FR2865820A1 - Producing a database for selecting a catalyst for a given reaction comprises analyzing a set of different reaction mixtures containing the same reactivity probe and a catalyst - Google Patents

Abstract

Producing a database for selecting a catalyst for a given reaction comprises preparing a set of different reaction mixtures containing the same reactivity probe and a catalyst, analyzing each reaction mixture after reaction, and assigning to the database an analytical result characterizing different reaction products of the probe.

Description

The present invention relates to the field of catalysis and aims in particular

  to propose a method for constituting a database making it possible to rapidly identify one or more catalysts that can be used for the transformation of a compound and more particularly of at least one of its reaction units, according to a reaction

given chemical.

  Organic synthesis by the catalytic route, and in particular by heterogeneous catalysis, is a synthetic route particularly appreciated at the industrial level. In fact, the use of a catalyst generally makes it possible to accelerate the reaction rate, to lower the reaction temperature and / or to increase the yield thereof. In addition, the heterogeneous catalysts, that is to say insoluble in the reaction medium as opposed to so-called homogeneous catalysts, have the significant advantage of being easily separated from the reaction products, at the end of the chemical reaction considered.

  Unfortunately, there is currently no simple and quick way to identify the catalyst (s) likely to show the best selectivity and / or efficiency for a given chemical reaction. The identification of this type of catalyst is a very often empirical approach.

  Conventionally, a catalyst presumed effective is tested as such and, depending on the result obtained, different possibilities are possible. In particular, in the particular case where the catalyst does not give satisfaction either it can be abandoned and another catalyst tested, or it can be modified to optimize its reactivity. Finally, the operational conditions selected can also be modified. This approach is of course time consuming and therefore expensive.

  An alternative is to use combinatorial chemistry. According to this approach, a large number of chemical variants of a presumed effective catalyst for a given reaction is synthesized and tested to characterize the most effective catalyst (s) to effect the reaction. However, this second approach is not entirely satisfactory. In particular, it involves testing, for each new compound to be converted, all the catalysts and constituting a new catalyst library for each new chemical reaction envisaged. Indeed, the reactivity of the catalysts is generally not archived and even less correlated to a particular structure of the compounds involved in the reaction in question and / or defined reaction conditions. However, it is known that for a given catalyst, several degrees of reactivity are likely to exist on the one hand the structure of the compounds to be transformed and, on the other hand, the medium and the reaction conditions retained.

  The present invention aims in particular to make it possible quickly to establish a database useful for identifying at least one catalyst meeting a reaction criterion.

  The invention meets this need by means of a method for constituting a database making it possible in particular to select at least one catalyst suitable for a reaction, this process comprising the following steps: x) preparing a plurality of different reaction media containing a single reactivity probe and each at least one catalyst, y) analyzing, by an analytical method, each reaction medium after reaction, z) assigning in the database, to the reactivity probe, a result of the analysis according to step y ), this result characterizing the different reaction products obtained in the reaction medium, where appropriate with their respective yields from this reactivity probe.

  By assigning in the database to the reactivity probe a result of the analysis, it must be understood that a link is established in the base at least between the probe, or even the reaction medium, and the result of the analysis. . This result can relate to the yield of the products of the reaction. Such links may make it possible to convert the results of the analysis in terms of the nature and / or transformation of the reaction units, and thus be useful for responding to a request to determine at least one catalyst capable of carrying out a transformation of the reaction units. a reaction unit or to study the influence of the composition of a catalyst on its reactivity and selectivity.

  The plurality of different reaction media may comprise at least two reaction media containing different catalysts. The same reaction media can be used for different probes.

  The analytical method can be a method of liquid or gas phase chromatography.

  Steps x) to z) above may be repeated for a plurality of different reactivity probes.

  Reaction unit denotes a unit having at least one function or bond that can be chemically transformed.

  This unit may especially consist for example of a saturated bond of a carbon atom with at least one heteroatom, or an unsaturated bond between two carbon atoms, between a carbon atom and at least one heteroatom or between two heteroatoms, which are identical. or different.

  The unsaturated bonds between two carbon atoms may be for example Csp hydrocarbon bonds of alkynic type, or Csp2 of alkene type.

