 to 0.2 MPa.

The inventive process for dehydrogenative coupling as describe above can be carried out in the customary devices and/or reactors known to the person skilled in the art of liquid-gas reaction in which the catalyst is present in the liquid phase. For the inventive, it is in principle possible to use all reactors which are fundamentally suitable for gas-liquid reactions under the stated temperature and the stated pressure. Suitable standard reactors for gas-liquid and for liquid-liquid reaction systems are discussed for example in K. Henkel, “Reactor Types and Their Industrial Applications”, Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH Verlag GmbH & Co. KGaA, chapter 3.3: “Reactors for gas-liquid reactions”, to which reference is hereby made. Examples which may be mentioned are stirred tank reactors, tubular reactors or bubble column reactors. The supply of alcohols, catalyst I and solvent can take place here simultaneously or separately from one another. The reaction here can be carried out discontinuously in batch mode or continuously, semi-continuously with recycle or without recycle. The average residence time in the reaction space is generally 15 minutes to 100 h, in particular 1 h to 50 h.

The inventive process for dehydrogenative coupling of alcohols can be carried neat but also in the presence of a solvent. Suitable solvents are selected from aliphatic hydrocarbons, aromatic hydrocarbons, esters, ethers, and mixtures thereof. Preferred solvents arealiphatic hydrocarbons such as pentane, hexane, heptane, octane or cyclohexane;aromatic hydrocarbons such as benzene, toluene, xylenes, ethylbenzene, mesitylene or benzotrifluoride;esters such as methyl acetate, ethyl acetate, t-butyl acetate;ketones such as acetone and cyclohexanoneethers such as dioxane, tetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether, diisopropyl ether or diethylene glycol dimethyl ether;

If desired, mixtures of two or more of the afore-mentioned solvents can also be used.

Preference is given to using aliphatic hydrocarbons, aromatic hydrocarbons, ethers and mixtures thereof as solvents.

In one embodiment of the present invention, the inventive process is characterized in that the reaction is carried out in the presence of a solvent selected from aliphatic hydrocarbons, aromatic hydrocarbons, ethers and mixtures thereof.

The work-up of the reaction mixture obtained in the inventive process for dehydrogenative coupling of alcohols and the isolation of the esters are performed in a customary manner, for example by filtration, an aqueous extractive work-up or by distillation as separation method, for example under reduced pressure. The ester is obtained in sufficient purity by applying such measures or a combination thereof, preventing additional purification steps. Alternatively, further purification can be accomplished by methods commonly used in the art, such as chromatography. Preferably the work-up is performed by distillation and the catalyst remains in the residue of the distillation to allow recycling of transition metal catalyst TMC1.

A further aspect of the invention relates to a transition metal complex of formula


wherein M, R1, R2and R3are defined as described above, that meansM is a transition metal selected from metals of groups 7, 8, 9 and 10 of the periodic table of elements according to IUPAC, in particular ruthenium,R1are identical or different and are each hydrogen or an organic radical having from 1 to 40 carbon atoms, in particular are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical,R2are identical or different and are each hydrogen or an organic radical having from 1 to 40 carbon atoms, in particular are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, andR3is an organic radical having from 1 to 40 carbon atoms which is bound via a carbon atom to the oxygen atom, in particular is a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocy-cloalkyl radical, a C6to C40aryl radical, a C7to C40arylalkyl radical or a C2to C40heteroaromatic radical, or R3is C(═O)R4, wherein R4is hydrogen, a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C4aryl radical, a C7to C40arylalkyl radical or a C2to C40heteroaromatic radical, which in each case is bound via a carbon atom to the oxygen atom,or R3together with R1or R3together with R2, together with the atoms connecting them, form a divalent organic group having from 1 to 40 carbon atoms,
where preferred embodiments of said variables M, R1, R2and R3have been described above.

