WO2002094740A2 - Hydrogenation processes performed in ionic liquids - Google Patents

Hydrogenation processes performed in ionic liquids Download PDF

Info

Publication number
WO2002094740A2
WO2002094740A2 PCT/GB2002/002333 GB0202333W WO02094740A2 WO 2002094740 A2 WO2002094740 A2 WO 2002094740A2 GB 0202333 W GB0202333 W GB 0202333W WO 02094740 A2 WO02094740 A2 WO 02094740A2
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
process according
aryl
straight chain
independently selected
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/GB2002/002333
Other languages
French (fr)
Other versions
WO2002094740A8 (en
WO2002094740A3 (en
Inventor
Kris Anderson
Peter Goodrich
Christopher Hardacre
Sarah Elizabeth Jane Mcmath
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Queens University of Belfast
Original Assignee
Queens University of Belfast
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
Priority to DK02735575T priority Critical patent/DK1387819T3/en
Priority to EP02735575A priority patent/EP1387819B1/en
Priority to AU2002310587A priority patent/AU2002310587A1/en
Priority to DE60230259T priority patent/DE60230259D1/en
Priority to JP2002591415A priority patent/JP4558276B2/en
Priority to US10/478,039 priority patent/US7667058B2/en
Application filed by Queens University of Belfast filed Critical Queens University of Belfast
Priority to CA002446835A priority patent/CA2446835A1/en
Publication of WO2002094740A2 publication Critical patent/WO2002094740A2/en
Publication of WO2002094740A3 publication Critical patent/WO2002094740A3/en
Publication of WO2002094740A8 publication Critical patent/WO2002094740A8/en
Anticipated expiration legal-status Critical
Priority to US12/612,149 priority patent/US7803974B2/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
    • C07B35/02—Reduction
    • 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
    • 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
    • C07C29/14—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 a —CHO group
    • C07C29/141—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 a —CHO group with hydrogen or hydrogen-containing gases
    • 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
    • C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
    • 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
    • C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
    • C07C29/175—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds with simultaneous reduction of an oxo group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/62—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by hydrogenation of carbon-to-carbon double or triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C5/00—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms
    • C07C5/02—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation
    • C07C5/08—Preparation of hydrocarbons from hydrocarbons containing the same number of carbon atoms by hydrogenation of carbon-to-carbon triple bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2521/00—Catalysts comprising the elements, oxides or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium or hafnium
    • C07C2521/02—Boron or aluminium; Oxides or hydroxides thereof
    • C07C2521/04—Alumina
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2521/00—Catalysts comprising the elements, oxides or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium or hafnium
    • C07C2521/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2521/00—Catalysts comprising the elements, oxides or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium or hafnium
    • C07C2521/06—Silicon, titanium, zirconium or hafnium; Oxides or hydroxides thereof
    • C07C2521/08—Silica
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2521/00—Catalysts comprising the elements, oxides or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium or hafnium
    • C07C2521/12—Silica and alumina
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2521/00—Catalysts comprising the elements, oxides or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium or hafnium
    • C07C2521/18—Carbon
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2523/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00
    • C07C2523/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals
    • C07C2523/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals of the platinum group metals
    • C07C2523/42—Platinum
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2523/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00
    • C07C2523/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals
    • C07C2523/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals of the platinum group metals
    • C07C2523/44—Palladium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2523/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00
    • C07C2523/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals
    • C07C2523/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of noble metals of the platinum group metals
    • C07C2523/46—Ruthenium, rhodium, osmium or iridium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2523/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00
    • C07C2523/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group C07C2521/00 of the iron group metals or copper
    • C07C2523/74—Iron group metals
    • C07C2523/755—Nickel
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2527/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • C07C2527/02—Sulfur, selenium or tellurium; Compounds thereof
    • C07C2527/053—Sulfates or other compounds comprising the anion (SnO3n+1)2-
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2527/00—Catalysts comprising the elements or compounds of halogens, sulfur, selenium, tellurium, phosphorus or nitrogen; Catalysts comprising carbon compounds
    • C07C2527/20—Carbon compounds
    • C07C2527/232—Carbonates
    • 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

