CZ20012641A3 - Identification method of catalysts by employing mass spectrometry - Google Patents

Abstract

Screening methods to identify catalysts or to identify improved catalysts using mass spectrometric analysis of products of catalysis, particularly catalyst-bound intermediate products in the catalytic cycle. The methods are applicable, in particular, to screening of organometallic compounds for catalytic function. Moreover, 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. In specific embodiments, 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.

Description

Method of S-Croon Catalysts by Mass Spectrometry

Technical field

The invention relates to a rapid screening method for identifying compounds exhibiting activity as catalysts using mass spectrometry. Said method is illustrated by the rapid screening of catalysts for polymerization using tandem mass spectrometry and gas-phase ion-molecular reactions, and is specifically applied to the screening of organometallic catalysts used to prepare polyolefins. The screening method of the invention has advantages in high sensitivity (in mg scale), in very short assay times (one hour), in simultaneous competitive screening of multiple catalysts directly according to the ability of high polymer formation (compared to derived properties such as heat release), in good conditions widespread use with large combination libraries, and implicit coding for catalyst mass identity. Simple ion-molecular reactions are used to simplify the mass spectrum of complex mixtures formed during analysis.

BACKGROUND OF THE INVENTION

The identification, preparation and testing of individual catalysts have been carried out for a long time. Screening of catalyst libraries to identify new improved catalysts is a recent phenomenon. The screening of libraries of compounds that can be prepared by the combination method is used extensively in biological systems and to identify potential therapeutic agents. High performance combination screening of organometallic catalysts now occupies a central position in the emerging area of combinatorial screening methods for materials. (Currently, a review of catalyst screening has been published: Jandeleit B. et al., (1998) Cat.Tech. 2: 101). Certain strategies are used to carry out the screening of catalysts corresponding to certain aspects of catalysis in measurable quantities. Preferred strategic procedures include rapid and applicable procedures for very small samples. Chromatography (Francis M.B., (1999), Angew.Chem. 111: 987), thermography (Taylor S.J. and Morken J.P. (1988), Science,

280: 267; Reetz M.T. et al., (1998), Angew Chem., 110: 2792), fluorescence quenching (Cooper A. C. et al., (1998),

J. Am. Chem., 120: 9971), parallel reactions in microwells (Burgess K. et al., (1996), Angew. Chem., 108: 192; Senkan SM, (1998), Nature, 394). 350) and methods using polymeric carrier beads (Cole BM et al., (1996), Angew. Chem.,

108: 1776 Boussie T.R. et al., (1998), Angew. Chem., 110: 3472).

Only methods on polymer carrier beads were used to identify organometallic catalysts in polymerization reactions, other methods were not applicable for various technical reasons. Also, the polymer bead method used to screen catalysis for polyolefins involved difficult coding limiting the suitability of the method.

Catalyst screening strategies typically involve determining the rate of reaction or the number of repeated determinations of the products of the catalyzed reaction. Emphasis is placed on miniaturization and acceleration of the methods commonly used to determine the product. For example, the rate of reaction corresponding to heat release is determined thermographically, wherein said assay is suitable for determining total catalyst activity. For catalysts of polymerization reactions (current progress in new homogeneous Ziegler-Natta catalysts is summarized in:

GJP et al., (1999), Angew. Chem., 111: 448), on the other hand, overall catalytic activity is only one of several important catalytic properties required for high-efficiency screening. Key properties of polymerization products which include: average molecular weight (M _w , weight average molecular weight, or M _n , number average molecular weight), and molecular weight distribution (M _w / M _n , degree of dispersibility, as it promotes the representation of heavier chains while M _n supports the representation of lighter chains) cannot be obtained in commonly used rapid assays. Conventional methods for determining the above-mentioned polymer properties, such as size exclusion chromatography (also referred to as gel permeation chromatography or gpc), light scattering, viscosity, or determination of colligative properties, require large amounts of sample and are poorly suited for efficient screening.

SUMMARY OF THE INVENTION

The invention provides methods for screening catalysts using mass spectrometric analysis of catalyst-bound intermediates in the catalyst cycle or catalysis products. The methods are particularly applicable to screening catalysts for polymerization reactions. More specifically, the methods include a two-phase (or two-stage) mass spectrometry detection method in which ions are separated after the catalytic reaction formed in the first ionization stage and the catalyst associated with the selected ion is identified in the second stage using a tandem mass spectrometer. In specific embodiments, sample labeling may not be used in the screening methods of the invention because the identity of the catalyst is implicitly included.

9,999 · in the molecular weight of the product (usually an intermediate) since the catalyst (or part thereof) remains associated with the product.

The methods of the invention are particularly useful for screening polymerization catalysts since they allow to avoid spectrum overloads that can occur when dividing oligomer and polymer length products as well as analyzing polymerization products using one type of catalyst. In addition, the selection applied to the polymerization catalysts is straightforward in that the analysis of the polymer chain growth is used directly instead of another property only correlating with chain growth.

One or more test catalysts are used in the methods of the invention. The catalysts to be tested are contacted with a selected type of reactant under selected conditions. Said reactant is a compound or mixture of compounds upon which the effects of the catalyst produce the desired product. The reaction conditions are chosen such that the selected catalytic reaction can proceed. Then, after a selected period of time allowing the selected reaction to proceed to the formation of the desired product, for example, growth of the polymer chain and differentiation of the activity of the reaction catalysts. After stopping the reaction, the reaction mixture is introduced into the first stage of the tandem mass spectrometer, subjected to ionization and mass analysis. Optionally, the extinguished reaction mixture may be subjected to partial purification, solvent removal, dilution, concentration, dilution, chemical derivatization to allow more convenient analysis, removal of impurities or similar treatment prior to introduction into the mass spectrometer.

Some ions formed in the first stage of the tandem mass spectrometer are separated for introduction into the second stage of the spectrometer. The ions resulting from reactions are selected

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99> · with the catalyst being evaluated. For example, when screening polymerization catalysts, ions are selected according to their ion masses, i.e., ions with effective masses (m / z) greater than the selected separation limit, selected based on the results obtained with the best catalysts. given time. The selected ions are introduced into the second stage of the mass spectrometer where they undergo a reaction providing daughter ions to identify the catalyst catalysing the formation of products whose ions have been selected in the first stage.

For example, again in the polymerization reactions, the selected high weight ions containing the longest polymer chains are subjected in the second stage to reactive collisions with neutral components to form daughter ions. Ion-molecular reactions involving precipitation-induced dissociation can be used to generate daughter ions. Preferred ion-molecular reactions include reactions in which the product, e.g., a polymer chain, is cleaved from the attached catalyst or part of the catalyst to give an ion that can be directly, advantageously and unambiguously assigned to the catalyst. Thus, mass analysis of the daughter ions produced allows identification of the type of catalyst whose effects are derived from the products from which the selected ions are derived.

