WO2000043771A1 - Selection de catalyseurs par spectrometrie de masse - Google Patents

Selection de catalyseurs par spectrometrie de masse Download PDF

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Publication number
WO2000043771A1
WO2000043771A1 PCT/IB2000/000062 IB0000062W WO0043771A1 WO 2000043771 A1 WO2000043771 A1 WO 2000043771A1 IB 0000062 W IB0000062 W IB 0000062W WO 0043771 A1 WO0043771 A1 WO 0043771A1
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reaction
catalyst
chain
catalysts
mass
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PCT/IB2000/000062
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Peter Chen
Christian Hinderling
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Thales Technologies, Ag
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Priority to AU30689/00A priority Critical patent/AU3068900A/en
Priority to EP00900760A priority patent/EP1149286A1/fr
Priority to JP2000595141A priority patent/JP2003506665A/ja
Priority to PL00349046A priority patent/PL349046A1/xx
Priority to HU0105237A priority patent/HUP0105237A3/hu
Priority to KR1020017009205A priority patent/KR20010093267A/ko
Publication of WO2000043771A1 publication Critical patent/WO2000043771A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N31/00—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
    • G01N31/10—Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods using catalysis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B01J2219/00707—Processes involving means for analysing and characterising the products separated from the reactor apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00738—Organic catalysts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/00745—Inorganic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/00745—Inorganic compounds
    • B01J2219/00747—Catalysts
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B30/00—Methods of screening libraries
    • C40B30/08—Methods of screening libraries by measuring catalytic activity
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/18—Libraries containing only inorganic compounds or inorganic materials
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes

Definitions

  • Described here is a rapid screening method for identifying compounds having catalyst activity which employs mass spectrometric analysis.
  • the method is exemplified for rapid screening of polymerization catalysts using tandem mass spectrometry and gas phase ion-molecule reactions and is specifically applied to screening of organometallic catalysts used in the production of polyolefms.
  • the screening method of this invention has the advantages of high sensitivity (mg-scale quantities), very short assay times (one hour), simultaneous competitive screening of multiple catalysts directly according to propensity for high polymer formation (rather than a derivative property such as heat release), good prospects for scaling to large combinatorial libraries, and implicit encoding of catalyst identity by mass.
  • Simple ion-molecule reactions are used to simplify the mass spectrum of complicated mixtures generated during screening.
  • CONFIRMATION C0PV a clumsy encoding procedure that limits its usefulness.
  • Catalyst screening strategies typically assay reaction rate or turnover number by rapid assay of the products of a catalyzed reaction. The emphasis is on the miniaturization and acceleration of methods used conventionally for product determination. For example, rate is correlated with heat release in the thermographic assay, which is appropriate for assays of overall catalytic activity.
  • rate is correlated with heat release in the thermographic assay, which is appropriate for assays of overall catalytic activity.
  • overall catalytic activity is only one of several important catalyst properties for which high-throughput screens are needed.
  • M w average molecular weight
  • M n the number-average molecular weight
  • M w /M n a measure of polydispersity because M w emphasizes the heavier chains, while M n emphasizes the lighter ones
  • M w /M n a measure of polydispersity because M w emphasizes the heavier chains, while M n emphasizes the lighter ones
  • the present invention provides methods for screening catalysts using mass spectrometric analysis of catalyst-bound intermediates in the catalytic cycle, or products of catalysis.
  • the methods are applicable, in particular, to screening of organometallic compounds for catalytic function.
  • the methods are applicable, in particular, to screening for catalysts for polymerization reactions. More specifically, the methods employ a two stage (or two step) mass spectrometric detection method in which ions formed in a first stage ionization and which are linked to catalyst performance are selected and the catalyst associated with the selected ion is identified in a second stage employing tandem mass spectrometry.
  • the screening methods of this invention avoid explicit encoding because the identity of the catalyst is implicitly contained in the product molecular mass (typically an intermediate product), since the catalyst (or a portion thereof) remains attached to the product.
  • the methods of this invention are particularly beneficial in screening for polymerization catalysts to avoid spectral congestion that can be created by the distribution of product oligomer and polymer lengths even for analysis of the polymerization products of a single catalyst species.