  For the purposes of the present invention, it is intended to cover, under the term heteroatom, an atom of nitrogen, oxygen, sulfur, phosphorus, silicon, boron, etc.

  Representative and non-limiting examples of reaction units include the following: c = C; \ C CH = C \ X; CH = IOC; CH = C N; Cf 2 N CH 2 O; CH2 X; C N; N C; O \ \ Il / C = 0; VS; N = N; N = O; O O; N-0;

X / / N P /

  Where X represents a halogen atom.

  The database may contain for each listed catalyst information about the reaction medium in which it has been tested for its catalytic activity.

  The database can individually list the reaction patterns present on the reactivity sensors.

  At least for a portion of the reaction units listed in the database, may be associated with each listed reaction pattern information to qualify the status of the links associated therewith. It is important to note that the link state does not bode well for their responsiveness. Thus, it is not identical in a reducing or oxidizing medium.

  More precisely, the link state of a reaction unit can be indexed using an integer, called link state, and can vary from 0 to 3, the value generally describing the absence of link and the value 2 characterizing a double bond.

  As a result, each pair reaction reaction unit may be associated with a pair of states of bonds that can qualify the degree of reactivity of said pattern before and after exposure to said reaction medium.

  For example, in case of no reaction, the state of the original links is preserved; in case of reduction, the state of the links decreases by at least one unit; (A state equal to zero means the break of a link). A decrease of one unit may correspond, for example, to the transformation of a triple bond into a double bond or a double bond into a single bond or alternatively to replace a halogen with a hydrogen.

  The database is preferably a relational database having a first entity in which information relating to the reaction units listed in the database is recorded, a second entity containing information relating to the link state of at least one pattern. in the first entity, a third entity in which information associated with the different reaction media is recorded, and at least one fourth entity in which information related to the analysis results of the reaction media is recorded at the end of a reaction. reaction.

  For at least one reactivity probe, a file can be generated gathering all the results covering all the transformations that have been performed at said probe.

  The database according to the invention can usefully be exploited according to a method making it possible to deliver at least one information relating to the reactivity of a catalyst with respect to the chemical conversion of at least one reaction unit, this process being able to characterized in that it comprises at least the steps of: a) acquiring data relating to said transformation and, where appropriate, to the structural environment of the reaction pattern to be transformed, b) identifying in a database providing information the reactivity of a set of catalysts with respect to reaction units listed in the database and present on reactivity probes, at least one listed reaction pattern related to the pattern to be transformed, c) selecting in the base of according to a part of the identified reaction unit thus identified and secondly of the transformation to be carried out at least one catalyst having the reactivity required for the transformation.

  By listed reaction pattern related to the pattern to be transformed, it should be understood that the reaction pattern listed in the database is identical to the reaction pattern to be transformed or sufficiently close structurally to think that the catalyst to be selected is useful for the transformation to be performed. Its reactivity may be equivalent to that of the pattern to be transformed and results in the expected chemical transformation or equivalent chemical transformation.

  By structural environment is meant the environment resulting from the combination and the spatial arrangement of all the reaction units constituting the same molecular entity.

  The reactivity of a reaction unit is likely to vary significantly depending on whether or not it has, in its immediate structural environment, other reaction units. For example, an ethylenic function, depending on whether it is located at an aromatic ring or a CH 2 unit, will not exhibit the same degree of reactivity in a catalytic hydrogenation reaction.

  The database can advantageously give access to information that provides information on the influence of the structural environment of a listed reaction pattern.

  The membership of the reaction units listed in reactivity probes that may comprise several reaction units may make it possible to take into account, as the case may be, the reaction influence aspect for the selection of the catalysts, that is to say the influence undergone. by a reaction unit in terms of reactivity, because of its associated structural environment.

  By definition, a reaction has the objective of transforming, assembling and / or dissociating one or more reaction units of a compound without, if necessary, modifying other motifs also present. The terms chemical transformation and chemical reaction encompass not only conventional, organic or inorganic chemistry, but also biochemistry, and the transformation or reaction may be biological.

  In general, the chemical reactions that can take place in the reaction media are formation or bond-breaking reactions, especially C-C, -CO, -CN, C = N, and C = C.

