WO2006106484A1 - Hydrogenation of esters with ru/tetradentate ligands complexes - Google Patents

Hydrogenation of esters with ru/tetradentate ligands complexes Download PDF

Info

Publication number
WO2006106484A1
WO2006106484A1 PCT/IB2006/051028 IB2006051028W WO2006106484A1 WO 2006106484 A1 WO2006106484 A1 WO 2006106484A1 IB 2006051028 W IB2006051028 W IB 2006051028W WO 2006106484 A1 WO2006106484 A1 WO 2006106484A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
optionally substituted
groups
formula
alkyl
Prior art date
Application number
PCT/IB2006/051028
Other languages
French (fr)
Inventor
Lionel Saudan
Philippe Dupau
Jean-Jacques Riedhauser
Patrick Wyss
Original Assignee
Firmenich Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=36694347&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2006106484(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Firmenich Sa filed Critical Firmenich Sa
Priority to MX2007012298A priority Critical patent/MX2007012298A/en
Priority to BRPI0608686A priority patent/BRPI0608686A2/en
Priority to JP2008504897A priority patent/JP5388570B2/en
Priority to ES06727827T priority patent/ES2432561T3/en
Priority to EP06727827.5A priority patent/EP1868965B1/en
Priority to CN2006800086311A priority patent/CN101142155B/en
Publication of WO2006106484A1 publication Critical patent/WO2006106484A1/en
Priority to US11/854,906 priority patent/US7989665B2/en
Priority to IL186319A priority patent/IL186319A/en
Priority to US12/694,688 priority patent/US8124816B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/02—Formation or introduction of functional groups containing oxygen of hydroxy or O-metal groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/189—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms containing both nitrogen and phosphorus as complexing atoms, including e.g. phosphino moieties, in one at least bidentate or bridging ligand
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
    • C07C29/149—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof with hydrogen or hydrogen-containing gases
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/32—Oxygen atoms
    • C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/30—Oxygen atoms, e.g. delta-lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/0046—Ruthenium compounds
    • C07F15/0053—Ruthenium compounds without a metal-carbon linkage
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/5004—Acyclic saturated phosphines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/5022—Aromatic phosphines (P-C aromatic linkage)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic saturated phosphonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/60—Reduction reactions, e.g. hydrogenation
    • B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
    • B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
    • B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B01J2531/0255—Ligands comprising the N2S2 or N2P2 donor atom set, e.g. diiminodithiolates or diiminodiphosphines with complete pi-conjugation between all donor centres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/80—Complexes comprising metals of Group VIII as the central metal
    • B01J2531/82—Metals of the platinum group
    • B01J2531/821—Ruthenium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
    • C07C2602/28—Hydrogenated naphthalenes