Definitions

  • This invention relates to hydrogenation processes, and their products.
  • hydrogenation also includes hydro-dehalogenation.
  • the present invention aims to overcome these disadvantages and further, provides novel processes that allow hydrogenation reactions to be performed with better selectivities than hitherto.
  • a process for the catalytic hydrogenation of a compound containing at least one unsaturated carbon- carbon bond comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.
  • the invention further provides a process for the hydro-dehalogenation of a compound containing at least one C-Cl, C-Br or C-l bond, the process comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.
  • the present invention includes a heterogeneous process for the hydro-dechlorination of a compound, wherein a compound containing at least one C-Cl bond, and a hydrogenation agent are admixed in the presence of an ionic liquid.
  • the invention may thus be defined in its first aspect as a heterogeneous process for the hydrogenation of unsaturated aliphatic carbons in a compound, wherein the compound and a hydrogenating agent are admixed in the presence of an ionic liquid.
  • ionic liquid refers to a liquid that is capable of being produced by melting a solid, and when so produced, consists solely of ions.
  • Ionic liquids may be derived from organic salts, especially salts of heterocyclic nitrogen-containing compounds, and such ionic liquids are particularly preferred for use in the processes of the present invention.
  • An ionic liquid may be formed from a homogeneous substance comprising one species of cation and one species of anion, or can be composed of more than one species of cation and/or anion. Thus, an ionic liquid may be composed of more than one species of cation and one species of anion. An ionic liquid may further be composed of one species of cation, and one or more species of anion.
  • ionic liquid may refer to a homogeneous composition consisting of a single salt (one cationic species and one anionic species) or it may refer to a heterogeneous composition containing more than one species of cation and/or more than one species of anion.
  • ionic liquid includes compounds having both high melting temperature and compounds having low melting points, e.g. at or below room temperature (i.e. 15-30°C). The latter are often referred to as "room temperature ionic liquids" and are usually derived from organic salts having pyridinium and imidazolium-based cations.
  • a feature of ionic liquids is that they have particularly low (essentially zero) vapour pressures.
  • Many organic ionic liquids have low melting points (e.g. less than 100°C, particularly less than 100°C, and around room temperature, e.g. 15-30°C. Some have melting points well below 0°C.
  • Ionic liquids may be regarded as consisting of two components, which are a positively charged cation and a negatively charged anion.
  • any compound that meets the criteria of being a salt (consisting of an anion and cation) and which is fluid at or near the reaction temperature, or exists in a fluid state during any stage of the reaction can be defined as an ionic liquid especially suitable for use in the process of the present invention.
  • suitable ionic liquids for use in the present invention include salts of alkylated or polyalkylated heteroaryl compounds, such as salts of alkylated pyridine, pyridazine, pyrimidine, pyrazine, imidazole, pyrazole, oxazole and triazole.
  • suitable ionic liquids include those having the following formula:
  • R a is a C-i to C 40 , (preferably C to C 2 o and more preferably C 4 to C 12 ) straight chain or branched alkyl group or a C 3 to C 8 cycloalkyl group, wherein said alkyl or cycloalkyl group which may be substituted by one to three groups selected from: C ⁇ to C 6 alkoxy, C 6 to C 10 aryl, CN, OH, N0 2 , Ci to C 3 _ aralkyl and C t to C 30 alkaryl;
  • R b , R c , R d , R e and R f can be the same or different and are each independently selected from H or any of the R a groups as defined above; and A represents an anion having a charge n-; wherein n may be 1-3.
  • n is 1.
  • R a is an unsubstituted alkyl or cycloalkyl group as defined above.
  • R b , R c , R d , R ⁇ and R f are preferably hydrogen.
  • the cation is preferably 1 ,3-dialkylimidazolium.
  • Other cations for this process include other substituted pyridinium or alkyl- or poly-alkylpyridinium, alkyl imidazolium, imidazole, alkyl or poly-alkylimidazolium, alkyl or polyalkylpyrazolium, ammonium, alkyl or polyalkyl ammonium, alkyl or poly-alkyl phosphonium cations.
  • the anion for the present processes is preferably a phosphate or amide.
  • Other anions include sulfur-containing anions such as sulfate or sulphite, nitrogen- containing anions, such as nitrate, nitrite, alkylsulfate, or a chloride, bromide or other halide, hydrogensulfate, oxoanions of metals, selenium, tellurium, phosphorus, arsenic, antimony, bismuth based anions, and boron halide anions, such as tetrafluoroborate, [BF 4 ].
  • Particularly preferred ionic liquids are imidazolium, pyridinium or pyrazolium salts.
  • ionic liquids useful for the process of the present invention include those based on imidazolium cations having the formula:
  • each R a may be the same or different and each is independently selected from Ci to C 40 straight chain or branched alkyl which may be substituted by one to three groups selected from: Ci to C 6 alkoxy, C 6 to C 10 aryl, CN, OH, N0 2 , Ci to C 30 aralkyl and d to C 30 alkaryl;
  • A represents one or more species of anion having charge n-; and n represents 1-3.
  • ionic liquids based on pyridinium cations having the formula:
  • R a is selected from C ⁇ to C 40 straight chain or branched alkyl which may be substituted by one to three groups selected from: C, to C 6 alkoxy, C 6 to C ⁇ 0 aryl, CN, OH, N0 2 , Ci to C 30 aralkyl and Ci to C 30 alkaryl;
  • A represents one or more species of anion having charge n-; and n represents 1-3.
  • R a is independently selected from C, to C 40 , preferably C, to C 20 , and even more preferably, C to C 12 , straight chain or branched alkyl.
  • Preferred ionic liquids include those of the above formulae wherein A represents a single species of anion having charge n-; anions having a charge of 1 are especially preferred.
  • Ionic liquids useful in the present processes include those wherein A represents an anion selected from boron or phosphorus fluorides, N0 3 , S0 4 , HS0 4 , HC0 3 , [(CF 3 S ⁇ 2 ) 2 N], [AsF 6 ], alkylsulfonates, mono- or difluorinated alkyl sulfonates including perfluorinated alkylsulfonates, carboxylic acid anions, fluorinated carboxylic acid anions and metal halides.
  • A represents an anion selected from boron or phosphorus fluorides, N0 3 , S0 4 , HS0 4 , HC0 3 , [(CF 3 S ⁇ 2 ) 2 N], [AsF 6 ], alkylsulfonates, mono- or difluorinated alkyl sulfonates including perfluorinated alkylsulfonates, carboxylic acid anions, fluorinated carboxylic acid an
  • ionic liquids having the above formulae wherein A represents an anion selected from [PF 6 ], [BF 4 ], [OS0 2 CF 3 ], [OS0 2 (CF 2 ) 3 CF 3 ], [OC0 2 CF 3 ], [OC0 2 (CF 2 ) 3 CF 3 ], [OC0 2 CH 3 ], nitrate, sulfate, hydrogen sulfate, hydrogen carbonate, acetate, trifluoroacetate, lactate, t(CF 3 S0 2 ) 2 N], [B(alkyl) 4 ] wherein each alkyl can be the same or different and can be any straight chain or branched Ci to C 10 alkyl (preferably Ci to C 6 alkyl) group, [SbF 6 ] ' and [AsF 6 ].
  • A represents an anion selected from [PF 6 ], [BF 4 ], [OS0 2 CF 3 ], [OS0 2 (CF 2 ) 3 CF 3 ], [OC0 2 CF 3 ],
  • each alkyl can be the same or different and can be any straight chain or branched Ci to C 10 alkyl (preferably C, to C 6 alkyl) group, [SbF 6 ] " and [AsF 6 ].
  • ionic liquids include those wherein the anion is phosphate or an amide.
  • the anions [PF 6 ] hexafluorophosphate
  • [BF 4 ] tetrafluoroborate
  • [(CF 3 S0 2 ) 2 N] ⁇ bis[(trifluoromethyl)sulfonyl]amide or bistriflimide) are particularly preferred, especially for the imidazolium- and pyridinium-cation-based ionic liquids.
  • the present invention provides a process for the hydrogenation of a wide range of unsaturated aliphatic carbons, such as alkenes (including dienes, conjugated dienes, and trienes) and alkynes, which may contain a wide range of other functional groups.
  • unsaturated aliphatic carbons such as alkenes (including dienes, conjugated dienes, and trienes) and alkynes, which may contain a wide range of other functional groups.
  • unsaturated aliphatic carbons such as alkenes (including dienes, conjugated dienes, and trienes) and alkynes, which may contain a wide range of other functional groups.
  • unsaturated aliphatic carbons such as alkenes (including dienes, conjugated dienes, and trienes) and alkynes, which may contain a wide range of other functional groups.
  • the present processes it has been possible to achieve selective hydrogenation of the unsaturated carbon-carbon bond without significant reduction of e.g. carbonyl groups which may
  • a wide range of compounds containing at least one unsaturated carbon-carbon bond can be hydrogenated in accordance with the processes of the present invention.
  • the processes of the present invention can also be used to hydrogenate compounds containing at least one C ⁇ C bond, as well as compounds containing multiple C ⁇ C bonds (e.g. up to two C ⁇ C bonds).
  • suitable substrates include compounds containing from 2 to 50 carbon atoms, preferably from 4 to 25 carbon atoms and more preferably from 6 to 20 carbon atoms.
  • the hydrogenation process of the present invention may be applied to a wide range of compounds containing at least one unsaturated carbon-carbon bond, including alkenes, alkynes, esters, ethers, carboxylic acids, amines, amides, alcohols, fatty acids and esters thereof, steroids, prostaglandins, nitriles, aldehydes, ketones, isoprenoids, flavonoids, icosanoids, compounds containing a heterocyclic moiety wherein the heteroatom(s) can be nitrogen or oxygen, and compounds containing an aromatic moiety, such aryl-containing (e.g. phenyl-containing) compounds.
  • aryl-containing e.g. phenyl-containing
  • Preferred substrates include alkenes, alkynes, aldehydes, fatty acids and esters thereof, including those containing an ⁇ , ⁇ - unsaturated carbonyl moiety.
  • Especially preferred carbonyl-containing compounds which are suitable substrates for the hydrogenation process of the present invention include those having the formula:
  • R 1 is selected from hydrogen or d to C 20 straight chain or branched alkyl or C 3 to C 8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C 6 to C 10 aryl, C 8 -C 2 o aralkyl, C 8 -C 20 alkaryl,
  • C 3 to C 8 cycloalkyl, hydroxyl, F, CF 3 , 0, d to C 6 alkylamino, d to C ⁇ dialkylamino, -CN, COOR 3 , CONR 3 or OR 3 wherein R 3 is selected from H, d to C 20 alkyl and C 6 to C 10 aryl; or C 6 to C 10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C 10 alkyl, hydroxyl, F, CF 3 , CN, COOR 4 , CONR 4 or OR 4 wherein R 4 is selected from H, d to C 20 alkyl; and
  • R 1 is selected from hydrogen; d to C 20 straight chain or branched alkyl or C 3 to C 8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C 6 to C ⁇ 0 aryl, C 8 -C 20 aralkyl, C 8 -C 20 alkaryl,
  • R 3 is selected from H, d to C- 20 alkyl and C ⁇ to C 10 aryl; or C 6 to C 10 aryl; and
  • R 1 is selected from hydrogen; d to C 10 straight chain or branched alkyl;
  • R 2 represents Ci to C 20 straight chain or branched alkenyl or C 5 to C 8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from Ci to C 20 alkyl or C 6 to C ⁇ 0 aryl.
  • R 1 is selected from hydrogen; Ci to C ⁇ 0 straight chain or branched alkyl; and R 2 represents Ci to C 20 straight chain or branched alkenyl or C 5 to C 8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with Ci to
  • the hydrogenation process of the present invention is particularly suitable for compounds as defined above wherein an ⁇ , ⁇ -unsaturated carbonyl moiety is present.
  • Suitable compounds include cinnamaldehyde, 2-octenal, citral, methylvinylketone, 3-cyclohexene-1-carboxaldehyde and benzylidine acetone.
  • Alkenes which may be hydrogenated using the present process include those having the formula:
  • R 4 is selected from H and d to C 20 alkyl.
  • R 5 , R 6 , R 7 and R 8 are the same or different and each is independently selected from: - hydrogen;
  • R 5 , R 6 , R 7 and R 8 are the same or different and each is independently selected from: - hydrogen;
  • Ci to C 20 straight chain or branched alkyl or C 3 to C 8 cycloalkyl; and C 2 to C 20 straight chain or branched alkenyl.
  • R 5 , R 6 , R 7 and R 8 are the same or different and each is independently selected from hydrogen; Ci to C 2 o straight chain or branched alkyl; and C 2 to C 20 straight chain or branched alkenyl.
  • alkenes of the above formula wherein R 5 and R 7 each represents hydrogen are particularly preferred.
  • Preferred alkene substrates are those wherein R 5 , R 6 and R 7 each represents hydrogen and R 8 is as defined in any preceding passage.
  • the hydrogenation process of the present invention may be applied to a wide range of alkenes including those having the formula
  • R 5 , R 6 and R 7 are as defined in any of the preceding passages.
  • Especially preferred alkene substrates include those as defined above wherein R 5 , R 6 , R 7 or R 8 represents a C 2 to C 20 straight chain or branched alkenyl.
  • the process of the present invention is also suitable for the hydrogenation of alkynes including those having the formula:
  • R 9 and R 10 are each independently selected from: hydrogen;
  • Ci to C 20 straight chain or branched alkyl or C 3 to C 8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C 2 to C ⁇ 0 alkenyl, C 5 to C 8 cycloalkenyl, C 6 to C 10 aryl, C 8 -C 20 aralkyl, C 8 -C 20 alkaryl, C 3 to C 8 cycloalkyl, hydroxyl, F, CF 3 , 0, Ci to C 6 alkylamino, Ci to C 6 dialkylamino, -CN, COOR 3 , CONR 3 or OR 3 wherein R 3 is selected from H, Ci to C 20 alkyl and C ⁇ to C ⁇ 0 aryl; and C 6 to C ⁇ o aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to do alkyl, hydroxyl, F, CF 3 , CN, COOR 4
  • alkyne substrates are those wherein R 9 and R 10 are each independently selected from: hydrogen;
  • Ci Ci to C 2 o straight chain or branched alkyl or C 3 to C 8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C ⁇ to C ⁇ 0 aryl, C 8 -C 2 o aralkyl, C 8 -C_o alkaryl, C 3 to C 8 cycloalkyl, hydroxyl or OR 3 wherein R 3 is selected from H, Ci to C 20 alkyl and C ⁇ to C ⁇ 0 aryl; and
  • R 9 and R 10 are each independently selected from: hydrogen; - Ci to C 2 o straight chain or branched alkyl or C 3 to C 8 cycloalkyl; and
  • R 9 and R 10 are each independently selected from: hydrogen;
  • Ci to C 20 straight chain or branched alkyl or C 3 to C 8 cycloalkyl
  • Especially preferred alkynes of the above formula are those wherein at least one of
  • R 9 or R 10 is hydrogen.
  • the substrate may be any compound having at least one C-Cl, C-Br or C-l bond.
  • Suitable substrates include those wherein the compound has the formula:
  • aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C 10 alkyl, hydroxyl, F, CF 3 , CN, COOR 4 , CONR 4 or OR 4 wherein R 4 is selected from H and Ci to C 20 alkyl; - heteroaryl; or heterocycloalkyl; and X represents CI, Br or I
  • P represents: - d to C 2 o straight chain or branched alkyl or C 3 to C 8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C 6 to C 10 aryl, C 8 -C 20 aralkyl, C 8 -C 20 alkaryl, C 3 to C 8 cycloalkyl, hydroxyl; C 6 to do aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, or hydroxyl; heteroaryl; or heterocycloalkyl are preferred.
  • the hydro-dehalogenation process of the present invention is particularly suitable for compounds containing at least one C-Cl bond.
  • the present invention extends to any product obtainable by the processes herein described.
  • any suitable heterogeneous hydrogenation catalyst may be used.
  • heterogeneous hydrogenation catalysts are those comprising palladium or platinum.
  • the heterogeneous hydrogenation catalysts are preferably in the form of a finely divided metal.
  • the catalyst is supported on an inert support, such as activated carbon, alumina, silica, silica-alumina, carbon black, graphite, titania, zirconia, calcium carbonate, and barium sulfate.
  • inert support materials are selected from activated carbon, carbon black, graphite, alumina or silica.
  • the hydrogenation catalysts for use in the present invention are heterogeneous, i.e. they do not dissolve in the ionic liquid, but instead remain as a suspension therein.
  • the catalyst is preferably non-colloidal, i.e. the catalyst particle size, including support (if any) is greater than 20, preferably greater than 50, and preferably greater than 100 ⁇ m.
  • the processes of the present invention preferably employ as catalyst, a platinum or palladium group metal, particularly in supported form, e.g. on carbon, graphite or alumina.
  • the hydrogenating agent employed in the present process is typically molecular hydrogen or an organic or inorganic hydrogen transfer agent.
  • Hydrogen transfer agents [see e.g. Johnstone et a/., Chem. Rev. (1985), 85, 129 and Brieger et al. Chem. Rev. (1974), 74, 567-580] are compounds which can release hydrogen and which are themselves oxidised.
  • An example of such a hydrogen transfer agent is cyclohexene, which undergoes the following reaction in the presence of e.g. a palladium catalyst and an alkene substrate:
  • the alkene is hydrogenated whilst the cyclohexene is oxidised to benzene.
  • Suitable hydrogenating agents include molecular deuterium, HD, molecular tritium, HT, DT, or an organic or inorganic hydrogen, deuterium or tritium transfer agent.
  • the hydrogenating agent is molecular hydrogen or an organic or inorganic hydrogen transfer agent. Molecular hydrogen is especially preferred as the hydrogenating agent.
  • the hydrogenation process of the present invention is preferably conducted at temperatures of from 15°C to 200°C, preferably 15°C to 140°C, and more preferably from 20°C to 100°C. Good results are obtained at temperatures of 40°C to 60°C.
  • reaction may be conducted at atmospheric pressure.
  • the reaction may be conducted at pressures of 101 kPa (i.e. atmospheric pressure) to 8 MPa.
  • pressures of 101 kPa i.e. atmospheric pressure
  • such reactions are conducted at pressures of from 150 kPa (preferably from 1 MPa) to 5 MPa and more preferably from 2.5 MPa to 4.5 MPa.
  • reaction pressures of 3 MPa to 4.2 MPa Good results may be obtained using reaction pressures of 3 MPa to 4.2 MPa.
  • Hydrogenation reactions represent one of the largest uses of heterogeneous catalysts in the chemical industry. A range of reactions is possible from dehalogenation to simple reductions of alkene to selective reductions of ⁇ , ⁇ -unsatu rated carbonyl containing molecules. Ionic liquids have not been used previously for any heterogeneously catalysed reactions and provide distinct advantages over many conventional organic and aqueous solvents where selectivity may be poor and/or there are problems with product separation and recycle of the catalyst/solvent system.