The catalysts to be tested can be provided in the form of a library comprising a set of compounds within a range of different variants of their structure in order to find the relationship of the structure to the catalytic function. For example, a set of proposed polymerization catalysts is contacted with the selected monomer under reaction conditions (pH, temperature, solvent, etc.) that result in polymerization. In specific embodiments, a sample of the reaction mixture is introduced into a mass spectrometer in a manner in which the coupling of the reaction product (s) to the catalyst is protected, eg, the catalyst (or part thereof) remains associated with a growing polymer chain resulting from of monomers in the polymerization reaction.

In specific embodiments, the mass spectrometric methods of the invention can be used to analyze the spatial arrangement of polymers prepared using a given catalyst. By generating kinetic data (see Example 3), it is possible to determine the average molecular weight and molecular weight distribution of all polymer chains, not just the metal-bound chains (i.e., the catalyst bound). After the catalyzed reaction, it is possible to determine in the mass spectrum the distribution of the chains not including the chain transfer (oligomeric chains bound to the metal ending methyl groups) and the chains comprising the chain transfer (oligomeric chains bound to the metal ending the hydrogen groups). By evaluating experimental results of chain distribution not involving chain transfer (s) including chain transfer with a general kinetic scheme for polymerization with Zegler-Natta catalysts, absolute initiation, propagation and chain transfer rates for given reaction conditions can be obtained. From these values it is possible to determine the average molecular weight and the average molecular weight distribution of the catalytic reaction products of the evaluated catalysts without explicit preparation or isolation of the crude polymer. The average molecular weight and molecular weight distribution of the polymer products can be used as the catalyst selection criteria.

The process of the invention is particularly suitable for screening ionic or ion-paired polymerization catalysts. A set of catalysts containing more than two different catalysts is contacted with a monomer, usually ethylene, but which may be any other one of the simple substituted olefins, in an organic solvent. After polymerization proceeding to the coupling of several hundred monomer units, the reaction is interrupted by the addition of another ligand such as CO, isocyanides, ethers, esters, phosphites, sulfoxides or by addition of another of the coordination ligands. The reaction mixture solution is introduced into the tandem mass spectrometer by electrospray ionization after the reaction has been stopped.

In the first stage of the mass spectrometer, high-ion ions which contain the catalyst (or part of the catalyst) attached to the longest polymer chains formed in the above reaction are separated. Selected ions are associated with more active catalysts. In the second stage of the spectrometer, the selected ions are then subjected to ion-molecular reactions, e.g. collision-induced dissociation, leading to cleavage of the oligomer / polymer chain from the catalyst. The daughter ion (s) remaining after the ion-molecular reaction is then analyzed in the second stage of the mass spectrometer to identify the type of catalyst by which the highest molecular weight polymer chains are formed. The excellent simplification of the mass spectrum by means of an ion-molecular reaction is a unique feature of the present invention. The decomposition of the parent ion into the daughter ion makes it possible to identify the polymer distribution and to determine the kinetic parameters of one catalyst in the presence of other catalysts.

Description of the figures in the attached drawings

Fig. 1A represents the mass spectrometry of the electrospray reaction mixture complexes (Ia-1c), after stopping the reaction and diluting the mixture to a concentration of about ¹ M ³ mol / L for each component into ethylene saturated CH 2 Cl 2. The reaction is allowed to proceed at -30 ° C for about 1 hour and then quenched by addition of DMSO α

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9999 • Dilute 10 times. The quenched and diluted reaction mixture was introduced using an electrospray ionization into a Finnigan tandem mass spectrometer MAT TSQ-7000. The spectrum shown in FIG. 1A was recorded by scanning from the first quadrupol. The mass spectrum contains several series of polymer ions and is very complex.

Giant. 1B and 1C show the mass spectra of the daughter ions obtained from the quenched reaction mixture of FIG. 1A from the first quadrupole with an ω / z ion removal setting below 1000 and om / z below 600 respectively, the remaining ions being subjected to collision-induced dissociation by xenon (~ 0, 5 mTorr (6.7 · 10 ³ Pa) at a nominal ionic energy of 40 eV.

Figure 2A represents the mass spectrum with ionization of the electrospray of the reaction mixture complex (Ia-1h), after stopping the reaction and diluting the mixture to a concentration of about 10 ^-3 mol / l for each component into ethylene saturated CH ₂ Cl ₂ . The reaction was allowed to proceed at -10 ° C for about 1 hour and then quenched and diluted. The quenched and diluted reaction mixture was introduced using an electrospray ionization into a Finnigan tandem mass spectrometer MAT TSQ-7000. The spectrum shown in Fig. 2A was recorded by scanning from the first quadrupol. The mass spectrum contains several series of polymer ions and is very complex.

Fig. 2B is an electrospray mass spectrometry of the reaction mixture containing (1c), after stopping the reaction and diluting the mixture (to a concentration of 10 ³ mol / l into CH ₂ Cl ₂ saturated with ethylene), depicting a series of oligomeric and polymeric ions formed using a single catalyst .

Giant. 3A and 3B show the mass spectra of daughter ions obtained from the quenched reaction mixture of FIG. 2A from FIG.

0 · * «·· ♦ of the first quadrupol with an om / z ion removal setting below 2200 and om / z below 1000, with the remaining ions subjected to xenon-induced collision-induced collision (~ 0.5 mTorr ie 6.7-10 ^-3 Pa) at a nominal ionic energy of 40 eV.

Fig. 4A is a mass spectrum using ionization electrospray of the reaction mixture containing procatalyst (10) after the reaction is stopped and dilution of the mixture (4.45-10 ^-3 mol / l into CH 2 Cl 2) saturated with ethylene and activated with AgOTf as described in Example 3. the mass spectrum depicts the ions of the ions of the chain not subject to chain transfer. Fig. 4B is an enlargement of the mass spectrum of Fig. 4A in the range m / z 1000 to m / z 2500.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides mass spectrometric assay methods suitable for screening and selecting compounds having catalytic activity or improved catalytic activity. The methods can be used to identify compounds from a group of multiple candidate compounds having catalytic effects for a selected reaction or to identify improved catalysts from a group of known catalysts. The method may be applied to a library of compounds for which the catalytic activity for a given reaction is unknown or to a library of compounds having known catalytic activity.

In the latter group, one can identify from the group of known compounds those having the highest activity or those which provide products having the desired structure or properties. Said methods are particularly suitable for screening compounds for their activity as catalysts for polymerization or for screening a set of catalysts likely to have such activity, and

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To select the ones that are most effective, such as those that support the fastest and most efficient response.

According to the invention, it is possible to evaluate catalysts (or identifiable portions of the catalysts) that remain associated with the growing polymer chain, or are linked for at least some time. Such a catalyst remains attached, i.e., attached to the growing polymer chain in some way. The linkage between the catalyst and the polymer chain may be mediated by a covalent, ionic, or hydrogen bond, provided that said bond does not significantly break during the introduction of the sample into the mass spectrometer. The method of the invention is particularly suitable for screening organometallic complexes used as catalysts, wherein the catalysis product remains associated (at least for some time) with the organometallic catalyst.

According to the invention, properties of a finite bulk polymer such as M _w or polydispersity M _w / M _n can be determined for the polymerization product with respect to the polymerization catalyst by a given polymerization catalyst. These properties can be determined for one or more catalysts to be evaluated and can be used to select or identify a catalyst with the desired activity.