Definitions

  • the present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Ru complexes with tetradentate ligands, in hydrogenation processes for the reduction of esters or lactones into the corresponding alcohol or diol respectively.
  • Reduction of an ester functional group to the corresponding alcohol is one of the fundamental reactions in organic chemistry, and is used in a large number of chemical processes.
  • two main types of processes are known to achieve such a transformation.
  • Such types of processes are the following: a) hydride processes, in which a silyl or metal hydride salt, such as LiAlH 4 , is used; b) hydrogenation processes, in which molecular hydrogen is used.
  • One of the mandatory and characterizing elements of hydrogenation processes is the catalyst or the catalytic system which is used to activate the molecular hydrogen in view of the reduction.
  • the development of useful catalysts or catalytic systems for the hydrogenation of an ester functional group represents still an important need in chemistry.
  • ruthenium/phosphine complexes obtained by the reaction of ruthenium oxide or carboxylate precursor with a mono-, di- or tri-phosphine ligand (an example of which is described by Elsevier et al. in ChenxCommun., 1998, 1367).
  • the ruthenium metal is coordinated only by "acac" ligands and phosphine atoms, limiting thus the diversity of the ligand structure and coordination sphere around the metal center.
  • the experimental conditions require very high pressures (at least 70-130 bars) and temperatures (120-180° C).
  • the present invention relates to processes for the reduction by hydrogenation, using molecular H 2 , of a C 3 -C 7 O substrate containing one or two esters, or lactones, functional groups into the corresponding alcohol, or diol, characterized in that said process is carried out in the presence of a base and at least one catalyst or pre-catalyst in the form of a ruthenium complexes of a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group.
  • the substrate can be a compound of formula (I)
  • R a and R b represent, simultaneously or independently, a linear, branched or cyclic C 1 -C 3O aromatic, alkyl or alkenyl group, optionally substituted; or R a and R b are bonded together and form a C 4 -C 2 O saturated or unsaturated group, optionally substituted.
  • the corresponding alcohols (i.e (II-a) and (II-b)), or the corresponding diol (H'), of said substrate (I) are of formula
  • R a and R b are defined as in formula (I).
  • a compound of formula (II) i.e. II-a or II-b
  • H' a compound of formula (H')
  • a linear, branched or cyclic aromatic, alkyl, or alkenyl group it is meant that said R a or R b can be in the form of, e.g., a linear alkyl group or can also be in the form of a mixture of said type of groups, e.g. a specific R a may comprises a linear alkyl, a branched alkenyl, a (poly)cyclic alkyl and an aryl moiety, unless a specific limitation to only one type is mentioned.
  • a group is mentioned as being in the form of more than one type of topology (e.g. linear, cyclic or branched) and/or unsaturation (e.g. alkyl, aromatic or alkenyle) it is meant also a group which may comprise moieties having any one of said topologies or unsaturations, as above explained.
  • the substrate is an ester, or lactone, that will provide an alcohol, or a diol, that is useful in the pharmaceutical, agrochemical or perfumery industry as final product or as an intermediate.
  • Particularly preferred substrate is an ester, or lactone, that will provide an alcohol, or diol, which is useful in the perfumery industry as final product or as an intermediate.
  • the substrate is a C5-C30 compound of formula (I), and in particular one may cite those wherein R a and R b represent simultaneously or independently a linear, branched or cyclic C 1 -C 3 O aromatic or alkyl group optionally substituted, or a cyclic C5-C30 alkenyl group optionally substituted; or R a and R b are bonded together and form a C 4 -C 2 O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
  • R a and R b represent simultaneously or independently a linear, branched or cyclic C 1 -C 3 O aromatic or alkyl group optionally substituted, or a cyclic C5-C30 alkenyl group optionally substituted; or R a and R b are bonded together and form a C 4 -C 2 O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
  • the substrate is a Cs-C 2 O compound of formula (I), wherein R a and R b represent simultaneously or independently a linear, branched or cyclic Cs-C 18 aromatic or alkyl group, optionally substituted, or a cyclic C 5 -C 1 S alkenyl group, optionally substituted; or R a and R b are bonded together and form a C 4 -C 2 O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
  • R a and R b represent simultaneously or independently a linear, branched or cyclic Cs-C 18 aromatic or alkyl group, optionally substituted, or a cyclic C 5 -C 1 S alkenyl group, optionally substituted; or R a and R b are bonded together and form a C 4 -C 2 O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
  • R a and/or R b represent an alkenyl group then the carbon-carbon double bond is not terminal and is not conjugated.
  • R a and R b are one, two or three halogen, OR C , NR C 2 or R c groups, in which R c is a hydrogen atom, a halogenated C 1 -C 2 group or a C 1 to C 1 O cyclic, linear or branched alkyl, or alkenyl group, preferably a C 1 to C 4 linear or branched alkyl or alkenyl group.
  • R c is a hydrogen atom, a halogenated C 1 -C 2 group or a C 1 to C 1 O cyclic, linear or branched alkyl, or alkenyl group, preferably a C 1 to C 4 linear or branched alkyl or alkenyl group.
  • R c is a hydrogen atom, a halogenated C 1 -C 2 group or a C 1 to C 1 O cyclic, linear or branched alkyl, or alkenyl group, preferably a C 1 to C 4 linear or branche
  • Non-limiting examples of substrates are alkyl cinnamates, sorbates or salycilates, alkyl esters of natural (fatty or not) acids, Sclareolide, spirolactones, allylic ester, di alkyl diesters, (un) substituted benzoic esters, and ⁇ - ⁇ unsaturated esters.
  • the substrate can be selected from the group consisting of sclareolide, Cg-C 15 spirolactones and C 1 -C 4 alkyl esters of 4-methyl-6-(2,6,6-trimethyl-l-cyclohexen-l-yl)-3-hexenoic acid.
  • 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 ruthenium complex as described above.
  • the complex can be in the form of an ionic or neutral species.
  • the ruthenium complex can be of the general formula
  • L4 represents a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group; and each Y represents, simultaneously or independently, CO, a hydrogen or halogen atom, a hydroxyl group, or a C 1 -C 6 alkoxy or carboxylic radical, or also a BH 4 or AlH 4 group; X represents a C3-C30 mono-phosphine or a solvent; Z represents a non-coordinated anion; and n is 0, 1 or 2.
  • L4 is a tetradentate ligand, such as a Cg-C 45 compound, wherein the coordinating groups consist of two amino or imino group and two phosphino group, and in particular said amino groups are a primary (i.e. NH 2 ) or a secondary (i.e. NH) amino groups.
  • each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a hydroxy radical, a C 1 to C 6 alkoxy radical, such as a methoxy, ethoxy or isopropoxy radical, or a C 1 to Ce acyloxy radical such as a CH 3 COO or CH 3 CH 2 COO radical. More preferably, each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH 3 COO or CH 3 CH 2 COO radical.
  • X represents a mono- phosphine of formula PR d 3 , wherein R d is a C 1 -C 12 group, such as linear, branched or cyclic alkyl, alkoxy or aryloxy group optionally substituted, substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. More particularly R d may represent a substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. Possible substituents are those cited below for L4.
  • X may also be a solvent
  • solvent has to be understood according to the usual meaning in the art and includes compounds used as diluent in the preparation of the complex or during the invention's process, non limiting examples are dimethylsulfoxide, acetonitrile, dimethylformamide, an alcohol (e.g. an C 1 -C 4 alcohol), or also THF, acetone, pyridine or a C 3 -Cg ester or the substrate of the invention's process.
  • Z represents a halogen atom, a hydroxyl group, or a C 1 -C 6 alkoxy, phenoxy or carboxylic radical.
  • the complex of formula (1) represents, in general for practical reasons, a preferred embodiment of the invention.
  • L4 can be a compound of formula
  • dotted lines indicate a single or double bond
  • z is 1 if the nitrogen atom belongs to an amino group (the dotted lines are single bonds) or is 0 if the nitrogen atom belongs to an imino group (one dotted line is a double bond);
  • R 2 and R 3 when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C 1 to C 8 alkyl or alkenyl group optionally substituted, a C 6 to C 1 O aromatic group optionally substituted, or an OR 2 or NR 2 R 3 group, R 2 and R 3 being a C 1 to C 8 alkyl or alkenyl group; or said groups R 2 and R 3 bonded to the same P atom, when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R 2 and R 3 groups are bonded ;
  • A represents a -(CR 9 2 ) t - group or a diphenyl, dinaphthyl, C 5 -C 12 metallocediyl, phenylene (-C O H 4 -) or naphthylene (-C 1 OH 6 -) group optionally substituted;
  • B represents a diphenyl
  • R 9 , R 10 and R 11 taken separately, represent, simultaneously or independently, a hydrogen atom, a C 1 -C 1 O linear, branched or cyclic alkyl or alkenyl group optionally substituted or a
  • R 11 or R 9 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
  • said metallocenediyl such as for example a ferrocenediyl
  • said metallocenediyl can be in the form of a metallocene-l,l'-diyl or of a metallocene- 1 ,2-diyl.
  • a and/or B are diphenyl or dinaphthyl groups they are preferably in their 1,1' form, and when said A and/or B are phenylene or naphthylene group they are in a ortho or meta form or for the naphthylene also as naphthalene- 1,8-diyl derivarive.
  • L4 can be a compound of formula (4- A) or (4-B):
  • R 2 and R 3 when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C 1 to C 8 alkyl or alkenyl group optionally substituted, a C 6 to C 10 aromatic group optionally substituted, or an OR 2 or NR 2 R 3 group, R 2 and R 3 being a C 1 to C 8 alkyl or alkenyl group; or said groups R 2 and R 3 , when taken together, form a saturated or unsaturated ring optionally substituted, having 4 or 5 to 10 atoms and including the phosphorus atom to which said R 2 and R 3 groups are bonded ; R 9 , R 10 and R 11 , taken separately, represent, simultaneously or independently, a hydrogen atom, a C 1 -C 8 linear, branched or cyclic alkyl or alkenyl group optionally substituted or a Ce to C 1 O aromatic group optionally substituted; two adjacent or geminal R 9 , taken together, may form a, preferably C 5 to C 8 , ring
  • R 2 and R 3 may represent, simultaneously or independently, a linear, branched or cyclic C 1 to C 6 alkyl group optionally substituted, a phenyl group optionally substituted; said groups R 2 and R 3 , taken together, may form a saturated or unsaturated ring optionally substituted, having 4, 5, 6 or 7 atoms and including the phosphorus atom to which said R 2 and R 3 groups are bonded .
  • R 2 and R 3 may represents a linear, branched or cyclic C 1 to C 6 alkyl group optionally substituted or an phenyl group optionally substituted.
  • ligand L4 is a compound of formula
  • R 2 and R 3 taken separately, represent simultaneously or independently a linear, branched or cyclic alkyl group containing 1 to 6 carbon atoms or a phenyl group optionally substituted; or the two R 2 and R 3 bonded to the same P atom, taken together, form a ring having 5 to 7 atoms and including the phosphorus atom to which they are bonded;
  • R 9 , R 10 and R 11 taken separately, represent, simultaneously or independently, a hydrogen atom, a C 1 -C 4 linear or branched alkyl group optionally substituted or a phenyl group optionally substituted; the two R 9 , taken together, may form a C 4 -C 8 , or preferably a
  • C 5 -C 7 ring including the carbon atom to which said R 9 groups are bonded; two adjacent R 11 , taken together, may form a phenyl group optionally substituted and including the carbon atom to which said R 11 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
  • Possible substituents of the various groups A, B, R 2 , R 3 , R 9 , R 10 and R 11 are one or two halogen, C 1 to C 1 O alkoxy, polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR, NR 2 , quaternary amine or R groups, wherein R is a C 1 to Ce alkyl, or a C5 to C 12 cycloalkyl, aralkyl (such as benzyl, phenethyl etc..) or aromatic group, the latter being also optionally substituted by one, two or three halogen, sulfonates groups or C 1 -C 8 alkyl, alkoxy, amino, nitro, sulfonates, halo- or perhalo-hydrocarbon or ester groups.
  • halo- or perhalo-hydrocarbon it is meant groups such as CF 3 or CClH 2 for instance.
  • said substituents can be, and in particular when said groups are or contain phenyl groups or moieties, one or two halogen, C 1 to C5 alkoxy or polyalkyleneglycols groups, COOR, NR 2 or R groups wherein R is a C 1 to C 4 alkyl, or a C5-6 cycloalkyl, aralkyl or aromatic group, the latter being also optionally substituted as above defined.
  • R 9 , R 10 and R 11 are one or two halogen atoms or R 8 , OR 8 or NR 8 2 , R 8 being a C 1 to Ce alkyl groups or a C 1 to C 4 alkyl groups.
  • A, B, R 2 , R 3 , R 9 , R 10 , R 11 and k have the same meaning as above, as well as those of formula (4-F) or (4-G) are new, with the exception of N,N'-l,2-ethanediylidenebis[2- (diphenylphosphino-)benzenemethanamine and of N,N'-2,3-butanediylidenebis[2- (diphenylphosphino-)benzenemethanamine, and are therefore also an object of the present invention.
  • the invention complexes where the tetradentate ligand is a compound of formula (2'), (4-B'), (4-C), (4-F) or (4-G) are also new, with the exception of dichloro[N,N'-l,2-ethanediylidenebis[2-(diphenylphosphino- ⁇ P)benzenemethanamine- KN]] -Ruthenium, and are also an object of the present invention.
  • ligands described above can be obtained by applying standard methods which are well known in the state of the art and by the person skilled in the art. Therefore, their preparation does not require a specific description. For example one may revert to WO 02/40155.
  • the complexes of formula (1) can be prepared and isolated prior to their use in the process according to the general methods described in the literature. A method is described in the Example.
  • the complexes can be prepared in situ, by several methods, in the hydrogenation medium, without isolation or purification, just before their use.
  • a complex of formula (1) consists in reacting an appropriate Ru complex of formula [Ru("diene")("allyl") 2 ], wherein "diene” represents a cyclic or linear hydrocarbon containing two carbon-carbon double bonds, conjugated or not, such as for example 1,5-cyclooctadiene (COD) or norbornadiene, and "allyl” represents a linear or branched C 3 to C 8 hydrocarbon radical containing one carbon-carbon double bond such as methylallyl or allyl, with a non coordinating acid such as HBF 4 Et 2 O, and then treating the resulting solution with the required amount of a ligands L4, such as defined previously, to give a solution of a catalyst according to formula (1).
  • the mixture thus obtained can also be treated with a base in the presence of a primary or secondary alcohol.
  • the complexes of formula (I) can be prepared by reacting an appropriate Ru complex such as, [RuCl 2 (PPh 3 ) 3 ], [RuCl 2 (cod)] or [RuCl 2 (arene)] 2 with the required amount of a ligands L4, such as defined previously (cod representing a cyclooctadiene and arene being e.g. a benzene or naphthalene).
  • complex of formula (I) can also be obtained in situ from complexes which have a similar formula and which in presence of, for example an alcohol and a base, are converted into a compound of formula (I).
  • complexes which have a similar formula and which in presence of, for example an alcohol and a base, are converted into a compound of formula (I).
  • X, Y, and Z have other meaning.
  • a base can be the substrate itself, if the latter is basic, a corresponding alcoholate or any base having preferentially a pK a above 11. According to a particular embodiment of the invention said base may have a pK a above 14. It is also understood that preferably said base does not reduce itself a substrate of formula (I).
  • alkaline or alkaline-earth metal carbonates such as cesium carbonate, an alkaline or alkaline-earth metal hydroxides, C 1- io amidures, Cio- 2 6 phosphazene or an alcoholate of formula (R 13 O) 2 M or R 13 OM', wherein M is an alkaline-earth metal, M' is an alkaline metal or an ammonium NR 1 V " , R 13 stands for hydrogen or a C 1 to Ce linear or branched alkyl radical and R 14 stands for a C 1 to C 1 O linear or branched alkyl radical, such as sodium or potassium alcoholates.
  • R 13 stands for hydrogen or a C 1 to Ce linear or branched alkyl radical
  • R 14 stands for a C 1 to C 1 O linear or branched alkyl radical, such as sodium or potassium alcoholates.
  • other suitable bases can be used.
  • said base is an alkaline alcoholate of formula R 13 OM'.
  • the processes of the invention consist in the hydrogenation of a substrate using a ruthenium complex and a base.
  • a typical process implies the mixture of the substrate with the ruthenium complex, a base and optionally a solvent, and then treating such a mixture with molecular hydrogen at a chosen pressure and temperature.
  • the complexes of the invention can be added to the reaction medium in a large range of concentrations.
  • concentration values those ranging from 50 ppm to 50000 ppm, relative to the amount of substrate.
  • the complex concentration will be comprised between 100 and 20000 ppm. 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 and on the pressure of H 2 used during the process, as well as the desired time of reaction.
  • Useful quantities of base, added to the reaction mixture may be comprised in a relatively large range.
  • the hydrogenation reaction can be carried out in the presence or absence of a solvent.
  • 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 aromatic solvents such as toluene or xylene, hydrocarbon solvents such as hexane or cyclohexane, ethers such as tetrahydrofuran or MTBE, polar solvents such as primary or secondary alcohols such as isopropanol or ethanol, or mixtures thereof.
  • aromatic solvents such as toluene or xylene
  • hydrocarbon solvents such as hexane or cyclohexane
  • ethers such as tetrahydrofuran or MTBE
  • polar solvents such as primary or secondary alcohols such as isopropanol or ethanol, or mixtures thereof.
  • the choice of the solvent is a function of the nature of the complex and the person skilled in the art is well able to
  • the reaction can be carried out at a H 2 pressure comprised between 10 5 Pa and 8OxIO 5 Pa (1 to 80 bars) or even more if desired.
  • 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.
  • the temperature at which the hydrogenation can be carried out is comprised between O 0 C and 12O 0 C, more preferably in the range of between 5O 0 C and 100 0 C.
  • 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.
  • the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 100 0 C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. Then, the reaction mixture was diluted with aq. IN HCl (50 mL) and extracted with MTBE (100 mL). Gas chromatography after silylation of an aliquot showed the following products: methyl benzoate (1.7%), benzyl alcohol (94.6%), benzoic acid (3.7%). Then, the organic phase was washed successively with aq. IN KOH (50 mL) and aq. sat.
  • Ligands L-I to L-4 were prepared according to Rautenstrauch, V. et al in WO 02/40155.
  • Ligand L-6 was prepared according to DuBois, T. D. Inorganic Chem. 1972, 11(4), 718-
  • Typical reaction condition is described bellow for RuCl 2 (L-I): Under argon, a solution of methyl 3-cyclohexene-l-carboxylate (2.810 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2 x 1 mL), to a Keim autoclave equipped with a glass liner containing RuCl 2 (L-I) (8.4 mg, 0.01 mmol, 0.05 mol%), solid NaOMe (109.7 mg, 2.0 mmol, 10 mol%), and THF (10 mL).
  • the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 100 0 C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. The glass liner was removed from the autoclave, and the reaction mixture was diluted with citric acid 10% w/w (25 mL) and extracted with MTBE (100 mL).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Ru complexes with tetradentate ligands, having at least one amino or imino coordinating group and at least one phosphino coordinating group, in hydrogenation processes for the reduction of esters or lactones into the corresponding alcohol or diol respectively.

