WO2005105734A1

WO2005105734A1 - Separation of unsymmetrical diimines by liquid chromatography

Info

Publication number: WO2005105734A1
Application number: PCT/US2005/014597
Authority: WO
Inventors: Maurice S. Brookhart; Vasilly Kotov
Original assignee: University Of North Carolina At Chapel Hill
Priority date: 2004-04-27
Filing date: 2005-04-27
Publication date: 2005-11-10
Also published as: CN1942433A; EP1758848A1

Abstract

Novel unsymmetrical diimines containing a polar group are made by preparing a mixture of the unsymmetrical diimine and two symmetrical diimines, for example by reacting a dicarbonyl compound with two primary amines. The unsymmetrical diimine is then purified by liquid chromatography. The unsymmetrical diimines are useful as ligands in olefin polymerization catalysts.

Description

SEPARATION OF UNSYMMETRICAL DIIMINES BY LIQUID CHROMATOGRAPHY FIELD OF THE INVENTION A mixture of a novel unsymmetrical diimine containing a polar group and two symmetrical diimines is prepared, and the diimines separated by liquid chromatography. TECHNICAL BACKGROUND Diimines of various types are useful as chemical intermediates, and are especially useful as ligands in transition metal complexes which are part of olefin polymerization catalyst systems, see for instance U.S. Patents 5,955,555, 6,103,658, 6,200,925 and 6,579,823. In many instances these diimines are symmetrical, that is the organic group attached to the two imino nitrogen atoms in the diimine by a single bond are identical. Since imine groups are most commonly made by reacting a carbonyl group (ketone or aldehyde) with a primary amine, in such a synthesis a symmetrical diimine is made by reacting two carbonyl groups in the same compound with the same diimine. For various reasons it is sometimes preferred that a diimine be unsymmetrical, that is each of the groups attached to an imino nitrogen atom through a single bond are different. While these can sometimes be made by the sequential reaction of two different primary amines with a dicarbonyl compound, oftentimes a mixture of symmetrical and unsymmetrical diimines, which are difficult to separate, is formed. In some instances, in an unsymmetrical diimine, one of the organic groups attached to an imino ni- trogen atom by a single bond may desirably contain a polar group, see for instance World Patent Application 02/79276, which is hereby included by reference. It has been found that if two different primary amines are reacted either simultaneously or sequentially with a dicarbonyl compound to form an unsymmetrical diimine a mixture of symmetrical and unsymmetri- cal diimines usually results, but these diimines (one symmetrical which contains two polar groups, one symmetrical which contains no polar groups, and one unsymmetrical which contains one polar group) are readily separable by using some form of liquid chromatography. The unsymmetrical diimine may therefore be isolated in pure form, along with the two symmetrical diimines, which may then be used, or recycled to form additional unsymmetrical diimine. SUMMARY OF THE INVENTION This invention concerns a process for the preparation of an unsymmetrical diimine, comprising, forming a mixture of an unsymmetrical diimine and two symmetrical diimines, and then subjecting said mixture to liquid chromatography and isolating said unsymmetrical diimine, provided that said unsymmetrical diimine has a polar group attached to the group bonded to one of the imino carbon atoms by a single bond. Also disclosed herein is an unsymmetrical diimine of the formula

R¹- — Y- -R N N / \ , R² R³ (I) wherein: each R¹ is independently hydrogen, a heteroatom connected monovalent radical, hydrocarbyl, or substituted hydrocarbyl, Y is a covalent bond or a divalent bridging group; R² is hydrocarbyl or substituted hydrocarbyl; and R³ is substituted hydrocarbyl containing a polar group; and provided that both of R¹ taken together may form a ring; and R² and R³ are different. DETAILS OF THE INVENTION Herein certain terms are used, and some of them are defined be- low: By a "diimine" is meant a compound of the formula