  • Particular ionic liquids discussed herein include; 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF 6 ), 1-hexyl-3-methylimidazolium hexafluorophosphate (C 6 mimPF 6 ), 1-octyl-3-methylimidazolium hexafluorophosphate (C 8 mimPF 6 ), 1-decyl-3-methylimidazolium hexafluorophosphate (C 10 mimPF 6 ),
  • 1-dodecyl-3-methylimidazolium hexafluorophosphate (C ⁇ 2 mimPF 6 ), 1 -ethyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide (emimNTf 2 ), 1 -hexyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide (C 6 mimNTf 2 ), 1-hexylpyridinium tetrafluoroborate (C 6 py BF 4 ), 1-octylpyridinium tetrafluoroborate (C 8 py BF 4 ),
  • Alkyl (including alkyl portions of alkyoxy, alkaryl, aralkyl, alkylamino, dialkylamino) represents straight and branched carbon chains containing from 1 to 40 carbon atoms, preferably 1 to 40 carbon atoms, and more preferably 4 to 12 carbon atoms.
  • Cycloalkyl represents saturated carbocyclic rings branched or unbranched containing from 3 to 20 carbon atoms, preferably 3 to 8 carbon atoms. Such cycloalkyl groups include cyclopentyl and cyclohexyl.
  • Heterocycloalkyl represents a saturated, branched or unbranched carbocyclic ring containing from 3 to 12 carbon atoms, preferably from 4 to 6 carbon atoms, wherein the carbocyclic ring is interrupted by 1 to 3 heteroatom moieties selected from -0-, or -N(d to C ⁇ alkyl), or NH.
  • Such heterocycloalkyl groups include 2- or 3- tetrahydrofuranyl, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-piperizinyl, morpholinyl, 2- or 3- pyrrolidinyl and 2- or 4-dioxanyl.
  • alkenyl represents straight and branched carbon chains having at least one carbon to carbon double bond and containing from 2 to 40 carbon atoms, preferably 2 to 20 carbon atoms and more preferably from 2 to 12 carbon atoms.
  • alkenyl as used herein includes dienes (including conjugated dienes) trienes and tetraenes.
  • Alkynyl represents straight and branched carbon chains having at least one carbon to carbon triple bond and containing from 2 to 20 carbon atoms, preferably 2 to 20 carbon atoms and more preferably from 2 to 12 carbon atoms.
  • Aryl including aryl moieties in e.g. aralkyl represents a carbocyclic group containing from 6 to 15 carbon atoms (preferably from 6 to 10 carbon atoms) and having at least one aromatic ring, with all available substitutable carbon atoms of the carbocyclic group being intended as possible points of attachment.
  • Preferred aryl groups include phenyl and naphthyl.
  • aryl includes such carbocyclic groups being optionally substituted with, 1 to 3 of the following substituents: Ci to C 6 alkyl, OH, 0(d to C 6 alkyl), phenoxy, CF 3 , (d to C 6 alkyl)amino, di(C ⁇ to C 6 alkyl)amino, -000(0, to C 6 alkyl) or N0 2 .
  • Heteroaryl represents cyclic groups having at least one heteroatom selected from -O- or -N-, said heteroatom interrupting a carbocyclic ring structure and having a sufficient number of delocalised pi electrons to provide aromatic character, with the aromatic heterocyclic groups preferably containing from 2 to 14 carbon atoms.
  • Suitable heteroaryl groups include pyridine, indole, imidazole, pyridazine, pyrazine, oxazole, triazole, pyrazole, and purines and pyrimidines.
  • Figure 1a Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/graphite catalyst in bmimPF ⁇ .
  • Figure 1b Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in bmimPF 6 .
  • Figure 2a Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/Al 2 0 3 catalyst in bmimPF ⁇ .
  • Figure 2b Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/Al 2 0 3 catalyst in bmimPF 6 .
  • Figure 3a Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/graphite catalyst in propan-2-ol.
  • Figure 3b Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in propan-2-ol.
  • Figure 4 Variation in conversion and selectivity towards 2 with ionic liquid volume following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in emimNTf 2 .
  • Figure 5 Variation in conversion and selectivity towards 2 with temperature following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in emimNTf 2 .
  • Figure 6 Variation in conversion of 1 to 3 with pressure following cinnamaldehyde reduction over 10wt% Pd/C catalyst in bmimBF 4 .
  • Figure 7 Kinetic study for the conversion (conv) and chemoselectivity (cs) in the hydrogenation of citral to citronellal in 10wt% Pd/C and 10wt% Pd/C modified catalysts in bmimBF 4
  • Figure 8 Variation in conversion of 1-nonyne and selectivity towards 1-nonene with time following 1-nonyne reduction over 10wt% Pd/C catalyst in C 6 PyBF 4 at 30°C and 3 x 10 5 Pa.
  • Figure 9a Variation in conversion and selectivity towards styrene with pressure following phenyl acetylene reduction over 5wt% Pd/CaC0 3 at 30°C after 4 hr.
  • Figure 9b Variation in conversion and selectivity towards styrene with temperature following phenyl acetylene reduction over 5wt% Pd/CaC0 3 at 3 x 10 5 Pa for 4 hr.
  • Figure 9c Variation in conversion and selectivity towards styrene with time following phenyl acetylene reduction over Pd/CaC0 3 at 3 x 10 5 Pa & 30°C.
  • ionic liquids for use in the present invention including those employed in the following examples can be made by process such as those disclosed in WO 01/40146.
  • Cinnamaldehyde, 1 can undergo reduction using hydrogen gas over a heterogeneous catalyst to produce three products, cinnamylalcohol, 2, hydrocinnamaldehyde, 3, and 3-phenylpropanol, 4.
  • the reactions may proceed in two different pathways 1 to 2 to 4 or 1 to 3 to 4 as shown below.
  • This reaction has been studied extensively by many workers with an aim to control the selectivity and promote the formation of cinnamylalcohol and hydrocinnamaldehyde without further reduction to 3-phenylpropanol.
  • These investigations have concentrated on the effect of promoters on the catalyst such as doping with tin or using zeolite based catalysts.
  • the aim of this study was to develop ionic liquids for heterogeneously catalysed reactions and specifically in this case to investigate whether the solvent could act as a promoter without the need to use expensive catalysts.
  • the reactions were performed under a hydrogen pressure of 4 MPa and a temperature of 60°C.
  • the platinum catalysts were pre-reduced in flowing hydrogen at 350°C for 1 h.
  • Ionic liquid (2ml), 17.5mg (5wt% Pt catalyst), and cinnamaldehyde 0.5ml (substrate/metal ⁇ 800/1) were introduced to the autoclave and purged three times with argon.
  • Hydrogen at 4 MPa was introduced and the autoclave heated to the required temperature.
  • the reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released.
  • the reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid.
  • Product selectivities and conversions were determined using GC-FID.
  • Table 1 summarises the results of an initial screening for the hydrogenation of cinnamaldehyde using 5% Pt/graphite in a range of ionic liquids.
  • imidazolium ionic liquids achieve the highest yields and selectivity with the trend [NTf 2 ] “ > [PF 6 ] “ > [BF 4 ] “ .
  • the best system, emimNTf 2 is hydrophobic enabling chloride removal efficient simply by washing with water. It has very low viscosity, which makes it easy to handle and allow for catalyst dispersion.
  • Figures 1a, 1b, 2a and 2b show the hydrogenation of cinnamaldehyde using Pt/graphite or Pt/alumina in bmimPF 6 .
  • the reaction stops after 5-7 hrs with the conversion rate slowing significantly after 3-5 hrs.
  • the selectivity is high towards cinnamylalcohol 2 however, with increasing reaction time some hydrocinnamaldehyde 3 and 3-phenylpropanol 4 forms.
  • 3 occurs because of isomerisation between 2 and 3 catalysed by the supported catalyst in the ionic liquid.
  • Catalyst deactivation is likely to be the cause of the conversion being limited.
  • a blank experiment in which the hydrogenation was carried out under normal experimental conditions for 6hrs without any substrate, cooled, the substrate was added and the reaction performed once more. Under these conditions, no reaction was observed indicating that the ionic liquid, and not the substrate/products, was responsible for the catalyst poisoning.
  • Poisoning by the ionic liquid could be the result of a number of variables, for example pore blocking, the blocking sites by strongly adsorbed species or halide contamination from the ionic liquid manufacture.
  • Experiments were performed in the presence of trace halide from HCI and NaCI to assess the contribution of halide deactivation. No conversion was observed in these reactions showing that firstly the ionic liquids are used were virtually halide free and secondly, absence of halide impurities is important if these reactions are to proceed. The major consequence of this is that unless electrolysis is performed prior to use, these reactions are limited to hydrophobic ionic liquids, which may be washed with water to remove trace chloride.
  • Table 2 Variation in hydrogenation of 1 using 5% Pt/graphite with increasing alkyl chain length in [C n mim]+ ionic liquids.
  • Table 3 The results for the reduction of four different compounds with 5wt% Pt/G in C 6 mim NTf 2 ionic liquid are shown in table 3.
  • Table 3 The reduction of four different substrates at 60°C and 4 MPa after four hours with 5wt% Pt/G in C 6 mim NTf 2 .
  • Palladium metal is known to reduce double bonds in preference to carbonyl groups, however, in ⁇ , ⁇ -unsatu rated systems there is little or no selectivity in common organic solvents. Cinnamaldehyde hydrogenation carried out in propan-2-ol using Pd/activated carbon yielded the fully saturated compound, 3-phenylpropanol, 4.
  • the palladium catalysts were used as received.
  • Ionic liquid (2ml), 5.5mg (10wt% Pd catalyst), and cinnamaldehyde 0.5ml (substrate/metal - 800/1 ) were introduced to the autoclave and purged three times with argon.
  • Hydrogen at 40 x 10 5 Pa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released.
  • reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid.
  • Product selectivities and conversions were determined using GC-FID.
  • Table 4 summarizes the results from reduction of cinnamaldehyde using Pd/C in a range of ionic liquids.
  • Figure 6 shows the variation of conversion after 4 h with hydrogen pressure.
  • the pressure study showed that, even at low pressures such as 5 x 10 5 Pa there was significant conversion, after 4h of the reaction. After 24 h, 93% conversion to hydrocinnamaldehyde 3 at 5 x 10 5 Pa was observed. At all pressures, only hydrocinnamaldehyde is found.
  • the palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (10wt% Pd catalyst), and methyl oleate 0.5ml (substrate/metal ⁇ 800/1) were introduced to the autoclave and purged three times with argon. Hydrogen at 1 MPa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 4 h, upon which the reaction is cooled and the pressure released.
  • reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid.
  • Product selectivities and conversions were determined using GC-FID.
  • Methyl oleate 9 was hydrogenated to methyl stearate 10 with 100 % conversion and selectivity after 4 h reaction at 60 °C in C 6 pyBF 4 , bmimPF 6 and emimNTf 2 ionic liquids. Following extraction the reaction was recycled and achieved the same conversions and selectivity. No cleavage of the ester group was observed and there was no loss of the catalyst to the extractant phase.
  • the palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (10wt% Pd/C), and citral 0.5ml (substrate/metal ⁇ 800/1 ) were introduced to the autoclave and purged three times with argon. Hydrogen at 4 MPa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released.
  • reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid.
  • Product selectivities and conversions were determined using GC-FID.
  • Citral has three sites of hydrogenation; the conjugate double bond, the carbonyl group and the isolated double bond.
  • the hydrogenation of citral 11 a compound with a 'methyl blocking group', proceeded with selective hydrogenation of the double bond to produce citronellal 13.
  • Literature reports had suggested that the selectivity in traditional solvents was governed by temperature.
  • the temperature study produced conversion and selectivities analogous to those obtained using cinnamaldehyde 1 as the substrate. From 30°C-60°C, the conversion increases whilst maintaining high selectivity. Above 60°C the formation of the alcohol, citronellol 14, leads to a decrease in selectivity.
  • the citral used for the experiment contains ⁇ 65% (E), 35%(Z) isomers. However, it is interesting to observe that the ratio of E/Z isomers of the unreacted citral in these experiments was still 65/35 indicating that the catalytic system did not discriminate between the isomers, even though it was only selective for the reduction of the conjugated double bond. Even at high temperatures and pressures, were citronellol 14 was formed there was no evidence for the formation of the completely hydrogenated product 3,7-dimethyl octan-1-ol 15 or geraniol/nerol 12.
  • Table 9 highlights the use of proline as a modifier on the reaction.
  • (R)-proline the unnatural enantiomer, as a chiral modifier again produces similar conversion and chemoselectivity as the natural (S)-enantiomer.
  • the use of citronellal as a promoter/modifier on recycle was not observed to increase chemoselectivity or conversion.
  • Addition of fresh amounts of proline as well as the use of a proline saturated system shows excellent chemoselectivity and conversion on recycle.
  • Standard reaction 10wt%Pd/C (5.5mg), 5wt%Pd/Ti0 2 (11mg), bmimBF 4 2ml, citral 0.52ml.
  • catalyst is modified at 30°C/1 MPa H 2 for 1 h, citral is injected and left to react for 5h.
  • Table 10 shows the effect of a proline saturated ionic liquid on the recycle of 10 wt% Pd/C catalyst.
  • the modified catalyst greatly increases the conversion upon the initial run and successive recycles while still maintaining 100% selectivity.
  • the unmodified catalyst also shows 100% selectivity over the three recycles performed, the conversions upon recycle are much lower than modified catalyst.
  • Table 10 Catalyst recycle for 10wt% Pd/C modified (sat. Proline) hydrogenation in bmim BF 4 .
  • a salt of proline may remain suspended in the ionic liquid.
  • separation of the product can easily be carried out by extraction procedures.
  • the palladium on carbon catalysts were used as received used whereas the platinum catalysts and palladium on alumina were pre-reduced in flowing hydrogen at 350°C for 1h.
  • Ionic liquid (2ml) 5.5mg (10wt% Pd on carbon), 11 mg (5wt% palladium on alumina), 19.5 mg (5wt% platinum on alumina), 19.5 mg (5wt% platinum on graphite), and substrate (substrate/metal - 200/1) were introduced to the autoclave and purged three times with argon. Hydrogen at the desired pressure was introduced and the autoclave heated to the required temperature. The reaction is left to stir for the desired time period, upon which the reaction is cooled and the pressure released. The reaction products are extractable using water.
  • Table 11 shows the conversion and selectivity for the reaction to 16 over 17.
  • the palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (5wt% Pd on calcium carbonate, 10wt% Pd on activated carbon, 5wt%Pd/CaC0 3 lead poisoned), and substrate (substrate/metal ⁇ 800/1 ) were introduced to the autoclave and purged three times with argon. Hydrogen at the desired pressure was introduced and the autoclave heated to the required temperature. The reaction is left to stir for the desired time period, upon which the reaction is cooled and the pressure released. The reaction products were extracted using organic solvent or distillation, which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
  • Table 14 shows the conversion and selectivity for the reduction of 1-nonyne using 10% Pd/C and 5% Pd/CaC0 3 in a series of different alkyl chain length [Pyridinium] * [BF 4 ] ' ionic liquids
  • Table 14 Reduction of 1-nonyne using 5wt% Pd/CaC0 3 and 10wt% Pd/C at 30°C and 3 x 10 5 Pa for 4 hours.
  • Table 14 shows that 10wt% Pd/C gives complete reduction to the alkane after four hours.
  • the kinetic graph in figure 8 shows that 10wt%Pd/C is 100% selective, although only at low conversions.
  • the 5wt% Pd/CaC0 3 /C ⁇ PyBF system shows 100% selectivity towards the alkene up to at least 55% conversion, although the C 4 pyridinium BF shows lower selectivity after 4h under these reaction conditions.
  • Table 15 shows the conversion and selectivity for the reduction of three different substrates using the 5wt % Pd/CaC0 3 /C 6 PyBF system.
  • Table 15 Reductions of different substrates using 5wt% Pd/CaC0 3 at 30°C & 3 x 10 5 Pa for 4hrs.
  • Table 15 shows that high selectivity towards the alkene is achievable for all three substrates.
  • the conversion and selectivity of phenyl acetylene towards styrene for a series of experiments varying the reaction pressure, temperature and length of reaction time are shown in figures 9a, 9b and 9c.
  • Figure 9c shows that when the reaction proceeds for longer than three hours, the selectivity drops off dramatically due to further hydrogenation to ethyl benzene, indicating that the only way to achieve maximum selectivity is to keep the reaction time and subsequently the level of conversion low.
  • the inverse behaviour of the selectivity with respect to the conversion explains why as of yet there are no conditions found where 100% conversion and 100% selectivity can be achieved.
  • Table 16 shows the reduction of phenyl acetylene in a range of ionic liquids using 5wt% Pd/CaC0 3 poisoned with lead (Lindlars catalyst).
  • Table 16 Reductions of phenyl acetylene using Lindlars Catalyst at 30°C and 5 x 10 5 Pa for 4 hours.
  • Lindlars catalyst maybe used in conjunction with range of ionic liquids to achieve at least 97% conversion with 100% selectivity for the reduction of phenyl acetylene to styrene.
  • Ionic liquids provide a medium for heterogeneously catalysed hydrogenations, which competes well with conventional solvents. Using unmodified carbon or oxide based platinum group metal catalysts, good selectivity to a range of products is achievable simply by selecting a particular ionic liquid. In these systems it is believed that the ionic liquid modifies the surface and allows the high selectivity to be achieved. Aside from the high selectivity, the use of ionic liquids for hydrogenation reactions provide other advantages over conventional solvents, such as the ease of extraction of the product molecule from the ionic liquid without the need to filter and reactivate the catalyst. This procedure leads to catalyst loss industrially and is a major safety hazard when used on a large scale.
  • the ionic liquid based heterogeneous catalyst systems do deactivate significantly during the reaction compared with organic solvent systems. In these reactions, the ionic liquids cannot be treated as general solvents, as different ionic liquids promote different selectivities, which allows good control over the products without the need to change the catalyst.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Catalysts (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Saccharide Compounds (AREA)