Description

HYDROGENATION OF ESTERS WITH RU/TETRADENTATE LIGANDS
COMPLEXES
Technical field The present invention relates to the field of catalytic hydrogenation and, more particularly, to the use of Ru complexes with tetradentate ligands, in hydrogenation processes for the reduction of esters or lactones into the corresponding alcohol or diol respectively.
Prior Art
Reduction of an ester functional group to the corresponding alcohol is one of the fundamental reactions in organic chemistry, and is used in a large number of chemical processes. In general, two main types of processes are known to achieve such a transformation. Such types of processes are the following: a) hydride processes, in which a silyl or metal hydride salt, such as LiAlH4, is used; b) hydrogenation processes, in which molecular hydrogen is used.
From a practical point of view, hydrogenation processes are more attractive as they can be run using small amounts of catalyst (typically 10 to 1000 ppm relative to the substrate) and in the presence of small quantities or even in the absence of solvent. Furthermore, hydrogenation processes do not require the use of highly reactive and expensive hydrides, and do not produce important amounts of aqueous waste.
One of the mandatory and characterizing elements of hydrogenation processes is the catalyst or the catalytic system which is used to activate the molecular hydrogen in view of the reduction. The development of useful catalysts or catalytic systems for the hydrogenation of an ester functional group represents still an important need in chemistry.
Amongst the few catalysts or catalytic systems known to perform such reductions one may cite the ruthenium/phosphine complexes, obtained by the reaction of ruthenium oxide or carboxylate precursor with a mono-, di- or tri-phosphine ligand (an example of which is described by Elsevier et al. in ChenxCommun., 1998, 1367). In this type of complex the ruthenium metal is coordinated only by "acac" ligands and phosphine atoms, limiting thus the diversity of the ligand structure and coordination sphere around the metal center. As a consequence of such little diversity the tuning of the activity and of the performance of the hydrogenation process is not easy. Furthermore, the experimental conditions require very high pressures (at least 70-130 bars) and temperatures (120-180° C).
Therefore, there is a need for hydrogenation processes using alternative catalysts or pre-catalysts, preferably having a greater diversity in the ligand structures and coordination spheres around the metal center and allowing the use of softer experimental conditions.
Description of the invention
In order to overcome the problems aforementioned, the present invention relates to processes for the reduction by hydrogenation, using molecular H2, of a C3-C7O substrate containing one or two esters, or lactones, functional groups into the corresponding alcohol, or diol, characterized in that said process is carried out in the presence of a base and at least one catalyst or pre-catalyst in the form of a ruthenium complexes of a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group.
According to a particular embodiment of the invention, the substrate can be a compound of formula (I)
Figure imgf000003_0001
wherein Ra and Rb represent, simultaneously or independently, a linear, branched or cyclic C1-C3O aromatic, alkyl or alkenyl group, optionally substituted; or Ra and Rb are bonded together and form a C4-C2O saturated or unsaturated group, optionally substituted. The corresponding alcohols (i.e (II-a) and (II-b)), or the corresponding diol (H'), of said substrate (I), are of formula
Figure imgf000003_0002
wherein Ra and Rb are defined as in formula (I). A compound of formula (II) (i.e. II-a or II-b) will be obtained in the case where Ra and Rb are not bonded together, while a compound of formula (H') will be obtained in the case where Ra and Rb are bonded together.
It is understood that by "a linear, branched or cyclic aromatic, alkyl, or alkenyl group" it is meant that said Ra or Rb can be in the form of, e.g., a linear alkyl group or can also be in the form of a mixture of said type of groups, e.g. a specific Ra may comprises a linear alkyl, a branched alkenyl, a (poly)cyclic alkyl and an aryl moiety, unless a specific limitation to only one type is mentioned. Similarly, in all the below embodiments of the invention when a group is mentioned as being in the form of more than one type of topology (e.g. linear, cyclic or branched) and/or unsaturation (e.g. alkyl, aromatic or alkenyle) it is meant also a group which may comprise moieties having any one of said topologies or unsaturations, as above explained.
A particular embodiment of the invention's process is shown in Scheme 1:
Figure imgf000004_0001
(I) (π-a) (ii-b)
According to a further embodiment of the invention, the substrate is an ester, or lactone, that will provide an alcohol, or a diol, that is useful in the pharmaceutical, agrochemical or perfumery industry as final product or as an intermediate. Particularly preferred substrate is an ester, or lactone, that will provide an alcohol, or diol, which is useful in the perfumery industry as final product or as an intermediate.
According to another embodiment of the invention, the substrate is a C5-C30 compound of formula (I), and in particular one may cite those wherein Ra and Rb represent simultaneously or independently a linear, branched or cyclic C1-C3O aromatic or alkyl group optionally substituted, or a cyclic C5-C30 alkenyl group optionally substituted; or Ra and Rb are bonded together and form a C4-C2O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
According to a further embodiment of the invention the substrate is a Cs-C2O compound of formula (I), wherein Ra and Rb represent simultaneously or independently a linear, branched or cyclic Cs-C18 aromatic or alkyl group, optionally substituted, or a cyclic C5-C1S alkenyl group, optionally substituted; or Ra and Rb are bonded together and form a C4-C2O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
Furthermore, according to a yet further embodiment, when Ra and/or Rb represent an alkenyl group then the carbon-carbon double bond is not terminal and is not conjugated.
Possible substituents of Ra and Rb are one, two or three halogen, ORC, NRC 2 or Rc groups, in which Rc is a hydrogen atom, a halogenated C1-C2 group or a C1 to C1O cyclic, linear or branched alkyl, or alkenyl group, preferably a C1 to C4 linear or branched alkyl or alkenyl group. As other possible substituents one may also cite a group COORC, which can also be reduced to the corresponding alcohol during the invention's process, according to the molar amount of H2 used, as well known by a person skilled in the art.
Non-limiting examples of substrates are alkyl cinnamates, sorbates or salycilates, alkyl esters of natural (fatty or not) acids, Sclareolide, spirolactones, allylic ester, di alkyl diesters, (un) substituted benzoic esters, and β-γ unsaturated esters. In particular, the substrate can be selected from the group consisting of sclareolide, Cg-C15 spirolactones and C1-C4 alkyl esters of 4-methyl-6-(2,6,6-trimethyl-l-cyclohexen-l-yl)-3-hexenoic acid. One can also cite the di alkyl esters of 1 ,4-dicarboxylate-cyclohexane, the di C1-S alkyl esters of the C2-1O alkanediyl-dicarboxylates, C1-S alkyl cyclopropanecarboxylates, mono-, di- or tri-methoxybenzoic esters.
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 ruthenium complex as described above. The complex can be in the form of an ionic or neutral species.
According to an embodiment of the invention, the ruthenium complex can be of the general formula
[Ru(L4)Y2] [Ru(L4)(X)n(Y)2_n](Z)n
(1) (2)
wherein L4 represents a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group; and each Y represents, simultaneously or independently, CO, a hydrogen or halogen atom, a hydroxyl group, or a C1-C6 alkoxy or carboxylic radical, or also a BH4 or AlH4 group; X represents a C3-C30 mono-phosphine or a solvent; Z represents a non-coordinated anion; and n is 0, 1 or 2.
In particular L4 is a tetradentate ligand, such as a Cg-C45 compound, wherein the coordinating groups consist of two amino or imino group and two phosphino group, and in particular said amino groups are a primary (i.e. NH2) or a secondary (i.e. NH) amino groups.
In a particular embodiment of the invention, in formula (1) or (2), each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a hydroxy radical, a C1 to C6 alkoxy radical, such as a methoxy, ethoxy or isopropoxy radical, or a C1 to Ce acyloxy radical such as a CH3COO or CH3CH2COO radical. More preferably, each Y represents, simultaneously or independently, a hydrogen or chlorine atom, a methoxy, ethoxy or isopropoxy radical, or a CH3COO or CH3CH2COO radical.
In a particular embodiment of the invention, in formula (2), X represents a mono- phosphine of formula PRd 3, wherein Rd is a C1-C12 group, such as linear, branched or cyclic alkyl, alkoxy or aryloxy group optionally substituted, substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. More particularly Rd may represent a substituted or unsubstituted phenyl, diphenyl or naphthyl or di-naphthyl group. Possible substituents are those cited below for L4. X may also be a solvent, the term "solvent" has to be understood according to the usual meaning in the art and includes compounds used as diluent in the preparation of the complex or during the invention's process, non limiting examples are dimethylsulfoxide, acetonitrile, dimethylformamide, an alcohol (e.g. an C1-C4 alcohol), or also THF, acetone, pyridine or a C3-Cg ester or the substrate of the invention's process. In a particular embodiment of the invention, in formula (2), Z represents a halogen atom, a hydroxyl group, or a C1-C6 alkoxy, phenoxy or carboxylic radical.
The complex of formula (1) represents, in general for practical reasons, a preferred embodiment of the invention.
According to a particular embodiment of the invention, L4 can be a compound of formula