  • the screen as applied to polymerization catalysts, is direct in that it assays polymer chain growth itself rather than a property which may be correlated with chain growth.
  • one or more test catalysts are provided.
  • the test catalysts are contacted with a selected reactant species under selected reaction conditions.
  • the reagent species is a compound or mixture of compounds upon which the catalyst acts to generate a desired product. Reaction conditions are selected to promote a selected catalytic reaction.
  • the catalytic reaction is quenched after a selected time sufficient to allow the selected reaction to proceed to generate product, e.g., for polymer chains to grow, and allow differentiation of catalyst activity.
  • the reaction mixture is introduced into the first stage of a tandem mass spectrometer, subjected to ionization, and mass analysis.
  • the quenched reaction mixture Prior to introduction into the mass spectrometer, the quenched reaction mixture can optionally be subjected to partial purification, solvent removal, dilution, concentration, or chemical derivatization to improve analysis, remove impurities or the like.
  • Certain ions formed in the first stage of the tandem mass spectrometer are selected for introduction into the second stage of the spectrometer. Ions are selected which derive from the catalyst activity that is being screened. For example, in screens for polymerization catalysts ion mass selection can be employed, i.e. ions with mass/charge ratio (m/z) greater than a selected cutoff mass can be selected as derived from the best catalysts, e.g., those that promote the longest chains in the time given.
  • the selected ions are introduced into the second stage of the mass spectrometer where they are subjected to a reaction to give daughter ions that allow identification of the catalyst which catalyzed formation of the products whose ions were selected from the first stage.
  • the selected high mass ions, associated with the longest polymer chains formed are subjected in the second stage to reactive collisions with neutrals to generate daughter ions.
  • Ion-molecule reactions including collision-induced dissociation, can be employed to generate daughter ions.
  • Preferred ion molecule reactions are those which cleave the product, e.g., the polymer chain, from its associated catalyst or portion of the catalyst, leaving an ion that can be directly, and preferably, uniquely related to the catalyst.
  • Mass analysis of the daughter ions generated allows identification of the catalyst species responsible for the products from which the selected ions derive.
  • the test catalysts can be provided as a library encompassing a plurality of compounds spanning a range of structural variants to assess the relationship of structure to catalytic function.
  • a library of candidate polymerization catalysts is contacted with a selected monomer under reaction conditions (pH, temperature, solvent, etc.) that promote polymerization.
  • the reaction mixture sample is introduced into the mass spectrometer in a manner that preserves association of the catalyst with the reaction product(s), e.g., the catalyst (or a portion thereof) remains associated with the growing polymer chain formed from reagent monomers in a polymerization reaction.
  • the mass spectrometric methods of this invention can also be employed to obtain bulk properties of polymers that result from the use of a catalyst.
  • the average molecular weight and molecular weight distribution of all polymer chains, not just metal-bound (i.e., catalyst bound) polymers can be determined by the generation of kinetic data (as provided in Example 3). Distributions of odd chains (metal -bound oligomer chains with methyl endgroups) and even chains (metal bound oligomer chains with hydrogen endgroups) are observed in the mass spectrum after catalytic reaction. Fitting of the experimental odd/even distribution data with the general kinetic scheme for Ziegler-Natta polymerization yields absolute rates for initiation, propagation, and chain-transfer for a set of reaction conditions. These rates allow determination of average molecular weight and molecular weight distribution of products from catalytic reaction of screened catalysts without explicit preparation or isolation of bulk polymer. Average molecular weight and molecular weight distribution of polymeric products can be used as screening criteria for catalyst selection.
  • the method of this invention is particularly suited to screening of ionic and/or ion pair polymerization catalysts.
  • a library of catalysts consisting of more than two distinct catalysts is contacted with an excess of monomer, usually ethylene, but which can be other simply substituted olefins, in organic solution.
  • the reaction is then quenched with an additional ligand, such as CO, isocyanides, ethers, esters, phosphites, sulfoxides or other coordinating ligands, after polymerization has proceeded up to addition of a few hundred monomer units.
  • the resulting quenched solution is then electro sprayed into a tandem mass spectrometer.