  Representative and non-limiting of these chemical reactions, mention may be made of halogenation reactions, reduction, hydrogenation, in particular by heterogeneous catalytic, oxidation, hydrolysis, dehydration and esterification.

  The reactions considered according to the invention can thus be acidic catalytic reactions such as, for example, protection / deprotection reactions, basic catalytic reactions, metallocatalyzed multicomponent reactions, or trimerization reactions, for example.

  By transformation is meant localized reaction at a reaction unit. This term includes any type of transformation, assembly or dissociation, insofar as it is localized at the level of a reaction unit. The transformation of a reaction unit may reside in the formation of a coupling of two identical or different reaction units.

  By way of illustration of transformations likely to take place in a hydrogenation reaction, mention may especially be made of the following transformations: reduction of imine to amine, cleavage of a CN or benzyl CO bond, reduction of a halide, reduction of a nitro function to amine, a nitrile to amine, reduction of amide, reduction of an alkynic unit, reduction of a ketone to alcohol, reduction of a ketone to alkane and cutting of an ether unit.

  The formulation of a request in step a) may mention the reaction unit concerned and the nature of the transformation that it is desired to subject to it.

  The transformation can be formulated using the name of the transformation, for example by selecting it from a list on a drop-down menu. The transformation may also be formulated by indicating the variation of the bond state of the functional groups to be converted or retained at each reaction unit resulting from the transformation or the difference in the state of the bonds in the reaction unit considered between the states before and after transformation.

  Where appropriate, the data entry may include the formulation relating to the transformation and / or non-transformation of at least two different reaction units.

  In the case, for example, of a first reaction unit to be converted and a second reaction unit not to be converted, these first and second reaction units being present on a starting compound, the request may be aimed at selecting a catalyst capable of perform the transformation of the first pattern with sufficient yield while leaving the second intact, or at least transforming it sufficiently little.

  The request may also aim to select the optimal reaction medium for a given catalyst, which itself may have been preselected with said base.

  Acquisition of the data in step a) can still be performed by formulating a request to transform at least one starting compound.

  In this case, the method for delivering at least one information relating to the reactivity of a catalyst may comprise the analysis of the starting and ending compounds in order to identify the reactive reaction unit or units and the one or more not reacting. In view of this or these reagent units reacting and / or not reacting, at least one new request relating to at least one reaction unit of the starting compound can be formulated. This request may be formulated automatically, as the above analysis may be performed without the intervention of the user except to validate, if necessary, the analysis performed automatically.

  Thus, the above process may involve: - the decomposition of a starting compound involved in a reaction into different substructures, - the identification of the reaction unit (s) to be transformed and, where appropriate, - the identification of the reaction unit (s) to be preserved.

  The acquisition of the starting compound and the arrival compound can be carried out for example by drawing their structure, giving their name or an identifier referring to their structure.

  Step a) can be done via a computer network, including the Internet or Intranet. In this case, the intervention of the user may for example be limited to specify the identity of the starting and ending compounds.

  As indicated above, a plurality of reaction units listed in the database are present on reactivity probes. The reactivity probes used may be more particularly adapted to a given type of reaction.

  Reactivity probes can be natural or synthetic. It can in particular be molecules of low mass and may comprise from 10 to 30 carbon atoms. They can be saturated or unsaturated, linear or branched.

  In general, each reactivity probe comprises at least one reaction unit in a specific structural environment. They advantageously comprise at least two different reaction units or at least three reaction units of which at least two different units or at least four reaction units, at least two or even at least three different units.

  The presence of several reaction units on the same reactivity probe can make it possible to increase the number of reaction data acquired for each probe transformation test in a given reaction medium. The database can be completed more quickly. In addition, the presence of several reaction units can make it possible to highlight, where appropriate, the influence of the structural environment.

  The reactivity probes used may be more particularly adapted to a given type of reaction.

  For example, for a catalytic hydrogenation, the probes may for example have at least one reaction unit chosen from the following units: -C = C; C = C = 0; j = N; Arp \ X; Arp \ O. N = N \; This highly reactive unit may be associated with at least one second unit, or even two other units, known for a lower reactivity according to this same reaction. For example, for a given reactivity probe, it is these less reactive patterns and their spatial arrangement that will constitute the structural environment associated with the most reactive reaction pattern.