Figure imgf000007_0001
wherein the dotted lines indicate a single or double bond, z is 1 if the nitrogen atom belongs to an amino group (the dotted lines are single bonds) or is 0 if the nitrogen atom belongs to an imino group (one dotted line is a double bond);
R2 and R3, when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C1 to C8 alkyl or alkenyl group optionally substituted, a C6 to C1O aromatic group optionally substituted, or an OR2 or NR2 R3 group, R2 and R3 being a C1 to C8 alkyl or alkenyl group; or said groups R2 and R3 bonded to the same P atom, when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R2 and R3 groups are bonded ; A represents a -(CR9 2)t- group or a diphenyl, dinaphthyl, C5-C12 metallocediyl, phenylene (-COH4-) or naphthylene (-C1OH6-) group optionally substituted; B represents a diphenyl, dinaphthyl, C5-C12 metallocediyl, phenylene or naphthylene group optionally substituted or a group of formula
Figure imgf000007_0002
R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C1O linear, branched or cyclic alkyl or alkenyl group optionally substituted or a
Ce to C1O aromatic group optionally substituted; two adjacent or geminal R9, taken together, may form a Cs-1O ring including the carbon atom to which said R9 groups are bonded; a R10 group and a R9 group, in α-position to the same N atom, can be bonded together to form a C4-C6 saturated or unsaturated ring; two adjacent R11 groups can be bonded together to form a C5 to C1O aromatic ring optionally substituted or a C5-C12 metallocenediyl group optionally substituted and including the carbon atom to which said
R11 or R9 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
It is understood that, in any of the present embodiments, said metallocenediyl, such as for example a ferrocenediyl, can be in the form of a metallocene-l,l'-diyl or of a metallocene- 1 ,2-diyl.
Similarly when A and/or B are diphenyl or dinaphthyl groups they are preferably in their 1,1' form, and when said A and/or B are phenylene or naphthylene group they are in a ortho or meta form or for the naphthylene also as naphthalene- 1,8-diyl derivarive.
According to a particular embodiment of the invention, L4 can be a compound of formula (4- A) or (4-B):
Figure imgf000008_0001
(4-A) (4-B)
wherein the dotted lines indicate a single or double bond;
R2 and R3, when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C1 to C8 alkyl or alkenyl group optionally substituted, a C6 to C10 aromatic group optionally substituted, or an OR2 or NR2 R3 group, R2 and R3 being a C1 to C8 alkyl or alkenyl group; or said groups R2 and R3, when taken together, form a saturated or unsaturated ring optionally substituted, having 4 or 5 to 10 atoms and including the phosphorus atom to which said R2 and R3 groups are bonded ; R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C8 linear, branched or cyclic alkyl or alkenyl group optionally substituted or a Ce to C1O aromatic group optionally substituted; two adjacent or geminal R9, taken together, may form a, preferably C5 to C8, ring including the carbon atom to which said R9 groups are bonded; a R10 group and a R9 group, in α-position to the same N atom, can be bonded together to form a C4-C6 ring; two adjacent R11 groups can be bonded together to form a C6 to C1O aromatic ring optionally substituted or a C5-C12 metallocenediyl group optionally substituted and including the carbon atom to which said R11 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
According to an embodiment of the invention, R2 and R3 may represent, simultaneously or independently, a linear, branched or cyclic C1 to C6 alkyl group optionally substituted, a phenyl group optionally substituted; said groups R2 and R3, taken together, may form a saturated or unsaturated ring optionally substituted, having 4, 5, 6 or 7 atoms and including the phosphorus atom to which said R2 and R3 groups are bonded . Alternatively, R2 and R3 may represents a linear, branched or cyclic C1 to C6 alkyl group optionally substituted or an phenyl group optionally substituted.
Preferably, ligand L4 is a compound of formula
Figure imgf000009_0001
(4-C)
wherein the dotted lines indicate a single or double bond;
R2 and R3, taken separately, represent simultaneously or independently a linear, branched or cyclic alkyl group containing 1 to 6 carbon atoms or a phenyl group optionally substituted; or the two R2 and R3 bonded to the same P atom, taken together, form a ring having 5 to 7 atoms and including the phosphorus atom to which they are bonded;
R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C4 linear or branched alkyl group optionally substituted or a phenyl group optionally substituted; the two R9, taken together, may form a C4-C8, or preferably a
C5-C7, ring including the carbon atom to which said R9 groups are bonded; two adjacent R11, taken together, may form a phenyl group optionally substituted and including the carbon atom to which said R11 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
Possible substituents of the various groups A, B, R2, R3, R9, R10 and R11 are one or two halogen, C1 to C1O alkoxy, polyalkyleneglycols, halo- or perhalo-hydrocarbon, COOR, NR2, quaternary amine or R groups, wherein R is a C1 to Ce alkyl, or a C5 to C12 cycloalkyl, aralkyl (such as benzyl, phenethyl etc..) or aromatic group, the latter being also optionally substituted by one, two or three halogen, sulfonates groups or C1-C8 alkyl, alkoxy, amino, nitro, sulfonates, halo- or perhalo-hydrocarbon or ester groups. By "halo- or perhalo-hydrocarbon" it is meant groups such as CF3 or CClH2 for instance.
Alternatively said substituents can be, and in particular when said groups are or contain phenyl groups or moieties, one or two halogen, C1 to C5 alkoxy or polyalkyleneglycols groups, COOR, NR2 or R groups wherein R is a C1 to C4 alkyl, or a C5-6 cycloalkyl, aralkyl or aromatic group, the latter being also optionally substituted as above defined.
Alternatively, possible substituents of R9, R10 and R11 are one or two halogen atoms or R8, OR8 or NR8 2, R8 being a C1 to Ce alkyl groups or a C1 to C4 alkyl groups.
According to a specific embodiment of the invention the complexes of the formula (1) or (2) wherein Y is defined as above, and in particular represents H or Cl, and L4 represent a ligand of the formulae (4-D), (4-E), (4-F) or (4-G) :
Figure imgf000010_0001
(4-F) (4-G) wherein the dotted lines represent a single or double bond and Ph is a phenyl radical, R, taken separately, is C1-Cs alkyl or, taken together, are a C3-C6 group, and k is 1 or 0. The ligands of one of the formulae
Figure imgf000011_0001
wherein A, B, R2, R3, R9, R10, R11 and k have the same meaning as above, as well as those of formula (4-F) or (4-G) are new, with the exception of N,N'-l,2-ethanediylidenebis[2- (diphenylphosphino-)benzenemethanamine and of N,N'-2,3-butanediylidenebis[2- (diphenylphosphino-)benzenemethanamine, and are therefore also an object of the present invention.
Similarly the invention complexes where the tetradentate ligand is a compound of formula (2'), (4-B'), (4-C), (4-F) or (4-G) are also new, with the exception of dichloro[N,N'-l,2-ethanediylidenebis[2-(diphenylphosphino-κP)benzenemethanamine- KN]] -Ruthenium, and are also an object of the present invention.
The ligands described above can be obtained by applying standard methods which are well known in the state of the art and by the person skilled in the art. Therefore, their preparation does not require a specific description. For example one may revert to WO 02/40155.
In general, the complexes of formula (1) can be prepared and isolated prior to their use in the process according to the general methods described in the literature. A method is described in the Example.
Moreover, the complexes can be prepared in situ, by several methods, in the hydrogenation medium, without isolation or purification, just before their use.
One of the possible procedures to advantageously prepare in situ a complex of formula (1) consists in reacting an appropriate Ru complex of formula [Ru("diene")("allyl")2], wherein "diene" represents a cyclic or linear hydrocarbon containing two carbon-carbon double bonds, conjugated or not, such as for example 1,5-cyclooctadiene (COD) or norbornadiene, and "allyl" represents a linear or branched C3 to C8 hydrocarbon radical containing one carbon-carbon double bond such as methylallyl or allyl, with a non coordinating acid such as HBF4Et2O, and then treating the resulting solution with the required amount of a ligands L4, such as defined previously, to give a solution of a catalyst according to formula (1). Furthermore, the mixture thus obtained can also be treated with a base in the presence of a primary or secondary alcohol. Furthermore, the complexes of formula (I) can be prepared by reacting an appropriate Ru complex such as, [RuCl2(PPh3)3], [RuCl2 (cod)] or [RuCl2(arene)]2 with the required amount of a ligands L4, such as defined previously (cod representing a cyclooctadiene and arene being e.g. a benzene or naphthalene).
It is also understood that the complex of formula (I) can also be obtained in situ from complexes which have a similar formula and which in presence of, for example an alcohol and a base, are converted into a compound of formula (I). For example, from a complex wherein X, Y, and Z have other meaning.
To carry out the processes of the invention it is required also to use a base. Said base can be the substrate itself, if the latter is basic, a corresponding alcoholate or any base having preferentially a pKa above 11. According to a particular embodiment of the invention said base may have a pKa above 14. It is also understood that preferably said base does not reduce itself a substrate of formula (I). As non-limiting examples one may cite the following type of base: alcoholate, hydroxides, alkaline or alkaline-earth carbonates, phosphazenes, amides, basic alox, siliconates (i.e. silicium derivatives having SiO" or SiRO" groups), hydrides such as NaBH4, NaH or KH.