  • the high mass ions which are associated with the catalyst (or a portion of the catalyst) linked to the longest polymer chains formed during the reaction are selected in the first stage of the mass spectrometer. These selected ions will be associated with the more active catalysts.
  • the selected ions are then subjected in the second stage of the spectrometer to an ion-molecule reaction, e.g., collision-induced dissociation, to cleave off the oligomer/polymer chain from the catalyst.
  • the daughter ion(s) remaining after the ion- molecule reaction is mass-analyzed in the second stage of the mass spectrometer identify the catalyst species responsible for the production of the highest molecular weight polymer chains.
  • Figure 1 A is an electrospray mass spectrum of a quenched and diluted reaction mixture of complexes la-lc each approximately 10 "3 M in CH 2 C1 2 saturated with ethylene.
  • the reaction was allowed to react at -30 C for 1 hour before quenching with DMSO and 100- fold dilution.
  • the quenched and diluted reaction mixture was electrosprayed in a Finnigan MAT TSQ-7000 tandem mass spectrometer. The spectrum of this figure was recorded by scanning the first quadrupole.
  • the mass spectrum contains several series of polymeric ions and is very complex.
  • Figures IB and C are daughter ion mass spectra of the quenched reaction mixture of Fig. 1A with the first quadrupole set to reject ions below m/z 1000 and below m/z 600, respectively, and in which the remaining ions were subjected to collision-induced dissociation with xenon (-0.5 m Torr) at a nominal ion energy of 40 eV.
  • Figure 2A is an electrospray mass spectrum of a quenched and diluted reaction mixture of complexes la-lh each approximately 10 "3 M in CH 2 C1 2 saturated with ethylene.
  • the reaction mixture was allowed to react at -10 C for 1 hour before quenching and dilution.
  • the quenched and diluted reaction mixture was electrosprayed in a Finnigan MAT TSQ-7000 tandem mass spectrometer. The spectrum of this figure was recorded by scanning the first quadrupole.
  • the mass spectrum contains several series of polymeric ions and is very complex.
  • Figure 2B is an electrospray mass spectrum of a quenched and diluted reaction mixture of lc (10 "3 M in CH 2 C1 2 saturated with ethylene) illustrating the series of oligomeric and polymeric ions generated by a single catalyst.
  • Figures 3 A and B are daughter ion mass spectra of the quenched reaction mixture of Fig. 2 A with the first quadrupole set to reject ions below m/z 2200 and below m z 1000, respectively, and in which the remaining ions were subjected to collision-induced dissociation with xenon (-0.5 m Torr) at a nominal ion energy of 40 eN.
  • Figure 4A is an electrospray mass spectrum of a quenched and diluted reaction mixture of procatalyst 10 (4.45 xlO "3 M in CH 2 C1 2 ), saturated with ethylene and activated with
  • Figure 5 is a graph of the fit of odd and even chain distributions obtained from the mass spectra of Fig. 4 A and B to determine the rates of initiation, propagation and chain transfer for the catalytic reaction. See Example 3.
  • Figure 6 is a graph of computed average molecular weight and extent of polymerization (indicated as molar equivalents of ethylene consumed) at 9.8 C calculated using the rates of initiation, propagation and chain transfer determined from the fit to the odd- and even-chain distributions of the mass spectra of Fig. 4A and 4B.
  • This invention provides methods based on mass spectral analysis for screening and selection of compounds for catalytic activity or improved catalytic activity.
  • the methods can be used to identify compounds that are catalysts for a selected reaction from among a plurality of test catalysts or to identify improved catalysts from a plurality of known catalysts.
  • the methods can be applied to a library of compounds having no known activity to catalyze a selected reaction or can be applied to a library of compounds known to have a given activity. In the latter case, the methods can identify, among known catalysts, those that have the greatest activity or those which generate products having a desired structure or property. The methods are particularly useful for screening compounds for activity as polymerization catalysts or for screening a set of likely catalysts to select those having the greatest activity, e.g., for those promoting the fastest or most efficient reactions.
  • catalysts which remain associated with a growing polymer chain, at least part of the time, can be screened.