Abstract

Disclosed are heterogeneous processes (i) for the hydrogenation of a compound containing at least one unsaturated carbon-carbon bond, and (ii) for the hydro-dehalogenation of a compound containing at least one C-Cl, C-Br or C-l bond. The processes comprise reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.

Description

Hydrogenation Processes
This invention relates to hydrogenation processes, and their products. As used herein, the term "hydrogenation" also includes hydro-dehalogenation.
Hitherto, hydrogenation reactions have been carried out in organic solvents such as propan-2-ol. However, such solvents often need promoters to be selective and it is still necessary to extract the reaction product(s) from the solvent.
The present invention aims to overcome these disadvantages and further, provides novel processes that allow hydrogenation reactions to be performed with better selectivities than hitherto.
According to one aspect of the present invention, there is provided a process for the catalytic hydrogenation of a compound containing at least one unsaturated carbon- carbon bond, said process comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.
The invention further provides a process for the hydro-dehalogenation of a compound containing at least one C-Cl, C-Br or C-l bond, the process comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid. Thus, the present invention includes a heterogeneous process for the hydro-dechlorination of a compound, wherein a compound containing at least one C-Cl bond, and a hydrogenation agent are admixed in the presence of an ionic liquid.
The invention may thus be defined in its first aspect as a heterogeneous process for the hydrogenation of unsaturated aliphatic carbons in a compound, wherein the compound and a hydrogenating agent are admixed in the presence of an ionic liquid.
More than one ionic liquid or any combination of ionic liquids may be used in the present invention. The term "ionic liquid" refers to a liquid that is capable of being produced by melting a solid, and when so produced, consists solely of ions. Ionic liquids may be derived from organic salts, especially salts of heterocyclic nitrogen-containing compounds, and such ionic liquids are particularly preferred for use in the processes of the present invention.
An ionic liquid may be formed from a homogeneous substance comprising one species of cation and one species of anion, or can be composed of more than one species of cation and/or anion. Thus, an ionic liquid may be composed of more than one species of cation and one species of anion. An ionic liquid may further be composed of one species of cation, and one or more species of anion.
Thus, in summary, the term "ionic liquid" as used herein may refer to a homogeneous composition consisting of a single salt (one cationic species and one anionic species) or it may refer to a heterogeneous composition containing more than one species of cation and/or more than one species of anion.
The term "ionic liquid" includes compounds having both high melting temperature and compounds having low melting points, e.g. at or below room temperature (i.e. 15-30°C). The latter are often referred to as "room temperature ionic liquids" and are usually derived from organic salts having pyridinium and imidazolium-based cations.
A feature of ionic liquids is that they have particularly low (essentially zero) vapour pressures. Many organic ionic liquids have low melting points (e.g. less than 100°C, particularly less than 100°C, and around room temperature, e.g. 15-30°C. Some have melting points well below 0°C.
Ionic liquids may be regarded as consisting of two components, which are a positively charged cation and a negatively charged anion. Generally, any compound that meets the criteria of being a salt (consisting of an anion and cation) and which is fluid at or near the reaction temperature, or exists in a fluid state during any stage of the reaction can be defined as an ionic liquid especially suitable for use in the process of the present invention. For example, suitable ionic liquids for use in the present invention include salts of alkylated or polyalkylated heteroaryl compounds, such as salts of alkylated pyridine, pyridazine, pyrimidine, pyrazine, imidazole, pyrazole, oxazole and triazole. Thus, examples of suitable ionic liquids include those having the following formula:
Figure imgf000004_0001
wherein
Ra is a C-i to C40, (preferably C to C2o and more preferably C4 to C12) straight chain or branched alkyl group or a C3 to C8 cycloalkyl group, wherein said alkyl or cycloalkyl group which may be substituted by one to three groups selected from: C^ to C6 alkoxy, C6 to C10aryl, CN, OH, N02, Ci to C3_ aralkyl and Ct to C30 alkaryl;
Rb, Rc, Rd, Re and Rf can be the same or different and are each independently selected from H or any of the Ra groups as defined above; and A represents an anion having a charge n-; wherein n may be 1-3. Preferably, in the above compounds, n is 1.
Preferably, Ra is an unsubstituted alkyl or cycloalkyl group as defined above. Rb, Rc, Rd, Rβ and Rf are preferably hydrogen.
In preferred ionic liquids for use in the processes of the present invention, the cation is preferably 1 ,3-dialkylimidazolium. Other cations for this process include other substituted pyridinium or alkyl- or poly-alkylpyridinium, alkyl imidazolium, imidazole, alkyl or poly-alkylimidazolium, alkyl or polyalkylpyrazolium, ammonium, alkyl or polyalkyl ammonium, alkyl or poly-alkyl phosphonium cations.
The anion for the present processes is preferably a phosphate or amide. Other anions include sulfur-containing anions such as sulfate or sulphite, nitrogen- containing anions, such as nitrate, nitrite, alkylsulfate, or a chloride, bromide or other halide, hydrogensulfate, oxoanions of metals, selenium, tellurium, phosphorus, arsenic, antimony, bismuth based anions, and boron halide anions, such as tetrafluoroborate, [BF4].
Particularly preferred ionic liquids are imidazolium, pyridinium or pyrazolium salts.
Thus, ionic liquids useful for the process of the present invention include those based on imidazolium cations having the formula:
Figure imgf000005_0001
wherein each Ra may be the same or different and each is independently selected from Ci to C40 straight chain or branched alkyl which may be substituted by one to three groups selected from: Ci to C6 alkoxy, C6 to C10 aryl, CN, OH, N02, Ci to C30 aralkyl and d to C30 alkaryl;
A represents one or more species of anion having charge n-; and n represents 1-3. Also suitable for the processes of the present invention are ionic liquids based on pyridinium cations having the formula:
Figure imgf000006_0001
wherein
Ra is selected from C^ to C40 straight chain or branched alkyl which may be substituted by one to three groups selected from: C, to C6 alkoxy, C6 to Cι0 aryl, CN, OH, N02, Ci to C30 aralkyl and Ci to C30 alkaryl;
A represents one or more species of anion having charge n-; and n represents 1-3.
Preferably, in the above ionic liquids, Ra is independently selected from C, to C40, preferably C, to C20, and even more preferably, C to C12, straight chain or branched alkyl.
Preferred ionic liquids include those of the above formulae wherein A represents a single species of anion having charge n-; anions having a charge of 1 are especially preferred.
Ionic liquids useful in the present processes include those wherein A represents an anion selected from boron or phosphorus fluorides, N03, S04, HS04, HC03, [(CF3Sθ2)2N], [AsF6], alkylsulfonates, mono- or difluorinated alkyl sulfonates including perfluorinated alkylsulfonates, carboxylic acid anions, fluorinated carboxylic acid anions and metal halides.
Especially preferred are ionic liquids having the above formulae wherein A represents an anion selected from [PF6], [BF4], [OS02CF3], [OS02(CF2)3CF3], [OC02CF3], [OC02(CF2)3CF3], [OC02CH3], nitrate, sulfate, hydrogen sulfate, hydrogen carbonate, acetate, trifluoroacetate, lactate, t(CF3S02)2N], [B(alkyl)4] wherein each alkyl can be the same or different and can be any straight chain or branched Ci to C10 alkyl (preferably Ci to C6 alkyl) group, [SbF6]' and [AsF6].
Even more preferred are ionic liquids of the above formulae wherein A represents an anion selected from [PF6], [BF4], [OS02CF3], [OSθ2(CF2)3CF3], [OC02CF3],
[OC02(CF2)3CF3], [OC02CH3], [(CF3S02)2N], [B(alkyl)4] wherein each alkyl can be the same or different and can be any straight chain or branched Ci to C10 alkyl (preferably C, to C6 alkyl) group, [SbF6]" and [AsF6].
Other preferred ionic liquids include those wherein the anion is phosphate or an amide.
The anions [PF6] (hexafluorophosphate), [BF4] (tetrafluoroborate) and [(CF3S02)2N] {bis[(trifluoromethyl)sulfonyl]amide or bistriflimide) are particularly preferred, especially for the imidazolium- and pyridinium-cation-based ionic liquids.
In a first embodiment, the present invention provides a process for the hydrogenation of a wide range of unsaturated aliphatic carbons, such as alkenes (including dienes, conjugated dienes, and trienes) and alkynes, which may contain a wide range of other functional groups. For example, using the present processes, it has been possible to achieve selective hydrogenation of the unsaturated carbon-carbon bond without significant reduction of e.g. carbonyl groups which may be present in the substrate. Thus, the μse of ionic liquids in the present processes provides high, and at times very high, selectivities in such reactions.
A wide range of compounds containing at least one unsaturated carbon-carbon bond can be hydrogenated in accordance with the processes of the present invention. Suitable compounds that may be hydrogenated include compounds containing at least one C=C bond. The process of the present invention is also readily applicable to the hydrogenation of compounds containing multiple C=C bonds, e.g. one to four
C=C bonds, preferably one to three C=C bonds The processes of the present invention can also be used to hydrogenate compounds containing at least one C≡C bond, as well as compounds containing multiple C≡C bonds (e.g. up to two C≡C bonds).
The processes of the present invention can be readily applied to hydrogenate substrates having a wide molecular weight range. For example, suitable substrates include compounds containing from 2 to 50 carbon atoms, preferably from 4 to 25 carbon atoms and more preferably from 6 to 20 carbon atoms.
The hydrogenation process of the first aspect of the present invention may be used to hydrogenate both compounds containing only C=C or C≡C functionalities, or compounds having a wide range of other functional groups in addition to the unsaturated carbon-carbon bond to be hydrogenated. In the latter case, it has been found that the present process can be highly chemoselective, i.e. it is possible to achieve selective hydrogenation of e.g. the C=C or C≡C bonds only, without hydrogenation of other functional groups.
For alkyne substrates, it is possible, by varying the catalyst and ionic liquid, to achieve partial hydrogenation, e.g. of the C≡C bond to form a C=C bond. Further, by varying the catalyst and reaction conditions, complete hydrogenation to the alkane may be achieved.
The hydrogenation process of the present invention may be applied to a wide range of compounds containing at least one unsaturated carbon-carbon bond, including alkenes, alkynes, esters, ethers, carboxylic acids, amines, amides, alcohols, fatty acids and esters thereof, steroids, prostaglandins, nitriles, aldehydes, ketones, isoprenoids, flavonoids, icosanoids, compounds containing a heterocyclic moiety wherein the heteroatom(s) can be nitrogen or oxygen, and compounds containing an aromatic moiety, such aryl-containing (e.g. phenyl-containing) compounds.
Preferred substrates include alkenes, alkynes, aldehydes, fatty acids and esters thereof, including those containing an α,β- unsaturated carbonyl moiety. Especially preferred carbonyl-containing compounds which are suitable substrates for the hydrogenation process of the present invention include those having the formula:
O
Rl R2
wherein:
R1 is selected from hydrogen or d to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C2o aralkyl, C8-C20 alkaryl,
C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, d to C6 alkylamino, d to Cβ dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to C10 aryl; or C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H, d to C20 alkyl; and
R2 represents Ci to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from d to C20 alkyl, C6 to C10 aryl, C8-C20 aralkyl, C8-C2o alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, d to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to Cι0 aryl; or C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and d to C20 alkyl.
Preferably, in the above compounds:
R1 is selected from hydrogen; d to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to Cι0 aryl, C8-C20 aralkyl, C8-C20 alkaryl,
C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0 or OR3 wherein R3 is selected from H, d to C-20 alkyl and Cβ to C10 aryl; or C6 to C10 aryl; and
R2 represents d to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from d to C20 alkyl, C6 to d. aryl, C8-C20 aralkyl, Cβ-Ca) alkaryl, hydroxyl, F, CF3, =0 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to C10 aryl; or C6 to C10 aryl.
Also preferred are compounds of the above formula wherein: R1 is selected from hydrogen; d to C10 straight chain or branched alkyl; and
R2 represents Ci to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from Ci to C20 alkyl or C6 to Cι0aryl.
Especially preferred are those compounds wherein:
R1 is selected from hydrogen; Ci to Cι0 straight chain or branched alkyl; and R2 represents Ci to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with Ci to
C10 alkyl or phenyl.
The hydrogenation process of the present invention is particularly suitable for compounds as defined above wherein an α,β-unsaturated carbonyl moiety is present. In such compounds, it has been found that the carbon-carbon double bond can be hydrogenated selectively, i.e. the C=C bond can be hydrogenated in preference to the C=0 bond.
Specific examples of suitable compounds include cinnamaldehyde, 2-octenal, citral, methylvinylketone, 3-cyclohexene-1-carboxaldehyde and benzylidine acetone.
Alkenes which may be hydrogenated using the present process include those having the formula:
6 Cv 8
wherein:
R5, R6, R7 and R8 may be the same or different and each is independently selected from: hydrogen; Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to C10 alkenyl, C5 to C8 cycloalkenyl, Cβ to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, d to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and C6 to C10 aryl; C2 to C20 straight chain or branched alkenyl; C5 to C8 cycloalkenyl; or C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, hydroxyl, F, CF3, CN, COOR4,
CONR4 or OR4 wherein R4 is selected from H and d to C20 alkyl.
Preferably, R5, R6, R7 and R8 are the same or different and each is independently selected from: - hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to C10 alkenyl, C5to C8 cycloalkenyl, C6 to C10 aryl, Ce-d-o aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and C6 to C10 aryl; and
C2 to C20 straight chain or branched alkenyl.
Also preferred are compounds wherein R5, R6, R7 and R8 are the same or different and each is independently selected from: - hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl; and C2 to C20 straight chain or branched alkenyl.
Especially preferred are compounds wherein R5, R6, R7 and R8 are the same or different and each is independently selected from hydrogen; Ci to C2o straight chain or branched alkyl; and C2 to C20 straight chain or branched alkenyl.
Particularly preferred are alkenes of the above formula wherein R5 and R7 each represents hydrogen. Also preferred are alkenes of the above formula wherein R6 and R8 are each independently selected from Ci to C20 straight chain or branched alkyl, C3 to C8 cycloalkyl and C2 to C20 straight chain or branched alkenyl.
Preferred alkene substrates are those wherein R5, R6 and R7 each represents hydrogen and R8 is as defined in any preceding passage.
Thus, the hydrogenation process of the present invention may be applied to a wide range of alkenes including those having the formula
Figure imgf000012_0001
wherein R5, R6 and R7 are as defined in any of the preceding passages.
Especially preferred alkene substrates include those as defined above wherein R5, R6, R7 or R8 represents a C2 to C20 straight chain or branched alkenyl.
The process of the present invention is also suitable for the hydrogenation of alkynes including those having the formula:
10
R ≡CR
wherein R9 and R10 are each independently selected from: hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to Cι0 alkenyl, C5to C8 cycloalkenyl, C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, Ci to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and Cβ to Cι0 aryl; and C6 to Cιo aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to do alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and Ci to C20 alkyl.
Particularly suitable alkyne substrates are those wherein R9 and R10 are each independently selected from: hydrogen;
Ci to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: Cβ to Cι0 aryl, C8-C2o aralkyl, C8-C_o alkaryl, C3 to C8 cycloalkyl, hydroxyl or OR3 wherein R3 is selected from H, Ci to C20 alkyl and Cβ to Cι0 aryl; and
C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, hydroxyl, F or OR4 wherein R4 is selected from H and d to C20 alkyl.
Especially preferred are compounds wherein R9 and R10 are each independently selected from: hydrogen; - Ci to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl; and
Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F or OR4 wherein R4 is selected from H and Ci to C2, alkyl.
Also preferred are compounds wherein R9 and R10 are each independently selected from: hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl; and
Cθ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from to C10 alkyl, hydroxyl, or OR4 wherein R4 is selected from H and Ci to C10 alkyl. Alkynes of the above formula wherein R9 and R10 are each selected from hydrogen, Ci to do alkyl which may be substituted by hydroxyl, or phenyl are particularly preferred.
Especially preferred alkynes of the above formula are those wherein at least one of
R9 or R10 is hydrogen.
For the hydro-dehalogenation process of the present invention, the substrate may be any compound having at least one C-Cl, C-Br or C-l bond. Suitable substrates include those wherein the compound has the formula:
P-X
wherein: P represents a group selected from: d to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C2o aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, Ci to C6 alkylamino, d to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to C10 aryl;
C6 to Ci. aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and Ci to C20 alkyl; - heteroaryl; or heterocycloalkyl; and X represents CI, Br or I
Of these compounds, those wherein P represents: - d to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl; C6 to do aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, or hydroxyl; heteroaryl; or heterocycloalkyl are preferred.
Also preferred are those compounds wherein P represents:
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl; C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, or hydroxyl; heteroaryl, wherein said heteroaryl group is a purine or pyrimidine; or heterocycloalkyl.
The hydro-dehalogenation process of the present invention is particularly suitable for compounds containing at least one C-Cl bond.
The present invention extends to any product obtainable by the processes herein described.