The catalysts included in the library to be tested are usually structurally different, but in most cases differ in that they exhibit characteristic mass spectra, i. have one or more characteristic ions allowing the resolution of the catalysts in the final identity assessment in the second stage in which daughter ions are evaluated. The library may also contain a certain proportion of catalysts which, although structurally different, do not necessarily differ in mass spectra. In this case, the method of selection according to the invention is 9 " 9 " 9 " 9 "

It continues to identify at least one catalyst of the set (preferably with a small number of components) having catalytic activity. The identified set is then subjected to a further selection to determine whether one or more of the set ingredients has actual catalytic effects. Said second screening can be performed in various ways, for example by simply evaluating the efficacy of the individual catalysts of the set in separate polymerization reactions. The method also allows the identification of the best catalyst or the preferred catalysts of the set.

The individual catalysts evaluated in the library may be structurally similar, but contain different substituents (number, type) or different ligands (number, type). The library of test catalysts may contain separate catalysts that are homologous, isomeric, enantiomeric, and the like related structures. Said screening method is particularly suitable for the selection of organometallic catalysts, wherein the organometallic catalysts included in the library differ in the type of metal, the degree of valence, ligands or ligand substitutions.

The catalyst library can be prepared by methods known in the art using readily available starting components.

The library may contain known catalysts and the assay then involves determining their relative potencies or potential catalysts, and screening then refers to the selection of the most effective or most effective catalysts.

The term reaction product is generally used for each product, whether it is an intermediate or end product, and as bound to the catalyst or not (or to a portion of the catalyst).

Intermediate refers to any chemical compound, whether or not bound to a catalyst, which is a precursor

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9494 of the final product. The final product is the last product (which may be a mixture of chemical compounds) resulting from the complete reaction of the test catalyst (s), reactant (s) and activator or other reactant contained in the reaction mixture under assay conditions (solvent, temperature) allow the reaction to proceed until its end.

In the screening of the invention, the reaction is preferably stopped before the reaction is complete. Furthermore, in the process according to the invention, the reactant or reactants are usually used in excess to prevent their consumption before quenching the reaction mixture.

In polymer reactions, the final product is usually a bulky polymer, and the intermediates are oligomeric and polymer chains growing into bulky polymer as the reaction progresses to completion.

In the reaction to be evaluated, for example a polymerization reaction, it is possible to vary the conditions (e.g., pH, temperature or solvent) to determine the preferred reaction conditions for a given catalyst or to select the best catalyst for a given reaction condition. The reaction is allowed to proceed for a sufficient period of time before the reaction is interrupted to detect differences in catalyst performance. In the screening of polymerization catalysts, the reaction is preferably allowed to proceed in the presence of excess monomer until the coupling of 25 to several hundred monomers to the growing polymer chain.

The test sample of the reaction mixture, for example the reaction mixture from the polymerization reaction, is preferably introduced into the first stage of a mass spectrometer using ionization at atmospheric pressure, preferably using electrospray ionization.

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In specific cases, electrospray ionization tandem mass spectrometry (ESI-MS / MS) and gas-phase ion-jet reactions were used for rapid screening of Brookhart-type Pd (II) catalysts for olefin polymerization (Johnson LK et al., (1995), J. Am. Chem., 117: 6414; Johnson LK et al., (1996), J. Am. Chem., 118: 267). Extensive basic knowledge of the diimine complex chemistry has been described by Svoboda M. and Tom Dieck H., (1980), J. Organomet. Chem., 191: 321; Tom Diesck, H. et al., (1981), Z. Naturforsch., 36B: 283.

While electrospray ionization mass spectrometry (a complete monograph on this technique is Electrospray ionization Mass Spectrometry, RDCole, Ed., John Wiley: New York, 1997) has been by Fenne and co-authors since the introduction of this technique (Whitehouse CM et al., (1985) )

Anal. Chem., 57: 675) extensively applied to biopolymers, application to the chemistry of organometallic compounds only appears to date. Direct analytical applications were first published by Chait (Katta V., et al. (1990), J. Am. Chem. Soc., 112: 5348),

Colton and their collaborators (Colton R. and Traeger JC, (1992), Inorg.Chim.Acta, 201: 153; the work of these groups has been summarized in Colton R. et al., (1996), Mass Spec.Rev., 14:79). The study of the mechanisms of ion-molecular reactions of organometallic ions using electronospray ionization is ascribed to a co-operating group (Hinderling C. et al., (1997), Angew. Chem., 109: 272; Hinderling C. et al., (1997),

J. Am. Chem., 119: 10793; Feichtinger D. and Plattner D.A., (1997), Angew. Chem., 109: 1796; Feichtinger D. et al., (1998), J. Am. Chem. Soc., 120: 7175; Hinderling, C. et al. (1998), Angew. Chem., 110: 2831) and Posey et al. (Spence TG et al., (1997), J.Phys.Chem. A 101: 139; Spence TG et al., (1997), J.Phys.Chem. A 101: 1081; Spence TG et al., ( 1998, J.Phys.Chem A 102: 6101. Several other groups have published

Other applications (Wilson S.R. and Wu Y., (1993), Organometallics,

12: 1478; Alíprantis A.O. and Canary J.W. (1994),

Soc., 116: 6985; Kane-Maguire L.A.P. et al., (1995), J. Organomet. Chem., 486: 243; Lipshutz B.H. et al., (1996),

Soc., 118: 6796), and two groups dealt with the evaluation of polymerization reactions (Dzhabieva ZM et al., (1996), Russ.Chem.Bull., 45: 474; Saf R. et al. , (1996), Macromol., 29: 7651). However, none of these groups attempted to evaluate more than one catalyst at a time. Moreover, the mass spectra obtained were very complex due to the distribution of oligomeric and / or polymer ions produced even by using a single catalyst, which eliminates any possibility of screening. The present invention primarily involves ESI-MS / MS analysis of multiple ongoing, competitive, simultaneous, catalysed solution reactions. A unique feature of the process according to the invention is the use of an ion-molecular reaction, for example, in this case a CID reaction (collision-induced reaction), to simplify the otherwise complicated mass spectrum of the polymer mixture.

The combination of sensitivity, speed, direct assay and versatility demonstrated in the trials implies the possibility of screening large (n »100) libraries containing combinatorially prepared catalysts. The availability of automated sample injection equipment on eiektrospray ionization spectrometers facilitates automation of the entire screening.

According to the general mechanism of Ziegler-Natta polymerization, the chain length limitation, and hence the molecular weight of the polymer, is mainly due to the ratio of propagation rates to chain transfer rates. While the first of the aforementioned speeds can be detected in various ways, the methods for detecting said second speed are

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«9 9999 extremely limited. Brookhart reports propagation rates (Johnson LK et al., (1995)) for catalysts based on compound (10) in J. Am. Chem. Soc., 117: 6414. According to the results of the inventors, the values of propagation rates found were about half that reported in the literature. Since the method of activation was different, a triflate was used as the counterion in the work of the inventors, unlike tetrakis (pentafluoroborate) in the previous work, so said factor 1/2 is fully understood. Brookhart does not report any chain transfer rates, so no comparison can be made, it would be possible to calculate the molecular weight of the polymer compared to the M-value reported in the literature, but the values are found under conditions that are very distant for satisfactory comparison. treated in 100 ml solvent makes the direct test again difficult. However, it can be found that compound (10) was not evaluated as one of the best catalysts in the Brookhart work, which corresponds only to the average M _w value found in this work.