  • the catalyst remains associated, i.e., bonded, in some way to the growing polymer chain.
  • the association between the catalyst and the polymer chain may be through covalent, ionic or hydrogen bonding, so long as the association is not substantially disrupted during introduction of the sample into the mass spectrometer.
  • the method of this invention is particularly well suited to screening of organometallic complexes as catalysts where the product of catalysis remains associated (at least for some time) with the organometallic catalyst.
  • bulk polymer properties such as M w or polydispersity MNM n can be determined for the polymeric products of a given polymerization catalyst. These properties can be determined for reaction by one test catalyst or multiple test catalysts and used to selected or identify a catalyst with desired activity.
  • Test catalysts in a library to be screened are typically structurally distinct, but more generally are distinct in that they exhibit unique mass spectra, i.e., exhibiting one or more unique ions which allow distinct catalysts to be ultimately identified in the second stage daughter ions.
  • a library may also contain a portion of catalysts which although structurally distinct, are not necessarily distinct by mass spectrum.
  • the screening method of this invention results in the identification of a set (preferably a small number) of test catalysts which includes at least one catalytically active species. The set members identified must then be further screened to determine which member or members of the set are, in fact, catalysts.
  • the second screening can be performed in a variety of ways, for example, by simply assessing individual performance of the catalysts of the set in separate polymer reactions.
  • the method will also allow the identification of the best catalyst or the better catalysts among the set of catalyst identified.
  • Distinct test catalysts of the library may be structurally similar, but possess different substituents (number, type) or different ligands (number, type).
  • Test catalyst libraries may include distinct members that are homologs, isomers, enantiomers and like related structures.
  • the screening method is particularly appropriate for screening of organometallic catalysts in which library members may differ in metal, valence state, ligands, or ligand substitution.
  • a library of catalysts can be prepared by well-known methods of synthesis, including combinatorial methods, employing readily available starting materials. Libraries can include known catalysts which are assayed for their relative activity or potential catalysts which are screened for the presence of activity or to select for the most active catalysts.
  • reaction product is generically used herein to refer to any product, whether an intermediate or final product, and whether or not the product is bound to a catalyst (or a portion of a catalyst).
  • An intermediate product refers to any chemical species, whether or not it is bound to catalyst, which is a precursor to a final product.
  • a final product is the ultimate product (which may represent a mixture of chemical species) which would result from complete reaction of test catalyst(s), reactant compounds(s) and any activator or coreactant present in the reaction mixture under the assay conditions (solvent, temperature) if the reaction were allowed to go to completion.
  • the reaction mixtures are preferably quenched before completion of reaction.
  • the reactant compound or compounds are typically in excess to avoid their depletion prior to quenching.
  • the final product is typically a bulk polymer and the intermediate products are oligomers and polymer chains that would grow into the bulk polymer if the reaction proceeded to completion.
  • the test reaction e.g., the polymerization reaction
  • conditions can be varied (e.g., pH, temperature, or solvent) to identify preferred reaction conditions for a given catalyst or to select the best catalyst for given reaction conditions.
  • the test reaction is allowed to proceed for a sufficient time before quenching to allow differences in catalyst activity to be detected.
  • the reaction is preferably allowed to proceed in the presence of excess monomer until from about 25 to several hundred monomers are added to the growing polymer chain.
  • test reaction sample e.g., the polymerization reaction mixture
  • the test reaction sample is preferably introduced into the first stage of the mass spectrometer using atmospheric pressure ionization and more preferably using electrospray ionization.
  • electrospray ionization tandem mass spectrometry ESI-MS/MS
  • gas-phase ion-molecule reactions have been used for the rapid screening of Brookhart- type Pd(II) olefin polymerization catalysts (Johnson, L.K. et al. (1995) J. Am. Chem. Soc. 117:6414; Johnson L.K. et al. (1996) J. Am. Chem. Soc. 118:267).
  • Much of the basic chemistry of the diimine complexes was explored by Svoboda, M. and torn Dieck, H. (1980)
  • the limiting chain length, and therefore the polymer molecular weight is determined primarily by the ratio of the propagation rate to the chain-transfer rates. Whereas the former rate can be measured by a number of techniques, there are extremely limited ways to obtain the latter.