One can cite, as non-limiting examples, alkaline or alkaline-earth metal carbonates, such as cesium carbonate, an alkaline or alkaline-earth metal hydroxides, C1- io amidures, Cio-26 phosphazene or an alcoholate of formula (R13O)2M or R13OM', wherein M is an alkaline-earth metal, M' is an alkaline metal or an ammonium NR1V", R13 stands for hydrogen or a C1 to Ce linear or branched alkyl radical and R14 stands for a C1 to C1O linear or branched alkyl radical, such as sodium or potassium alcoholates. Of course, other suitable bases can be used.
According to an embodiment of the invention, said base is an alkaline alcoholate of formula R13OM'. As previously mentioned the processes of the invention consist in the hydrogenation of a substrate using a ruthenium complex and a base. A typical process implies the mixture of the substrate with the ruthenium complex, a base 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 50 ppm to 50000 ppm, relative to the amount of substrate. Preferably, the complex concentration will be comprised between 100 and 20000 ppm. 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 and on the pressure of H2 used during the process, as well as the desired time of reaction.
Useful quantities of base, added to the reaction mixture, may be comprised in a relatively large range. One can cite, as non-limiting examples, ranges between 5 to 50000 molar equivalents, relative to the complex (e.g. base/com = 5 to 50000), preferably 20 to 2000, and even more preferably between 50 and 1000 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 aromatic solvents such as toluene or xylene, hydrocarbon solvents such as hexane or cyclohexane, ethers such as tetrahydrofuran or MTBE, polar solvents such as primary or secondary alcohols such as isopropanol or ethanol, or mixtures thereof. The choice of the solvent is 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 105 Pa and 8OxIO5 Pa (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 5OxIO5 Pa (1 to 50 bar). The temperature at which the hydrogenation can be carried out is comprised between O0C and 12O0C, more preferably in the range of between 5O0C and 1000C. 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.
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, and 31P at 161.9 MHz) spectrometer and normally measured at 300 K, in CDCl3 unless indicated otherwise. Chemical shifts are listed in ppm.
Exemple 1
Preparation of N,N'-bis{ r2-(diphenylphosphino)phenyllmethylene]-2,2-dimethyl-l,3- propanediamine (L-5)
Under argon, a solution of 2-(diphenylphosphino)benzaldehyde (522.7 mg, 1.8 mmol) and 2,2-dimethyl-l,3-propanediamine (93.3 mg, 0.9 mmol) in toluene (15 mL) was stirred at room temperature for 15h. Then the reaction mixture was heated at 8O0C (oil bath) for 2h 30 min. Next, the solvent was removed in vacuo, and an orange solid was recovered (476.8 mg, 0.74 mmol, 82%).
1H NMR (CD2Cl2, 400 MHz): δ 8.78 (d, / = 4.6 Hz, 2H), 7.96 (dd, / = 7.7, 4.1 Hz, 2H),
7.3-7.2 (m, 24H), 6.87 (dd, / = 7.7, 4.1Hz, 2H), 3.19 (s, 4H), 0.69 (s, 6H). 13C NMR (CD2CL2, 100 MHz): δ 160 (d, / = 20.2 Hz, CH=N), 140.3 (d, / = 17.8 Hz,
Carom), 137.7 (d, / = 20.2 Hz, Carom), 137.4 (d, / = 10.5 Hz, Carom), 134.4 (d, / = 20.2 Hz, CHarom), 134.1 (d, / = 20.2 Hz, CHarom), 133.7 (CHarom), 130.2
(CHarom), 129.1 (CHarom), 128.9 (d, / = 7.3 Hz, CHarom), 128.4 (d, / = 4.8
Hz, CHarom), 70.7 (CH2), 36.9 (C), 24.4 (CH3). 31Pj 1H) NMR (CD2CL2, 100 MHz): δ -12.8. This ligand is a novel one, as well as the ruthenium complex comprising it.
Example 2
Catalytic Hydrogenation of various esters using complexes of formula (1) a) using pre-formed complex
A typical catalytic hydrogenation using preformed RuCl2(L-I) as pre-catalyst is described below with methyl benzoate as substrate: Under argon, a solution of methyl benzoate (2.721 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2 x 1 mL), to a Keim autoclave equipped with a glass liner containing RuCl2(L-I) (7.9 mg, 0.01 mmol, 0.05 mol%), solid NaOMe (107.9 mg, 2.0 mmol, 10 mol%) and THF (10 mL). The autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 1000C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. Then, the reaction mixture was diluted with aq. IN HCl (50 mL) and extracted with MTBE (100 mL). Gas chromatography after silylation of an aliquot showed the following products: methyl benzoate (1.7%), benzyl alcohol (94.6%), benzoic acid (3.7%). Then, the organic phase was washed successively with aq. IN KOH (50 mL) and aq. sat. NaCl (3 x 50 mL), and dried over MgSO4 anh. Filtration and removal of the solvent in vacuo gave a yellow liquid (2.085 g). Purification by flash chromatography on silica gel with pentane/Et2O (2/1) as elution mixture gave pure benzyl alcohol (1.742 g, 16.1 mmol, 80%) as a colourless liquid. 1H NMR (CDCl3, 400 MHz): δ 7.38-7.25 (m, 5H), 4.65 (s, 2H), 2.02 (s, IH). 13C NMR (CDCL3, 100 MHz): δ 140.9 (s), 128.6 (d), 127.6 (d), 126.9 (d), 62.3 (t).
b) using in- situ formed complex
A typical catalytic hydrogenation using in-situ formed RuCl2(L-4) as pre-catalyst is described below with methyl benzoate as substrate: Under argon, a solution of methyl benzoate (2.723 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2 x 1 mL), to a Keim autoclave equipped with a glass liner containing [RuCl2 (pαra-cymene)]2 (6.5 mg, 0.01 mmol, 0.05 mol%), ligand L-4 (12.2 mg, 0.02 mmol, 0.1 mol%), solid NaOMe (108.1 mg, 2.0 mmol, 10 mol%) and THF (10 mL). Then a solution of tridecane (368.8 mg, 0.02 mmol), as internal Standard, is added in THF (2 mL), followed by more THF (2 x 1 mL). The autoclave was then pressurised with hydrogen gas at 50 bars and placed in a thermostatted oil bath set at 1000C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. Then, the reaction mixture was diluted with MTBE (100 mL) and washed successively with aq. IN HCl (50 mL) and aq. sat. NaCl (3 x 50 mL). Gas chromatography after silylation of an aliquot showed the following products: benzyl alcohol (97.4%), benzoic acid (2.6%). GC yield based on the internal standard gave a yield of 90% of benzyl alcohol.
Using methyl benzoate as a test substrate several complexes (Table 1), bases and solvent, as reported in Table 2, were tested under these conditions.
Table 1: Structure of ligands
Figure imgf000016_0001
Ligands L-I to L-4 were prepared according to Rautenstrauch, V. et al in WO 02/40155. Ligand L-6 was prepared according to DuBois, T. D. Inorganic Chem. 1972, 11(4), 718-
722.
Table 2: Hydrogenation of methyl benzoate using complexes of formula (1)
Figure imgf000017_0001
Reaction conditions: Substrate (20 mmol), H2 gas (50 bars), THF (14 mL) at 1000C during 2h 30min.
1} Com/Base: complex/base molar ratio in ppm relative to the substrate. 2) Based on internal standard (analysed by GC) otherwise indicated. In brackets isolated yield after chromatography on silica gel.
3) Conversion (in %, analysed by GC) of methyl benzoate into benzyl alcohol after 1 hour.
4) Reaction run at 6O0C during 6h. 5) Reaction run with H2 gas (10 bars) during 6h.
6) Complex generated in-situ with L-4 and [RuCl2 (pαra-cymene)]2
7) Complex generated in-situ with L-5 and [RuCl2 (pαra-cymene)]2
8) Complex generated in-situ with L-6 and [RuCl2(pαra-cymene)]2 and reaction run during 1 hour. Several other esters, whose structure and names are described in Table 3, were hydro genated under the conditions described above using preformed RuCl2(L-I). Isolated yield are given in Table 4.
Table 3: Structure and names of substrates used
Figure imgf000018_0001
Table 4: Hydrogenation of esters using RuCl2(L-I)
Figure imgf000018_0002
Figure imgf000019_0001
Sub.: Substrate as described in Table 3.
Conv.: Conversion (in %, analysed by GC after silylation) of ester to alcohol after 2h
30min.
Reaction conditions: Substrate (20 mmol), H2 gas (50 bars), RuCl2(L-I) 0.05 mol%,
NaOMe 10 mol%, THF (14 mL) at 1000C during 2h 30min.
Exemple 3
Chemo selective Hydrogenation of Esters using with complexes of formula (1)
Hydrogenation of methyl 3-cyclohexene-l-carboxylate was taken as model substrate using complexes RuCl2(L-I) and RuCl2(L-2). Structures of ligands are described in Table 1 and the results are summarised in Table 5. Typical reaction condition is described bellow for RuCl2(L-I): Under argon, a solution of methyl 3-cyclohexene-l-carboxylate (2.810 g, 20 mmol) in THF (2 mL) was added with a syringe, followed by more THF (2 x 1 mL), to a Keim autoclave equipped with a glass liner containing RuCl2(L-I) (8.4 mg, 0.01 mmol, 0.05 mol%), solid NaOMe (109.7 mg, 2.0 mmol, 10 mol%), and THF (10 mL). Then, the autoclave was pressurised with hydrogen gas at 50 bars and placed in a thermosttated oil bath set at 1000C. After 2 h 30 min, the autoclave was removed from the oil bath, and cooled in a cold-water bath. The glass liner was removed from the autoclave, and the reaction mixture was diluted with citric acid 10% w/w (25 mL) and extracted with MTBE (100 mL). Gas chromatography after silylation showed the following products: methyl 3-cyclohexene-l-carboxylate (2%), cyclohexanemethanol (2%), 3-cyclohexene-l- methanol (91%), 3-cyclohexen-l-carboxylic acid (2%), 3-cyclohexene-l -methyl 3-cyclohexene-l-carboxylate (3%). Purification by flash chromatography on silica gel with pentane/Et2O (10/1 — > 1/1) as elution mixture gave the desired 3-cyclohexene-l- methanol (1.768 g, 15.4 mmol, 77%) as a colorless liquid. 1H NMR (CDCl3, 400 MHz): δ 5.68 (s, AB syst, 2H), 3.57-3.49 (m, AB syst, 2H), 2.2-2
(m, 3H), 1.9-1.7 (m, 4H), 1.35-1.2 (m, IH). 13C NMR (CDCL3, 100 MHz): δ 127.1 (CH), 125.9 (CH), 67.8 (CH2), 36.32 (CH), 28.1
(CH2), 25.2 (CH2), 24.6 (CH2).
Table 5: Chemo selectivity observed with complexes of formula (1)
Figure imgf000020_0001
Conv.: Conversion (in %, analysed by GC after silylation) of ester to alcohol after 2h
30min.
Reaction conditions: Substrate (20 mmol), H2 gas (50 bars), RuCl2(L-n) 0.05 mol%,
NaOMe 10 mol%, THF (14 mL) at 1000C during 2h 30min.
1} Reaction run at 8O0C during 5h.