20 chains not including chain transfer: R = CH ₃ chains including chain transfer: R = H

The procatalyst (10) provided this test was chosen because of the clear resolution of the distribution

Bt aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa aaaaaa If a better catalyst is used (a catalyst containing aromatic groups instead of o, o'-dimethyl groups of o, o'-diisopropyl groups corresponding to the best of the known catalysts, small peaks corresponding to the distribution of the chains including chain transfer are obtained) three speeds use the same experiment, but the difference between the values of the values for distributing the strings without the string transfer and the strings involving the string transfer will be greater. Using a commercially available quadrupole segmented devices with a dynamic range of -10 000-1 can be estimated that said method to screen enables analysis of up to M _w ~ 500,000, where the upper limit is used only when necessary to use mass spectrometry for quantitative determination of M _w . In practice, as a screening method, the method merely monitors and obtains the values required for screening, since the true molecular weight of the polymer can be obtained if successful by any suitable method. However, the same argument used to determine the actual rates of chain propagation and transmission depends on the length of the chain. However, if the change is a continuous and slow function of chain length, the integrity of the mass spectrum records is not impaired.

Ideally, it would be desirable that the three rates suitable for chain distribution without chain transfer and chains involving chain transfer be linearly independent to achieve a clear dependency. Although analytically this linear independence has not been confirmed, the evaluation of the properties of these parameters as variables implies that the three speeds can be specifically determined.

Qualitatively, the absolute propagation rate is primarily responsible for the position of the maximum and for the shape of the origin of the distribution of the "strings" without the "strings". chain transfer. The rate of propagation to initiation determines the width and shape of the end portion of the chain distribution without the chain transfer. The ratio of propagation rate to chain transfer rate determines the relative magnitude of the non-chain transfer chain distributions to the chains including chain transfer. The results of the kinetic model include a bell shape for chain distribution without chain transfer and uniformly decreasing curves with a steeper decline initially for chain distribution including chain transfer that are not otherwise affected.

The good fit of these curves with the three speeds indicates that the model is suitable for solution.

An important parameter for converting a given assay into a full screen is the ability to process a pooled set, ie multiple catalysts at the same time, and accessories allowing automated parallel determinations. The mass spectrometry method is very suitable for both types of requirements. For parallel determination, it is possible to use automated dispensers with which the commercially available spectrometers can be equipped. Compared to conventional methods for determining the molecular weight of polymers, the spectrometric method of the invention is faster, requires less sample and can be automated. Other approaches using mass spectrometry (methods of characterizing polymers by mass spectrometry are described:

Lorenz S.A. et al., (1999), Appl. Spec., 53: 18A; Festage R. et al., (1998), J. Am.Soc.Mass Spec., 9: 299; Hunt S.M. et al., (1998), Anal. Chem., 70: 1812; Jackson C.A. and Simonsick WJ, (1997), Curr.Opin.Solid State Mat.Sci., 2: 661) have the drawback of k directly analyzing the polymer instead of the metal-bound oligomers, resulting in the ionization process (in the case of electrospray) and / or range of analyzed masses for the spectrometer (in electrospray or MALDI) begin

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9 9 • 9 9999 especially problematic for polyethylene or polypropylene. This problem is a specific case of the advantages achieved by the present invention that the determination is based on catalyst-bound intermediates as opposed to analyzes of the final bulk products.

As with many Ziegler-Natta catalysts, the molecular weight of the final polymer is predominantly determined by chain transfer by the monomer (or polymer if the polymer concentration is high enough).

Elementary degrees of polymerization (for an overview of ZieglerNatt polymerization see: Ziegler catalyst, Fink G. et al. (Ed.), Springer-Verlag, Berlin, (1995) were investigated using computer programs by Ziegler and co-workers (Margl P. et al. (1999) , 121: 154 and cited works) and experimentally, this particular group of catalysts was studied by Brookhart Due to the very rapid monomer complexation, the quiescent stage of the Pd (II) diimine catalysts is in the form of a complex with ethylene; the ethylene consumption rate is in terms of zero order ethylene (Johnson LK et al., (1995), J. Am. Chem. Soc., 117: 6414).

A solution of CH 2 Cl 2 in a thermostat (5 mL, 9.8 ° C) pre-saturated with ethylene in which 2 mg (<5 µπιοί) of compound (10) was dissolved was activated with AgOTf, polymerization was allowed to proceed for 26 minutes. WHAT. (Some quenching double electron ligands such as DMSO and pyridine have been tested as quenchers. CO provides the most reliable results). The sample is removed, diluted 50-fold and analyzed on a Finnigan MAT TSQ-7000 modified electrospray mass spectrometer. The instruments and conditions of analysis have already been disclosed (Hinderling C. and Chen P., Angew.Chem., In press; Hinderling C et al., (1997), J. Am. Chem. Soc., 119: 10793;

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Feichtinger D. and Plattner D.A., (1997), Angew. Chem., 109: 1796;

Feichtinger D. et al., (1998), J. Am. Chem. Soc., 120: 7175; Hinderling C. et al., (1998), Angew. Chem., 110: 2831; Kim Y.M. and Chen P., (1999), Int. J. Mass Spec., 185-7: 87). The resulting mass spectrum is shown in Figure 4A. When evaluating the region m / z = 1000-2500 (Fig. 4B), two different regions of oligomeric ion distribution are evident. The oligomeric chains attached to the metal with methyl end groups are referred to as non-chain transfer chains and correspond to chains formed at the catalytic center without transfer to the actual chain. The oligomeric chains bonded to the metal with hydrogen-terminated groups are referred to as chain transfer chains and correspond to chains formed at a catalytic center subject to at least one transfer to the chain itself. Although both types of chains, non-chain transfer chains and chain transfer chains are formed by the addition of ethylene units, they are offset by 14 weight units. A particular set of reaction conditions using a general kinetic scheme for Ziegler-Natta polymerization adapted to a specific group of Brookhart catalysts can accommodate the two types of distributions and by integrating differential equations it is possible to obtain specific absolute initiation, propagation and chain transfer rates.