  The number of probes is preferably chosen so as to include all the chemical transformations likely to be involved in a given reaction. For example, for a hydrogenation can be represented through these probes the various possibilities of hydrocarbon unsaturation, aromatic or non-aromatic, the various carboxylated functions COOR, CHO, CO, CONH2, carboimine functions, ....

  By way of non-limiting illustration of reactivity probes that are suitable for the invention, mention may be made especially of those having the structures represented below:

VS

  The database may furthermore contain information, associated with each catalyst and / or reaction pattern listed, which may be very diverse and in particular the database may contain data which provide information on the activity of at least a part of the data. catalysts listed for various reaction conditions, including the temperature of the reaction medium, the acidity, the pressure, the presence of solvents, the type of analysis method, etc.

  The database can be loaded on a computer server where computers can connect for example a personal computer, portable or fixed. The data can be saved on a computer medium.

  The catalysts listed in the database may be of a chemical nature, organic or inorganic, and in particular of organometallic nature, or else biological in the image of proteins, cells or enzymes.

  In this case, it can be all the catalysts that can be used in homogeneous or heterogeneous catalytic synthesis.

  The chemical conversion catalysts comprise most of the elements of the periodic table and are generally solid under the usual reaction conditions.

  By way of nonlimiting illustration of these catalysts, mention may especially be made of catalysts based on bismuth, tin, nickel, palladium, antimony, ruthenium, titanium, zirconium, iridium, copper, cobalt, rhodium, platinum and rare earth elements.

  These catalysts can be tested individually or in combination.

  These catalysts can also be in a supported form. The type of support may be chosen from inert clays, zeolites, ceramics, carbon or an inert organic material. It can also be metal oxides like Al2O3. These supports can be used in various solid forms such as honeycombs, particles or networks.

  By way of non-limiting illustration of the catalysts according to the invention, mention may in particular be made of the following catalysts: Pd / Al 2 O 3; PdBaSO4; Pd / CaCO3; Pd / PEI; PdICaCO3, Pd / C; Pt / C; Ru / C; Re / C; Rh / C; RhIAl2O3; Ir / C; Ir / CaCO3.

  The catalysts may or may not be specialized with respect to a biological or chemical reaction, for example a hydrogenation reaction.

  The reactivity of the catalysts can be assessed in terms of yield and / or selectivity. However, this catalytic activity can also result in a lack of activity for the chemical conversion of a reaction unit and be of interest in this respect. Similarly, this reactivity can be reflected in the manifestation of a particular selectivity in the reaction.

  Generally, a catalyst is considered active, within the meaning of the present invention, when it makes it possible to carry out the chemical reaction in question with the sufficient yield.

  The database can provide information on the reactivity of all the catalysts selected, vis-à-vis the reactivity probes and reaction units listed, for the same or different reaction conditions. This can make it possible to better appreciate the specificity of the catalysts and thus optimize the knowledge of their performance in terms of efficiency and especially of selectivity.

  The reaction conditions may be those generally used for the chemical reaction under consideration. They generally require the choice of a solvent medium, its degree of dilution, co-reactants, a temperature of a pressure and / or the pH of the reaction medium.

  Co-reactive means any compound which by its presence in the reaction medium is likely to participate in the reaction such as carbon monoxide for example, and / or to affect the yield and / or the selectivity of the reaction. It may especially be an acidic compound, basic, a chelating metal. It is in particular by adjusting these parameters related to the reaction conditions that it may be possible to control more precisely the nature of the final product and / or to orient the selectivity of the reaction between two functions or towards the privileged formation of a diastereomeric form of the final product.

  The invention will be better understood on reading the detailed description which follows, and on examining the appended drawing, in which: FIG. 1 schematically represents various entities of a database conforming to FIG. FIGS. 2 to 9 show examples of entities of the database; FIGS. 10 to 12 schematically represent examples of chromatograms; FIG. 13 represents a virtual chromatogram; FIG. algorithm for generating a virtual chromatogram, and FIG. 15 represents an example of a virtual chromatogram obtained during the execution of the algorithm of FIG. 14.

