Indian Patents. 270002:1,4-HYDROGENATION OF SORBOL WITH RU COMPLEXES

Title of Invention	1,4-HYDROGENATION OF SORBOL WITH RU COMPLEXES
Abstract	The present invention relates to the use of Ru complexes, having a pentamethyl- cyclopentadienyl and a cycloocladine as ligands, together with some acidic additives for improving the selectivity in the 1,4-hydrogenation of sorbol into the corre- sponding Z-alkene as major product.

Full Text	1.4-HYDROGENATION OF SORBOL WITH RU COMPLEXES Technical field The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of specific Ru complexes with cyclopentadienyl derivatives, as one of the ligands, in 1,4-hydrogenation processes for the reduction of sorbol into the corresponding Z-alkene, as major product. Prior Art Selective 1,4-hydrogenation of conjugated dienes, in general, into their Z-alkene is a very interesting reaction in organic chemistry, since it renders accessible a number of compounds which are obtained in general with a poor selectivity. One of the mandatory and characterizing elements of such processes is the catalyst or the catalytic system. The development of useful catalysts or catalytic systems for the 1,4-hydrogenation of sorbol into the corresponding Z-alkene is still an important, difficult and unpredictable task in chemistry. The chemical industry is always eager for higher selectivity, as well as to maintain a high conversion or yield. From the prior art it is known that sorbic acid can be hydrogenated into the corresponding Z-alkene in the presence of [(Cp)RuCO(phosphine)](anion) or [(Cp)RuCO(sorbic acid)](anion) complexes, (Cp* representing a CsMes or pentamethyl- cyclopentadienyl ligand; see Driessen et al, in Chem.Commun., 2000, 217 or in J.Organomet.Chem, 1998, 141), however the yields (conversions x selectivity) are quite low. Furthermore, in EP 1394170, it is reported the cisoid hydrogenation of sorbic acid and sorbol using as catalytic systems the complex [(Dienyl)Ru(acyclic diene)](anion) (in particular [(Cp)Ru(sorbic acid)](anion) or [(Cp)Ru(sorbol)](anion). In this document it is expressively reported that the use of cyclic diene, instead of acyclic diene, is highly detrimental to the overall yield. The only conditions displayed as providing good yields require nitromethane as solvent, the latter being relatively toxic and hazardous for industrial applications. Finally, Table 4 of said document shows that the addition of Lewis acids is highly detrimental to the yields. Therefore, there is a need for processes using alternative catalytic systems systems possibly providing high selectivity and/or conversions. Description of the invention In order to overcome the problems aforementioned, the present invention relates to processes for the catalytic reduction by 1,4-hydrogenation, using molecular H2, of sorbol (I) into the corresponding Z-alkene (II) (i.e. Z-hex-3-en-ol) characterized in that said process is carried out in the presence of at least an acidic additive of the type specified further below, the catalyst or pre-catalyst being a ruthenium complex comprising as ligand a cyclopentadienyl derivative. The invention's process is shown in Scheme 1: Scheme 1 wherein compound (II) is in a Z configuration. A particular embodiment of the invention is a process for the catalytic reduction by 1,4-hydrogenation, using molecular H2, of sorbol of formula into the corresponding Z-alkene, of formula wherein the isomer of configuration Z is predominant; said process being characterized in that it is carried out in the presence of - at least one ruthenium catalyst or pre-catalyst of formula wherein C5Me5epresents pentamethyl-cyclopentadienyl, COD a cyclooctadiene ligand and X represents a non coordinated anion, n represents 2, 1 or 0 and L' represents a solvent; and - at least an acidic additive of the type described further below, preferably in a total amount of about 0.1, or even 0.2, to 100 molar equivalents, relative to the compound (III). Concerning compound (II), since it is an olefin, it can be obtained in the form of a mixture of two isomers, i.e. the one having a configuration Z (Z-alkene (II)) or the one having a configuration E (E-alkene (II')) It is understood that according to the invention the alkene obtained is in the form of a mixture Z-alkene and E-alkene, wherein the ratio Z-alkene / E-alkene (Z/E) is above 1. According to a particular embodiment, said ratio is above 10 or even above 20. In another particular embodiment, said Z/E ratio can be above 30 or even above 35, and in some cases ratio of above 45 or more can be obtained. In any case the presence of the