In the processes of the present invention, any suitable heterogeneous hydrogenation catalyst may be used. Particularly suitable are heterogeneous hydrogenation catalysts comprising nickel (e.g. Raney nickel), palladium, ruthenium, iridium, rhodium and platinum having an oxidation state of zero.
Especially preferred heterogeneous hydrogenation catalysts are those comprising palladium or platinum.
The heterogeneous hydrogenation catalysts are preferably in the form of a finely divided metal.
Typically, the catalyst is supported on an inert support, such as activated carbon, alumina, silica, silica-alumina, carbon black, graphite, titania, zirconia, calcium carbonate, and barium sulfate. Preferred inert support materials are selected from activated carbon, carbon black, graphite, alumina or silica.
The hydrogenation catalysts for use in the present invention are heterogeneous, i.e. they do not dissolve in the ionic liquid, but instead remain as a suspension therein.
However, the catalyst is preferably non-colloidal, i.e. the catalyst particle size, including support (if any) is greater than 20, preferably greater than 50, and preferably greater than 100 μm.
The processes of the present invention preferably employ as catalyst, a platinum or palladium group metal, particularly in supported form, e.g. on carbon, graphite or alumina.
The hydrogenating agent employed in the present process is typically molecular hydrogen or an organic or inorganic hydrogen transfer agent. Hydrogen transfer agents [see e.g. Johnstone et a/., Chem. Rev. (1985), 85, 129 and Brieger et al. Chem. Rev. (1974), 74, 567-580] are compounds which can release hydrogen and which are themselves oxidised. An example of such a hydrogen transfer agent is cyclohexene, which undergoes the following reaction in the presence of e.g. a palladium catalyst and an alkene substrate:
Figure imgf000016_0001
In such a process, the alkene is hydrogenated whilst the cyclohexene is oxidised to benzene.
Other suitable hydrogenating agents include molecular deuterium, HD, molecular tritium, HT, DT, or an organic or inorganic hydrogen, deuterium or tritium transfer agent. Preferably, however, the hydrogenating agent is molecular hydrogen or an organic or inorganic hydrogen transfer agent. Molecular hydrogen is especially preferred as the hydrogenating agent.
The hydrogenation process of the present invention is preferably conducted at temperatures of from 15°C to 200°C, preferably 15°C to 140°C, and more preferably from 20°C to 100°C. Good results are obtained at temperatures of 40°C to 60°C.
Where a non-gaseous hydrogenating agent is employed, the reaction may be conducted at atmospheric pressure.
Where a gaseous hydrogenating agent such as molecular hydrogen is used, the reaction may be conducted at pressures of 101 kPa (i.e. atmospheric pressure) to 8 MPa. Typically, such reactions are conducted at pressures of from 150 kPa (preferably from 1 MPa) to 5 MPa and more preferably from 2.5 MPa to 4.5 MPa.
Good results may be obtained using reaction pressures of 3 MPa to 4.2 MPa.
Hydrogenation reactions represent one of the largest uses of heterogeneous catalysts in the chemical industry. A range of reactions is possible from dehalogenation to simple reductions of alkene to selective reductions of α,β-unsatu rated carbonyl containing molecules. Ionic liquids have not been used previously for any heterogeneously catalysed reactions and provide distinct advantages over many conventional organic and aqueous solvents where selectivity may be poor and/or there are problems with product separation and recycle of the catalyst/solvent system.
We believe we have found the first application of heterogeneous catalysts in ionic liquids for hydrogenation reactions. After the hydrogenation reaction, the hydrogenation catalysts remain suspended in the ionic liquid and are thus easily recyclable without the need to expose the catalyst to air or filter the catalyst from the reaction mixture. This increases the safety of hydrogenation processes especially where recycle of the catalyst is required. Ionic liquids also provide a medium where selectivity can be tuned for a given catalyst over conventional organic solvents. Particular ionic liquids discussed herein include; 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6), 1-hexyl-3-methylimidazolium hexafluorophosphate (C6mimPF6), 1-octyl-3-methylimidazolium hexafluorophosphate (C8mimPF6), 1-decyl-3-methylimidazolium hexafluorophosphate (C10mimPF6),
1-dodecyl-3-methylimidazolium hexafluorophosphate (Cι2mimPF6), 1 -ethyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide (emimNTf2), 1 -hexyl-3-methylimidazolium bis((trifluoromethyl)sulphonyl)amide (C6mimNTf2), 1-hexylpyridinium tetrafluoroborate (C6py BF4), 1-octylpyridinium tetrafluoroborate (C8py BF4),
1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4).
Unless indicated otherwise, the terms used herein have the meanings as indicated below:
"Alkyl" (including alkyl portions of alkyoxy, alkaryl, aralkyl, alkylamino, dialkylamino) represents straight and branched carbon chains containing from 1 to 40 carbon atoms, preferably 1 to 40 carbon atoms, and more preferably 4 to 12 carbon atoms.
"Cycloalkyl" represents saturated carbocyclic rings branched or unbranched containing from 3 to 20 carbon atoms, preferably 3 to 8 carbon atoms. Such cycloalkyl groups include cyclopentyl and cyclohexyl.
"Heterocycloalkyl" represents a saturated, branched or unbranched carbocyclic ring containing from 3 to 12 carbon atoms, preferably from 4 to 6 carbon atoms, wherein the carbocyclic ring is interrupted by 1 to 3 heteroatom moieties selected from -0-, or -N(d to Cβ alkyl), or NH. Such heterocycloalkyl groups include 2- or 3- tetrahydrofuranyl, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-piperizinyl, morpholinyl, 2- or 3- pyrrolidinyl and 2- or 4-dioxanyl.
"Alkenyl" represents straight and branched carbon chains having at least one carbon to carbon double bond and containing from 2 to 40 carbon atoms, preferably 2 to 20 carbon atoms and more preferably from 2 to 12 carbon atoms. Thus, the term "alkenyl" as used herein includes dienes (including conjugated dienes) trienes and tetraenes.
"Cycloalkenyl" represents saturated carbocyclic rings branched or unbranched containing from 3 to 20 carbon atoms, preferably 3 to 8 carbon atoms, wherein the ring contains at least one C=C bond. Cyclohexenyl and cyclopentenyl are particularly preferred cycloalkenyl groups.
"Alkynyl" represents straight and branched carbon chains having at least one carbon to carbon triple bond and containing from 2 to 20 carbon atoms, preferably 2 to 20 carbon atoms and more preferably from 2 to 12 carbon atoms.
"Aryl" including aryl moieties in e.g. aralkyl represents a carbocyclic group containing from 6 to 15 carbon atoms (preferably from 6 to 10 carbon atoms) and having at least one aromatic ring, with all available substitutable carbon atoms of the carbocyclic group being intended as possible points of attachment. Preferred aryl groups include phenyl and naphthyl. Unless otherwise indicated, the term "aryl" includes such carbocyclic groups being optionally substituted with, 1 to 3 of the following substituents: Ci to C6 alkyl, OH, 0(d to C6 alkyl), phenoxy, CF3, (d to C6 alkyl)amino, di(Cι to C6 alkyl)amino, -000(0, to C6 alkyl) or N02.
"Heteroaryl" represents cyclic groups having at least one heteroatom selected from -O- or -N-, said heteroatom interrupting a carbocyclic ring structure and having a sufficient number of delocalised pi electrons to provide aromatic character, with the aromatic heterocyclic groups preferably containing from 2 to 14 carbon atoms.
Suitable heteroaryl groups include pyridine, indole, imidazole, pyridazine, pyrazine, oxazole, triazole, pyrazole, and purines and pyrimidines.
The present invention will be discussed in more detail by way of the following examples and figures:
Figure 1a: Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/graphite catalyst in bmimPFβ. Figure 1b: Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in bmimPF6.
Figure 2a: Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/Al203 catalyst in bmimPFβ.
Figure 2b: Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/Al203 catalyst in bmimPF6.
Figure 3a: Variation in product distribution with time following cinnamaldehyde 1 reduction over 5wt% Pt/graphite catalyst in propan-2-ol.
Figure 3b: Variation in conversion and selectivity towards 2 with time following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in propan-2-ol.
Figure 4: Variation in conversion and selectivity towards 2 with ionic liquid volume following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in emimNTf2.
Figure 5: Variation in conversion and selectivity towards 2 with temperature following cinnamaldehyde reduction over 5wt% Pt/graphite catalyst in emimNTf2.
Figure 6: Variation in conversion of 1 to 3 with pressure following cinnamaldehyde reduction over 10wt% Pd/C catalyst in bmimBF4.
Figure 7: Kinetic study for the conversion (conv) and chemoselectivity (cs) in the hydrogenation of citral to citronellal in 10wt% Pd/C and 10wt% Pd/C modified catalysts in bmimBF4
Figure 8: Variation in conversion of 1-nonyne and selectivity towards 1-nonene with time following 1-nonyne reduction over 10wt% Pd/C catalyst in C6PyBF4 at 30°C and 3 x 105 Pa. Figure 9a: Variation in conversion and selectivity towards styrene with pressure following phenyl acetylene reduction over 5wt% Pd/CaC03 at 30°C after 4 hr.
Figure 9b: Variation in conversion and selectivity towards styrene with temperature following phenyl acetylene reduction over 5wt% Pd/CaC03 at 3 x 105 Pa for 4 hr.
Figure 9c: Variation in conversion and selectivity towards styrene with time following phenyl acetylene reduction over Pd/CaC03 at 3 x 105 Pa & 30°C.
EXAMPLES
In the examples hereinafter, all reactions were carried out in a Baskerville mini autoclave. For all results, the selectivity is defined as follows:
% selectivity n = _ , ., - x 100
Sum of the % products formed where %n is the percentage yield of n.
The ionic liquids for use in the present invention including those employed in the following examples can be made by process such as those disclosed in WO 01/40146.
Fxamplf? 1
1.0 Hydrogenation of cinnamaldehyde using platinum based catalysts
Cinnamaldehyde, 1 , can undergo reduction using hydrogen gas over a heterogeneous catalyst to produce three products, cinnamylalcohol, 2, hydrocinnamaldehyde, 3, and 3-phenylpropanol, 4. The reactions may proceed in two different pathways 1 to 2 to 4 or 1 to 3 to 4 as shown below. This reaction has been studied extensively by many workers with an aim to control the selectivity and promote the formation of cinnamylalcohol and hydrocinnamaldehyde without further reduction to 3-phenylpropanol. These investigations have concentrated on the effect of promoters on the catalyst such as doping with tin or using zeolite based catalysts. The aim of this study was to develop ionic liquids for heterogeneously catalysed reactions and specifically in this case to investigate whether the solvent could act as a promoter without the need to use expensive catalysts.
Figure imgf000022_0001
Each system was compared with propan-2-ol as a benchmark solvent. In the best cases, recycle of the catalyst was attempted. This research shows the potential of ionic liquids to promote selectivity in heterogeneously catalysed reactions with the ability to recycle the catalyst without the need to reactivate it. Some mechanistic details have also been studied and show that isomerisation between 2 and 3 dominates the overall selectivity of the reduction rather than secondary reduction processes.
Unless otherwise stated the reactions were performed under a hydrogen pressure of 4 MPa and a temperature of 60°C. The platinum catalysts were pre-reduced in flowing hydrogen at 350°C for 1 h. Ionic liquid (2ml), 17.5mg (5wt% Pt catalyst), and cinnamaldehyde 0.5ml (substrate/metal ~ 800/1) were introduced to the autoclave and purged three times with argon. Hydrogen at 4 MPa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released. The reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
Table 1 summarises the results of an initial screening for the hydrogenation of cinnamaldehyde using 5% Pt/graphite in a range of ionic liquids.
Table 1 Cinnamaldehyde hydrogenation3 variation with ionic liquid type using 5%
Pt/graphite catalyst.
Figure imgf000023_0001
Reactions carried out at 6 hours at 60°C and 4 MPa H2; bionic liquid recycled; cnitric acid added. d3 hours reaction (at 6 hours the selectivity = 18%)
These results suggest that the hydrogenation of cinnamaldehyde is inhibited in [BF4]" ionic liquids and that [NTf2]" based systems are more active than those containing
[PF6]". Although the conversions for the ionic liquid systems were lower in comparison with propan-2-ol, higher selectivity was maintained at high conversion. It should be noted that in all the ionic liquid reactions, the yield of 4 was negligible whereas in the propan-2-ol reactions this formed the majority of product at 100% conversion. Other anions tested included nitrate, sulfate, hydrogensulphate, hydrogencarbonate, acetate, trifluoroacetate and (S)-lactate; these resulted in little or no conversion. Replacing Pt/graphite with Pt/alumina resulted in lower selectivities and conversions in general.
The addition of trace amounts of nitric acid increased the yield from 47 to 60% without any significant effect on selectivity. It is not clear as yet whether the acid changes the nature of the catalyst surface or influences the redox chemistry of the reaction. The addition of acid is detrimental to the workup, however, since it increases the ionic liquid solubility in common organic solvents, which results in leaching of both the catalyst and the ionic liquid into the organic phase during extraction.
A number of reductions were also carried out in pyridinium and ammonium ionic liquids with little success. Pyridinium and ammonium BF4 and bistriflimides liquids showed no reaction as was the case for pyrollidinium and piperidinium bistriflimides. It is also worth noting that all of the 'solid' solvents employed (for example pyridinium PF6 systems) gave no reaction despite melting below the reaction temperature of 60°C.
From the initial screening, imidazolium ionic liquids achieve the highest yields and selectivity with the trend [NTf2]" > [PF6]" > [BF4]". The best system, emimNTf2, is hydrophobic enabling chloride removal efficient simply by washing with water. It has very low viscosity, which makes it easy to handle and allow for catalyst dispersion.
1.1 Kinetic study on the hydrogenation of cinnamaldehyde
Two kinetic studies were carried out to compare the effect of catalyst support. Figures 1a, 1b, 2a and 2b show the hydrogenation of cinnamaldehyde using Pt/graphite or Pt/alumina in bmimPF6. In both cases, the reaction stops after 5-7 hrs with the conversion rate slowing significantly after 3-5 hrs. Initially the selectivity is high towards cinnamylalcohol 2 however, with increasing reaction time some hydrocinnamaldehyde 3 and 3-phenylpropanol 4 forms. We believe that the formation of 3 occurs because of isomerisation between 2 and 3 catalysed by the supported catalyst in the ionic liquid. This is more pronounced in the case of Pt/Al203 catalysts where a maximum in the selectivity is clearly observed. In both reactions only trace (<2%) of the totally saturated product, 4, is formed. Separate experiments studying the isomerisation of cinnamylalcohol in the presence of Pt catalysts in a range of ionic liquids under an inert atmosphere at 60°C gave up to 60% isomerisation to hydrocinnamaldehyde after 4 hrs. (Note the blank reactions and those performed in propan-2-ol gave negligible conversion). In agreement with the hydrogenation experiments Pt/alumina is more effective than Pt/graphite for the isomerisation.
These kinetic runs may be compared with a similar study using Pt/graphite in propan-2-ol performed at 60°C, shown in Figures 3a and 3b. More conversion is found in propan-2-ol, however, the selectivity towards 2 is poor above 75% conversion. At lower temperatures the selectivity and conversion are both poor.
Catalyst deactivation is likely to be the cause of the conversion being limited. To assess whether the substrate or ionic liquid was causing the deactivation, a blank experiment in which the hydrogenation was carried out under normal experimental conditions for 6hrs without any substrate, cooled, the substrate was added and the reaction performed once more. Under these conditions, no reaction was observed indicating that the ionic liquid, and not the substrate/products, was responsible for the catalyst poisoning.
Poisoning by the ionic liquid could be the result of a number of variables, for example pore blocking, the blocking sites by strongly adsorbed species or halide contamination from the ionic liquid manufacture. Experiments were performed in the presence of trace halide from HCI and NaCI to assess the contribution of halide deactivation. No conversion was observed in these reactions showing that firstly the ionic liquids are used were virtually halide free and secondly, absence of halide impurities is important if these reactions are to proceed. The major consequence of this is that unless electrolysis is performed prior to use, these reactions are limited to hydrophobic ionic liquids, which may be washed with water to remove trace chloride.
Deactivation via strongly adsorbed species was investigated by varying the ionic liquid to catalyst/substrate ratio. The results of this study are shown in Figure 4. Varying the volume of ionic liquid used resulted in little variation in selectivity; however, the conversion was found to vary strongly. Significantly, a maximum in conversion is observed. This occurs at smaller ionic liquid volumes than had been used previously.
1.2 Recycle
The initial screening results (Table 1 ) showed that although it was possible to recycle the ionic liquid, however, in general recycle of the ionic liquid/platinum catalyst resulted in little reaction. Using the optimum conditions found from Figure 4, recycle of the catalyst and ionic liquid was possible. The ionic liquid was simply extracted without removing the catalyst resulting in 99% of the starting material and products being removed, and fresh cinnamaldehyde added. Using this system, 42% conversion and 80% selectivity was achieved after 6 hours compared with 85% conversion and 81 % selectivity for the fresh catalyst system. It should be noted that, extraction results in little transfer of catalyst to the extracting phase and on recycle the catalyst was not pre-activated in hydrogen. As described in the experimental, the normal procedure for the reaction with platinum catalysts is to activate the catalyst in flowing hydrogen at temperature prior to reaction. Without this procedure little reaction occurs and the fact that recycle is possible without further activation shows a significant benefit of using ionic liquids as solvents over conventional organic solvent Osystems.
1.3 Temperature study on the effect of conversion/selectivity
Optimisation with respect to temperature was also performed and the results are shown in Figure 5.
Selectivity and conversion map each other with a maximum in both at 60°C. The selectivity maximum presumably indicates a balance between adsorption and isomerisation. At low temperatures, desorption is low and hence secondary reactions occur whereas at higher temperature isomerisation from 2 to 3 is favoured. Two competing effects may also cause the maximum in conversion, reaction rate and hydrogen solubility. The former rises with temperature whereas the latter drops. Above 90°C significant polymerisation occurred. 1.4 Hydrogenation of cinnamaldehyde in Cn-methylimidazolium ionic liquids