R¹ π Y π — R¹ N N / \ , R² R³ (I)

wherein each R¹ is independently hydrogen, a heteroatom connected monovalent radical, hydrocarbyl, or substituted hydrocarbyl, Y is a cova- lent bond or a divalent bridging group, and R² and R³ are each independently hydrocarbyl or substituted hydrocarbyl, provided that both of R¹ taken together may form a ring. By an "α-diimine" is meant a compound of formula (I) in which Y is a covalent bond. By an "unsymmetrical diimine" is meant a diimine of formula (I) in which R² and R³ are different. By "an unsymmetrical diimine containing a polar group" is meant a diimine in which R² contains at least one polar group, and R³ contains no polar groups or one or more less polar groups. By "liquid chromatography" is meant any method by which a solute containing two or more different compounds is dissolved in a liquid, and the resulting solution is passed over an adsorbent that separates two or more of the solute compounds. The solute compounds are typically re- moved from the adsorbent by eluting with liquid (solvent). Such methods are well know, see for instance P. Lembke, et al in Ullmann's Encyclopedia of Chemical Technology, 6^th Ed., Vol. 19, Wiley-VCH, Weinheim, p. 567-636, and C. F. Simpson, Ed., Techniques in Liquid Chromatography, John Wiley & Sons, Chichester, 1982, both of which are hereby included by reference. A "hydrocarbyl group" is a univalent group containing only carbon and hydrogen. If not otherwise stated, it is preferred that hydrocarbyl groups herein preferably contain 1 to about 30 carbon atoms. By "substituted hydrocarbyl" herein is meant a hydrocarbyl group that contains one or more substituent groups that are inert under the process conditions to which the compound containing these groups is subjected (e.g., an inert functional group, see below). The substituent groups also do not substantially detrimentally interfere with the polymerization process or operation of the polymerization catalyst system. If not other- wise stated, it is preferred that substituted hydrocarbyl groups herein contain 1 to about 30 carbon atoms. Included in the meaning of "substituted" are chains or rings containing one or more heteroatoms, such as nitrogen, oxygen and/or sulfur, and the free valence of the substituted hydrocarbyl may be to the heteroatom. In a substituted hydrocarbyl, all of the hydro- gens may be substituted, as in trifluoromethyl. By "(inert) functional group" herein is meant a group other than hydrocarbyl or substituted hydrocarbyl that is inert under the process conditions to which the compound containing the group is subjected. The functional groups also do not substantially interfere with any process described herein that the compound in which they are present may take part in. Examples of functional groups include halo (fluoro, chloro, bromo and iodo), ether such as -OR²⁵, -CO₂R²², -NO₂, and -NR²² ₂, wherein each R²² is independently hydrocarbyl or substituted hydrocarbyl. In cases in which the functional group may be near a transition metal atom the functional group should not coordinate to the metal atom more strongly than the groups in compounds which are shown as coordinating to the metal atom, that is they should not displace the desired coordinating group. By "aryl" is meant a monovalent aromatic group in which the free valence is to the carbon atom of an aromatic ring. An aryl may have one or more aromatic rings which may be fused, connected by single bonds or other groups, such as 9-anthracenyl or 1-naphthyl. Unless otherwise stated aryl groups preferably contain 5 to 30 carbon atoms. By "substituted aryl" is meant a monovalent aromatic group substituted as set forth in the above definition of "substituted hydrocarbyl". Suitable substituents include alkyl, aryl such as phenyl, halo, alkoxy, ester, dialkylamino and nitro. Similar to an aryl, a substituted aryl may have one or more aromatic rings that may be fused, connected by single bonds or other groups; however, when the substituted aryl has a heteroaromatic ring, the free valence in the substituted aryl group can be to a heteroatom (such as nitrogen) of the heteroaromatic ring instead of a carbon. Unless otherwise stated, substituted aryl groups contain 5 to about 30 carbon atoms. „^• "Alkyl group" and "substituted alkyl group" have their usual meaning