acidic additive in the prescribed concentration range allows to improve said ratio. The substrate (I), due to the fact that it is a diene, can be in the form of a mixture of its three configuration isomers, i.e. the (Z,Z), (E,Z) and (E,E) isomers. According to a particular embodiment of the invention, said substrate can be essentially in the form of its (Z,Z) isomer (e.g. comprising at least 99% w/w of the isomer (Z,Z)). The process of the invention is characterized by the use, as catalyst or pre-catalyst (hereinafter referred to as complexes unless specified otherwise), of a specific type of ruthenium complex as [Ru(C5Me5)(COD)(L')n]X, as defined above. According to a particular embodiment of the invention, L' can be acyclic or cyclic non aromatic ketones or esters, such as acetone or methyl acetate. The ketone can be coordinated in its enolic form. The COD ligand can be any isomer of cyclooctadiene, namely cycloocta-1,5-diene (1,5-COD), cycloocta-1,4-diene (1,4-COD), cycloocta-1,3-diene (1,3-COD). Particular examples of the non-coordinated anion X are C1O4-,R1SO3-, wherein R1 is a chlorine of fluoride atom or an C1-C8 fluoroalkyl or fluoroaryl group, BF4,- PF6-, SbCl6% SbF26-, or BRV, wherein R2 is a phenyl group optionally substituted by one to five groups such as halide atoms or methyl or CF3 groups. According to a preferred embodiment of the invention, the anion is BF4, PF6, ClO4-, C6F5SO3-, BPh4-, CF3SO3- or yet B[3,5-(CF3)2C6H4]4-, even more preferably BF4. As examples of the complex (III) one may cite the following: [Ru(C5Me5)(1,3- COD)]BF4. In a general way, the complexes of formula (III) can be prepared and isolated prior to their use in the process according to the general methods described in the literature (for example see F. Bouachir et al.; Organometallics, 1991, pg 455). It is also understood that the complex of formula (III) can also be obtained in situ from complexes which have a similar formula and are cationic or anionic according to the standard knowledge of a person skilled in the art. For example, reaction can be run using [Ru(C5Me5)(COD)Y] (Y being F, Cl, Br or I and method for preparation having been described by P.J. Fagan et al. in Organometallics, 1990, 9, pg 1843-1852) as precursors in the presence of the substrate and silver or tallium salts). To carry out the processes of the invention it is required also to use at least an acidic additive. By "acidic additive" it is meant a compound capable of providing at least one proton to the catalytic cycle. Said acidic additive is preferably an organic or inorganic acid having a pKa comprised between 0.8 and 7, but in the case of phenols or boron derivatives said pKa can range up to 10. Furthermore, said acidic additive and can be selected from the group consisting of: - a compound of formula R3(3-x)MO(OH)x, wherein R3 is a R4or R4O group wherein R4 is a C1-C10 group, M is P or As and x is 1 or 2; and - a boron derivative of formula R3B(OH)2, wherein R3 is as defined above; and - phenol or a phenol substituted by up to three C1-C4 alkyl, alkoxy or carboxylic groups, nitro groups or halogen atoms; and - a C1-C12 mono-carboxylic non-amino acid; and - a HOOCCH=CHCOOH di-acide, and the tetronic acid. By "mono-carboxylic non-amino acid" it is meant here a mono-carboxylic acid which is not substituted by a primary, secondary or tertiary amino group or heteroaromatic nitrogen derivatives. According to a particular embodiment, said R3(3-x)MO(OH)x acids can be a derivative wherein R3 is a C1-C8 alkyl or alkoxyl group or a C1-C8 phenyl or phenoxyl group optionally substituted, M is P or As and x is 1 or 2. Similarly said R2B(OH)2 acids can be those wherein R3 is a C1-C8 alkyl or alkoxyl group or a C1-C8 phenyl or phenoxyl group optionally substituted. According to another embodiment of the invention, said acid can be the phenol or a phenol substituted by one C1-C4 alkyl, alkoxy or carboxylic group, a nitro group or a halogen atom. Furthermore, according to another particular embodiment of the invention, said acidic additive can be a mono-carboxylic acid of formula R5COOH, wherein R5 represents a C1-C12 hydrocarbon group or a C1-C12 halogenated or per-halogenated hydrocarbon group, optionally substituted by one alcohol group or one or two ether or ester groups. According to a further embodiment, said carboxylic acid is advantageously selected from the group consisting of: - a carboxylic acid of formula R5COOH, wherein R5 represents a halogenated or per-halogenated C1-C8 hydrocarbon group; a R6CH(OR6) group, R6 being a hydrogen atom or a C1-C6 hydrocarbon group; a C1-C12 