  FIG. 1 illustrates a relational database 5 according to the invention, of which entities 5a to 5g have been represented in a simplified manner.

  The database 5 can store information, for example in the form of tables consisting of columns and rows.

  FIG. 2 is a partial representation of the Compound entity 5a in which, for each compound listed in the base, including, in particular, the reactivity probes, reaction units, and the reaction products, an ID, for example a number, the name of the compound, the reference MOL-ID of a table generated by a commercial tool such as Chem Draw including the drawing, the molecular weight, the raw formula, etc ..., and if applicable the number of NbrPartComp links that can be modified during the reactions.

  The database 5 also includes a 5b entity called Tbl PartComp which contains information concerning the indices of reactivity of each compound listed in the entity 5a.

  The entity 5b contains an ID-PartComp primary key, the IDCompound identifier of the compound to which the links belong, and the Name name of each link, this name possibly including, for example, the number of the link within the compound, and the state Level bonds, 0 may mean that there is no link capable of being transformed, the link being for example CH, 1 may mean for example that the link is of type CX or C = C, 2 may mean for example that the connection is of type C = C, etc ...

  In the example under consideration, a large number of experiments are carried out to test the reactivity of the reactivity probes in predefined reaction media, and thus constitute the database with useful information concerning the properties of the catalysts listed in the database. data vis-à-vis the reactivity sensors.

  These experiments can be carried out for example according to a standardized procedure by means of plates, also called blocks, each comprising a plurality of wells, each plate being associated with a given reactivity probe, each well comprising a different reaction medium, that is, that is to say, comprising, for example, in addition to the reactivity probe, a particular catalyst, particular co-reactants, if appropriate, particular solvents, etc.

  The entity 5c, called Mixture, makes it possible to record in the base 5 the information associated with a given reaction medium.

  In this entity 5c can thus be recorded for each reaction medium, as seen in FIG. 4, a primary key ID, the identifier (s) ID-Reagent of the compound or compounds of the medium in which the reaction is carried out, each identifier being for example a number, the identifier ID-Catalyst of the catalyst used, the latter being for example a number also.

  The ID-Reagent and ID-Catatalyst identifiers refer, for example, to compounds referenced in the Name column in the 5h Reagent and 5i Catalyst tables, partially represented in FIGS. 5 and 7.

  The database 5 further comprises Chromato 5d and Signal 5e entities, in which are recorded information related to the chromatographic analysis of the reaction media of the plates. These entities 5d and 5e have been partially represented in FIGS. 7 and 9. The constituents of each well of a given plate are analyzed by

  liquid chromatography or gas chromatography and the Chromato entity keeps the information of each chromatographic injection that corresponds to the result of a reaction.

  Three examples of chromatograms obtained by reacting the same reactivity probe in three different reaction media have been shown in FIGS. 1 to 13 to detect the presence of the compounds C1 to C4.

  In the entity 5d are recorded for example, as can be seen in the examination of FIG. 9, a primary key ID, the date of injection Date of Injection, the identifier ID-Mixture of the reaction medium, whose detail is known from entity 5c, the identifier ID-Compound of the reactivity probe, whose name and other characteristics are known to entity 5a and the name Name of Chromato of the analytical method used, which can to be a number.

  The entity 5e retains the information of a chromatographic signal, i.e. a chromatographic peak.

  In the entity 5e are recorded for example, as can be seen in the examination of FIG. 8, a primary key ID Signal, the ID-Chromato identifier of the chromatogram to which the peak belongs, the identifier ID-Compound of each compound corresponding to a signal, the retention time Retention Time, expressed for example in minutes and hundredths of minutes, the yield Yield expressed for example in percentage and the area area of the peak.

  The entities 5d and 5e can be loaded automatically from at least one result file automatically generated by the chromatograph.

  Such a file may for example be in the form of Table 10 Result partially shown in Figure 9.

  This table includes a column number which contains the number of the rows of the table, and seven fields in which are recorded respectively, for the field 1, the name of the reagents, for the field 2 the order number of the signal in the chromatogram, for the field 3 the retention time, for the field 4 the signal area, for the field 5 the catalyst and the name of the analysis, for the field 6 the number of the analysis and for the field 7 the yield.

