Catalytic process

Details Catalytic process Catalytic process

2000-08-25

2001-11-27

Barts, Samuel (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Amino nitrogen containing

C564S446000, C564S472000, C564S473000

Reexamination Certificate

active

06323370

ABSTRACT:

The present invention concerns an improved catalytic process. In particular, it concerns a reductive amination process in the presence of a homogeneous iridium catalyst.
Reductive amination is the term used for the process of introducing alkyl groups into ammonia or an amine using an aldehyde or ketone in the presence of a reducing agent. There are large scale reductive amination processes carried out using heterogeneous catalysts, under severe and exacting reaction conditions. These heterogeneous catalysts are used as amongst other reasons it is easy to separate off the catalyst once the reaction is complete. This may be done for instance by filtration. Homogeneous hydrogenation has not generally been used. This is because severe conditions are also require often 50-350° C. and 10-300 atmospheres pressure. It would be desirable to carry out such hydrogenation processes under much milder conditions.
A successful homogeneous reductive amination could lead to an attractive and profitable industrial process. For, example, arylbenzylamines, which can be produced by reacting amines and benzyl halides together, are useful as antioxidants in many synthetic and petroleum lubricants (BK Blandlish et al E.P. 22, 281 (1983) Chem. Abs. 94: 15959b). However, although high yields of arylbenzylamines have been reported, this route is expensive and not environmentally friendly. Also, it is not easy to adapt current methodology to give chiral materials. The production of chiral amines may be of particular importance in the production of pharmaceuticals and agrochemicals.
There are very few homogeneous catalysts for direct reductive amination at the present time, and the development of a method for reductive amination using a homogeneous catalyst could represent a major innovation. This is the problem the present invention sets out to solve. In this regard, the present inventors have found that [Ir(COD)(L)]+, where COD=cyclooctadiene and L=(R
3
P)
2
or a chelating bisphosphine is a promising homogeneous catalyst for hydrogenation, and more importantly, reductive amination reactions. Certain iridium complex catalysts are known to catalyse imine hydrogenation (J.Organometallic Chem. 527, (1997), 75-82 and Chem. Ind. (Dekker) (1995), 62 (Catalysis of Organic Reactions, 181-8). However these catalysts have not previously been used to catalyse reductive amination reactions.
Accordingly, in the first aspect, the present invention provides a method for the reductive amination of a carbonyl-containing compound R
1
R
2
CO, where R
1
and R
2
are either H, alkyl, aryl or heterocyclic, or where R
1
and R
2
together form an aliphatic ring structure, with an amine NHR
3
R
4
where R
3
and R
4
are H, alkyl, aryl, or heterocyclic, or R
3
and R
4
may together form a heterocyclic ring structure, in the presence of a homogeneous iridium catalyst and gaseous hydrogen.
In the second aspect the present invention provides a method for the reductive amination of a carbonyl-containing compound of general formula R
1
R
2
CO, where R
1
and R
2
are either H, alkyl, aryl or heterocyclic, or where R
1
and R
2
together form an aliphatic ring structure, with an amine of general formula NHR
3
R
4
where R
3
and R
4
are H, alkyl, aryl, or heterocyclic, or R
3
and R
4
may together form a heterocyclic ring structure, in the presence of a homogeneous iridium catalyst which is attached to a solid support, and gaseous hydrogen.
In one particular embodiment of the invention R
1
, R
2
, R
3
and R
4
may contain further substituents such as alcohol groups, ester groups, or halogen groups.
This synthesis may be achieved through the use of iridium pre-catalysts such as [Ir(diolefin)(L1)(L2)]X where the diolefin may be typically cyclooctadiene or norbornadiene (bicyclo[2.2.1]hepta-2,5-diene) and L1 and L2 are ligands containing a phosphorus donor atom e.g triphenyl phosphine or a heterocyclic nitrogen atom e.g pyridine. Additionally L1 and L2 may be part of the same bidentate ligand e.g. L1+L2=1,2-bis(diphenylphospino)ethane (dppe), The bidentate ligand may be present as a single enantiomer of a chiral compound e.g S,S-(+)-DIOP allowing the process to be used for the synthesis of chiral amines. S,S-(+)-DIOP is (S,S)-(+)-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane. X is a non-coordinating anion which may typically be a halide or for instance ClO
2
−
, BF
4
−
, PF
6
−
, BPh
4
−, RSO
3
— or a similar group.
Suitable pre-catalysts for a reaction of this sort are [Ir(COD)(dppb)]PF
6
, (dppb=1,4-bis(diphenylphosphino)butane), [Ir(COD)(BINAP)]PF
6
(BINAP=2,2′-bis(diphenylphosphino)1, 1′-binaphthyl), [Ir(COD)(DIOP)]PF
6
DIOP=2,3-O isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane).
Ir(COD)(pyridine)(PC y
3
)]PF
6
(PCy
3
=tricyclohexylphosphine). These pre-catalysts may be preformed or may be formed in situ, for example by mixing of [{IrCl(COD)}
2
]+dppb, dppe or BINAP or from [Ir(COD)(pyridine)
2
]PF
6
+dppb or dppe.
The reactions of the present invention may be carried out in the presence of a solvent. Suitable solvents include alcohols for instance methanol or ethanol, ethers such as tetrahydrofuran, halogenated solvents for example dichloromethane or 1,2-dichloroethane or hydrocarbons for example toluene. Such solvents may be used in admixture with water.
The reaction is carried out in the presence of gaseous hydrogen at a pressure from 0-10 bar and preferably in the range from 1-5 bar. Moderate temperatures may be used for the reactions of the present invention preferably in the range from 0-150° C. and more preferably in the range from 20-100° C. Even more preferably the reaction may be carried out in the range from 40-70° C. Reaction times will be dependent on the nature of the two main reactants, but will typically be a few hours to a few days and most typically 2-24 hours.
Attachment to a solid support facilitates recovery of the catalyst at the end of the reaction. Suitable methods for the immobilisation of iridium pre-catalysts may include but are not limited to, ionic binding (where the support provides the non-coordinating anion X, and may be typically a hydrocarbon resin in the form of beads or fibres bearing anionic groups such as sulphonate or carboxylate, or an inert support such as zeolite modified with ionic binding material such as poly-oxometallate, e.g polytungstic acid) or covalent binding (where the support provides one or both of the neutral donor ligands L1 or L2, for example as a pendant group bound to a hydrocarbon resin, optionally in the form of beads or fibres.
In a further embodiment of these two aspects of the present invention the iridium pre-catalyst may be isolated prior to use in the reaction or may be generated in situ by reaction of a suitable compound such as [Ir(diolefin)(halide)]
2
or [Ir(diolefin)(pyridine)
2
]X with ligands L. Suitable reaction conditions for the preparation of such compounds will be known to those skilled in the art (see for example Inorg. Synth. vol 24, 173).
Separation or isolation of the product may be carried out by methods known to those skilled in the art and may include filtration, chromatography and so on.


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Bedford, R.B.; Chaloner, P.A.; Dewa, S.Z.; López, G; Hitchcock, P.B.; Momblona, F; and Serrano, J.L., “Anomalous reactivity of triphenylarsine and triarylphosphines of low basicity with [Ir(cod) (py)2] [PF6] and use of the complexes as precatalysts for imine hydrogenation,”Journal of Organometallic Chemistry, vol. 527, 1997, pp. 75-82.
Bedford, R.B.; Chaloner, P.A.; Claver, C.; Fernandez, E.; Hitchcock, P.B.; and Ruiz, A., “Homogene

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