  • Procatalyst 10 was chosen for the test because it gave odd-chain and even-chain distributions which are easily seen in Figs. 4A and 4B. If a better catalyst were to be used (The catalyst with o,o '-diisopropyl rather the o,o '-dimethyl groups on the aromatic moieties gives exceedingly small peaks corresponding to even-chain distribution, consistent with it being the best of the reported catalysts), the same exercise could be done to extract the three rates, but the difference in magnitude between the odd-chain and even-chain distribution would have been greater. With commercial quadrupole or sector instruments delivering a dynamic range of ⁇ 10,000-to-l, one can estimate that the present screening method should function up to M w -500,000.
  • the three rates in the fit to the odd- and even-chain distributions would be linearly independent so that a unique fit can be achieved. While an analytical proof of linear independence has not been done, an examination of the behavior of the fitting functions as the parameters are varied suggests that the three rates can be uniquely determined.
  • the absolute propagation rate is primarily responsible for the position of the maximum and the shape of the leading edge of the odd distribution.
  • the ratio of propagation to initiation rate determines the width and the shape of the trailing edge of the odd-chain distribution.
  • the ratio of the propagation to chain-transfer rate determines the relative magnitudes of the odd- versus even-chain distributions.
  • the mass spectrometric method is well-suited.
  • automation can be done with autosamplers available for the commercial spectrometers.
  • the present mass spectrometric method is faster, requires much less sample, and is more amenable to automation.
  • Other mass spectrometric approaches mass spectrometric approaches to polymer characterization have been described: Lorenz, S.A. et al. (1999) Appl. Spec. 53:18A;
  • the final polymer molecular weight is largely determined by chain-transfer with monomer (or polymer, if the concentration becomes high enough).
  • monomer or polymer, if the concentration becomes high enough.
  • the elementary steps in the polymerization (a complete overview of Ziegler-Natta polymerization can be found: Ziegler Catalysts, Fink, G. et al. (ed.), Springer-
  • Metal-bound oligomer chains with hydrogen endgroups correspond to chains built on a catalytic center that has undergone chain-transfer at least once. Although both the odd and even chains are built by addition of ethylene units, they are displaced from one another by 14 mass units.
  • the two distributions can be fitted, by integration of the differential rate equations, to yield unique, absolute rates for initiation, propagation, and chain-transfer for the particular set of conditions in the reaction.
  • the methods herein have been described employing conventional tandem mass spectrometry, but can be implemented employing other mass spectrometric methods known in the art which allow separation of initially generated ions by mass and further analysis of the selected ions.
  • Ions can be generated by a variety of ionization methods known in the art.
  • the methods of ionization appropriate for use in this screening method provide ions in which the catalyst (or a portion of the catalyst) remains associated with the reaction product on initial ionization. Further, the ionization method chosen preferably does not invalidate the selection criteria, e.g., in polymerization catalyst screening, the initial ionization method employed does not itself substantially affect ion polymer chain length.
  • Catalyst screening methods specifically exemplified herein rely on selection of higher mass-to-charge ratio ions associated with the longest polymer chains formed in the mass/charge test reaction.
  • Other ion selection criteria may be applied to the ions formed in the first stage of the mass spectrometer. For example, an intermediate range of ion masses may be selected, or a particular ion or set of ions associated with a desired type of chain branching may be selected as can happen when electrospray or MALDI is used for the direct mass spectrometric analysis of high polymers.
  • Screening for polymerization catalysts is preferably based on an assay or prediction of the properties of the bulk polymer produced by a given catalyst under given conditions.
  • catalyst activity which, is one of the less important properties.
  • Average molecular weight and its distribution, in the bulk polymer, are the generally more important criteria for screening for polymerization catalysts.
  • This invention also provides a method by which electrospray ionization mass spectrometry is used to determine kinetic parameters from metal-bound oligomer distributions that predict the bulk polymer properties of material produced by the catalyst.
  • Unique in this method is the observation and use of the so-called even- versus odd-chain distributions to determine the important ratio of propagation to chain transfer rates. This ratio is the single most important determinant of polymer molecular weight.