  To calculate the yield, we start by calculating the sum S of the areas appearing in the column of the field 4 and corresponding to the same analysis, that is to say having the same analysis number in the field 6.

  Then, for a given row, the value carried in the column of field 7 is equal to 100 times that carried in the column of field 4, divided by S. No calculation of yield is made when the values appearing in the column of field 3 are zero.

  The 5d entity can be loaded automatically from the Result file.

  The identifier ID is incremented automatically with each new analysis recorded in the database, the column Naine of Chromato can be filled by the data appearing in field 5 of the Result table, the Date of injection column can be taken as the date of the day. and the number carried in the ID-Mixture column is obtained by processing the fields 1 and 5. The Program and IDCompound columns of the entity 5d can be filled during the preparation of the plates.

  The entity 5e can also be filled automatically, the ID-signal identifier being for example a number incremented automatically for each new analysis recorded in the database, the identifier ID-Chromato is taken equal to the ID number of the last analysis processed, the Retention Time column is populated from the data in field 3 of the Result table, as well as for the Area column that corresponds to field 4 of the result table and the Yield yield column in field 7 of the Result table.

  Concerning the filling of the ID-Compound column of the entity 5e, that is to say the assignment to each signal of the chromatogram of a chemical compound, one can proceed as follows.

  All the signals obtained with the same analytical method, that is to say having the same number in the Program column of the 5d entity and the same reactivity probe, that is to say the same number in the column ID-Compound of the 5d entity, can be assigned to a virtual chromatogram that would have been obtained by a fictitious experiment giving at once all the transformation products of a given reactivity probe.

  The virtual chromatogram is advantageous in that it enables a compound to be automatically assigned to a large number of signals at each peak.

  Once all the signals of this virtual chromatogram are assigned to specific compounds, the corresponding compound can be assigned to any comparable signal obtained with the same analytical method. This may facilitate the analysis of the reaction result for a new catalyst or different operating conditions, since there is no chemical analysis of compounds whose retention times substantially coincide with those of compounds already analyzed. This analysis mode makes it possible to quickly build up the database.

  A very schematic example of a virtual chromatogram, constructed from the signals of the chromatograms of FIGS. 10 to 12, has been represented in FIG. 13.

  An example of a method for generating such a virtual chromatogram will now be described.

  Firstly, a first list A is generated from the data of the entities 5d and 5e with all the lines which concern the same reactivity probe, that is to say which have the same identifier ID-Compound in the 5d entity and the same analytical method, ie the same Program number.

  This list is sorted in the decreasing direction of the number of signals present in each analysis, that is to say having the same number in the ID-Chromato column. Peaks representing less than 5% of the total peak area of an assay are considered insignificant and no attempt is made to assign a compound to them.

  Then, a second list B is generated with all the signals of the first analysis of the list A, that is to say the one comprising the largest number of peaks. This second list B is sorted in the increasing direction of the retention times.

  Then, a third list C of all the signals present in all the analyzes of the list A is established and the virtual chromatogram is generated by completing the list B according to the algorithm of FIG.

  This algorithm is implemented with a given value for the minimum duration Tm tolerated between two signals to consider them as distinct. A low value of Tm results in a chromatogram with many signals while a high value generates a chromatogram with few signals. Tm is for example equal to 0.2 min.

  In step 50, the signals of the list C are read sequentially and a retention time variable TI is initialized to 0.

  For each signal W of the list C thus read, of retention time Te, there is at step 51 sequential reading of the signals of the list B, each signal X of this list being associated with a retention time Tb.

  In step 52, it is determined whether the retention time Tc of the signal W of the list C being read is greater than TI and smaller than the retention time Tb of the signal X of the list B being read. less Tm.

  If not, step 53 is performed during which the value Tb + Tm is assigned to the variable TI and the next signal X of the list B is read, with corresponding retention time Tb. Then, in step 54, if list B is not finished, go back to step 52.

  If in step 52 the retention time Tc is greater than T1 and the retention time Tc is less than Tb-Tm, which corresponds, for example, to the situation of FIG. 17, step 55 is during which we check that the list B is not finished or that Tc and superior to TI.