Values were determined for _init = 0.01, k = 0.044 and _{prop tr} ans ⁼ 0.00045 s ^-1 satisfactory rate of initiation, propagation and chain transfer. The whole procedure can be repeated at several temperatures to obtain data to solve Arrhenius equations. In a previous attempt to solve this task, the non-Arrhenius initiation rate behavior explained by a heterogeneous system was found; on the other hand, the inventors found E ^prop a = 18.9 and E ^tran % -21.4 kcal / mol (i.e. 79.130 kJ / mol and 89.597 kJ respectively). The obtained values of chain initiation, propagation and transfer rates can also be used to calculate the mean molecular ·· · * 9 ·

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In the weight and extent of polymerization as a function of time assuming a constant ethylene concentration and dilution of the polymer solution. Under these assumptions using kinites ⁼ 0.01, kprop = 0.044 and ktrans = 0.00045 s ^-1 , the polydispersity Mw / M _n = 2 is theoretically expected. In the case of more real-life conditions, e.g. at a higher polymer concentration, it is necessary to account for the expression rates of the chain transfer to either the monomer or the polymer. In this case M _w / M _n > 2 can be assumed.

The above methods are carried out using conventional tandem mass spectrometry but can also be used in other mass spectrometric analytical methods known in the art to allow separation of initially generated ions based on their mass and further analysis of selected ions. Said ions are formed by various ionization methods known in the art. Ionization methods suitable for use in the screening of the invention include methods wherein the catalyst (or part of the catalyst) remains associated with the reaction product of the first ionization. Further, the selected ionization method preferably does not interfere with the selection criteria, for example when screening a polymerization catalyst, the first ionization method itself does not significantly affect the polymer ion chain length.

Catalyst screening methods specifically exemplified in the embodiments of the invention are based on the selection of ions with a higher mass / charge ratio associated with the longest polymer chains formed in the charged particle formation reaction. Other criteria may also be applied to the selection of ions formed in the first stage of the mass spectrometer. For example, it is possible to select medium ions or a particular ion or group of ions associated with the desired type of chain branching, wherein said method is used in direct mass spectrometric determination of high »9« polymer compounds using electrospray or MALDI ionization.

The screening of polymerization catalysts is usually based on the determination or prediction of the properties of high molecular weight polymers prepared under given conditions. The methods used so far in high throughput screening only determine the reaction rate, i.e. the activity of the catalyst, which is one of the minor parameters. In general, the more important parameters of screening polymerization catalysts are the average molecular weight of the high molecular weight polymer and its distribution.

The invention also provides a method by which electrospray ionization mass spectrometry is used from the distribution of metal-bound oligomers to determine kinetic parameters from which the properties of a final high molecular weight polymer prepared from the catalyst can be predicted. The specificity of the method is to determine the chains in which there is no chain transfer and the chains including chain transfer, and to use these results to determine a significant ratio of propagation rate to chain transfer rate. This ratio is one of the most important factors for the molecular weight of the polymer.

This methodology is applicable to other polymerization catalysts (for example, palladium-based catalysts for ollefin-CO copolymerization: Brookhart M. et al., (1992),

Soc., 114: 5894; Drent E. and Budzelaar P. H. M., (1996), Chem. Rev., 96: 663; for cobalt and iron catalysts for olefin polymerization: Smáli B.L. et al., (1998),

J. Am. Chem., 120: 4049; to molybdenum and tungsten-based ROMP catalysts: Goodall B.L. et al., (1993),

J.Appl. Polymer Sci., 47: 607; McCann M. et al., (1995),

0000

00 0 0 ·

J. Mol. Catalysis, A 96:31; Rhodes L.F., European Patent No. 0 435 146-2 (1990); Lubricated A.M., European Patent 0 755 938 A1 (1995)).

In addition, the methods of the invention are applicable to catalyst selection for reactions other than polymerization. In preferred embodiments of the process, the catalyst (or a recognizable portion thereof) remains associated with the desired product of choice after the first ionization.

Specifically, the invention relates to a method of using tandem mass spectrometry to determine or screen two or more catalysts for efficiency for polymerization. The two-stage spectrometric assay of the present invention can also be used to determine or evaluate the catalytic activity of individual catalysts. The invention also relates to the use of ion-molecular reactions, such as dissociative collisions, to simplify the mass spectrum of oligomer / polymer mixtures. The mass spectrometry methods described in this application are generally used to evaluate polymerization reactions, such methods being used, for example, to determine the ratio of chain propagation to chain transfer in a given polymerization reaction in solution.

A general kinetic scheme for Ziegler-Natta polymerization is incorporated into this description by reference (Mayl et al., (1999) and applying standard computational methods known in the art. Numerical integration was performed using POWERSIM (Modell Data AS) using standard methods, that is, according to Euler or Runge-Kutt for up to fourth order equations.

In any case, the integration intervals were chosen so that the actual numerical calculation had a negligible effect on the output.

• 99 99 9999 · 9 99 • 9 «9 9 9 · 9 · 9 · · · · 9 9 9 9 • · 9 9 9 φφφ · 9

9,999,999

99 «9999 99» 9 9 «9999

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Screening of a small set of Brookhart Pd (II) complexes with various aryl groups on a diimine ligand.

1a R = CH _3: R 1 = K; R = H 1b R = CH ₃ ; R 1 = CH ₃ . R = H 1 CR = CH _3; · R = CH _{(CH3) 2;} R = H

Screening is performed according to the reaction scheme depicted in Scheme 1. A solution containing complexes (Ia), (1b), and (1c) (see Scheme 1) wherein the concentration of each component is about 10 ^-3 mol / L in CH 2 Cl 2 is saturated with ethylene and allowed to react for one hour at -30 ° C, then quenched with dimethylsulfoxide (DMSO) and finally diluted 100-fold. The resulting solution is immediately introduced by electrospray ionization into a Finnigan MAT TSQ-7000 tandem mass spectrometer under assay conditions as previously described (Hinderling C et al., (1997), Angew.Chem., 109: 272; Hinderling C. et al., ( 1997: J. Am. Chem., 119: 10793; Feichtinger D. and Plattner DA, (1997), Angew. Chem., 109: 1796; Feichtinger D. et al., (1998), J. Am. Chem. Soc., 120: 7175; Hinderling C. et al., (1998), Angew. Chem., 110: 2831). The electrospray ionization mass spectrum obtained by scanning the first quadrupol is complex, see Fig. 1A, and depicts a series of oligomeric and polymeric ions corresponding to each of the catalysts used, with an addition of zero to fifty ethylene units. Then »» ·· «·

The first quadrupol is set to remove all ions of matter below the separation limit, either m / z = 600 or m / z = 1000. Thereafter, collisions of the remaining ions with the xenon (~ 0.5 mTorr, i.e. 6.7-10.0 ³ Pa) are induced in the octopole ion conductor at a nominal ionic energy of 40 eV. The daughter ions for the two different separation limits sensed from the second quadrupol are shown in Figures 1B and 1C. As shown in Fig. 1B, the predominant mass spectrum peak corresponds to the ion (3c) and / or its daughter ion (s) resulting from the collision-induced elimination of the hydrocarbon chain from the ion chain formed by the catalyst (1c), indicating that the catalyst (1c) of the three catalysts is the best. By reducing the separation limit m / z = 1000 to m / z = 600, i.e., Fig. 1C, the ion (3b) and / or its daughter ion appear, indicating that catalyst (1b) is the second of the three catalysts. the best. For the same three catalysts, the order (1c)>(1b)> (Ia) has already been described in the literature (Johnson LK and Kiilian CM, (1995), J. Am. Chem. Soc., 117: 6414). The consistency of these mass spectrometry results with the conventional assay demonstrates the effectiveness of this new method for screening catalysts.