Claims

Claims
1. A process for the reduction by hydrogenation, using molecular H2, of a C3-C7O substrate containing one or two esters, or lactones, functional groups into the corresponding alcohol, or diol, characterized in that said process is carried out in the presence of a base and at least one catalyst or pre-catalyst in the form of a ruthenium complexes of a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group.
2. A process according to claim 1, characterized in that the catalyst or pre-catalyst is in the form of a ruthenium complexes of a tetradentate ligand wherein the coordinating groups consist of two amino or imino group and two phosphino group, and said amino groups are a primary (i.e. NH2) or a secondary (i.e. NH) amino groups.
3. A process according to claim 1 or 2, characterized in that the ruthenium complex is of formula
[Ru(L4)Y2] [Ru(L4)(X)n(Y)2_n](Z)n
(1) (2)
wherein L4 represents a tetradentate ligand wherein the coordinating groups consist of at least one amino or imino group and at least one phosphino group; and each Y represents, simultaneously or independently, CO, a hydrogen or halogen atom, a hydroxyl group, or a C1-C6 alkoxy or carboxylic radical, or a BH4 or ALH4 group; X represents a C3-C3O mono-phosphine or a solvent; Z represents a non-coordinated anion; and n is 0, 1 or 2.
4. A process according to claim 3, characterised in that the ruthenium complex is of formula
[Ru(L4)Y2] (1) wherein L4 and Y have the meaning indicated in claim 3.
5. A process according to claim 3 or 4, characterised in that L4 is a ligand of formula
Figure imgf000022_0001
wherein the dotted lines indicate a single or double bond, z is 1 if the nitrogen atom belong to an amino group (the dotted lines are single bonds) or is 0 if the nitrogen atom belong to an imino group (one dotted lines is a doble bond);
R2 and R3, when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C1 to C8 alkyl or alkenyl group optionally substituted, a C6 to C1O aromatic group optionally substituted, or an OR2 or NR2 R3 group, R2 and R3 being a C1 to C8 alkyl or alkenyl group; or said groups R2 and R3 bonded to the same P atom, when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R2 and R3 groups are bonded ; A represents a -(CR9 2)k- group or a diphenyl, dinaphthyl, C5-C12 metallocediyl, phenylene (-COH4-) or naphthylene (-C1OH6-) group optionally substituted;
B represents a diphenyl, dinaphthyl, C5-C12 metallocediyl, phenylene or naphthylene group optionally substituted or a group of formula
R11
R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C1O linear, branched or cyclic alkyl or alkenyl group optionally substituted or a Ce to C1O aromatic group optionally substituted; two adjacent or geminal R9, taken together, may form a C5_lo ring including the carbon atom to which said R9 groups are bonded; a R10 group and a R9 group, in α-position to the same N atom, can be bonded together to form a C4-C6 saturated or unsaturated ring; two adjacent R11 groups can be bonded together to form a C5 to C1O aromatic ring optionally substituted or a C5-C12 metallocenediyl group optionally substituted and including the carbon atom to which said
R11 or R9 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1; and wherein the substituents of A, B, R2, R3, R9, R10 and R11 are one or two halogen, C1 to C1O alkoxy, poly alky leneglycols, halo- or perhalo-hydrocarbon, COOR, NR2, quaternary amine or R groups, wherein R is a C1 to Ce alkyl, or a C5 to C12 cycloalkyl, aralkyl or aromatic group, the latter being also optionally substituted by one, two or three halogen, sulfonates groups or C1-Cg alkyl, alkoxy, amino, nitro, sulfonates, halo- or perhalo-hydrocarbon or ester groups.
6. A process according to claim 5, characterised in that L4 is a ligand of formula (4- A) or (4-B)
Figure imgf000023_0001
(4-A) (4-B)
wherein the dotted lines indicate a single or double bond;
R2 and R3, when taken separately, represent, simultaneously or independently, a linear, branched or cyclic C1 to C8 alkyl or alkenyl group optionally substituted, a Ce to C1O aromatic group optionally substituted, or an OR2 or NR2 R3 group, R2 and R3 being a C1 to C8 alkyl or alkenyl group; or said groups R2 and R3, when taken together, form a saturated or unsaturated ring optionally substituted, having 4 to 10 atoms and including the phosphorus atom to which said R2 and R3 groups are bonded ;
R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C8 linear, branched or cyclic alkyl or alkenyl group optionally substituted or a Ce to C1O aromatic group optionally substituted; two adjacent or geminal R9, taken together, may form a, preferably C5 to Cg, ring including the carbon atom to which said R9 groups are bonded; a R10 group and a R9 group, in α-position to the same N atom, can be bonded together to form a C4-C6 ring; two adjacent R11 groups can be bonded together to form a C6 to C1O aromatic ring optionally substituted or a C5-C12 metallocediyl group optionally substituted and including the carbon atom to which said R11 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
7. A process according to claim 5, characterised in that L4 is a ligand of formula
Figure imgf000024_0001
(4-C)
wherein the dotted lines indicate a single or double bond; R2 and R3, taken separately, represent simultaneously or independently a linear, branched or cyclic alkyl group containing 1 to 6 carbon atoms or a phenyl group optionally substituted; or the two R2 and R3 bonded to the same P atom, taken together, form a ring having 5 to 7 atoms and including the phosphorus atom to which they are bonded; R9, R10 and R11, taken separately, represent, simultaneously or independently, a hydrogen atom, a C1-C4 linear or branched alkyl group optionally substituted or a phenyl group optionally substituted; the two R9, taken together, may form a C4-Cg ring including the carbon atom to which said R9 groups are bonded; two adjacent R11, taken together, may form a phenyl group optionally substituted and including the carbon atom to which said R11 groups are bonded; and k are, simultaneously or independently, equal to 0 or 1.
8. A process according to claim 5, characterised in that L4 is a ligand of formula of the formulae (4-D), (4-E), (4-F) or (4-G)
Figure imgf000025_0001
Figure imgf000025_0002
(4-F) (4-G)
wherein the dotted lines represent a single or double bond and Ph is phenyl radical, R, taken separately, is C1-C5 alkyl or, taken together, are a C3-C6 group, and k is 1 or 0.
9. A process according to any one of claims 1 to 8, characterised in that the base has a pKa above 14.
10. A process according to claim 9, characterised in that the base is an alkaline or alkaline-earth metal carbonates, an alkaline or alkaline-earth metal hydroxides, C1^o amidures, Qo-26 phosphazene or an alcoholate of formula (R13O)2M or R13OM', wherein M is an alkaline-earth metal, M' is an alkaline metal or an ammonium NR1V", R13 stands for hydrogen or a C1 to C6 linear or branched alkyl radical and R14 stands for a C1 to C10 linear or branched alkyl radical.
11. A process according to anyone of claims 1 to 10, characterised in that the substrate is a compound of formula (I) O i— —^~- — r\" -"R (I)
wherein Ra and Rb represent, simultaneously or independently, a linear, branched or cyclic C1-C3O aromatic, alkyl or alkenyl group optionally substituted; or Ra and Rb are bonded together and form a C4-C2O saturated or unsaturated group, optionally substituted; and wherein the substituents of Ra and Rb are a COORC, group, one, two or three halogen, ORC, NRC 2 or Rc groups, in which Rc is a hydrogen atom, a halogenated C1-C2 group or a C1 to C1O cyclic, linear or branched alkyl, or alkenyl group.
12. A process according to claim 11, characterised in that the substrate is a Cs-C3O compound of formula (I) wherein Ra and Rb represent simultaneously or independently a linear, branched or cyclic C1-C3O aromatic or alkyl group optionally substituted, or a cyclic C5-C30 alkenyl group, optionally substituted; or Ra and Rb are bonded together and form a C4-C2O saturated or unsaturated linear, branched, mono-, di- or tri-cyclic group, optionally substituted.
13. A ligand of formula (2'), (4-B') or (4-C)
Figure imgf000026_0001
(T) (4-B1) (4-C1)
wherein A, B, R2, R3, R9, R10, R11 and k have the same meaning as in anyone of claim 5 to 7, or of formula (4-F) or (4-G) as defined in claim 8, provided that N,N'-1,2- ethanediylidenebis[2-(diphenylphosphino-)benzenemethanamine and N,N'-2,3- butanediylidenebis[2-(diphenylphosphino-)benzenemethanamine are excluded.
14. A complex of formula (1) or (2), as defined in claim 3, characterized in that L4 is a ligand of formula (2'), (4-B') or (4-C'),as defined in claim 13, or (4-F) or (4-G) as defined in claim 8, provided that dichloro[N,N'-l,2-ethanediylidenebis[2- (diphenylphosphino-κP)benzenemethanamine-κN]]-Ruthenium is excluded.
15. As a ligand of formula (3), N,N'-bis{ [2-(diphenylphosphino)phenyl]methylene}- 2,2-dimethyl-l,3-propanediamine.
16. A complex of formula (1) or (2), as defined in claim 3, characterized in that L4 is as defined in claim 15.
PCT/IB2006/051028 2005-04-05 2006-04-04 Hydrogenation of esters with ru/tetradentate ligands complexes WO2006106484A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
MX2007012298A MX2007012298A (en) 2005-04-05 2006-04-04 Hydrogenation of esters with ru/tetradentate ligands complexes.
BRPI0608686A BRPI0608686A2 (en) 2005-04-05 2006-04-04 process for reduction by hydrogenation, ligand, and complex
JP2008504897A JP5388570B2 (en) 2005-04-05 2006-04-04 Hydrogenation of esters using Ru / tetradentate ligand complexes
ES06727827T ES2432561T3 (en) 2005-04-05 2006-04-04 Hydrogenation of esters with Ru / tetradentate ligand complexes
EP06727827.5A EP1868965B1 (en) 2005-04-05 2006-04-04 Hydrogenation of esters with ru/tetradentate ligands complexes
CN2006800086311A CN101142155B (en) 2005-04-05 2006-04-04 Hydrogenation of esters with ru/tetradentate ligands complexes
US11/854,906 US7989665B2 (en) 2005-04-05 2007-09-13 Hydrogenation of esters with Ru/tetradentate ligands complexes
IL186319A IL186319A (en) 2005-04-05 2007-09-25 Hydrogenation of esters with ru/tetradentate ligand complexes
US12/694,688 US8124816B2 (en) 2005-04-05 2010-01-27 Hydrogenation of esters with Ru/tetradentate ligands complexes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IB2005000938 2005-04-05
IBPCT/IB2005/000938 2005-04-05

