Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2002-02-04
2004-09-07
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C502S155000, C502S158000, C502S159000, C568S814000
Reexamination Certificate
active
06787676
ABSTRACT:
Organic compounds containing hydroxyl groups, including those in optically active form, are important intermediates, for example for the preparation of pharmaceutical active ingredients, crop protection agents, fragrances and liquid-crystalline substances.
EP-A 718 265 discloses a process for the preparation of non-chiral and optically active alcohols in which a carbonyl compound is reacted with hydrogen in the presence of a homogeneous catalyst, a base and an organic compound containing nitrogen. The homogeneous catalyst may, for example, be a ruthenium complex containing phosphine ligands, the base may be an alkali metal or alkaline earth metal hydroxide, and the organic compound containing nitrogen may be an amine.
A disadvantage of this process is the use of a homogeneous catalyst, which hinders work-up of the reaction mixture and the preparation of products which are not contaminated with catalysts or constituents thereof. Furthermore, the isolation of the valuable catalyst or its constituents is possible, if at all, only with high technical complexity and expenditure. Finally, it is difficult to carry out processes using homogeneous catalysts in a continuous manner.
Homogeneous catalysts are characterized by high selectivities and activities which are not generally achieved by corresponding heterogeneous catalysts.
It therefore had to be taken into consideration that in the present case as well, when transferring from homogeneous to heterogeneous catalysts, any advantages, e.g. with regard to work-up of the reaction mixture, purity of the product prepared, catalyst recovery and continuous reaction procedure, can only be realised in conjunction with serious disadvantages, e.g. with regard to selectivity and activity.
We have now found a process for the preparation of non-chiral and optically active alcohols in which a carbonyl compound is reacted with hydrogen in the presence of a catalyst, a base and optionally a diamine, which is characterized in that the catalyst used is a support-bonded Ru(II)-phosphine-diamine-Ru complex catalyst of the formula (I).
Hal=Cl or Br (I)
A short time ago (Synlett 2000, No. 5 680-682), a process for the asymmetric hydrogenation of ketones became known which is carried out using a heterogeneous catalyst component which contains BINAP structural elements incorporated in the main chain. This is an oligomeric diisocyanate adduct with the name “poly-NAP” (see Tetrahedron Letters 41 (2000), 643-646), which is significantly different from the catalysts used according to the invention which contain support-bonded bisphosphine-diamine-Ru(II) complexes. The support-bonded catalysts used according to the invention are, for example in contrast to poly-NAP, insoluble in all solvents. A significant advantage of the process according to the invention is that, because of the multiplicity of chiral bisphosphines which are suitable for constructing support-bonded catalysts, a large number of different heterogeneous bisphosphine components can be provided in order, in combination with the amine components of the catalyst system, to achieve the optimum processing method for the substrate in question.
Catalysts which contain support-bonded bisphosphine ligands and which are suitable as precursors for the novel catalysts used according to the invention are known or can be obtained analogously to the preparation of ones which are known (see e.g. J. Org. Chem. 63, 3137 (1998), GB-A 96-19684, EP-A 496 699, EP-A 496 700, EP-A 728 768, J. Mol. Catal. A 107 (1-3), 273 (1996) and 13th International Conference on Org. Synth., Warsaw, July 1-5, 2000, Book of Abstracts, PB-4, p. 227).
A process for the preparation of non-chiral alcohols using such catalysts in the presence of amines and a base has not, however, hitherto been considered.
According to the invention, alcohols are obtained by reacting a carbonyl compound with hydrogen in an advantageous manner if the hydrogenation is carried out using a catalyst of the formula (I) in the presence of a base.
where
Hal is chlorine or bromine.
It is also possible to carry out the hydrogenation using a support-bonded, insoluble catalyst of the formula (II) if both a base and also a diamine are present in the reaction mixture at the same time during the hydrogenation. In this case, a catalyst of the formula (I) is formed in situ.
where
Hal is chlorine or bromine.
Preference is, however, given according to the invention to using catalysts of the formula (I) which already contain support-bonded Ru(II) complexes which, in each case contain both bisphosphine and also diamine ligands.
Suitable supports for He catalyst to be used according to the invention are inorganic materials, e.g. silica gels, and organic materials, e.g. crosslinked polymers.
Examples of inorganic supports which may be mentioned are: silicates or metal oxides in powder form with an average particle size between 10 nm and 2000 &mgr;m, preferably 10 nm and 500 &mgr;m. The particles may either be compact or porous, in the latter case the internal surface area being between 1 and 1200 m
2
. Examples of oxidic supports which may be mentioned are SiO
2
, TiO
2
, ZrO
2
, MgO, WO
3
, Al
2
O
3
, and La
2
O
3
, and examples of silicates are silica gels, aluminas, zeolites and porous glass (controlled pore glass). Preferred supports are silica gels and aluminium oxides.
Organic catalyst supports are, for example, crosslinked bead polymers which can be obtained by suspension polymerization with the addition of bifunctional monomers from styrene, acrylates or methacrylates or (meth)acrylamides.
In order to permit a binding of the bisphosphine ligands, these supports must contain reactive groups. Suitable for this purpose are, for example, primary and secondary amino groups, hydroxyl, carboxyl and isocyanate groups, and groups which contain reactive halogen, such as benzylic chlorine or bromo(ar)alkyl.
Such groups can be introduced as early as during the preparation of the bead polymer using functional comonomers such as acrylic acid, methacrylic acid, 2-hydroxyethyl acrylate, 2-methyl-2-isocyanato-propyl acrylate or by subsequent modification of the support, e.g. by chloromethylation of the crosslinked polystyrene bead polymer, which may optionally be followed by a further functionalization, such as, for example, saponification and polyether grafting. The preparation of such polymers with reactive groups is known.
It has proven advantageous to arrange the modification of the support such that a greater distance is maintained between support and bisphosphine, a spacer being advantageous which consists of an alkylene or aralkylene or an alkyleneoxy chain optionally with incorporated ester, ether, amide, urethane or urea groups and includes at least 12 atoms between support and bisphosphine.
The inorganic support—in particular silica gels—can be modified in a manner known per se by reaction with silicic esters or chlorosilanes which each contain suitable functional groups, in order to introduce reactive groups suitable for the desired linking, such as, for example, amino groups. Examples of compounds suitable for such a modification which may be mentioned are 3-aminopropyl-triethoxysilane, trichlorovinylsilane and 3-mercaptopropyl-triethoxysilane.
It is also possible to react the inorganic support with suitable modified bisphosphine derivatives directly to give the fixed bisphosphine (derivatives) according to the invention. For this modification, bisphosphine derivatives are used which contain functional groups of the formula
Si(OR)
3-n
(R)
n
or
Si(R′)
n
Cl
3-n
,
where
R is alkyl,
R′ is alkyl or alkoxy and
n is 0-2.
The reaction takes place analogously to known modifications of silica gels with chlorosilanes or silicic esters.
For the preparation of the catalysts used according to the invention, chelate-forming bisphosphines are used which contain functional groups which can generate a covalent bond with reactive groups on a suitable if suitably modified, insoluble support.
Examples of functional groups of the bisphosphine derivatives used
Norris McLaughlin & Marcus PA
Shippen Michael L.
Studiengesellschaft Kohle mbH
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