(see above for substituted under substituted hydrocarbyl). Unless otherwise stated, alkyl groups and substituted alkyl groups preferably have 1 to about 30 carbon atoms. By a "heteroatom connected monovalent radical" is meant a substi- tuted hydrocarbyl which is a monovalent radical or group which is connected to the rest of the compound through a valence of a heteroatom (an atom other than C and H). The group may be more than monovalent if it is part of a ring connected by a bridging group. In a formation of the mixture of diimines containing the unsymmetri- cal diimine of formula (I), a dicarbonyl compound (II) may be reacted with two primary amines R²NH₂ (III) and R³NH₂ (IV), per the reaction:

(1) R¹- II II 4. II II N N N + II II / \ N N + H₂0 / R² (V) R³ R² \ ₂ / \ , (VI) ^R R³ (VII) ^R

Typical techniques for forming imines from carbonyl compounds may be used, such as heating, the use of catalysts, and removal of the byproduct water to drive the reaction to completion. Typical catalysts include Bron- sted acids such as p-toluenesulfonic and sulfuric acids. Water may be removed by azeotropic distillation or by chemical removal by forming a hydrate by reacting the water, for instance with CaO. Most commonly the three diimines obtained in equation (1) will be present in relative quantities that reflect a random statistical formation of the diimines. In equation (1 ) the reaction with (II) and (IV) may be carried out simultaneously or sequentially in any order. If sequentially and a symmetrical diimine is formed preferentially in the first step, the second step should be run under conditions that at least partially randomizes the R² and R³ groups in the diimines formed. Since all of the imine group forming reactions are in fact equilibria, this is usually readily accomplished. Oftentimes the reaction(s) involved in equation 1 are run in a solvent or a liquid medium. At the end of the reaction the solvent may be removed, for example by vaporization, or the solution (assuming the prod- ucts are soluble) may be used directly for the liquid chromatography, assuming the solvent is suitable for use in chromatography. The diimines may be concentrated by removal of some of solvent before the chromatography is started. If the solvent is completely removed the diimines may be redissolved in another solvent and that solution used for the liquid chroma- tography. Forms of liquid chromatography useful in the present process include column chromatography, flash chromatography, and high-pressure liquid chromatography, and flash chromatography is preferred. Generally speaking in liquid chromatography the solute is adsorbed on an adsorbent, often called the stationary phase, and that components of the solute are separated because they are more or less strongly adsorbed on the solid phase. Solvents are used to separate and "move" the various solute compounds on the stationary phase, and eventually to elute these separated solute compounds from the stationary phase. Sometimes compounds are separated because they have different polarity, and in those instances the solvent polarity is sometimes gradually changed, for instance from less to more polar, by using appropriate solvents and solvent mixtures. Preferred stationary phases are silica gel and alumina. If we assume in equation (I) that R² has the only polar group in the compounds (V), (VI) and (VII), then (VI) will be the most polar diimine, (V) will be less polar, and (VII) the least polar. Therefore if the diimines are eluted in the order least polar to most polar, (VI) will elute first, (V) second, and (VII) third. Depending on the solid phase and solvent(s) used, as well as the diimines being chromatographed, this order will not always follow. However because of the polarity differences of these three types of diimines, separation will usually be achieved, even though a small amount of experimentation may be necessary. It has been found that when polar groups, are not present in these diimines, separation by chromatography is generally more difficult. This is compounded by the fact that these diimines may be in equilibrium with each other, particularly if water is present. Whether polar groups are present or not, chromatography conditions that favor reequilibration of the diimines, such as highly acidic conditions and/or high temperatures should preferably be avoided. In (I), and the corresponding primary amines and dicarbonyl compound from which it is prepared, it is preferred that: Both of R¹ are alkyl, more preferably methyl, or a heteroatom connected monovalent radical which taken together may form a ring, or both of R¹ taken together are