hydrocarbon group, optionally substituted by one or two ether or ester groups, the optional substituent being by one two or three C1-C4 alkyl, alkoxy or carboxylic groups, or nitro groups or halogen atoms. One can cite, as non-limiting examples, of said acidic additive the following: (BuO)2PO(OH), (tBuO)2PO(OH), (PhO)2PO(OH), (PhCH2O)2PO(OH), tBuPO(OH)2, Ph2PO(OH), PhPO(OH)2, PhAsO(OH)2, (Me)2AsO(OH), CF3COOH, HCF2COOH, maleic or fumaric acid, glycolic acid, pyruvic acid, sorbic, acetic or oleic acid, tetronic acid, C6H13B(OH)2, PhB(OH)2, p-OMe-benzoic, benzoic or p-(COOMe)-benzoic acid, phenoL 3,5-dimethoxy-phenol or 2-methoxy-phenol. Of course, other suitable acidic additives responding to the above description can be used. According to another embodiment of the invention, said acidic additive can be selected from the group consisting of: - a compound of formula R32MO(OH) or R3MO(OH)2, wherein R3 is a C1-C6 alkyl or alkoxyl group or a C1-C8 phenyl or phenoxyl and M is P or As; and - maleic or glycolic acid and an halogenated or per-halogenated C1-C7 mono-carboxylic acid. As previously mentioned the processes of the invention consist in the hydrogenation of a substrate using a ruthenium complex and an acidic additive. A typical process implies the mixture of the substrate with the ruthenium complex, at least one acidic additive and optionally a solvent, and then treating such a mixture with molecular hydrogen at a chosen pressure and temperature. The complexes of the invention, an essential parameter of the process, can be added to the reaction medium in a large range of concentrations. As non-limiting examples, one can cite as complex concentration values those ranging from 0.01 mol% to 5 mol%, the molar percentage being relative to the amount of substrate. Preferably, the complex concentration will be comprised between 0.03 mol% to 2 mol%. It goes without saying that the optimum concentration of complex will depend, as the person skilled in the art knows, on the nature of the latter, on the nature of the substrate, on the nature of the solvent and on the pressure of H2 used during the process, as well as the desired time of reaction. Useful quantities of acidic additive, added to the reaction mixture, may be comprised in a relatively large range. Apart from the one above cited, one can cite, as non-limiting examples, total amounts ranging between 0.5 to 50 molar equivalents, relative to the complex, preferably 0.8 to 20, and even more preferably between about 2 and about 10 molar equivalents. The hydrogenation reaction 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 hydrogenation reactions can be used for the purposes of the invention. Non-limiting examples include non-aromatic solvents such as C1-C12 non aromatic ketones, esters, alkanes ethers, chlorinated alkanes and alcohols or mixtures thereof. According to an embodiment of the invention the solvent is advantageously selected amongst the C1-C12 alkyl ketones, esters, ethers or chlorinated alkanes and mixtures thereof. In particular and as non-limiting examples one may cite the following: acetone ethyl acetate, MTBE, THF, iso-propyl acetate, Et2O, dichloromethane, 1,2-dichloethane, EtOH, MeOH, pentane, hexane. The choice of the solvent can be done as a function of the nature of the complex and the person skilled in the art is well able to select the solvent most convenient in each case to optimize the hydrogenation reaction. In the hydrogenation process of the invention, the reaction can be carried out at a H2 pressure comprised between 105Pa and 80xl05Pa (1 to 80 bars) or even more if desired. Again, a person skilled in the art is well able to adjust the pressure as a function of the catalyst load and of the dilution of the substrate in the solvent. As examples, one can cite typical pressures of 1 to 30x 105 Pa (1 to 30 bar). The temperature at which the hydrogenation can be carried out is comprised between 0°C and 120°C, more preferably in the range of between 40°C and 100°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. Examples The invention will now be described in further detail by way of the following examples, wherein the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art. All the procedures described hereafter have been carried out under an inert atmosphere unless stated otherwise. Hydrogenations were carried out in open glass tubes placed inside a stainless steel autoclave. H2 gas (99.99990%) was used as received. All substrates and solvents were distilled from appropriate drying agents under Ar. NMR spectra were recorded on a Bruker AM-400 (1H