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/854,906 Continuation US7989665B2 (en) 2005-04-05 2007-09-13 Hydrogenation of esters with Ru/tetradentate ligands complexes

Publications (1)

Publication Number Publication Date
WO2006106484A1 true WO2006106484A1 (en) 2006-10-12

Family

ID=36694347

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2006/051028 WO2006106484A1 (en) 2005-04-05 2006-04-04 Hydrogenation of esters with ru/tetradentate ligands complexes

Country Status (10)

Country Link
US (1) US8692022B2 (en)
EP (1) EP1868965B1 (en)
JP (1) JP5388570B2 (en)
CN (1) CN101142155B (en)
BR (1) BRPI0608686A2 (en)
ES (1) ES2432561T3 (en)
IL (1) IL186319A (en)
MX (1) MX2007012298A (en)
RU (2) RU2007140871A (en)
WO (1) WO2006106484A1 (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1970360A1 (en) 2007-03-16 2008-09-17 Takasago International Corporation Method for producing alcohols
WO2008120475A1 (en) 2007-04-03 2008-10-09 Kaneka Corporation Method for producing alcohol by hydrogenating lactone and carboxylic acid ester in liquid phase
JP2009001545A (en) * 2007-05-22 2009-01-08 Takasago Internatl Corp Method for producing alcohols
WO2009055912A1 (en) * 2007-10-30 2009-05-07 Kanata Chemical Technologies Inc. Cationic transition metal catalysts
EP2161251A1 (en) * 2008-09-09 2010-03-10 Takasago International Corporation Alcohol production method by reducing ester or lactone with hydrogen
JP2010511036A (en) * 2006-11-27 2010-04-08 フイルメニツヒ ソシエテ アノニム Hydrogenation of esters with RU / bidentate ligand complexes
WO2010061350A1 (en) 2008-11-28 2010-06-03 Firmenich Sa Hydrogenation of ester, ketone or aldehyde groups with ruthenium complexes having a di-amine and a phosphorous-nitrogen bidentate ligand
WO2012105431A1 (en) 2011-02-03 2012-08-09 セントラル硝子株式会社 METHOD FOR PRODUCING β-FLUOROALCOHOL
US8344187B2 (en) 2008-07-08 2013-01-01 Tokyo Institute Of Technology Practical method for reducing esters or lactones
WO2013171302A1 (en) * 2012-05-16 2013-11-21 Givaudan Sa Process for the chemoselective reduction of terminally saturated carboxylic esters
WO2014139030A1 (en) * 2013-03-15 2014-09-18 Goussev Dmitri Complex catalysts based on amino-phosphine ligands for hydrogenation and dehydrogenation processes
EP2415741A4 (en) * 2009-03-31 2015-03-18 Sumitomo Chemical Co Method for producing alcohol compound
WO2016113758A1 (en) 2015-01-15 2016-07-21 Council Of Scientific & Industrial Research Catalytic hydrogenation process for the synthesis of terminal diols from terminal dialkyl aliphatic esters
WO2016128997A1 (en) 2015-02-10 2016-08-18 Council Of Scientific And Industrial Research Phenanthroline based pincer complexes useful as catalysts for the preparation of methanol from carbondioxide
US9745332B2 (en) 2011-07-18 2017-08-29 The Governors Of The Univerity Of Alberta Catalysts and processes for the hydrogenation of amides
US10266467B2 (en) 2017-08-02 2019-04-23 Eastman Chemical Company Synthesis of glycols via transfer hydrogenation of alpha-functional esters with alcohols
US10266466B2 (en) 2017-08-02 2019-04-23 Eastman Chemical Company Iron-catalyzed transfer hydrogenation of esters to alcohols
WO2019138000A1 (en) 2018-01-10 2019-07-18 Basf Se Use of a ruthenium catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters and a ruthenium complex comprising said tetradentate ligand
WO2019138216A1 (en) 2018-01-08 2019-07-18 University Court Of The University Of St Andrews Manganese-catalysed hydrogenation of esters
WO2019175158A1 (en) 2018-03-16 2019-09-19 Firmenich Sa Hydrogenation of carbonyls with tetradentate pnnp ligand ruthenium complexes
US10435349B2 (en) 2017-08-02 2019-10-08 Eastman Chemical Company Iron-catalyzed cross-coupling of methanol with secondary or tertiary alcohols to produce formate esters
US10544077B2 (en) 2017-08-02 2020-01-28 Eastman Chemical Company Process for making formic acid utilizing higher-boiling formate esters
US10570081B2 (en) 2017-08-02 2020-02-25 Eastman Chemical Company Process for making formic acid utilizing lower-boiling formate esters

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5283931B2 (en) * 2007-03-16 2013-09-04 高砂香料工業株式会社 Method for producing alcohols
CA2845017C (en) 2011-08-18 2020-09-08 Dmitri GOUSSEV Hydrogenation and dehydrogenation catalyst, and methods of making and using the same
CN103772142B (en) * 2012-10-19 2018-04-27 中国科学院上海有机化学研究所 Ruthenium complex and the method for preparing methanol and glycol
US9840527B2 (en) 2013-06-20 2017-12-12 Kuraray Co., Ltd. Metal complex including tridentate aminodicarbene ligand and hydrogenation reduction method using same
MX2016006964A (en) * 2013-12-18 2016-09-27 Firmenich & Cie Hydrogenation of esters with fe/tridentate ligands complexes.
CN103709196B (en) * 2014-01-13 2016-08-17 武汉大学 Coordination compound and application thereof containing PA base tetradentate ligands
CN103980317B (en) * 2014-05-28 2017-01-25 南开大学 Dipyridyl tetradentate ligand ruthenium complex as well as preparation method and application thereof
CN109553509A (en) * 2018-12-17 2019-04-02 西安近代化学研究所 A kind of preparation method of five fluorine propyl alcohol of 2,2,3,3,3-
CN113797977B (en) * 2020-06-12 2022-11-29 沈阳中化农药化工研发有限公司 Ruthenium catalyst and application thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002040155A1 (en) * 2000-11-17 2002-05-23 Firmenich S.A. Process for hydrogenation of carbonyl and iminocarbonyl compounds using ruthenium catalysts comprising tetradentate diimino-diphosphine ligands