A study into the effect of increasing alkyl chain length (C4-C12) in the imidazolium systems is summarized in Table 2. This demonstrates that there is no advantage in the use of higher chain ionic liquids since, although the selectivity remains constant, the yield decreases steadily as chain length increases. One would expect that increasing the chain length would result in increased hydrogen solubility in the ionic liquid and this might, in turn, increase the conversion rate as the side chain lengthened. However, as the side chain lengthens, the ionic liquid becomes more viscous and mass transfer effects dominate the reaction, reducing the rate.
Table 2: Variation in hydrogenation of 1 using 5% Pt/graphite with increasing alkyl chain length in [Cnmim]+ ionic liquids.
Figure imgf000027_0001
* ionic liquid is a solid at room temperature
1.5 Hydrogenation of different substrates in C6mim NTf with 5wt% Pt/G
A variety of different unsaturated aldehydes were reduced, so as to demonstrate that hydrogenations in ionic liquids are not restricted to the compounds reduced thus far.
The results for the reduction of four different compounds with 5wt% Pt/G in C6mim NTf2 ionic liquid are shown in table 3. Table 3: The reduction of four different substrates at 60°C and 4 MPa after four hours with 5wt% Pt/G in C6mim NTf2.
Figure imgf000028_0001
The results shown in Table 3 demonstrate that in the case of the substrates trans-2- octenal and methyl vinyl ketone, there was 100% formation of the fully saturated alcohol. For 3-cyclohexene-1-carboxaldehyde, 20% of the product was saturated aldehyde and for the reduction of benzylideneacetone the selectivity was found to be greater than 90% towards the alcohol product. It is worth noting that these reactions have not been optimised and therefore do not represent either the optimum in selectivity or activity in this or any other ionic liquid. Example 2
2.0 Hydrogenation of cinnamaldehyde in ionic liquids using 10% Pd/activated carbon
Palladium metal is known to reduce double bonds in preference to carbonyl groups, however, in α,β-unsatu rated systems there is little or no selectivity in common organic solvents. Cinnamaldehyde hydrogenation carried out in propan-2-ol using Pd/activated carbon yielded the fully saturated compound, 3-phenylpropanol, 4.
Unless otherwise stated the reactions were performed under a hydrogen pressure of
4 MPa and a temperature of 60°C. The palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (10wt% Pd catalyst), and cinnamaldehyde 0.5ml (substrate/metal - 800/1 ) were introduced to the autoclave and purged three times with argon. Hydrogen at 40 x 105 Pa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released.
The reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
Table 4 summarizes the results from reduction of cinnamaldehyde using Pd/C in a range of ionic liquids.
Table 4 Cinnamaldehyde hydrogenation variation with ionic liquid type using 10% wt Pd/activated carbon
Figure imgf000030_0001
It is clear from the table that the ionic liquid can adjust the selectivity towards hydrocinnamaldehyde, 3. Unlike in the case of platinum catalysts, all tonic liquid systems were found to be active, [PFβ]" and [BF4]' systems gave high selectivity towards 3, in general, whereas [NTf2]' gave a mixture of products. Under no conditions was cinnamyl alcohol produced using Pd/C.
2.1 Recycle
Recycle of the palladium catalyst/ionic liquid was possible but as with the platinum case a reduction in conversion was observed on reuse. For example, recycle of Pd/C in bmimBF4 showed 100% selectivity with conversion of 17%. Similar selectivities and conversions were observed for the 2nd, 3rd, 4th, 5th and 6th recycles. We believe that pore blocking may be the cause of the deactivation, at least in the case of activated carbon catalysts. Washing the catalyst with acetonitrile, prior to recycle after a first run had little effect on the conversion achieved. Increasing the catalyst loading from 800/1-100/1 increased the initial rate and all recycle (up to 5 recycles performed) showed 100% conversion and selectivity after 4h to hydrocinnamaldehyde 3. 2.2 Effect of pressure on reaction rates
Figure 6 shows the variation of conversion after 4 h with hydrogen pressure. The pressure study showed that, even at low pressures such as 5 x 105 Pa there was significant conversion, after 4h of the reaction. After 24 h, 93% conversion to hydrocinnamaldehyde 3 at 5 x 105 Pa was observed. At all pressures, only hydrocinnamaldehyde is found.
2.3 Temperature study on the effect of conversion/selectivity
The conversion of cinnamaldehyde increases with increasing temperature up to 60°C, whilst maintaining 100% selectivity to hydrocinnamaldehyde. Above 60°C, the selectivity decreases due to the hydrogenation of the carbonyl group, resulting in the formation of the fully saturated alcohol 4. There was no evidence for the formation of 4, when these reactions are run under standard conditions as described in the experimental procedure, even after prolonged reaction time (24 h).
Table 5 Cinnamaldehyde hydrogenation variation with temperature using 10% Pd/activated carbon.
Figure imgf000031_0001
Example 3
3.0 Palladium catalysed hydrogenation of methyl oleate
The palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (10wt% Pd catalyst), and methyl oleate 0.5ml (substrate/metal ~ 800/1) were introduced to the autoclave and purged three times with argon. Hydrogen at 1 MPa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 4 h, upon which the reaction is cooled and the pressure released.
The reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
H3C(CH2) /=\ (CH2)7CO-CH3 H3C(CH2) (CH2)-CO2CH3
10
Methyl oleate 9 was hydrogenated to methyl stearate 10 with 100 % conversion and selectivity after 4 h reaction at 60 °C in C6pyBF4, bmimPF6 and emimNTf2 ionic liquids. Following extraction the reaction was recycled and achieved the same conversions and selectivity. No cleavage of the ester group was observed and there was no loss of the catalyst to the extractant phase.
The so-formed product, 10, remains in the upper layer of the reaction mixture, i.e. above the ionic-liquid phase. Consequently, the product can be readily isolated by decantation, thus avoiding the need for extraction procedures. Thus, the use of ionic liquids in the hydrogenation of fatty acid esters may permit operation on a large scale by a continuous process. Additionally, it is noted that the hydrogenation reactions may be carried out in relatively small quantities of ionic liquid. Example 4
4.0 Palladium catalysed hydrogenation of citral
The palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (10wt% Pd/C), and citral 0.5ml (substrate/metal ~ 800/1 ) were introduced to the autoclave and purged three times with argon. Hydrogen at 4 MPa was introduced and the autoclave heated to the required temperature. The reaction is left to stir for 6h, upon which the reaction is cooled and the pressure released.
The reaction products were extracted using diethyl ether (2x10ml), which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
Citral has three sites of hydrogenation; the conjugate double bond, the carbonyl group and the isolated double bond. The hydrogenation of citral 11 , a compound with a 'methyl blocking group', proceeded with selective hydrogenation of the double bond to produce citronellal 13. Literature reports had suggested that the selectivity in traditional solvents was governed by temperature.
Figure imgf000033_0001
15 Table 6: Citral hydrogenation variation with ionic liquid type using 10wt% Pd/C catalyst.
Figure imgf000034_0001
From Table 6, the results suggest that generally the [BF ]" and the [PF6]' ionic liquids are more selective than the [NTf2]\ however all ionic 'iquids tested are much more selective than propan-2-ol.
The temperature study produced conversion and selectivities analogous to those obtained using cinnamaldehyde 1 as the substrate. From 30°C-60°C, the conversion increases whilst maintaining high selectivity. Above 60°C the formation of the alcohol, citronellol 14, leads to a decrease in selectivity. The citral used for the experiment contains ~65% (E), 35%(Z) isomers. However, it is interesting to observe that the ratio of E/Z isomers of the unreacted citral in these experiments was still 65/35 indicating that the catalytic system did not discriminate between the isomers, even though it was only selective for the reduction of the conjugated double bond. Even at high temperatures and pressures, were citronellol 14 was formed there was no evidence for the formation of the completely hydrogenated product 3,7-dimethyl octan-1-ol 15 or geraniol/nerol 12.
Table 7: Pd/C catalysed hydrogenation of citral at various temperatures in bmimBF4
Figure imgf000035_0001
4.1 Modification of heterogeneous catalysts with amino acids
A series of palladium catalysts loaded onto to activated carbon, alumina and titania modified with (S)-proline (pro), (S)-phenylalanine (phal) and (S)-2-aminobutyric acid (aba) along with the alkaloid cinchonidine (cine) were studied in the hydrogenation of citral.
Initial studies (Table 8) were carried out at 30°C and 1 MPa on the palladium catalysts modified with proline according to the following procedure. The chiral modifier (0.01 mmol) was added to a suspension of ionic liquid 2ml containing the palladium catalyst. The mixture was stirred for 1h at 30°C under 1 MPa of hydrogen to modify the catalyst surface before addition of the substrate molecule (0.52ml of citral). The reaction was then re-pressurised to 1 MPa of H2 and left to stir for 5h, upon which the pressure is released.
The reaction products were extracted using organic solvent or distillation, which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID. Table 8: Heterogeneous hydrogenation1 of citral over modified Pd
Figure imgf000036_0001
1Catalyst, modifier (0.01 mmol) and solvent (2ml) combined and stirred for 1hr at 30°C/1 MPa H2; citral (0.52ml) is added, S/C 600/1. Autoclave is filled up to
1 MPa H2and stirred for 5h. 2Denotes recycle.
These results showed that citral is hydrogenated with excellent chemoselectivities in ionic liquid (Table 8). Furthermore, all of the catalysts give much higher chemoselectivities when employed in ionic liquid compared with propan-2-ol and cyclohexane.
An attempted recycle of the 10wt% Pd/C/ bmimBF system resulted in very poor conversion (4%) and a drop in chemoselectivity from 88% to 80%. Similar recycles of 5wt%Pd/AI203 and 5wt%Pd/Ti02 in bmimBF4 gave similar chemoselectivities as the initial run but the conversions decreased. The use of other chiral modifiers, such as phenylalanine, 2-aminobutyric acid and cinchonidine with 5wt% Pd/Ti02 in bmimBF4 showed no advantage over the proline based system. A kinetic study of the conversion and chemoselectivity of a 10wt% Pd/C modified catalyst (proline) versus an unmodified catalyst shows that the reaction is faster in the modified system but the chemoselectivity drops with time (Figure 7). The unmodified catalyst maintains 100% chemoselectivity throughout the reaction. The decrease in chemoselectivity observed with the modified catalyst is due to the over hydrogenation to citronellol.
Table 9 highlights the use of proline as a modifier on the reaction. (R)-proline, the unnatural enantiomer, as a chiral modifier again produces similar conversion and chemoselectivity as the natural (S)-enantiomer. The use of citronellal as a promoter/modifier on recycle was not observed to increase chemoselectivity or conversion. Addition of fresh amounts of proline as well as the use of a proline saturated system shows excellent chemoselectivity and conversion on recycle.
Table 9: Effect of modifiers on catalyst recyclability
Figure imgf000037_0001
Standard reaction: 10wt%Pd/C (5.5mg), 5wt%Pd/Ti02 (11mg), bmimBF4 2ml, citral 0.52ml. catalyst is modified at 30°C/1 MPa H2 for 1 h, citral is injected and left to react for 5h.
1Denotes recycle of above run.
20.01mmol proline added to original cycle and modified for 1h. 35% wt citronellal added to original cycle and modified for 1 h. 4Standard reaction system run overnight.
5lonic liquid is saturated with (S)-proline before addition of 10wt% Pd/C. βUse of (R)-proline.
Table 10 shows the effect of a proline saturated ionic liquid on the recycle of 10 wt% Pd/C catalyst. The modified catalyst greatly increases the conversion upon the initial run and successive recycles while still maintaining 100% selectivity. Although the unmodified catalyst also shows 100% selectivity over the three recycles performed, the conversions upon recycle are much lower than modified catalyst.
Table 10: Catalyst recycle for 10wt% Pd/C modified (sat. Proline) hydrogenation in bmim BF4.
Figure imgf000038_0001
If a salt of proline is used, such a salt may remain suspended in the ionic liquid. Thus, separation of the product can easily be carried out by extraction procedures.
Example 5
Heterogeneously catalysed dehalogenation of 6-chloropurine.
The palladium on carbon catalysts were used as received used whereas the platinum catalysts and palladium on alumina were pre-reduced in flowing hydrogen at 350°C for 1h. Ionic liquid (2ml), 5.5mg (10wt% Pd on carbon), 11 mg (5wt% palladium on alumina), 19.5 mg (5wt% platinum on alumina), 19.5 mg (5wt% platinum on graphite), and substrate (substrate/metal - 200/1) were introduced to the autoclave and purged three times with argon. Hydrogen at the desired pressure was introduced and the autoclave heated to the required temperature. The reaction is left to stir for the desired time period, upon which the reaction is cooled and the pressure released. The reaction products are extractable using water.
The reaction conversion and selectivity was analysed by HPLC.
Figure imgf000039_0001
15 16 17
Table 11 shows the conversion and selectivity for the reaction to 16 over 17.
Table 11 : Hydro-dehalogenation of 6-chloropurinec in bmim
Figure imgf000040_0001
Figure imgf000040_0002
determined by HPLC, reaction monitored after 4h bionic liquid volume 2ml c1mmol of substrate added
Pressure had little effect on selectivity for the platinum or palladium systems but lower pressure seemed to result in lower conversions. All of the catalysts used showed good conversion and good selectivity in the ionic liquids studied.
Table 12:Catalyst recycle for dechlorinations of 6-chloropurine in BmimBF
Figure imgf000041_0001
Recycle of Pd/Al203 and Pd/CaC03 systems was conducted at 60"C and 4 MPa of hydrogen S/C 200/1. Catalyst deactivation is thought to be a common problem through poisoning by HX, sintering or coking. Sintering of the catalyst is not thought to be an issue, as this has only been reported to occur in gas phase reactions. Table 12 shows that catalyst deactivation in ionic liquids is possibly due to hydrogen halide formation which is eliminated by the use of a basic support. The slight decrease in activity over the recycles may be due to coking.
The dehalogenation of a range of mono-substituted benzenes and substituted halofluorobenzenes is shown in Table 13. From Table 13 the selective dehalogenation of a range of substituted fluorobenzenes proceeds very smoothly producing only fluorobenzene. There is no spectral evidence for the defluorination to benzene or arene hydrogenation. Chlorobenzene proved to be more difficult to dehalogenate than bromobenzene but went to completion after 24h, when CaC03 was used as the support. It has been well documented that side reactions such as dimerisation and hydroisomerisation can occur during the dehalogenation of chlorobenzene, although this has not been observed in our systems. Table 13: Hydrogenation3 of substituted benzenes in bmimBF4
Figure imgf000042_0001
a60 C, 4 MPa S/C 100:1 , 4h "Monitored by GC Conversion to fluorobenzene dconversion to benzene
Example 6
Heterogeneously catalysed reduction of alkynes
The palladium catalysts were used as received. Ionic liquid (2ml), 5.5mg (5wt% Pd on calcium carbonate, 10wt% Pd on activated carbon, 5wt%Pd/CaC03 lead poisoned), and substrate (substrate/metal ~ 800/1 ) were introduced to the autoclave and purged three times with argon. Hydrogen at the desired pressure was introduced and the autoclave heated to the required temperature. The reaction is left to stir for the desired time period, upon which the reaction is cooled and the pressure released. The reaction products were extracted using organic solvent or distillation, which removes all the organic products whilst maintaining the catalyst in the ionic liquid. Product selectivities and conversions were determined using GC-FID.
Table 14 shows the conversion and selectivity for the reduction of 1-nonyne using 10% Pd/C and 5% Pd/CaC03 in a series of different alkyl chain length [Pyridinium]* [BF4]' ionic liquids
Table 14: Reduction of 1-nonyne using 5wt% Pd/CaC03 and 10wt% Pd/C at 30°C and 3 x 105 Pa for 4 hours.
Figure imgf000043_0001
Table 14 shows that 10wt% Pd/C gives complete reduction to the alkane after four hours. The kinetic graph in figure 8 shows that 10wt%Pd/C is 100% selective, although only at low conversions. The 5wt% Pd/CaC03 /CβPyBF system, shows 100% selectivity towards the alkene up to at least 55% conversion, although the C4 pyridinium BF shows lower selectivity after 4h under these reaction conditions. Table 15 shows the conversion and selectivity for the reduction of three different substrates using the 5wt % Pd/CaC03 /C6PyBF system.
Table 15: Reductions of different substrates using 5wt% Pd/CaC03 at 30°C & 3 x 105 Pa for 4hrs.
Figure imgf000044_0001
Table 15 shows that high selectivity towards the alkene is achievable for all three substrates. The conversion and selectivity of phenyl acetylene towards styrene for a series of experiments varying the reaction pressure, temperature and length of reaction time are shown in figures 9a, 9b and 9c.
The graphs of temperature and pressure shown in figures 9a and 9b indicate that an increase in either the temperature or pressure has the effect of increasing the conversion but decreasing the selectivity.
Figure 9c shows that when the reaction proceeds for longer than three hours, the selectivity drops off dramatically due to further hydrogenation to ethyl benzene, indicating that the only way to achieve maximum selectivity is to keep the reaction time and subsequently the level of conversion low. The inverse behaviour of the selectivity with respect to the conversion, explains why as of yet there are no conditions found where 100% conversion and 100% selectivity can be achieved.
Table 16 shows the reduction of phenyl acetylene in a range of ionic liquids using 5wt% Pd/CaC03 poisoned with lead (Lindlars catalyst).
Table 16: Reductions of phenyl acetylene using Lindlars Catalyst at 30°C and 5 x 105 Pa for 4 hours.
Figure imgf000045_0001
Lindlars catalyst maybe used in conjunction with range of ionic liquids to achieve at least 97% conversion with 100% selectivity for the reduction of phenyl acetylene to styrene.
Conclusion
Ionic liquids provide a medium for heterogeneously catalysed hydrogenations, which competes well with conventional solvents. Using unmodified carbon or oxide based platinum group metal catalysts, good selectivity to a range of products is achievable simply by selecting a particular ionic liquid. In these systems it is believed that the ionic liquid modifies the surface and allows the high selectivity to be achieved. Aside from the high selectivity, the use of ionic liquids for hydrogenation reactions provide other advantages over conventional solvents, such as the ease of extraction of the product molecule from the ionic liquid without the need to filter and reactivate the catalyst. This procedure leads to catalyst loss industrially and is a major safety hazard when used on a large scale. The ionic liquid based heterogeneous catalyst systems do deactivate significantly during the reaction compared with organic solvent systems. In these reactions, the ionic liquids cannot be treated as general solvents, as different ionic liquids promote different selectivities, which allows good control over the products without the need to change the catalyst.