at 400.1 MHz, 13C at 100.6 MHz) spectrometer and normally measured at 300 K, in CDCU unless indicated otherwise. Chemical shifts are listed in ppm. Example 1 Hydrogenation processes according to the invention Typical hydrogenation reaction procedure 2,4-Haxanedienol, solvent, [Ru(CsMes)(COD)]X and the acidic additive according to the invention were loaded altogether under inert atmosphere an autoclave and the mixture was purged at room temperature with nitrogen (2 bars, 3 times) and then hydrogen (2 bars, 3 times) under stirring. The autoclave was then pressurized to the desired hydrogen pressure and heated at the desired temperature. The reaction was followed by hydrogen absorption monitoring and/or GC analysis sampling. The ruthenium catalyst was easily removed by distillation on residues and product isomers mixture was usually recovered in more than 90% molar yield. The results obtained are summarized in the following tables. Table 1: influence of the acidic additive and of its presence on hydrogenation selectivity • reaction type: Table 2: influence of the acidic additive and of its presence on hydrogenation selectivity influence of the anion X Claims 1. A process for the catalytic reduction by 1,4-hydrogenation, using molecular H2, of sorbol of formula into the corresponding Z-alkene, of formula wherein the isomer of configuration Z is predominant; said process being characterized in that it is carried out in the presence of - at least one ruthenium catalyst or pre-catalyst of formula wherein CsMes represents pentamethyl-cyclopentadienyl, COD a cyclooctadiene ligand and X represents a non coordinated anion, n represents 2, 1 or 0 and L' represents a solvent; and - at least an acidic additive selected from the group consisting of: a compound of formula R3(3-x)MO(OH)x, wherein R3 is a R4or R4O group wherein R4 is a C1-C10 group, M is P or As and x is 1 or 2; and a boron derivative of formula R3B(OH)2, wherein R3 is as defined above; and phenol or a phenol substituted by up to three C1-C4 alkyl, alkoxy or carboxylic groups, nitro groups or halogen atoms; and C1-C12 mono-carboxylic non-amino acid; and a HOOCCH=CHCOOH di-acide, and the tetronic acid. 2. A process according to claim 1, characterised in that COD is cycloocta-l,5-diene, cycloocta-1,4-diene, cycloocta-1,3-diene. 3. A process according to claim 1, characterised in that X is ClO4-, R1SO3-, wherein R1 is a chlorine of fluoride atom or an C1-C8 fluoroalkyl or fluoroaryl group, BF4-, PF6-, SbClg6-, SbF6-, or BR24-, wherein R2 is a phenyl group optionally substituted by one to five groups such as halide atoms or methyl or CF3 groups. 4. A process according to claim 1, characterised in that said mono-carboxylic acid is selected from the group consisting of: - a carboxylic acid of formula R5COOH, wherein R5 represents a halogenated or per-halogenated C1-C8 hydrocarbon group; a R6CH(OR6) group, R6 being a hydrogen atom or a C1-C6 hydrocarbon group; a C1-C12 hydrocarbon group, optionally substituted by one or two ether or ester groups. the optional substituent being by one two or three C1-C4 alkyl, alkoxy or carboxylic groups, or nitro groups or halogen atoms. 5. A process according to claim 1, characterised in that said acidic additive is selected from the group consisting of: - a compound of formula R32MO(OH) or R3MO(OH)2, wherein R3 is a C1-C6 alkyl or alkoxyl group or a C1-C8 phenyl or phenoxyl and M is P or As; and - maleic or glycolic acid and an halogenated or per-halogenated C1-C7 mono-carboxylic acid. 6. A process according to claim 1, characterised in that said acid is: (BuO)2PO(OH), (tBuO)2PO(OH), (PhO)2PO(OH), (PhCH2O)2PO(OH), tBuPO(OH)2, Ph2PO(OH), PhPO(OH)2, PhAsO(OH)2, (Me)2AsO(OH), CF3COOH, HCF2COOH, maleic or fumaric acid, glycolic acid, pyruvic acid, sorbic, acetic or oleic acid, tetronic acid, C6H13B(OH)2, PhB(OH)2, p-OMe-benzoic, benzoic or p-(COOMe)-benzoic acid, phenol, 3,5- dimethoxy-phenol or 2-methoxy-phenoL 7. A process according to claim 1, characterised in that said process is carried out in the presence of a solvent selected amongst the C1-C12 alkyl ketones, esters, ethers or chlorinated alkanes and mixture thereof. 8. A process according to claim 1, characterised in that said acid is in a total amount of about 0.1 to 100 molar equivalents, relative to the compoand (III). The present invention relates to the use of Ru complexes, having a pentamethyl- cyclopentadienyl and a cycloocladine as ligands, together with some acidic additives for improving the selectivity in the 1,4-hydrogenation of sorbol into the corre- sponding Z-alkene as major product.