Example 2

Screening of the Brookhardt Catalyst Combination Library

Eight complexes (1a-h) (Scheme 2, where R, R 'and R are as described) of the test library are simultaneously prepared in a modified manner described in the literature using an initial equimolar mixture of eight individually prepared diimine ligands (Kliegman JM and Barnes RK, ( 1970), J. Org. Chem., 35: 3140) in diethyl ether, by treatment with one equivalent of [(cod) Pd (CH ₃ ) (Cl) (Rulke RE et al., (1993), Inorg.Chem., 32 : 5769) at room temperature, with an overnight reaction time, and including filtration »0 0000 • 0000

0 0 0 0 0 0 0 0 0 0 0 0 00 00

00

0 0

0 0 0 0 0

000 * orange precipitate and activation of solid products in CH ₂ Cl ₂ solution by AgOTf.

By checking the catalyst mixture before activation, a comparable concentration of all eight complexes was verified by ¹ H NMR.

Resonance signals of methyl groups are in the form of sharp singlets well separated from each other and other resonance signals. The mass spectrum with electrospray ionization of complex mixtures (activated by AgOTf and then quenched with acetonitrile) (Fig. 2A) shows the presence of all components (1a-h) again with comparable peak intensity. A solution of said mixture in ΟΗ ₂ Ο1 ₂ , where the concentration of each catalyst is of the order of 10 ' ³ mol / l, is saturated with ethylene and the reaction is allowed to proceed for one hour at -10 ° C, then quenched by adding 100 times 3% DMSO in CH ₂ C1 ₂ . Then, the solution is introduced using electrospray ionization into a MAT TSQ7000 tandem mass spectrometer as described in Example 1. The electrospray ionization mass spectrum removed from the first quadrupole is complex, containing a multiple, overlapping series of oligomeric and polymeric ions corresponding to each ethylene-bound catalyst type. units of zero to about one hundred, wherein the spectrum is shown in FIG. 2A. Additional spectrum complexity and broad peaks are due to the palladium isotope distribution (the following isotopes naturally occur: ¹⁰² Pd 1.02%, ¹⁰⁴ Pd 11.14%, ¹⁰⁵ Pd 22.23%, ¹⁰⁶ Pd 27, 33%, ¹⁰⁸ Pd 26, 46%, ^U0 Pd 11.72%) as well as ¹³ C satellite peaks (emphasized with polymer growth) that are not distributed over the spectrum. When the compound (1c) is reacted with ethylene, and the reaction mixture is quenched and subjected to ESI-MS analysis, the spectrum of oligomeric ions (see FIG. 2B) coincides with the predicted distribution based on Johnson LK et al. (1995), »1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 1995 · · ** ** ** ** · · · · · · · · · ·

Chem. Soc., 117: 6414; Johnson L.K. et al., (1996),

J. Am. Chem., 118: 267.

Only radiofrequency voltages are superimposed on the first quadrupol to pass ions with a higher m / z than a given separation limit, in this case m / z-2200 or rn / z-ICOO. it should be emphasized that high resolution is not necessary at this stage. Thereafter, collisions of transmitted ions with xenon (-0.5 mTorr, ie 6.7 · 10 ³ Pa) are induced in the octopole ion conductor at a nominal ion energy in the range of 30 to 80 eV.

Representative daughter ions for the two different separation limits sensed from the second quadrupol are shown in Figures 3A and 3B.

Figure 3A clearly shows the major peak (s) at m / z = 511, corresponding to the collision-induced ion (4c) induced by β-hydride removal of the hydrocarbon chain from the catalyst (1c) ion. A small sharp peak at m / z = 405 is a secondary product resulting from fragmentation corresponding to the diimine ligand without palladium. Secondary fragments of [4-Pd] (or [4e-Pd-Br]) unambiguously contain linkage to the parent ions (4), in which the parent ions lead to both (4) and secondary fragments. From these results, it is clear that of the eight potential catalysts (1a-h), the best actual catalyst is the complex (1c), in accordance with the prior art ^11] . Similarly, the spectrum of daughter ions with a lower mass separation limit (Fig. 3B) shows that the best catalysts are (1b), (1d) and (1e). Conformity of the mass spectrometric assay with the conventional assay demonstrates the effectiveness of the method of the invention used for screening catalysts. The order ((lc) >> (lb) - (ld) - (le)> other) coincides with the assumptions based on the argument that β-hydride elimination (and therefore chain transfer) is disadvantageous when for steric reasons «I • · • · ft.

2Ί

The arena groups are deflected by pressure from the plane. The similarity between (lb), (ld) and (le) suggests that the effects of electrons on catalyst performance are relatively small.

An interesting finding in concurrent screening that (1g) does not allow the formation of highly polymerized products was confirmed in a separate assay with dg) - These results indicate that the isopropyl groups on the arene group have little effect when the 1,2-diimine ligand skeleton is unsubstituted . Brookhart described reduction ^fl] average molecular weight (50krét) and yield (5 times) polymer prepared using (LG) in comparison to (c).

Example 3

Screening properties of prepared polymer

In the previous examples, oligomeric polyethylene chains were coupled to a cationic catalyst by mass spectrometry. On the other hand, with continued polymerization as the product becomes a bulk final product, most polymer chains are not metal bound, they are chain transfer products and elimination as evidenced by terminal olefinic groups. The required catalyst selection criteria include the average molecular weight and the molecular weight distribution of all polymer chains, not just the metal bound chains. The ESI-MS / MS method provides this information using kinetic data from which M _w and M _n / M _n can be calculated for all metal bound and free of metal.

The procatalyst solution (precursor to the catalyst) is saturated with ethylene and maintained at a constant ethylene pressure with efficient stirring to ensure that the monomer concentration remains unchanged. Addition of a suitable (o) o (o) o (o) o (o) o (o) o (o) o (o) o (o) o (o) o (o) o (o) o (o) o · * ·

Hl «« «· · · · · · · · · · · · · · After a selected period of time, a quencher such as Co is added to stop the polymerization. The solution was then diluted to a concentration suitable for ESI and analyzed by ESI-MS / MS. The parameters determined in this screening are shown in Scheme 3. The methyl-terminated metal chain oligomer chains, referred to as non-chain transfer chains, correspond to those formed at the catalytic center that are not subject to chain transfer. The hydrogen-terminated metal oligomer chains, referred to as chain transfer chains, correspond to chains formed at the catalytic center which are subject to at least one chain transfer. These chains form two separate distributions offset by 14 mass units each, whose mass spectra vary widely (see FIG. 4A and the enlarged m / z region of 1000-2500 in FIG. 4B). Using the general kinetic scheme for Ziegler-Natta catalysts according to T. Ziegler (see Scheme 4), with specific adaptations to a specific group, in this case Brookhart catalysts, the two types of distributions can be used to obtain specific absolute initiation, propagation and chain transfer for specific reaction conditions. By determining these parameters for a given catalyst and activator at different temperatures - the dilution determination is important - these rates can be used to determine the Arrhenius constants for the three processes. These parameters also allow prediction of the polymer properties of the final metal-free polymer prepared under actual conditions, which may include reactivation of the dead polymer (chain-to-polymer transfer instead of monomer), chain branching by 2.1 reinversions, etc. Systems of differential equations usually solve numerically but work on an analytical solution that allows a much faster solution.