Claims

1. A process for the catalytic hydrogenation of a compound containing at least one unsaturated carbon-carbon bond, said process comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.
2. A process according to Claim 1 wherein the compound contains at least one C=C bond.
3. A process according to Claim 1 or Claim 2 wherein the compound contains one to four C=C bonds.
4. A process according to Claim 3 wherein the compound contains one to three C=C bonds.
5. A process according to any preceding claim wherein the compound contains at least one C≡C bond.
6. A process according to Claim 5 wherein the compound contains up to two
C≡C bonds.
7. A process according to any preceding claim wherein the compound contains from 2 to 50 carbon atoms.
8. A process according to Claim 7 wherein the compound contains from 4 to 25 carbon atoms.
9. A process according to Claim 7 wherein the compound contains from 6 to 20 carbon atoms.
10. A process according to any preceding claim wherein the compound includes a moiety selected from alkenes, alkynes, esters, ethers, carboxylic acids, amines, amides, alcohols, nitriles, aldehydes and ketones; or where the compound is selected from fatty acids and esters thereof, steroids, prostaglandins, isoprenoids, flavonoids and icosanoids.
11. A process according to any preceding claim wherein the compound is selected from the group consisting of alkenes, alkynes, aldehydes, fatty acids and esters thereof and compounds containing an aromatic moiety.
12. A process according to Claim 1 wherein the compound has the formula:
O
R^
wherein:
R1 is selected from hydrogen or Ci to C2o straight chain or branched alkyl or C3 to Cβ cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to Cι0 aryl, C8-C o aralkyl, C8-C2o alkaryl,
C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, d to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to C10 aryl; or C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H, Ci to C20 alkyl; and
R2 represents d to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from Ci to C20 alkyl, C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, d to C6 alkylamino, d to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and C6 to C10 aryl; or C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from d to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H, d to do alkyl.
13. A compound according to Claim 12 wherein:
R1 is selected from hydrogen; d to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C20 aralkyl, C8-C2o alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and Cβ to C10 aryl; or Cβ to C10 aryl; and
R2 represents d to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from d to C20 alkyl, C6 to C10 aryl, C8-C2o aralkyl,
Cβ-do alkaryl, hydroxyl, F, CF3, =0 or OR3 wherein R3 is selected from H, d to C∞ alkyl and C6 to C10 aryl; or C6 to C10 aryl wherein said aryl group.
14. A process according to Claim 12 or Claim 13 wherein: R1 is selected from hydrogen; Ci to C10 straight chain or branched alkyl; and
R2 represents to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with 1-3 substituents independently selected from d to C20 alkyl or C6 to Cioaryl.
15. A process according to any of Claims 12 to 14 wherein:
R1 is selected from hydrogen; Ci to C10 straight chain or branched alkyl; and R2 represents d to C20 straight chain or branched alkenyl or C5 to C8 cycloalkenyl wherein said alkenyl or cycloalkenyl group may be substituted with d to C10 alkyl or phenyl.
16. A process according to any of Claims 10 to 14 wherein the compound comprises an α,β-unsatu rated carbonyl moiety.
17. A process according to any of Claims 11 to 15 wherein the compound is cinnamaldehyde, 2-octenal, methylvinylketone, 3-cyclohexene-1-carboxaldehyde and benzylidine acetone.
18. A process according to Claim 1 wherein the compound has the formula:
Rc
:c=c
Rc
wherein: R5, Rβ, R7 and R8 may be the same or different and each is independently selected from: hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to C 0 alkenyl, C5to C8 cycloalkenyl, C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, Ci to Cβ alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, d to C20 alkyl and C6 to C10 aryl; - C2 to C20 straight chain or branched alkenyl;
C5 to C8 cycloalkenyl; or
C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and Ci to C20 alkyl.
19. A process according to Claim 18 wherein:
R5, R6, R7 and R8 are the same or different and each is independently selected from: hydrogen; - Ci to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to C10 alkenyl, C5to C8 cycloalkenyl, C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and C6 to C10 aryl; and - C2 to C2o straight chain or branched alkenyl.
20. A process according to Claim 19 wherein:
R5, R6, R7 and R8 are the same or different and each is independently selected from: - hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl; and C2 to C20 straight chain or branched alkenyl.
21. A process according to Claim 20 wherein
R5, Rβ, R7 and R8 are the same or different and each is independently selected from hydrogen; Ci to C20 straight chain or branched alkyl; and C2 to C20 straight chain or branched alkenyl.
22. A process according to any of Claims 18 to 21 wherein R5 and R7 each represents hydrogen.
23. A process according to any of Claims 18 to 22 wherein R6 and R8 are each independently selected from Ci to C20 straight chain or branched alkyl, C3 to C8 cycloalkyl and C2 to C20 straight chain or branched alkenyl.
24. A process according to any of Claims 18-23 wherein R5, R6 and R7 each represents hydrogen and R8 is as defined in Claims 20 to 23.
25. A process according to Claim 18 wherein the compound has the formula:
R \ _ ^R7 R \ _ ^H R6^ H , R6^ H ,
Figure imgf000050_0001
wherein R5, R6 and R7 are as defined in any of Claims 18 to 21.
26. A process according to any of Claims 18 to 25 wherein R5, R6, R7 or R8 represents a C2 to C20 straight chain or branched alkenyl.
27. A process according to Claim 1 wherein the compound has the formula:
R9C* CR 10
wherein R and R are each independently selected from: hydrogen;
Ci to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C2 to Ci0 alkenyl, C5to C8 cycloalkenyl, C6 to C10 aryl, Cβ-do aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0,
Ci to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and Cβ to C10 aryl; and Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and Ci to C20 alkyl.
28. A process according to Claim 27 wherein R9 and R10 are each independently selected from: hydrogen; - Ci to do straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C20 aralkyl, C8-C20 alkaryl, C3 to C8 cycloalkyl, hydroxyl or OR3 wherein R3 is selected from H, Ci to C20 alkyl and Ce to Ci0 aryl; and - Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to C10 alkyl, hydroxyl, F or OR4 wherein R4 is selected from H and Ci to C20 alkyl.
29. A process according to Claim 28 wherein: R9 and R10 are each independently selected from: hydrogen;
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl; and Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to Ci0 alkyl, hydroxyl, F or OR4 wherein R4 is selected from H and Ci to C20 alkyl.
30. A process according to Claim 29 wherein R9 and R10 are each independently selected from: hydrogen; Ci to C2o straight chain or branched alkyl or C3 to C8 cycloalkyl; and C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to Ci0 alkyl, hydroxyl, or OR4 wherein R4 is selected from H and Ci to C10 alkyl.
31. A process according to Claim 30 wherein R9 and R10 are each selected from hydrogen, Ci to C10 alkyl which may be substituted by hydroxyl, or phenyl.
32. A process according to any of Claims 27 to 31 wherein at least one of R9 or R10 is hydrogen.
33. A process for the hydro-dehalogenation of a compound containing at least one C-Cl, C-Br or C-l bond, the process comprising reacting said compound with a hydrogenating agent and a heterogeneous hydrogenation catalyst in the presence of an ionic liquid.
34. A process according to Claim 33 wherein the compound has the formula:
P-X wherein: P represents a group selected from:
Ci to C20 straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to C10 aryl, C8-C o aralkyl, Cβ-C∞ alkaryl, C3 to C8 cycloalkyl, hydroxyl, F, CF3, =0, Ci to C6 alkylamino, Ci to C6 dialkylamino, -CN, COOR3, CONR3 or OR3 wherein R3 is selected from H, Ci to C20 alkyl and C6 to C10 aryl;
C6 to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to Ci0 alkyl, hydroxyl, F, CF3, CN, COOR4, CONR4 or OR4 wherein R4 is selected from H and Ci to C20 alkyl; - heteroaryl; or heterocycloalkyl; and X represents CI, Br or I
35. A process according to Claim 33 wherein P represents:
Ci to o straight chain or branched alkyl or C3 to C8 cycloalkyl wherein said alkyl or cycloalkyl group may be substituted with 1-3 substituents independently selected from: C6 to Ci0 aryl, C8-C20 aralkyl, C8-do alkaryl, C3 to C8 cycloalkyl, hydroxyl;
Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to Cι0 alkyl, or hydroxyl; heteroaryl; or heterocycloalkyl.
36. A process according to Claim 33 wherein P represents
Ci to o straight chain or branched alkyl or C3 to C8 cycloalkyl Cβ to C10 aryl wherein said aryl group may be substituted with 1-3 substituents independently selected from Ci to Cι0 alkyl, or hydroxyl; - heteroaryl, wherein said heteroaryl group is a purine or pyrimidine; or heterocycloalkyl.
37. A process according to any of Claims 33 to 36 wherein the compound contains at least one C-Cl bond.
38. A process according to any preceding claim wherein the ionic liquid is an imidazolium, pyridinium, pyridazinium, pyrazinium, oxazolium, triazolium or pyrazolium salt.
39. A process according to Claim 38 wherein the ionic liquids is a salt of an alkylated or polyalkylated compound of pyridine, pyridazine, pyrimidine, pyrazine, imidazole, pyrazole, oxazole or triazole.
40. A process according to Claim 38 or Claim 39 wherein the ionic liquid has the formula:
Figure imgf000054_0001
wherein
Ra is a Ci to o straight chain or branched alkyl or C3 to C8 cycloalkyl group, wherein said alkyl or cycloalkyl group which may be substituted by one to three groups selected from: Ci to C6 alkoxy, C6 to Ci0 aryl, CN, OH, N02, Ci to C30 aralkyl and Ct
Ϊ0 to C30 alkaryl; Rb, Rc, Rd, Re and Rf can be the . same or different and are each independently selected from H or any of the Ra groups as defined above; and
A represents an anion having a charge n-; wherein n may be 1-3.
41. A process according to Claim 40 wherein Ra represents C4 to Ci2 straight chain or branched alkyl.
42. A process according to Claim 41 wherein Rb, Rc, Rd, Re and Rfare hydrogen.
43. A process according to Claim 42 wherein n is 1.
44. A process according to Claim 38 wherein the ionic liquid has the formula:
Figure imgf000055_0001
wherein each Ra may be the same or different and each is independently selected from Ci to o straight chain or branched alkyl which may be substituted by one to three groups selected from: Ci to Cβ alkoxy, Cβ to Cι0 aryl, CN, OH,
N02, Ci to o aralkyl and Ci to C30 alkaryl;
A represents one or more species of anion having valency n; and n represents 1-3.
45. A process according to Claim 38 wherein the ionic liquid has the formula:
Figure imgf000055_0002
wherein
Ra is selected from Ci to C40 straight chain or branched alkyl which may be substituted by one to three groups selected from: Ci to Cβ alkoxy, Cβ to Cι0 aryl, CN, OH, N02, Ci to C30 aralkyl and d to C30 alkaryl;
A represents one or more species of anion having valency n; and n represents 1-3.
46. A process according to Claim 40 to Claim 45 wherein Ra is independently selected from Ci to C 0 straight chain or branched alkyl.
47. A process according to Claim 46 wherein Ra is independently selected from Ci to do straight chain or branched alkyl.
48. A process according to Claim 47 wherein each Ra and Rb is independently selected from C to Cι2 straight chain or branched alkyl.
49. A process according to Claim 48 wherein A represents a single species of anion having valency n.
50. A process according to Claim 40 to 49 wherein n is 1.
51. A process according to any of Claims 38 to 44 wherein A represents an anion selected from boron or phosphorus fluorides, N03, S04, HS04, HC03, [(CF3S02)2N], [AsFβ], alkylsulfonates, mono- or difluorinated alkyl sulfonates including perfluorinated alkylsulfonates, carboxylic acid anions, fluorinated carboxylic acid anions and metal halides.
52. A process according to Claim 51 wherein A represents an anion selected from [PF6], [BF4], [OS02CF3], [OS02(CF2)3CF3], [OC02CF3], [OC02(CF2)3CF3], [OC02CH3], nitrate, sulfate, hydrogen sulfate, hydrogen carbonate, acetate, trifluoroacetate, lactate, [(CF3S02)2N], [B(alkyl) ] wherein each alkyl can be the same or different and can be any straight chain or branched Ci to C10 alkyl group, [SbFβ]* and [AsF6].
53. A process according to Claim 52 wherein A represents an anion selected from [PF6], [BF4], [OS02CF3], [OS02(CF2)3CF3], [OC02CF3], [OC02(CF2)3CF3], [OC02CH3], [(CF3S02)2N], [B(alkyl)4] wherein each alkyl can be the same or different and can be any straight chain or branched Ci to Cι0 alkyl group, [SbF6]" and [AsF6].
54. A process according to Claim 53 wherein A represents an anion selected from [PFβ], [BF4] and [(CF3S02)2N].
55. A process according to any of Claims 40 to 55 wherein A represents a phosphate or an amide.
56. A process according to any preceding claim wherein the heterogeneous hydrogenation catalyst comprises nickel, palladium, ruthenium, iridium, rhodium and platinum.
57. A process according to Claim 56 wherein the heterogeneous hydrogenation catalyst comprises palladium or platinum.
58. A process according to Claim 56 or Claim 57 wherein the catalyst is supported on an inert support.
59. A process according to Claim 58 wherein the inert support comprises activated carbon, alumina, silica, silica-alumina, carbon black, graphite, titania, zirconia, calcium carbonate, and barium sulfate.
60. A process according to Claim 58 or Claim 59 wherein the inert support is selected from activated carbon, carbon black, graphite, alumina or silica.
61. A process according to any preceding claim wherein the particle size of the heterogeneous hydrogenation catalyst is up to 200 A.
62. A process according to Claim 61 wherein the particle size of the heterogeneous hydrogenation catalyst is from 20 A to 200 A.
63. A process according to any of Claims 1 to 60 wherein the catalyst particle size, including support (if any) is greater than 20, preferably greater than 50, and preferably greater than 100 μm.
64. A process according to any preceding claim wherein the hydrogenating agent is molecular hydrogen, molecular deuterium, HD, molecular tritium, HT, DT, or an organic or inorganic hydrogen, deuterium or tritium transfer agent.
65. A process according to any preceding claim wherein the hydrogenating agent is molecular hydrogen or an organic or inorganic hydrogen transfer agent.
66. A process according to Claim 65 wherein the hydrogenating agent is molecular hydrogen.
PCT/GB2002/002333 2001-05-18 2002-05-17 Hydrogenation processes performed in ionic liquids Ceased WO2002094740A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CA002446835A CA2446835A1 (en) 2001-05-18 2002-05-17 Hydrogenation processes performed in ionic liquids
EP02735575A EP1387819B1 (en) 2001-05-18 2002-05-17 Hydrogenation processes performed in ionic liquids
AU2002310587A AU2002310587A1 (en) 2001-05-18 2002-05-17 Hydrogenation processes performed in ionic liquids
DE60230259T DE60230259D1 (en) 2001-05-18 2002-05-17 HYDROGENATION METHOD IN THE PRESENCE OF IONIC LIQUIDS
JP2002591415A JP4558276B2 (en) 2001-05-18 2002-05-17 Hydrogenation method
DK02735575T DK1387819T3 (en) 2001-05-18 2002-05-17 Hydration processes performed in ionic liquids
US10/478,039 US7667058B2 (en) 2001-05-18 2002-05-17 Hydrogenation process
US12/612,149 US7803974B2 (en) 2001-05-18 2009-11-04 Hydrogenation processes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0112093.0A GB0112093D0 (en) 2001-05-18 2001-05-18 Hydrogenation processes
GB0112093.0 2001-05-18