Y is a covalent bond or -(CH₂)n- wherein n is 1 , 2 or 3, more preferably a covalent bond, or

R² is substituted aryl; and/or R³ is aryl or substituted aryl, preferably containing no polar groups except it may optionally contain halogen. Polar groups are groups which react with a support (or compounds attached to a support), or which may be reacted with a second compound to form a third compound which reacts with a support. For a description of various polar groups and their complementary reactive groups see US Patent Application 2002187892, which is hereby included by reference. A preferred type of polar group is a group that may hydrogen bond, such as hydroxyl, amino (especially primary and secondary amino), thiol, and car- boxyl. Another preferred type of polar group is an acid that has a pK_a (in water) of about 0 to about 15, more preferably about 3 to about 13. One type of preferred polar group, which is part of R2, is a group that may be used to bond, preferably cόvalently bond, a transition metal complex in which the unsymmetrical diimine is a ligand to a support. Thus the unsymmetrical diimine containing transition metal complex becomes a component of a catalyst system, preferably a polymerization catalyst sys- tem that is supported on a support. Such systems are well known in general, and specifically known for diimines, see World Patent Application 02/79276. Such preferred polar groups include hydroxyl, amino (especially primary and secondary amino), thiol, and carboxyl, and hydroxyl is especially preferred. Formation of such transition metal complexes is also well known; see for instance U.S. Patents 5,955,555, 6,103,658,

6,200,925 and 6,579,823, all of which are hereby included by reference. As noted above, usually a mixture of the unsymmetrical diimine and two symmetrical diimines will be obtained. The symmetrical diimines may be used for some purpose after their isolation. However in some in- stances it may be preferable to recover and further convert them to desired unsymmetrical diimine. This can be done by placing both of the symmetrical diimines (preferably in equimolar amounts) into the same reaction and reequilibrating them by, for instance, heating, addition of a catalyst and adding a bit of water. This will produce the mixture of unsymmet- rical and symmetrical diimines again, and they can be separated by liquid chromatography. This reequilibration can also be carried out in a reaction in which the symmetrical diimines are added to the mixtures of 2 different primary amines the dicarbonyl compound. If only one of the symmetrical diimines is placed in this reaction, then the stoichiometry should be adjusted so that the amounts of the two "primary amines" added (as primary amines or part of a diimine) should be about equimolar. The following illustrates a somewhat different overall synthesis of the unsymmetrical diimine. Two appropriate symmetrical diimines [made by a process similar to the reaction in equation (1 )], one having the appropriate polar group and the other not, may be prepared separately and then equilibrated to form a mixture of the two symmetrical diimines and the unsymmetrical diimine. The unsymmetrical diimine may then be purified us- ing liquid chromatography. Thus if one or both of the symmetrical diimines have no other uses, they may be recycled in the process to form unsymmetrical diimine. This is particularly valuable if the dicarbonyl compound and/or one or both of the primary amines is particularly expensive. Example 1