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1099070B (en) 1978-09-14 1985-09-18 Montedison Spa PROCESS FOR CATALYTIC HYDROGENATION OF OXALIC ESTERS
CN1049208C (en) * 1994-08-10 2000-02-09 中国石油化工总公司 Method for preparing 1,4-butanediol
CN1047597C (en) * 1997-06-02 1999-12-22 厦门大学 Chiral phosphine aminate-metal coordinate compound, the prepn. method thereof and the application in the asymmetrically catalytic hydrogenation
JP2001247499A (en) * 2000-03-09 2001-09-11 Sumitomo Chem Co Ltd Method for producing alcohol
CA2422029C (en) 2000-09-13 2008-11-18 Firmenich S.A. Catalytic hydrogenation processes
GB0210143D0 (en) 2002-05-02 2002-06-12 Davy Process Techn Ltd Process
JP2004300131A (en) 2003-03-20 2004-10-28 Mitsubishi Gas Chem Co Inc Method for producing alcohol by hydrogenation of ester

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002040155A1 (en) * 2000-11-17 2002-05-23 Firmenich S.A. Process for hydrogenation of carbonyl and iminocarbonyl compounds using ruthenium catalysts comprising tetradentate diimino-diphosphine ligands

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GAO J-X ET AL: "NEW CHIRAL CATALYSTS FOR REDUCTION OF KETONES", CHIRALITY, WILEY-LISS, NEW YORK, US, vol. 12, no. 5/6, 2000, pages 1383 - 1388, XP001038642, ISSN: 0899-0042 *
See also references of EP1868965A1 *

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010511036A (en) * 2006-11-27 2010-04-08 フイルメニツヒ ソシエテ アノニム Hydrogenation of esters with RU / bidentate ligand complexes
EP1970360A1 (en) 2007-03-16 2008-09-17 Takasago International Corporation Method for producing alcohols
US7569735B2 (en) 2007-03-16 2009-08-04 Takasago International Method for producing alcohols
WO2008120475A1 (en) 2007-04-03 2008-10-09 Kaneka Corporation Method for producing alcohol by hydrogenating lactone and carboxylic acid ester in liquid phase
JP2009001545A (en) * 2007-05-22 2009-01-08 Takasago Internatl Corp Method for producing alcohols
WO2009055912A1 (en) * 2007-10-30 2009-05-07 Kanata Chemical Technologies Inc. Cationic transition metal catalysts
US8344187B2 (en) 2008-07-08 2013-01-01 Tokyo Institute Of Technology Practical method for reducing esters or lactones
EP2161251A1 (en) * 2008-09-09 2010-03-10 Takasago International Corporation Alcohol production method by reducing ester or lactone with hydrogen
US8288575B2 (en) 2008-09-09 2012-10-16 Takasago International Corporation Alcohol production method by reducing ester of lactone with hydrogen
US8524953B2 (en) 2008-09-09 2013-09-03 Takasago International Corporation Alcohol production method by reducing ester or lactone with hydrogen
WO2010061350A1 (en) 2008-11-28 2010-06-03 Firmenich Sa Hydrogenation of ester, ketone or aldehyde groups with ruthenium complexes having a di-amine and a phosphorous-nitrogen bidentate ligand
EP2415741A4 (en) * 2009-03-31 2015-03-18 Sumitomo Chemical Co Method for producing alcohol compound
WO2012105431A1 (en) 2011-02-03 2012-08-09 セントラル硝子株式会社 METHOD FOR PRODUCING β-FLUOROALCOHOL
US8658840B2 (en) 2011-02-03 2014-02-25 Central Glass Company, Limited Method for producing β-fluoroalcohol
US9745332B2 (en) 2011-07-18 2017-08-29 The Governors Of The Univerity Of Alberta Catalysts and processes for the hydrogenation of amides
US9193651B2 (en) 2012-05-16 2015-11-24 Givaudan S.A. Process for the chemoselective reduction of terminally saturated carboxylic esters
WO2013171302A1 (en) * 2012-05-16 2013-11-21 Givaudan Sa Process for the chemoselective reduction of terminally saturated carboxylic esters
US10173209B2 (en) 2013-03-15 2019-01-08 Dmitri Goussev Complex catalysts based on amino-phosphine ligands for hydrogenation and dehydrogenation processes
WO2014139030A1 (en) * 2013-03-15 2014-09-18 Goussev Dmitri Complex catalysts based on amino-phosphine ligands for hydrogenation and dehydrogenation processes
WO2016113758A1 (en) 2015-01-15 2016-07-21 Council Of Scientific & Industrial Research Catalytic hydrogenation process for the synthesis of terminal diols from terminal dialkyl aliphatic esters
US9944579B2 (en) 2015-01-15 2018-04-17 Council Of Scientific & Industrial Research Catalytic hydrogenation process for the synthesis of terminal diols from terminal dialkyl aliphatic esters
US10449529B2 (en) 2015-02-10 2019-10-22 Council Of Scientific & Industrial Research Phenanthroline based pincer complexes useful as catalysts for the preparation of methanol from carbondioxide
US10758896B2 (en) 2015-02-10 2020-09-01 Council Of Scientific & Industrial Research Phenanthroline based pincer complexes useful as catalysts for the preparation of methanol from carbondioxide
WO2016128997A1 (en) 2015-02-10 2016-08-18 Council Of Scientific And Industrial Research Phenanthroline based pincer complexes useful as catalysts for the preparation of methanol from carbondioxide
US10544077B2 (en) 2017-08-02 2020-01-28 Eastman Chemical Company Process for making formic acid utilizing higher-boiling formate esters
US10266466B2 (en) 2017-08-02 2019-04-23 Eastman Chemical Company Iron-catalyzed transfer hydrogenation of esters to alcohols
US10266467B2 (en) 2017-08-02 2019-04-23 Eastman Chemical Company Synthesis of glycols via transfer hydrogenation of alpha-functional esters with alcohols
US10570081B2 (en) 2017-08-02 2020-02-25 Eastman Chemical Company Process for making formic acid utilizing lower-boiling formate esters
US10435349B2 (en) 2017-08-02 2019-10-08 Eastman Chemical Company Iron-catalyzed cross-coupling of methanol with secondary or tertiary alcohols to produce formate esters
WO2019138216A1 (en) 2018-01-08 2019-07-18 University Court Of The University Of St Andrews Manganese-catalysed hydrogenation of esters
WO2019138000A1 (en) 2018-01-10 2019-07-18 Basf Se Use of a ruthenium catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters and a ruthenium complex comprising said tetradentate ligand
US11413610B2 (en) 2018-01-10 2022-08-16 Basf Se Use of a transition metal catalyst comprising a tetradentate ligand for hydrogenation of esters and/or formation of esters, a process for hydrogenation of esters, a process for formation of esters and a transition metal complex comprising said tetradentate ligand
WO2019175158A1 (en) 2018-03-16 2019-09-19 Firmenich Sa Hydrogenation of carbonyls with tetradentate pnnp ligand ruthenium complexes
CN111417644A (en) * 2018-03-16 2020-07-14 弗门尼舍有限公司 Hydrogenation of carbonyl groups using tetradentate PNNP ligand ruthenium complexes
US11858948B2 (en) 2018-03-16 2024-01-02 Firmenich Sa Hydrogenation of carbonyls with tetradentate PNNP ligand ruthenium complexes

Also Published As

Publication number Publication date
MX2007012298A (en) 2007-10-16
CN101142155B (en) 2011-06-01
US20100280273A1 (en) 2010-11-04
RU2007140871A (en) 2009-05-20
BRPI0608686A2 (en) 2018-07-03
CN101142155A (en) 2008-03-12
IL186319A (en) 2011-11-30
EP1868965B1 (en) 2013-08-28
IL186319A0 (en) 2008-01-20
ES2432561T3 (en) 2013-12-04
EP1868965A1 (en) 2007-12-26
JP5388570B2 (en) 2014-01-15
JP2008537946A (en) 2008-10-02
RU2007140870A (en) 2009-05-20
US8692022B2 (en) 2014-04-08

Similar Documents

Publication Publication Date Title
EP1868965B1 (en) Hydrogenation of esters with ru/tetradentate ligands complexes
EP1868964B1 (en) Hydrogenation of esters with ru/bidentate ligands complexes
EP3083647B1 (en) Hydrogenation of esters with fe/tridentate ligands complexes
EP2089345B1 (en) Hydrogenation of esters with ru/bidentate ligands complexes
US8124816B2 (en) Hydrogenation of esters with Ru/tetradentate ligands complexes
IL154822A (en) Catalytic hydrogenation processes and catalysts used therein
IL274879A (en) Hydrogenation of carbonyls with tetradentate pnnp ligand ruthenium complexes
CN107750243B (en) Hydrogenation of aldehyde or ketone compounds using FE/tridentate ligand complexes
WO2010038209A1 (en) Hydrogenation of esters or carbonyl groups with phosphino-oxide based ruthenium complexes
EP2370207A1 (en) Hydrogenation of ester, ketone or aldehyde groups with ruthenium complexes having a di-amine and a phosphorous-nitrogen bidentate ligand

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2006727827

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 3360/KOLNP/2007

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 11854906

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 200680008631.1

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 186319

Country of ref document: IL

WWE Wipo information: entry into national phase

Ref document number: MX/a/2007/012298

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 2008504897

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

WWW Wipo information: withdrawn in national office

Ref document number: DE

WWE Wipo information: entry into national phase

Ref document number: 2007140870

Country of ref document: RU

WWP Wipo information: published in national office

Ref document number: 2006727827

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 11854906

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0608686

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20071001