Full Text

1.4-HYDROGENATION OF SORBOL WITH RU COMPLEXES
Technical field
The present invention relates to the field of catalytic hydrogenation and, more
particularly, to the use of specific Ru complexes with cyclopentadienyl derivatives, as one
of the ligands, in 1,4-hydrogenation processes for the reduction of sorbol into the
corresponding Z-alkene, as major product.
Prior Art
Selective 1,4-hydrogenation of conjugated dienes, in general, into their Z-alkene is
a very interesting reaction in organic chemistry, since it renders accessible a number of
compounds which are obtained in general with a poor selectivity.
One of the mandatory and characterizing elements of such processes is the catalyst
or the catalytic system. The development of useful catalysts or catalytic systems for the
1,4-hydrogenation of sorbol into the corresponding Z-alkene is still an important, difficult
and unpredictable task in chemistry. The chemical industry is always eager for higher
selectivity, as well as to maintain a high conversion or yield.
From the prior art it is known that sorbic acid can be hydrogenated into the
corresponding Z-alkene in the presence of [(Cp*)RuCO(phosphine)](anion) or
[(Cp*)RuCO(sorbic acid)](anion) complexes, (Cp* representing a CsMes or pentamethyl-
cyclopentadienyl ligand; see Driessen et al, in Chem.Commun., 2000, 217 or in
J.Organomet.Chem, 1998, 141), however the yields (conversions x selectivity) are quite
low.
Furthermore, in EP 1394170, it is reported the cisoid hydrogenation of sorbic acid
and sorbol using as catalytic systems the complex [(Dienyl)Ru(acyclic diene)](anion) (in
particular [(Cp*)Ru(sorbic acid)](anion) or [(Cp*)Ru(sorbol)](anion). In this document it
is expressively reported that the use of cyclic diene, instead of acyclic diene, is highly
detrimental to the overall yield. The only conditions displayed as providing good yields
require nitromethane as solvent, the latter being relatively toxic and hazardous for
industrial applications. Finally, Table 4 of said document shows that the addition of Lewis
acids is highly detrimental to the yields.
Therefore, there is a need for processes using alternative catalytic systems
systems possibly providing high selectivity and/or conversions.

Description of the invention
In order to overcome the problems aforementioned, the present invention relates to
processes for the catalytic reduction by 1,4-hydrogenation, using molecular H2, of
sorbol (I) into the corresponding Z-alkene (II) (i.e. Z-hex-3-en-ol) characterized in that
said process is carried out in the presence of at least an acidic additive of the type
specified further below, the catalyst or pre-catalyst being a ruthenium complex
comprising as ligand a cyclopentadienyl derivative.
The invention's process is shown in Scheme 1:
Scheme 1

wherein compound (II) is in a Z configuration.
A particular embodiment of the invention is a process for the catalytic reduction
by 1,4-hydrogenation, using molecular H2, of sorbol of formula

into the corresponding Z-alkene, of formula

wherein the isomer of configuration Z is predominant;
said process being characterized in that it is carried out in the presence of
- at least one ruthenium catalyst or pre-catalyst of formula

wherein C5Me5epresents pentamethyl-cyclopentadienyl, COD a cyclooctadiene
ligand and X represents a non coordinated anion, n represents 2, 1 or 0 and L'

represents a solvent; and
- at least an acidic additive of the type described further below, preferably in a total
amount of about 0.1, or even 0.2, to 100 molar equivalents, relative to the
compound (III).
Concerning compound (II), since it is an olefin, it can be obtained in the form of a
mixture of two isomers, i.e. the one having a configuration Z (Z-alkene (II)) or the one
having a configuration E (E-alkene (II'))

It is understood that according to the invention the alkene obtained is in the form
of a mixture Z-alkene and E-alkene, wherein the ratio Z-alkene / E-alkene (Z/E) is above
1. According to a particular embodiment, said ratio is above 10 or even above 20. In
another particular embodiment, said Z/E ratio can be above 30 or even above 35, and in
some cases ratio of above 45 or more can be obtained. In any case the presence of the
acidic additive in the prescribed concentration range allows to improve said ratio.
The substrate (I), due to the fact that it is a diene, can be in the form of a mixture
of its three configuration isomers, i.e. the (Z,Z), (E,Z) and (E,E) isomers. According to a
particular embodiment of the invention, said substrate can be essentially in the form of its
(Z,Z) isomer (e.g. comprising at least 99% w/w of the isomer (Z,Z)).
The process of the invention is characterized by the use, as catalyst or pre-catalyst
(hereinafter referred to as complexes unless specified otherwise), of a specific type of
ruthenium complex as [Ru(C5Me5)(COD)(L')n]X, as defined above.
According to a particular embodiment of the invention, L' can be acyclic or cyclic
non aromatic ketones or esters, such as acetone or methyl acetate. The ketone can be
coordinated in its enolic form.
The COD ligand can be any isomer of cyclooctadiene, namely cycloocta-1,5-diene
(1,5-COD), cycloocta-1,4-diene (1,4-COD), cycloocta-1,3-diene (1,3-COD).
Particular examples of the non-coordinated anion X are C1O4-,R1SO3-, wherein R1
is a chlorine of fluoride atom or an C1-C8 fluoroalkyl or fluoroaryl group, BF4,- PF6-,
SbCl6% SbF26-, or BRV, wherein R2 is a phenyl group optionally substituted by one to five