To a suspension of 1.00 g acenaphtenequinone (5.48 mmol/1 eq) in 50ml of toluene was added 0.83 g of 2-(4-aminophenyl)ethanol (6.02 mmol/1.1 eq), 1.94g of 2,4,6-triphenylaniline (6.02 mmol/1.1 eq) and 0.06 g of p-toluenesulfonic acid monohydrate (0.06 mol%). The reaction mixture was refluxed for 7 d. The water was removed by azeotropic distillation. The reaction was followed by thin layer chromatography on silica us- ing Whatman 250 μm Layer, flexible plates for TLC, PE SIL G/UV (Whatman pic, Kent ME16 OLS, UK) to ensure completion of the reaction. The unsymmetrical diimine was purified by flash chromatography (ethyl acetate: hexane / 1 :1 volume) and isolated in 30% yield (1.0g), as a deep- red solid. Flash chromatography was carried out under standard condi- tions using procedures described in W. C. Still, et al., J. Org. Chem., vol. 43, p. 2923-2925 (1978), which is hereby included by reference. A 36 cm long x 4.5 cm diameter column was used and it was about 2/3 filled with silica gel (Scientific Adsorbents #02826-25, particle size 22-63 μm, pore size 60 Angstroms, Scientific Adsorbents, Inc., Atlanta, GA 30340, USA). Two products symmetrical diimine 1 containing no hydroxyl groups (R_f = 0.83) and unsymmetrical diimine 2 containing one hydroxyl group (R_f = 0.36) were isolated by flash chromatography. The solvent was removed under vacuum. The diimines 1 and 2 were obtained, as deep-red solids in 8.5% (0.37g) and 30% (1g) yields correspondingly. Diimine 3 containing 2 hydroxyl groups apparently remained on the column and probably could have been eluted with a more polar solvent (mixture). H NMR (300 MHz, CDCI₃, 25°C): 2.93 (m, 2 H, CH₂), 4.14 (m, 2 H, ■ OCH₂), 6.68, 6.78, 6.87, 6.98, 7.26, 7:39, 7.53, 7.63,.7.77 (number of m, Σ 27 H, Ar).

Claims

1. A process for the preparation of an unsymmetrical diimine, comprising, forming a mixture of an unsymmetrical diimine and two symmetrical diimines, and then subjecting said mixture to liquid chromatography to isolate said unsymmetrical diimine, provided that said unsymmetrical diimine has a polar group attached to a group bonded to one of the imino carbon atoms by a single bond.

2. The process as recited in claim 1 wherein said unsymmetrical diimine has the formula R¹- -R¹ N N \ R R° (I) wherein: each R¹ is independently hydrogen, a heteroatom connected monovalent radical, hydrocarbyl, or substituted hydrocarbyl, Y is a covalent bond or a divalent bridging group; R² is hydrocarbyl or substituted hydrocarbyl; and R³ is substituted hydrocarbyl containing a polar group; and provided that both of R¹ taken together may form a ring; and R² and R³ are different.

3. The process as recited in claim 1 or 2 wherein each R¹ is methyl or both of R¹ taken together are

4. The process as recited in claim 1 , 2 or 3 wherein Y is a covalent

bond, -(CH₂)_n- wherein n is 1 , 2 or 3, or

5. The process as recited in any one of claims 1 to 4 wherein R² is substituted aryl, and R³ is aryl or substituted aryl. 6. The process as recited in any one of claims 1 to 5 wherein said polar group is selected from the group consisting of hydroxyl, amino, thiol, and carboxyl. 7. The process as recited in claim 6 wherein said polar group is hydroxyl. 8. The process as recited in any one of claims 1 to 7 wherein a stationary phase is silica gel or alumina. 9. An unsymmetrical diimine of the formula

R' -Y- -R' N \ R^Δ (I) wherein: each R¹ is independently hydrogen, a heteroatom connected monovalent radical, hydrocarbyl, or substituted hydrocarbyl, Y is a covalent bond or a divalent bridging group; R² is hydrocarbyl or substituted hydrocarbyl; and R³ is substituted hydrocarbyl containing a polar group; and provided that both of R¹ taken together may form a ring; and R² and R³ are different. 10. The unsymmetrical diimine as recited in claim 9 wherein each R¹ is methyl or both of R¹ taken together are

11. The unsymmetrical diimine as recited in claim 9 or 10 wherein Y

is a covalent bond, -(CH2)_n- wherein n is 1 , 2 or 3, or

12. The unsymmetrical diimine as recited in claim 9, 10, or 11 wherein R² is substituted aryl, and R³ is aryl or substituted aryl. 13. The unsymmetrical diimine as recited in any one of claims 9 to 12 wherein said polar group is selected from the group consisting of hydroxyl, amino, thiol, and carboxyl. 14. The unsymmetrical diimine as recited in claim 13 wherein said polar group is hydroxyl.