  • This methodology is applicable to other polymerization catalysts, for example
  • the methods herein have application to catalyst selection in non- polymerization applications.
  • This invention specifically relates to a method in which tandem mass spectrometry is used to assay or screen two or more catalysts for polymerization activity.
  • the two stage mass spectrometric method described herein can also be used to assay or investigate the catalytic activity of individual catalysts.
  • the invention also relates to the use of ion-molecule reactions, such as dissociative collisions, to simplify the mass spectrum of oligomer/polymer mixtures in a mass spectrometer.
  • the mass spectrometric methods described herein can be generally employed to investigate polymerization reactions, for example the methods can be applied to determine the ratio of chain propagation to chain transfer in a given solution-phase polymerization reaction.
  • the general kinetic scheme for Ziegler-Natta polymerization is implemented by reference to the Mayl et al. (1999) reference and by application of standard computational methods know in the art.
  • the numerical integration was performed by the POWERSIM (Modell Data AS) software package using standard methods, i.e., Euler's method or Runge- Kutta up to fourth-order. In each case, integration intervals were chosen so that the numerical method itself had a negligible effect on the outcome.
  • Example 1 Screening a small library of Brookhart Pd(II) complexes with different aryl groups on the diimine ligand.
  • Figs. IB and C The daughter ion spectra for the two different cutoffs, recorded by scanning the second quadrupole, are shown in Figs. IB and C, respectively.
  • Fig. IB is the predominance of the mass peak corresponding to ion 3c and/or its daughter ion(s), formed by collision-induced elimination of the hydrocarbon chain from the ion built from catalyst lc, indicating that lc is the best polymerization catalyst of the three.
  • the transmitted high-mass ions were collided against xenon (- 0.5 mTorr) in an octopole ion guide at nominal ion energies between 30 and 80 eV. Representative daughter ion spectra for the two different cutoffs, recorded by scanning the second quadrupole, are shown in Figure 3A and B, respectively.
  • the secondary fragments [4 - Pd] (or [4e - Pd -Br]) were unambiguously associated with the original ions 4 by performing parent ion scans on both 4 and the secondary fragment masses.
  • Example 3 Screening for Bulk Polymer Properties
  • the mass spectrometric measurement analyzes oligomeric polyethylene chains that are attached to the cationic catalyst.
  • most of the polymer chains are not metal- bound — they are products of chain-transfer and elimination, as evidenced by olefinic endgroups.
  • the average molecular weight and molecular weight distribution of all polymer chains, not just for metal-bound ones, are desired criteria for catalyst selection.
  • the ESI-MS/MS method provides this information by generating the kinetic data from which M w and M w /M n for all polymer, metal-bound and metal- free, can be computed.
  • a solution of procatalyst (a precursor from which the active catalyst is generated) is saturated with ethylene and kept under a constant pressure of ethylene with efficient agitation to ensure that monomer concentration is unchanging.
  • Activation in situ is done by addition of the appropriate activator.
  • a quencher such as CO is added to halt polymerization.
  • the solution is diluted to ESI concentrations and analyzed by ESI-MS/MS.
  • the parameters of this screen are given in Scheme 3.
  • Metal-bound oligomer chains with hydrogen endgroups correspond to chains built on a catalytic center that has undergone chain transfer at least once.
  • the odd and even chains form two distinct distributions displaced from one another by 14 mass units, with very different envelopes, visible in the mass spectrum (see Figure 4A and the enlargement of the m/z 1000-2500 region in Fig. 4B).
  • T. Ziegler Scheme 4
  • the two distributions can be fitted to yield unique, absolute rates for initiation, propagation, and chain-transfer for the particular set of conditions in the reaction.
  • a not-very-good catalyst (Scheme 3) was intentionally chosen in this example so that the two distributions, i.e., odd and even, would be simultaneously visible in the raw data.
  • Figures 5 and 6 show the quality of the fit. Similar measurements for a total of three temperatures give, for example, Arrhenius activation energies for propagation and chain- transfer of ⁇ 18.9 and 21.4 kcal/mol, respectively. For the propagation reaction, our value is about 1 kcal/mol lower than that reported by Brookhart for a slightly different catalyst (o,o'- diisopropyl instead of 0,0 '-dimethyl) with a different counterion and different solvent.