groups such as halide atoms or methyl or CF3 groups.
According to a preferred embodiment of the invention, the anion is BF4, PF6,
ClO4-, C6F5SO3-, BPh4-, CF3SO3- or yet B[3,5-(CF3)2C6H4]4-, even more preferably BF4.
As examples of the complex (III) one may cite the following: [Ru(C5Me5)(1,3-
COD)]BF4.
In a general way, the complexes of formula (III) can be prepared and isolated prior
to their use in the process according to the general methods described in the literature (for
example see F. Bouachir et al.; Organometallics, 1991, pg 455).
It is also understood that the complex of formula (III) can also be obtained in situ
from complexes which have a similar formula and are cationic or anionic according to the
standard knowledge of a person skilled in the art. For example, reaction can be run using
[Ru(C5Me5)(COD)Y] (Y being F, Cl, Br or I and method for preparation having been
described by P.J. Fagan et al. in Organometallics, 1990, 9, pg 1843-1852) as precursors in
the presence of the substrate and silver or tallium salts).
To carry out the processes of the invention it is required also to use at least an
acidic additive. By "acidic additive" it is meant a compound capable of providing at least
one proton to the catalytic cycle. Said acidic additive is preferably an organic or inorganic
acid having a pKa comprised between 0.8 and 7, but in the case of phenols or boron
derivatives said pKa can range up to 10.
Furthermore, said acidic additive and can be selected from the group consisting of:
- a compound of formula R3(3-x)MO(OH)x, wherein R3 is a R4or R4O group wherein R4 is
a C1-C10 group, M is P or As and x is 1 or 2; and
- a boron derivative of formula R3B(OH)2, wherein R3 is as defined above; and
- phenol or a phenol substituted by up to three C1-C4 alkyl, alkoxy or carboxylic groups,
nitro groups or halogen atoms; and
- a C1-C12 mono-carboxylic non-amino acid; and
- a HOOCCH=CHCOOH di-acide, and the tetronic acid.
By "mono-carboxylic non-amino acid" it is meant here a mono-carboxylic acid
which is not substituted by a primary, secondary or tertiary amino group or
heteroaromatic nitrogen derivatives.
According to a particular embodiment, said R3(3-x)MO(OH)x acids can be a
derivative wherein R3 is a C1-C8 alkyl or alkoxyl group or a C1-C8 phenyl or phenoxyl
group optionally substituted, M is P or As and x is 1 or 2.

Similarly said R2B(OH)2 acids can be those wherein R3 is a C1-C8 alkyl or alkoxyl
group or a C1-C8 phenyl or phenoxyl group optionally substituted.
According to another embodiment of the invention, said acid can be the phenol or
a phenol substituted by one C1-C4 alkyl, alkoxy or carboxylic group, a nitro group or a
halogen atom.
Furthermore, according to another particular embodiment of the invention, said
acidic additive can be a mono-carboxylic acid of formula R5COOH, wherein R5
represents a C1-C12 hydrocarbon group or a C1-C12 halogenated or per-halogenated
hydrocarbon group, optionally substituted by one alcohol group or one or two ether or
ester groups. According to a further embodiment, said carboxylic acid is advantageously
selected from the group consisting of:
- a carboxylic acid of formula R5COOH, wherein R5 represents
a halogenated or per-halogenated C1-C8 hydrocarbon group;
a R6CH(OR6) group, R6 being a hydrogen atom or a C1-C6 hydrocarbon group;
a C1-C12 hydrocarbon group, optionally substituted by one or two ether or ester groups,
the optional substituent being by one two or three C1-C4 alkyl, alkoxy or carboxylic
groups, or nitro groups or halogen atoms.
One can cite, as non-limiting examples, of said acidic additive the following:
(BuO)2PO(OH), (tBuO)2PO(OH), (PhO)2PO(OH), (PhCH2O)2PO(OH), tBuPO(OH)2,
Ph2PO(OH), PhPO(OH)2, PhAsO(OH)2, (Me)2AsO(OH), CF3COOH, HCF2COOH,
maleic or fumaric acid, glycolic acid, pyruvic acid, sorbic, acetic or oleic acid, tetronic
acid, C6H13B(OH)2, PhB(OH)2, p-OMe-benzoic, benzoic or p-(COOMe)-benzoic acid,
phenoL 3,5-dimethoxy-phenol or 2-methoxy-phenol. Of course, other suitable acidic
additives responding to the above description can be used.
According to another embodiment of the invention, said acidic additive can be
selected from the group consisting of:
- a compound of formula R32MO(OH) or R3MO(OH)2, wherein R3 is a C1-C6 alkyl or
alkoxyl group or a C1-C8 phenyl or phenoxyl and M is P or As; and
- maleic or glycolic acid and an halogenated or per-halogenated C1-C7 mono-carboxylic
acid.
As previously mentioned the processes of the invention consist in the
hydrogenation of a substrate using a ruthenium complex and an acidic additive. A typical
process implies the mixture of the substrate with the ruthenium complex, at least one