Tt tt tt tt tt tt

9Q · ♦ * * tttt * · ·

Methods of solution by standard computer programs are also used in the art.

In this example, the catalyst having the best efficiency was deliberately selected so that both types of distributions, i.e. the distribution of the chains not involving the chain transfer and the distribution of the chains comprising the chain transfer, were simultaneously visible in the obtained outputs. The distribution values of the non-chain transfer chains and the chain transfer chains from the mass spectra shown in FIGS. 4A and 4b are used to determine the initiation, propagation and chain transfer rates for this catalytic reaction. For example, by similar assays for a total of three temperatures, Arrhenius activation propagation and chain transfer energy of ~ 18.9 and 21.4 kcal / mol (i.e., 79.130 kJ / mol and 89.597 kJ / mol) were found. For the propagation-related reaction mechanism, the value found by the inventors is about 1 kcal / mol (4186.8 J / mol) lower than the Brookhart reading for a slightly different catalyst (o, o'-diisopropyl-o, o'-dimethyl) with another counterion and in another solvent. Brookhart does not provide any data on chain transfer at all, but the M _w value obtained from the kinetic parameters of the method of the invention is well qualitatively comparable to the value assumed in Brookhart's work.

As mentioned above, very little data is available for comparison. In addition, under normal laboratory conditions, carrying out the polymerization to the end product allows the chain to be transferred to the polymer as well as to the monomer because the polymer concentration becomes high enough. As a result, M a and especially Μ _ω / Μ _η begin to depend on detailed polymerization conditions. This can be taken into account without great difficulty in the calculation, but for screening purposes it must be emphasized that it is possible to satisfactorily predict the development of M _w and M _w / M _n values even without including these phenomena in the model.

By varying the three velocities in the above dependencies, it appears that the three parameters are close to linear independence. The maximum distribution of chains not involving chain transfer and their high-weight edge is predominantly directly related to the absolute rate of propagation. The breadth of distribution of the chains not including the chain transfer is determined by the ratio of the initiation and propagation rates. The relative magnitude of the distributions of the strings not involving the chain transfer to the strings comprising the chain transfer corresponds to the ratio of the propagation rate to the chain transfer rate. The shapes of the kinetic model distributions are very close to the curves obtained from the experimental distributions, suggesting that the kinetic model includes all major effects.

The average molecular weight and polymerization size corresponding to the consumption of ethylene molar equivalents can be calculated for a given temperature by the initiation, propagation and chain transfer rates determined from the chain distributions not including the chain transfer and the chains including the chain transfer shown in the mass spectra in FIGS.

In the catalyst leading to a high M _w polymer, the ratio of the non-chain transfer chains to the chain transfer chains is also large. The upper limit M _w for analytical processing in this manner should be in the dynamic range of the mass spectrometric determination, ie the ability to distinguish a small peak near the much larger neighboring peak. For transmission type spectrometers such as quadrupole and sector commercially available instruments, the dynamic range is -10,000, which means that β * ♦ · · can be processed

Up to 500,000 samples can be further improved by using scintillation-based detectors and 16- or 20-bit A-D converters. FC-ICR spectrometers are less suitable because of their limited dynamic range; both FT-ICR spectrometers and ion-trapped quadrupole mass spectrometers have the disadvantage of insufficient statistical evaluation (less than 10,000 ions are captured within a given period).

The mechanism proposed by T.Ziegler refers to the chain branching rate to the chain transfer rate, where both reactions occur in the same transient state. In the view of the inventors, it is appropriate to derive an algorithm for these relationships.

The polydispersity of the polymer in this example, M _w / M _n = 2, corresponds to chain length limiting polymerization. According to Brookhart, polydispersities exceeding 2 lead to chain transfer to the polymer rather than to the monomer. In a typical experiment for which M _w / M _n -4 is reported, said author prepared 40 g of polyethylene in 100 ml of solvent. The polymerization process is clear, the polymer concentration increases during polymerization to such an extent that the polymer competes with ethylene for binding to the catalyst. This phenomenon is readily included in the integration code for the calculation, which means that the effects of concentration on polydispersity can be predicted from measurements of the same diluted solution used to calculate Mn.

In the experiments of the present inventors, catalysts in conjunction with MAO lead to a large number of low weight peaks, while continuing persistent signals of the basic constituents - oligomeric ions bound to the metal are still evident. This interference can make it difficult to obtain clear quantitative distributions of chains including chain transfer and chain transfer without chain transfer. However, in the manner of the MS / MS as described above, 9 9, 9 9 9 99 9 9

·

9 9

9999 involving the selection of oligomeric ions and subsequent treatment of CID to form palladium hydride, it is possible to circumvent the problems caused by the use of MAO. When all ions are selected and the CID is processed and the parent spectrum of palladium hydride masses is recorded, the distribution of the non-chain transfer chains and the chains including chain transfer without interference with MAO-derived peaks is obtained.

The chemical reactions that are part of the assay of the invention can in principle be as long or as slow as they are used for any assay in the same reaction. It should be noted, however, that the method of the invention determines the properties of a polymer with a high degree of polymerization based on the evaluation of metal-bound oligomers and therefore the time required for the chemical portion of the assay can be reduced compared to the time required for the final polymer assay. The time fraction of the actual mass spectrometric determination is in the range of about 1 to 5 minutes.

The devices used in the assays of the invention can operate with an automatic dosing device. The automatic dispenser can operate in anaerobic mode.

Before using the CH2Cl2 was distilled using CaH _second For electrospray ionization, flow rates of 5 to 15 μΐ / min, N ₂ gas at the jacket and a spray voltage of 5.0 kV are used. Very mild desolvation conditions (heated capillary 150 ° C, flax-tube potential of 52 V) were used. The procatalyst (10) is prepared by the following methods known in the art. Free diimine ligand, biacetyl-bis- (2,6-dimethylphenylimine) (Dieck HT et al., (1981), Z.Naturforschr., 32b: 283), 73.1 mg (0.25 mmol) and 66.3 mg (0.25 mmol) of (1,5-cyclooctadiene) Pd (Me) (Cl) (Rilke RE et al., (1993), Inorg.Chem., 32: 5769) are suspended in 3 · 5-cyclooctadiene.

9 ·

9 t

999

9 * 99

99 ·

·

9 9

9999 ml of ether and the mixture was stirred for 18 hours. The resulting orange precipitate was filtered off, washed thoroughly with ether and dried in vacuo. 101.0 mg of an orange solid are obtained (yield 90%).

1 H-NMR (300 MHz, CDCl ₃ ) δ 7.17-7.05 (m, 6H, Ar), 2.25 (s, 6H, Ar-CH ₃ ), 2.22 (s, 6H, Ar- CH ₃ ), 2.03 (s, 3H, N = C-CH ₃ ), 1.98 (s, 3H, N = C-CH ₃ ), 0.44 (s, 3H, Pd-CH ₃ ).