  • Varying the three rates in the fit shows that the three parameters are close to linearly independent.
  • the maximum of the odd chain distribution and its high-mass edge is largely determined by the absolute propagation rate.
  • the width of the odd chain distribution is determined by the ratio of initiation to propagation rate.
  • the relative magnitude of the odd chain vs. even chain distribution comes from the ratio of the propagation to chain-transfer rate.
  • the shapes of the distributions comes from the kinetic model; the close resemblance of the fit curves to the experimental distributions indicates that the kinetic model has included all major effects.
  • M w For a catalyst which makes polymer of high M w , the ratio of the odd chain to even chain distribution is also large.
  • the upper-limit of M w for which the method should work is determined by the dynamic range of the mass spectrometric determination, i.e. how small a peak can be seen in the presence of a much larger neighboring peak.
  • transmission-type mass spectrometers such as linear quadrupoles and sector instruments
  • commercial spectrometers have a dynamic range of -10,000, meaning that M w up to 500,000 can be treated by this method.
  • a further improvement could be achieved by use of a scintillation- based detector and 16- or 20-bit A-to-D converters.
  • FT-ICR spectrometers are less suitable because the dynamic range on the FT-ICR is limited; both FT-ICR and quadrupole ion trap mass spectrometers will have problems because of poor statistics (less than 10,000 ions trapped at a time).
  • the mechanism from T. Ziegler relates the chain branching rate to the chain transfer rate, both reactions proceeding through the same transition state. We need to do the derivation in order to formulate the algorithm.
  • the polydispersities in excess of two that Brookhart reports come from chain-transfer to polymer rather than monomer.
  • M w /M n ⁇ 4 was reported, he prepared 40 g polyethylene in 100 ml solvent.
  • polymer became concentrated enough to compete with ethylene for the binding site on the catalyst. This effect is easily built into the integration code for the calculation, which means that concentration effects on the polydispersity can be predicted from the same dilute solution measurements that give M w .
  • MAO introduces a large number of low mass peaks and some underlying continuum of signals — the metal-bound oligomeric ions are nevertheless still visible. The interference could have made the clean acquisition of quantitative odd chain and even chain distributions difficult.
  • MS/MS method used previously — selection of oligomeric ions and then CID to produce the palladium hydride — easily circumvents the problem posed by MAO. If all ions are selected, and then subjected to CID, a parent scan done on the mass of the palladium hydride will give the odd and even chain distributions without any interfering MAO-derived peaks.
  • the chemical reaction part of the assay is, in principle, as fast or as slow as it would be for any assay using the same reaction. It should be noted that, since we are determining high polymer properties from measurements on metal-bound oligomers, we should be able to reduce the time for the chemical part of the assay in comparison to any assay which works with bulk polymer.
  • the mass spectrometric part of the assay takes between 1 and 5 minutes.
  • the instruments employed in these assays can employ an autosampler. The autosampler can be operated anaerobically.
  • CH 2 C1 2 was distilled from CaH 2 before use. Electrospray-ionization was conducted with flow rates of 5 to 15 ⁇ l/min, N 2 sheath-gas, and a spray- voltage of 5.0 kV. Very mild desolvation-conditions (heated capillary 150°C, tube-len-potential 52 V) were employed.
  • the procatalyst 10 was prepared by an art-known method as follows. The free diimine ligand, biacetyl-bis-(2,6-dimethylphenylimine) (Dieck, H.T. et al. (1981) Z. Naturforsch.
  • This invention has been illustrated for the screening of certain organometallic polymerization catalysts for the production of polyolefms.
  • the invention is not, however, limited to the specifically exemplified catalysts or to the specifically exemplified polymerization reaction.
  • Methods, techniques and instrumentation other than those specifically disclosed herein can be employed in the practice of this invention.
  • a variety of mass spectrometric methods can be applied to achieve the ion-selection and daughter ion generation as described herein.
  • a variety of methods for ionization and generation of daughter ions are known in the art and can be employed to achieve the results described herein. All references cited herein are incorporated by reference herein in their entirety to the extent not inconsistent herewith.