acidic additive and optionally a solvent, and then treating such a mixture with molecular
hydrogen at a chosen pressure and temperature.
The complexes of the invention, an essential parameter of the process, can be
added to the reaction medium in a large range of concentrations. As non-limiting
examples, one can cite as complex concentration values those ranging from 0.01 mol% to
5 mol%, the molar percentage being relative to the amount of substrate. Preferably, the
complex concentration will be comprised between 0.03 mol% to 2 mol%. It goes without
saying that the optimum concentration of complex will depend, as the person skilled in
the art knows, on the nature of the latter, on the nature of the substrate, on the nature of
the solvent and on the pressure of H2 used during the process, as well as the desired time
of reaction.
Useful quantities of acidic additive, added to the reaction mixture, may be
comprised in a relatively large range. Apart from the one above cited, one can cite, as
non-limiting examples, total amounts ranging between 0.5 to 50 molar equivalents,
relative to the complex, preferably 0.8 to 20, and even more preferably between about 2
and about 10 molar equivalents.
The hydrogenation reaction 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 hydrogenation reactions can be used for the purposes of the invention. Non-limiting
examples include non-aromatic solvents such as C1-C12 non aromatic ketones, esters,
alkanes ethers, chlorinated alkanes and alcohols or mixtures thereof. According to an
embodiment of the invention the solvent is advantageously selected amongst the C1-C12
alkyl ketones, esters, ethers or chlorinated alkanes and mixtures thereof. In particular and
as non-limiting examples one may cite the following: acetone ethyl acetate, MTBE, THF,
iso-propyl acetate, Et2O, dichloromethane, 1,2-dichloethane, EtOH, MeOH, pentane,
hexane. The choice of the solvent can be done as a function of the nature of the complex
and the person skilled in the art is well able to select the solvent most convenient in each
case to optimize the hydrogenation reaction.
In the hydrogenation process of the invention, the reaction can be carried out at a
H2 pressure comprised between 105Pa and 80xl05Pa (1 to 80 bars) or even more if
desired. Again, a person skilled in the art is well able to adjust the pressure as a function
of the catalyst load and of the dilution of the substrate in the solvent. As examples, one
can cite typical pressures of 1 to 30x 105 Pa (1 to 30 bar).

The temperature at which the hydrogenation can be carried out is comprised
between 0°C and 120°C, more preferably in the range of between 40°C and 100°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.
Examples
The invention will now be described in further detail by way of the following
examples, wherein the temperatures are indicated in degrees centigrade and the
abbreviations have the usual meaning in the art.
All the procedures described hereafter have been carried out under an inert
atmosphere unless stated otherwise. Hydrogenations were carried out in open glass tubes
placed inside a stainless steel autoclave. H2 gas (99.99990%) was used as received. All
substrates and solvents were distilled from appropriate drying agents under Ar. NMR
spectra were recorded on a Bruker AM-400 (1H at 400.1 MHz, 13C at 100.6 MHz)
spectrometer and normally measured at 300 K, in CDCU unless indicated otherwise.
Chemical shifts are listed in ppm.
Example 1
Hydrogenation processes according to the invention
Typical hydrogenation reaction procedure
2,4-Haxanedienol, solvent, [Ru(CsMes)(COD)]X and the acidic additive according to the
invention were loaded altogether under inert atmosphere an autoclave and the mixture
was purged at room temperature with nitrogen (2 bars, 3 times) and then hydrogen (2
bars, 3 times) under stirring. The autoclave was then pressurized to the desired hydrogen
pressure and heated at the desired temperature. The reaction was followed by hydrogen
absorption monitoring and/or GC analysis sampling. The ruthenium catalyst was easily
removed by distillation on residues and product isomers mixture was usually recovered in
more than 90% molar yield.
The results obtained are summarized in the following tables.