Polymerization:

2.0 mg (4, 45 to 10 ~ ³ mmol) of compound (10) was dissolved in 5 ml of CH2Cl2 in a 20 ml Schlenk tube fitted with a thermocouple for measuring the internal temperature and cooled to the reaction temperature of 9.8 ° C. The solution was then saturated with ethylene for 30 minutes with vigorous stirring in an ethylene atmosphere. About 10 mg of AgOTf is then added to activate the catalyst. While continuing vigorous stirring under an ethylene pressure of 1 bar (10 ⁵ Pa); the polymerization reaction was allowed to proceed for 26 minutes. The reaction was then quenched by purging the solution with an intense stream of CO. Part of the solution was filtered through a plug of glass wool to remove the silver salts, 50-fold diluted with CH ₂ C1 ₂ and analyzed by mass spectrometry using electrospray ionization.

The invention is described as an example of the screening of some organometallic catalysts used to prepare polyolefins. However, the invention is not limited specifically to the catalysts or polymerization reactions described. In the practice of the invention, it is possible to use methods, embodiments and instrumentation other than those shown in the examples to illustrate the invention. In addition, various methods of initiating and generating daughter ions are known in the art and can be used to obtain the data of the invention.

»0 • 9 9 9 9

000 000 · 00

0 · • 00

0 «0000

All references cited herein are incorporated by reference in their entirety and are not in any way inconsistent with this disclosure.

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Determination of catalyst characteristics obtained from analysis of metal-bound oligomers and used to predict the properties of the final polymer

Solvent:

Procatalyst:

Activation:

CH ₂ Cl ₂ , 5 ml,

N, / 1

Pd 2 mg

CH 'CHa addition of solid AgOTf to a thermostatic solution presaturated with ethylene at 1 bar (10 ⁵ Pa),

Temperature:

9.8 ° C,

Response time:

minutes,

Reaction quencher:

Monitored ion:

R = CH ₃ (chains without chain transfer)

R = H (chains involving chain transfer)

Measurement time (MS) <5 min

Scheme 3 ·· ··· · I · 0 · · · · I · ϊ · 0 * * • 0 0 * · • 0 · 0 * ♦ · · 000 ·

Kinetic scheme:

LíM

LíM

LíM,

L ₂ hi

CHj

L ₂ M / ▼ C2H4

CHa (CKiCHiinCHa

LjM

L ₂ M

Mnít

CHa 'POP ‘(CH3CHaJCHa + C1H4 /

-1 m ₂ (CH 2 CH ₂ CH 2).

(CH ₂ CH ₃ ) ₂ kprop (CH ₂ CH ₇ INCH _{3 12} m ₂ y 2 (CH ₂ CH ₂ ) _B ), CH 3 * C ₂ K. / CH ₃ CH ₃ J 2

- L ₂ M + [CH 3 CH 3] fcans (CH 2 CH 3 /

^L '^ ^M (CHjCH ₃₎ MCHA

CHa coanCH ₂ CH ₂ > bH _{+ c} for XCHaCH 3 N -H

LM <-L ₂ M

Kprap

LM ₂ m + c ₂ h ₄ / (CH 3 CH 3 JH

L ₂ M 2 (CH ₂ CH ₂ ) n, H, and CH ₂ CH ₃

Assumptions:

(1) All rates for olefins are zero order, ie coordination is fast and olefin is in surplus *, (2) Propagation and chain transfer rate constants do not depend on chain length and structure, (3) Chain transfer and chain branching take place in a structural (4) The release of the olefin-terminated polymer is at a high pseudo-first order monomer concentration.

* Johnson L.K., Kilian C.M., Brookhart M.,

J. Am.Chem.Soc., 1995, 117, 6414, * Margl P., Deng L., Ziegler T., J. Am.Chem.Soc., 1999,

Claims (18)

A method for identifying a compound acting as a catalyst for a selected reaction comprising the steps of: providing one or more evaluated catalysts for the selected catalytic reaction; contacting the catalysts of interest with the selected reactant under conditions in which the selected catalytic reaction may proceed to form a reaction product from the reactant; - interruption of all catalytic reactions of the reactant. analyzing the products of the interrupted reaction by mass spectrometry in order to identify the ions contained in the mass spectrum which are associated with one or more selected reaction products, said selected product being each reaction intermediate linked to the rated catalyst or to a portion of the evaluated catalyst; and - analysis of the ions associated with the selected reaction products to determine the catalyst of interest which has enabled the formation of the selected product and thereby identify the compound which acts as the catalyst in the chosen reaction. Method according to claim 1, characterized in that the ions associated with the selected reaction product are analyzed using an ion-molecular reaction. · 1 · * ♦ · * ♦♦ ♦♦ · · · · Method according to claim 1 or 2, characterized in that the analysis of the products is carried out by eiektrospray ionization mass spectrometry. Method according to claim 1, 2 or 3, characterized in that the analysis of the products is carried out by tandem mass spectrometry with eiektrospray ionization. A method according to any of claims 1-4, characterized in that the selected reaction products are analyzed using collision-induced dissociation. The process according to any of claims 1-5, wherein the selected reaction is a polymerization reaction. 7. The method of claim 6, wherein the selected reaction products are analyzed using an ion-molecular reaction. 8. The process of any one of claims 1-7, wherein the selected reaction is an olefin polymerization reaction. The process according to any of claims 1-8, characterized in that the compounds to be evaluated are organometallic complexes. Process according to any one of claims 1-9, characterized in that the catalysts to be evaluated are organometallic complexes. Process according to any one of claims 1-10, characterized in that the catalysts to be evaluated are obtained in the form of a combination library. Fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe fe 12. The process of any one of claims 1-11, wherein the choice of ion formation reactions is based on their mass. The method of any one of claims 1-12, wherein the selected reaction is a polymerization reaction and wherein the product ions are ions with an m / z value higher than the selected mass separation limit. Method according to claim 13, characterized in that the mass separation limit corresponds to m / z = 1000. The process according to any of claims 1-7 or claims 9-14, wherein the selected reaction is olefin-CO copolymerization. 16. A method of determining the ratio of propagation rates to chain transfer rates in a catalysed polymerization reaction, comprising the steps of: reacting the evaluated polymerization catalyst with the selected monomer under selected conditions to form polymer products; - interruption of the reaction; - post-reaction analysis of the reaction products using mass spectrometry to determine the distribution of the chains including chain transfer / chains not including chain transfer and to determine the ratio of propagation rate to chain transfer rate. * 9999 * * 9 9 9 99 9999 17. The method of claim 16, wherein the distribution of the chains including chain transfer / chains not including chain transfer is determined by electrospray tandem mass spectrometry. The method of claim 16 or 17, wherein the catalyst is an organometallic complex and the distribution of the chains comprising chain transfer / chains not including chain transfer is determined by determining the ratio of polymer ions to chains comprising metal-chain-to-non-transfer polymer ions. chains bound to the metal.