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Abstract

L'invention concerne des techniques de sélection permettant d'identifier des catalyseurs ou des catalyseurs améliorés à l'aide d'une analyse en spectrométrie de masse de produits de catalyse, notamment de produits intermédiaires liés au catalyseur lors du cycle catalytique. Ces techniques s'appliquent en particulier à la sélection de composés organométalliques pour une utilisation en tant que catalyseurs. Ces techniques emploient de manière plus spécifique une détection par spectrométrie de masse en deux étapes, dans laquelle les ions formés lors de l'ionisation de la première étape, liés aux performances du catalyseur, sont sélectionnés. Le catalyseur associé à l'ion sélectionné est identifié lors de la seconde étape, à l'aide de la spectrométrie de masse tandem. Dans des modes de réalisation spécifiques, les techniques de sélection de l'invention évitent un codage explicite car l'identité du catalyseur est implicitement contenue dans la masse moléculaire du produit (généralement un produit intermédiaire), étant donné que le catalyseur (ou une partie de celui-ci) demeure lié au produit.
PCT/IB2000/000062 1999-01-22 2000-01-24 Selection de catalyseurs par spectrometrie de masse WO2000043771A1 (fr)

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AU30689/00A AU3068900A (en) 1999-01-22 2000-01-24 Mass spectrometric screening of catalysts
EP00900760A EP1149286A1 (fr) 1999-01-22 2000-01-24 Selection de catalyseurs par spectrometrie de masse
JP2000595141A JP2003506665A (ja) 2000-01-24 2000-01-24 触媒の質量分析スクリーニング
PL00349046A PL349046A1 (en) 1999-01-22 2000-01-24 Mass spectrometric screening of catalysts
HU0105237A HUP0105237A3 (en) 1999-01-22 2000-01-24 Mass spectrometric screening of catalysts
KR1020017009205A KR20010093267A (ko) 1999-01-22 2000-01-24 촉매의 질량 스펙트럼 스크리닝

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US11720599P 1999-01-25 1999-01-25
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US13641699P 1999-05-28 1999-05-28
US60/136,416 1999-05-28
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EP1284271A1 (fr) * 2001-08-16 2003-02-19 Bayer Ag Catalyseurs de polymerisation d'olefines
EP1577314A1 (fr) * 2001-03-12 2005-09-21 Tosoh Corporation Transition metal compound, catalyst for polymerization of olefin, and process for polymerization of olefin using the catalyst
US6974665B2 (en) 2001-09-06 2005-12-13 University Of Nebraska In situ screening to optimize variables in organic reactions
CN105136972A (zh) * 2015-09-09 2015-12-09 武汉理工大学 纳米光催化剂活性能力的对比检测方法

Families Citing this family (2)

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Publication number Priority date Publication date Assignee Title
KR102414474B1 (ko) * 2016-03-16 2022-06-30 한국과학기술원 형광단 금속-유기 복합체를 이용한 전기화학적 촉매의 광학적 스크리닝 방법
US10825672B2 (en) * 2016-11-21 2020-11-03 Waters Technologies Corporation Techniques for mass analyzing a complex sample based on nominal mass and mass defect information

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1577314A1 (fr) * 2001-03-12 2005-09-21 Tosoh Corporation Transition metal compound, catalyst for polymerization of olefin, and process for polymerization of olefin using the catalyst
EP1284271A1 (fr) * 2001-08-16 2003-02-19 Bayer Ag Catalyseurs de polymerisation d'olefines
US6974665B2 (en) 2001-09-06 2005-12-13 University Of Nebraska In situ screening to optimize variables in organic reactions
CN105136972A (zh) * 2015-09-09 2015-12-09 武汉理工大学 纳米光催化剂活性能力的对比检测方法

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CZ20012641A3 (cs) 2002-07-17
AU3068900A (en) 2000-08-07
EP1149286A1 (fr) 2001-10-31
KR20010093267A (ko) 2001-10-27
HUP0105237A3 (en) 2003-08-28
PL349046A1 (en) 2002-07-01

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