Table 1: influence of the acidic additive and of its presence on hydrogenation selectivity
• reaction type:

Table 2: influence of the acidic additive and of its presence on hydrogenation selectivity
influence of the anion X

Claims
1. A process for the catalytic reduction by 1,4-hydrogenation, using molecular H2, of
sorbol of formula

into the corresponding Z-alkene, of formula

wherein the isomer of configuration Z is predominant;
said process being characterized in that it is carried out in the presence of
- at least one ruthenium catalyst or pre-catalyst of formula

wherein CsMes represents pentamethyl-cyclopentadienyl, COD a cyclooctadiene
ligand and X represents a non coordinated anion, n represents 2, 1 or 0 and L'
represents a solvent; and
- at least an acidic additive selected from the group consisting of:
a compound of formula R3(3-x)MO(OH)x, wherein R3 is a R4or R4O group wherein R4 is
a C1-C10 group, M is P or As and x is 1 or 2; and
a boron derivative of formula R3B(OH)2, wherein R3 is as defined above; and
phenol or a phenol substituted by up to three C1-C4 alkyl, alkoxy or carboxylic groups,
nitro groups or halogen atoms; and
C1-C12 mono-carboxylic non-amino acid; and
a HOOCCH=CHCOOH di-acide, and the tetronic acid.
2. A process according to claim 1, characterised in that COD is cycloocta-l,5-diene,
cycloocta-1,4-diene, cycloocta-1,3-diene.
3. A process according to claim 1, characterised in that X is ClO4-, R1SO3-, wherein R1
is a chlorine of fluoride atom or an C1-C8 fluoroalkyl or fluoroaryl group, BF4-, PF6-,

SbClg6-, SbF6-, or BR24-, wherein R2 is a phenyl group optionally substituted by one to
five groups such as halide atoms or methyl or CF3 groups.
4. A process according to claim 1, characterised in that said mono-carboxylic acid is
selected from the group consisting of:
- a carboxylic acid of formula R5COOH, wherein R5 represents
a halogenated or per-halogenated C1-C8 hydrocarbon group;
a R6CH(OR6) group, R6 being a hydrogen atom or a C1-C6 hydrocarbon group;
a C1-C12 hydrocarbon group, optionally substituted by one or two ether or ester groups.
the optional substituent being by one two or three C1-C4 alkyl, alkoxy or carboxylic
groups, or nitro groups or halogen atoms.
5. A process according to claim 1, characterised in that said acidic additive is selected
from the group consisting of:
- a compound of formula R32MO(OH) or R3MO(OH)2, wherein R3 is a C1-C6 alkyl or
alkoxyl group or a C1-C8 phenyl or phenoxyl and M is P or As; and
- maleic or glycolic acid and an halogenated or per-halogenated C1-C7 mono-carboxylic
acid.
6. A process according to claim 1, characterised in that said acid is: (BuO)2PO(OH),
(tBuO)2PO(OH), (PhO)2PO(OH), (PhCH2O)2PO(OH), tBuPO(OH)2, Ph2PO(OH),
PhPO(OH)2, PhAsO(OH)2, (Me)2AsO(OH), CF3COOH, HCF2COOH, maleic or fumaric
acid, glycolic acid, pyruvic acid, sorbic, acetic or oleic acid, tetronic acid, C6H13B(OH)2,
PhB(OH)2, p-OMe-benzoic, benzoic or p-(COOMe)-benzoic acid, phenol, 3,5-
dimethoxy-phenol or 2-methoxy-phenoL
7. A process according to claim 1, characterised in that said process is carried out in
the presence of a solvent selected amongst the C1-C12 alkyl ketones, esters, ethers or
chlorinated alkanes and mixture thereof.
8. A process according to claim 1, characterised in that said acid is in a total amount
of about 0.1 to 100 molar equivalents, relative to the compoand (III).

The present invention relates to the use of Ru complexes, having a pentamethyl- cyclopentadienyl and a cycloocladine as ligands, together with some acidic additives for improving the selectivity in the 1,4-hydrogenation of sorbol into the corre-
sponding Z-alkene as major product.

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Patent Number

270002

Indian Patent Application Number

3250/KOLNP/2009

PG Journal Number

48/2015

Publication Date

27-Nov-2015

Grant Date

24-Nov-2015

Date of Filing

14-Sep-2009

Name of Patentee

INNOVAROMA SA

Applicant Address

1, ROUTE DES JEUNES, CH-1227 ACACIAS/GENEVA, SWITZERLAND

Inventors:

#	Inventor's Name	Inventor's Address
1	BONOMO, LUCIA	940, ROUTE DE VOUVRAY, F-01200 BELLEGARDE, FRANCE
2	DUPAU, PHILIPPE	940, ROUTE DE VOUVRAY, F-01200 BELLEGARDE, FRANCE

PCT International Classification Number

C07C 29/17

PCT International Application Number

PCT/IB2008/051222

PCT International Filing date

2008-04-02

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	07105557.8	2007-04-03	EUROPEAN UNION