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10478039 A-371-Of-International 2002-05-17
US12/612,149 Division US7803974B2 (en) 2001-05-18 2009-11-04 Hydrogenation processes

Publications (3)

Publication Number Publication Date
WO2002094740A2 true WO2002094740A2 (en) 2002-11-28
WO2002094740A3 WO2002094740A3 (en) 2003-03-13
WO2002094740A8 WO2002094740A8 (en) 2003-05-08

Family

ID=9914830

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2002/002333 Ceased WO2002094740A2 (en) 2001-05-18 2002-05-17 Hydrogenation processes performed in ionic liquids

Country Status (12)

Country Link
US (2) US7667058B2 (en)
EP (2) EP1921056B1 (en)
JP (3) JP4558276B2 (en)
AT (1) ATE417030T1 (en)
AU (1) AU2002310587A1 (en)
CA (1) CA2446835A1 (en)
DE (1) DE60230259D1 (en)
DK (1) DK1387819T3 (en)
ES (1) ES2318011T3 (en)
GB (1) GB0112093D0 (en)
PT (1) PT1387819E (en)
WO (1) WO2002094740A2 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005058782A1 (en) * 2003-12-18 2005-06-30 Exxonmobil Chemical Patents Inc. Improvements in or relating to hydrogenation
FR2910471A1 (en) * 2006-12-26 2008-06-27 Holis Technologies Catalytic asymmetric hydrogenation of a prochiral beta-substituted enamine, comprises placing a charge of the enamine in a reactor and subjecting the reaction medium in the reactor to a pressure of hydrogen and to a temperature
US7405329B2 (en) 2003-12-18 2008-07-29 Exxonmobil Chemical Patents Inc. Hydroformylation
US20090264691A1 (en) * 2006-04-26 2009-10-22 Sud Chemie Ag Porous heterogeneous catalyst coated with an ionic liquid
RU2529033C1 (en) * 2013-06-13 2014-09-27 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Волгоградский государственный технический университет" (ВолгГТУ) METHOD OF HYDROGENATING α, β-UNSATURATED KETONES
EP2286915A3 (en) * 2005-01-04 2015-03-11 The Queen's University of Belfast Ionic liquids with a cation comprising a basic moiety
US9327272B2 (en) 2009-10-30 2016-05-03 Clariant International Ltd. Method for producing a composite material
US12172147B2 (en) 2011-10-19 2024-12-24 Sud Chemie, Inc. Catalyst composition for selective hydrogenation with improved characteristics
EP4696672A1 (en) 2024-08-16 2026-02-18 ARLANXEO Deutschland GmbH Process for the synthesis of 2-chloro-1,3-butadiene and 2,3-dichloro-1,3-butadiene
WO2026037737A1 (en) 2024-08-16 2026-02-19 Arlanxeo Deutschland Gmbh Process for the synthesis of 2-chloro-1,3-butadiene and 2,3-dichloro-1,3-butadiene

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0112093D0 (en) * 2001-05-18 2001-07-11 Univ Belfast Hydrogenation processes
DE102005049568A1 (en) 2005-10-17 2007-04-19 Basf Ag Process for continuous hydrogenation or hydrogenating amination
US7622532B2 (en) * 2007-02-16 2009-11-24 William Marsh Rice University Synthesis of radioactive materials and compositions of same
TWI333946B (en) * 2007-04-26 2010-12-01 Cpc Corp Taiwan Method of selectively hydrogenating 2-methyl-buta-1,3-diene by using supported ionic liquid nano-pd catalyst
KR100963402B1 (en) * 2007-12-04 2010-06-14 성균관대학교산학협력단 Hydrogenation of Aromatic Compounds
CN102056877B (en) * 2008-06-09 2014-11-05 索维索莱克西斯公开有限公司 Method for manufacturing perfluorovinylethers
WO2010061909A1 (en) * 2008-11-27 2010-06-03 高砂香料工業株式会社 Asymmetric hydrogenation catalyst
JP5913352B2 (en) * 2010-11-29 2016-04-27 高砂香料工業株式会社 Asymmetric hydrogenation catalyst and method for producing optically active carbonyl compound using the same
KR101492871B1 (en) 2013-08-07 2015-02-13 한국과학기술연구원 Carbon based palladium catalyst and method for producing the same using ionic liquid and its catalystic application for HFC hydrogenation
CN104549494B (en) * 2013-10-28 2017-06-20 中国石油化工股份有限公司 Synthesize the catalyst of 1,4 cyclohexanedimethanols
CN111504933B (en) * 2020-05-12 2022-12-06 扬州工业职业技术学院 A method for analyzing and detecting new anti-AIDS drugs
CN114100689B (en) * 2021-11-29 2023-04-07 万华化学集团股份有限公司 Hydrogenation catalyst, preparation method and application thereof
CN114653403B (en) * 2022-03-18 2023-02-03 大连理工大学 Preparation method and application of bifunctional catalyst for preparing cyclohexanone by phenol hydrogenation

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5459233A (en) * 1977-10-17 1979-05-12 Teijin Ltd Preparation of aromatic hydrocarbons
JPS56133221A (en) * 1980-03-24 1981-10-19 Hodogaya Chem Co Ltd Dechlorinating method of chlorinated toluene
JPS60218330A (en) * 1984-04-16 1985-11-01 Mitsui Toatsu Chem Inc Dehalogenation
JPS63132848A (en) * 1986-11-22 1988-06-04 Idemitsu Kosan Co Ltd Selective hydrogenation of hydrocarbon compound having triple bond
JPS63291643A (en) * 1987-05-25 1988-11-29 Nippon Kayaku Co Ltd Selective hydrogenation reaction catalyst for phenylacetylenes
JPH0377836A (en) * 1989-08-17 1991-04-03 Ishihara Sangyo Kaisha Ltd Production of m-difluorobenzene
JPH03279338A (en) * 1990-03-28 1991-12-10 Tokuyama Sekiyu Kagaku Kk Production of unsaturated alcohol
US5490919A (en) * 1990-08-14 1996-02-13 State Of Isreal, Atomic Energy Commission Process for the dehalogenation of organic compounds
EP0598338B1 (en) * 1992-11-18 1997-03-12 Hoechst Aktiengesellschaft Process for the preparation of 1,3 - difluorbenzene
NL9401708A (en) * 1994-10-17 1996-06-03 Dsm Nv Process for the preparation of 3-phenylpropanal.
DE4438547A1 (en) * 1994-10-28 1996-05-02 Bayer Ag Process for the hydrogenation of unsaturated fatty acid esters
FR2735399B1 (en) * 1995-06-16 1997-07-25 Inst Francais Du Petrole NOVEL CATALYTIC COMPOSITION BASED ON TRANSITIONAL METAL COMPLEXES AND METHOD FOR THE HYDROGENATION OF UNSATURATED COMPOUNDS
JPH09249613A (en) * 1996-03-15 1997-09-22 Nissan Chem Ind Ltd New alicylic compound and its production
JP4216931B2 (en) * 1998-10-22 2009-01-28 株式会社日本触媒 Process for producing optically active 3-hydroxyisobutanoic acid esters
WO2000032572A2 (en) * 1998-12-04 2000-06-08 Symyx Technologies Combinatorial discovery and testing of ionic liquids
GB9928290D0 (en) 1999-12-01 2000-01-26 Univ Belfast Process for preparing ambient temperature ionic liquids
GB0024745D0 (en) * 2000-10-10 2000-11-22 Univ Belfast Oxidation of alkyl-aromatic compounds
GB0112093D0 (en) * 2001-05-18 2001-07-11 Univ Belfast Hydrogenation processes
JP2008271990A (en) * 2006-06-20 2008-11-13 Kyushu Univ Method for dehalogenation of organic halides by electrolytic reduction in ionic liquids

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7405329B2 (en) 2003-12-18 2008-07-29 Exxonmobil Chemical Patents Inc. Hydroformylation
WO2005058782A1 (en) * 2003-12-18 2005-06-30 Exxonmobil Chemical Patents Inc. Improvements in or relating to hydrogenation
US7586017B2 (en) 2003-12-18 2009-09-08 Exxonmobil Chemical Patents Inc. Hydrogenation
EP2286915A3 (en) * 2005-01-04 2015-03-11 The Queen's University of Belfast Ionic liquids with a cation comprising a basic moiety
US8334232B2 (en) * 2006-04-26 2012-12-18 Sud-Chemie Ag Porous heterogeneous catalyst coated with an ionic liquid
US20090264691A1 (en) * 2006-04-26 2009-10-22 Sud Chemie Ag Porous heterogeneous catalyst coated with an ionic liquid
WO2008096075A3 (en) * 2006-12-26 2008-10-09 Holis Technologies Method for the asymmetric hydrogenation of enamine and device for realising said method
FR2910471A1 (en) * 2006-12-26 2008-06-27 Holis Technologies Catalytic asymmetric hydrogenation of a prochiral beta-substituted enamine, comprises placing a charge of the enamine in a reactor and subjecting the reaction medium in the reactor to a pressure of hydrogen and to a temperature
US9327272B2 (en) 2009-10-30 2016-05-03 Clariant International Ltd. Method for producing a composite material
US12172147B2 (en) 2011-10-19 2024-12-24 Sud Chemie, Inc. Catalyst composition for selective hydrogenation with improved characteristics
US12172148B2 (en) 2011-10-19 2024-12-24 Sud Chemie, Inc. Catalyst composition for selective hydrogenation with improved characteristics
RU2529033C1 (en) * 2013-06-13 2014-09-27 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Волгоградский государственный технический университет" (ВолгГТУ) METHOD OF HYDROGENATING α, β-UNSATURATED KETONES
EP4696672A1 (en) 2024-08-16 2026-02-18 ARLANXEO Deutschland GmbH Process for the synthesis of 2-chloro-1,3-butadiene and 2,3-dichloro-1,3-butadiene
WO2026037737A1 (en) 2024-08-16 2026-02-19 Arlanxeo Deutschland Gmbh Process for the synthesis of 2-chloro-1,3-butadiene and 2,3-dichloro-1,3-butadiene

Also Published As

Publication number Publication date
GB0112093D0 (en) 2001-07-11
EP1921056B1 (en) 2015-04-22
EP1921056A1 (en) 2008-05-14
EP1387819A2 (en) 2004-02-11
ES2318011T3 (en) 2009-05-01
JP2010006842A (en) 2010-01-14
JP2009102385A (en) 2009-05-14
WO2002094740A8 (en) 2003-05-08
PT1387819E (en) 2009-03-23
US7667058B2 (en) 2010-02-23
US20040267034A1 (en) 2004-12-30
DE60230259D1 (en) 2009-01-22
CA2446835A1 (en) 2002-11-28
WO2002094740A3 (en) 2003-03-13
DK1387819T3 (en) 2009-04-06
ATE417030T1 (en) 2008-12-15
US7803974B2 (en) 2010-09-28
EP1387819B1 (en) 2008-12-10
AU2002310587A1 (en) 2002-12-03
JP2004533455A (en) 2004-11-04
US20100056782A1 (en) 2010-03-04
JP4558276B2 (en) 2010-10-06

Similar Documents

Publication Publication Date Title
US7803974B2 (en) Hydrogenation processes
JP2010534216A (en) Method for producing menthol by hydrogenation of isopulegol
EP0214530B1 (en) A method for producing cycloolefins
US7064239B2 (en) Preparation of 1,6-hexanediol
Tahara et al. Liquid-phase hydrogenation of car☐ ylic acid on supported bimetallic RuSn-Alumina catalysts
Künzle et al. Continuous enantioselective hydrogenation in fixed-bed reactor: towards process intensification
KR20180090994A (en) Isomerization of MDACH
US6472575B2 (en) Process for producing adamantane
EP0170915A2 (en) A method for producing cycloolefins
EP2269971B1 (en) Process for producing a 2-alkyl-2-cycloalkene-1-one
US4709085A (en) Cyclopropanation process
JP2565561B2 (en) Manufacturing method of 7-octene-1-ar
Hubert et al. Ruthenium-catalyzed allylation reaction in ionic liquid
Nozoe et al. Non-solvent hydrogenation of solid alkenes and alkynes with supported palladium catalysts
US4720597A (en) Process for the production of hydroxymethylcyclopropane (cyclopropylmethanol)
EP1309580B1 (en) Continuous process for the production of optically pure (s)-beta-hydroxy-gamma-butyrolactone
US20040044229A1 (en) Process for alpha,beta-dihydroxyalkenes and derivatives
JP6650140B2 (en) Catalyst composition for producing carbon monoxide and method for producing carbon monoxide
EP3950653A1 (en) Method for producing halogenated cycloalkane compound
US3520935A (en) Hydrogenation of cinnamic aldehyde
EP2479163B1 (en) Method for producing cyclohexyl alkyl ketones
CA2290780A1 (en) Method for producing 2-cyclododecyl-1-propanol
JPH08325172A (en) Method for producing cycloolefin
Isomerization 46.11 Synthesis by Isomerization of Unconjugated Dienes, Allenes, Alkynes, and Methylenecyclopropanes
JPH0213651B2 (en)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
CFP Corrected version of a pamphlet front page
CR1 Correction of entry in section i

Free format text: IN PCT GAZETTE 48/2002 UNDER (72, 75) REPLACE "STRANMILLS ROAD" BY "STRANMILLIS ROAD"

WWE Wipo information: entry into national phase

Ref document number: 2446835

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2002735575

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2002591415

Country of ref document: JP

WWP Wipo information: published in national office

Ref document number: 2002735575

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWE Wipo information: entry into national phase

Ref document number: 10478039

Country of ref document: US