  If so, in step 56, the peak W is added to the list B and the latter is sorted again.

  Then, in step 57, the next signal W of the list C, corresponding retention time Tc and Tl is initialized to O. At the next step 58, it is verified that the list C n ' is not finished and if so, go back to step 51.

  If the test is negative in step 55, go directly to step 57.

  Once the virtual chromatogram has been generated, a range of retention times can be assigned to each compound, taking for example as the lower bound of each range half of the sum of the retention times of the peak concerned and of that which precedes it.

  At each peak of a chromatogram can be associated, as can be seen in FIG. 10, a temporary time range 60 which, in the case of FIG. 10, is centered on the peak of the peak concerned and whose extent time on either side of the vertex of the peak corresponds to the minimum duration Tm tolerated between two signals. When two peaks are separated by at least this minimum duration Tm but less than twice this minimum duration, the provisional ranges assigned to the compounds corresponding to these peaks have a boundary 61 corresponding to the middle of the interval between the retention times. corresponding to the summits of the peaks, as can be seen in Figure 11.

  The database 5 can thus be established.

  Throughout the description, including the claims, the phrase having one must be understood to be synonymous with at least one, unless the opposite is specified.

Claims (14)

  A method for constituting a database (5) in particular for selecting at least one catalyst suitable for a reaction, comprising the following steps: x) preparing a plurality of different reaction media containing the same reactivity probe and each at least one catalyst, y) analyzing, by an analytical method, each reaction medium after reaction, z) assigning in the database to the reactivity probe a result of the analysis according to step y), this result characterizing different reaction products obtained from this reactivity probe.   2. Method according to the preceding claim, characterized in that the plurality of different reaction media comprises at least two reaction media containing different catalysts.   3. Method according to one of claims 1 and 2, characterized in that the analytical method is a method of liquid or gas phase chromatography.   4. Method according to any one of claims 1 to 3, characterized in that the steps x) to z) are repeated for a plurality of different reactivity probes.   5. Method according to any one of claims 1 to 4, characterized in that the database is a relational database comprising a first entity (5a) in which are recorded information relating to the reaction units listed in the database. a second entity (5b) containing information relating to the link state of at least one reaction unit listed in the first entity, a third entity (5c) in which information related to the different reaction media is recorded, and minus a fourth entity (5d) in which information relating to the results of analysis of the reaction media after a reaction is recorded.   6. Method according to any one of claims 1 to 5, characterized in that, for at least one reactivity sensor, a file is generated gathering all the results covering all the transformations that have been performed at said probe. .   7. Process according to any one of the preceding claims, characterized in that the reactivity probe comprises at least one reaction unit, preferably at least two reaction units.   8. Process according to claim 7, characterized in that at least one of the reaction units is chosen from: CHZ O; \ O Il / C = 0; VS\ ; X   -CH = C \; -CH = C \ - CH = C \; -CHZ N, X O N CHZ X; ≥N -; - c N; N C; -N = N-; N = 0; -O-O; \ / / P = 0; O-S -; Where X represents a halogen atom.   9. Method according to any one of the preceding claims, characterized in that the database contains for each catalyst listed information on the reaction medium in which it was tested for its catalytic activity.   10. Process according to any one of the preceding claims, characterized in that reaction units are individually listed in the database, these patterns being present on the reactivity probes, and in that for at least a part of the reaction units listed, are associated with each pattern listed information, including link states, to qualify the degree of responsiveness of the links associated with it.   11. Method according to the preceding claim, characterized in that the states of the links are represented by integers ranging from 0 to 3.   12. Method according to any one of the preceding claims, characterized in that the database contains information that provides information on the influence of the structural environment of a listed reaction pattern.   13. Process according to any one of the preceding claims, characterized in that the reaction media are chosen to carry out at least one of the following reactions: formation or bond-breaking reactions, especially CC, -CO, -CN; C = N; C = C.   14. Method according to any one of the preceding claims, characterized in that the database contains data that provide information on the activity of at least a portion of the catalysts listed according to different reaction conditions, including the temperature of the medium. reaction, acidity, pressure, the presence of solvents or the type of analytical method.