In one embodiment of the invention, the inventive transition metal complex of formula II is characterized in thatM is ruthenium (Ru),R1are identical and are each methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-hexyl, 1-octyl-isobutyl, adamantyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, cyclohexyl, cyclopentyl, tert.-butyl, p-tert.butyl-phenyl, o-tolyl, m-tolyl, p-tolyl, p-methoxy-phenyl, p-trifluoromethyl-phenyl, 4-biphenyl, or phenyl, in particular phenyl,R2are identical and are each methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 1-hexyl, 1-octyl-isobutyl, adamantyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, cyclohexyl, cyclopentyl, tert.-butyl, p-tert.butyl-phenyl, o-tolyl, m-tolyl, p-tolyl, p-methoxy-phenyl, p-trifluoromethyl-phenyl, 4-biphenyl, or phenyl, in particular phenyl,R3is C1to C18alkyl, preferably C1to C6alkyl, more preferably methyl, ethyl, isopropyl, cyclohexyl, cyclopentyl or tert.-butyl, substituted or unsubstituted C6to C18aryl, preferably p-tert.-butyl-phenyl, o-tolyl, m-tolyl, p-toly, naphtyl or phenyl, substituted or unsubstituted C to C18arylalkyl, preferably benzyl, a C1to C15alkanoyl radical, preferably formyl, acetyl, propionyl, or a substituted or unsubstituted C6to C15aroyl radical, preferably benzoyl, wherein R1and R2are identical.

The tetradentate ligand of formula I


wherein R1and R2are defined as described above, that meansR1are identical or different and are each an organic radical having from 1 to 40 carbon atoms, in particular are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical, andR2are identical or different and are each an organic radical having from 1 to 40 carbon atoms, in particular are identical or different and are each a C1to C40alkyl radical, a C3to C40cycloalkyl radical, a C2to C40heterocycloalkyl radical, a C6to C40aryl radical or a C2to C40heteroaromatic radical,

wherein preferred embodiments of said variables R1and R2have been described above,

can be prepared as shown in case of the preparation of ligand L, which can for example be synthesized from tris(2-chloroethyl)amine hydrochloride, diphenylphosphine and potassium tertbutoxide.



Suitable phosphines are commercially available. Alternative phosphines HPR1R2, that could be used instead of HPPh2are for example HPMe2, HPEt2, HPiPr2, HP(cy-Hex)2, HP(cy-Pent)2, HP(t-Bu)2, HP(o-tolyl)2, HP(m-tolyl)2or HP(p-tolyl)2. Most preferred is HPPh2.

A further aspect of the invention relates to a process for preparing the transition metal complex of formula II


as described above,

comprising the process step:

c) contacting a transition metal compound of formula VI

with a compound of formula VII,


wherein the variables M, R1, R2and R3are defined as described above, including preferred embodiments of said variables.

In one embodiment of the invention, the inventive process for preparing the transition metal complex of formula II is characterized in that the transition metal compound of formula VI and the compound of formula VII are contacted in a liquid phase.

In one embodiment of the invention, the inventive process for preparing the transition metal complex of formula II is characterized in that the transition metal compound of formula VI with R2and R1=phenyl is used.



Process step c) can be done independently of process step a) or process step b) or process step c) takes place while performing process step a) or process step b), that means the transition metal complex of formula II is formed in situ.

The transition metal compound of formula VI can be prepared from commercial and readily available metal carbonyls, for example from trirutheniumdodecacarbonyl, with a tetradentate ligand of formula I, such as ligand L, by contacting the starting materials in an inert solvent.



Suitable transition metal carbonyls can be Mn2CO1, Re2CO1, FeCO5, NiCO4, Ru3CO12, Os3CO12, Co2CO8, Rh4CO12or Ir4CO12, preferably Ru3CO12but also other precursors for the synthesis of the transition metal compound of formula VI can be used such as [Ru(PPh3)3(H)2CO]. By contacting [Ru(PPh3)3(H)2C] with a tetradentate ligand of formula I, such as ligand L, the three PPh3ligands are replaced and H2is released and the compound of formula VI is formed.

The present invention has following major advantages: The use of the transition metal catalyst TMC1 in the hydrogenation of carboxylic acid ester and in the formation of carboxylic acid esters from at least one primary alcohol does not require the addition of a base; the synthesis of the transition metal catalyst TMC1 can be realized in two steps from commercial starting materials; furthermore the same catalysts work for the ester hydrogenation as well as the dehydrogenative coupling of alcohols. Preferably an alcohol is chosen, which acts as an additive for catalyst activation, that is the formation of transition metal complexes of formula II, wherein said alcohol is identical with an alcohol formed by the ester hydrogenation or used as starting material in the dehydrogenative coupling reaction.

