FR2865819A1 - Selecting a catalyst useful for chemical transformation of a reaction motif comprises searching a database comprising information on the reactivity of a set of catalysts - Google Patents

Abstract

Selecting a catalyst useful for chemical transformation of a reaction motif comprises acquiring data relating to the transformation, searching a database comprising information on the reactivity of catalysts with respect to reaction motifs listed in the database and present in reactivity probes to identify a reaction motif, and selecting a catalyst with the required reactivity as a function of the reaction motif and the transformation. Selecting (M1) a catalyst useful for chemical transformation of a reaction motif comprises acquiring data relating to the transformation and optionally the structural environment of the reaction motif, searching a database comprising information on the reactivity of a set of catalysts with respect to reaction motifs listed in the database and present in reactivity probes to identify a reaction motif related to the motif to be transformed, and selecting a catalyst with the required reactivity from the database as a function of the reaction motif thus identified and the transformation to be carried out. An independent claim is also included for providing a catalyst for transforming a reaction motif of a compound by a given reaction by selecting a catalyst by (M1) and providing (especially manufacturing) the catalyst.

Description

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

  to propose a method and a device making it possible to rapidly identify one or more catalysts that can be used for the transformation of a compound and more particularly to

  least one of its reaction units, according to a given chemical reaction.

  Organic synthesis by the catalytic route, and in particular by heterogeneous catalysis, is a synthetic route particularly appreciated at the industrial level. Indeed, the use of a catalyst generally makes it possible to accelerate the speed of a reaction, 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 provide a method for rapidly identifying at least one catalyst responding to a reaction request.

  The subject of the present invention is, according to one of its aspects, a method for delivering at least one information relating to the reactivity of a catalyst with respect to a chemical conversion of at least one reaction unit, this which process can be 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 of data indicating 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 database based on one hand on the listed reaction unit thus identified and on the other hand the transformation to be carried out at least one catalyst having the required reactivity. for the transformation.

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

  This unit may especially consist of a saturated bond of a carbon atom with at least one halogen atom and / or a heteroatom, or an unsaturated bond between two carbon atoms, between a carbon atom and at least one heteroatom or between two heteroatoms, 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, a nitrogen, oxygen, sulfur, phosphorus, halogen or silicon atom.

  Representative and non-limiting examples of reaction units include the following: -C = C-; , C = -CH = C; -CH = C \; CH = C; -CHZ N X 0 N CH2-0; CH2 X; j = N-; C N; N C O \ C = O CX -N = N-; -N = 0; -0-0-; -0-; \ / / .N-P- / P = 0; O-S-; Where X represents a halogen atom.

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

  At least for part of the reaction units listed in the database, are associated with each listed reaction pattern information to qualify the state of the links that are likely to be associated with it. 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 specifically, the state of a reaction pattern can be indexed using an integer, said link state and can vary from 0 to 3, with the value zero generally describing the absence of link and the value 2 characterizing a double bond.

  As a result, each pair of reaction unit / reaction medium can be associated with a pair of bonding states aimed at qualifying the degree of reactivity of said unit before and after its exposure to said reaction medium.

  For example, in case of no reaction, the state of the bonds remains the same; in case of reduction, the state of the links decreases by at least one unit (a state equal to zero usually 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.

  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.

  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 has a ketone or methylene moiety, will not exhibit the same degree of reactivity in a catalytic hydrogenation or nucleophilic addition reaction.

  The database may contain 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 which may comprise several reaction units makes it possible to take into account, if appropriate, 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, due to 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 so-called 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 reactions forming or breaking bonds, especially C-C; CO; C-N; C = C = NouC.

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

  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, trimerization reactions and heterocycle formation, 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, 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 acquisition in step a) can be, for example, an input using a keyboard or a graphics tablet or the receipt of data, for example a file.

  In the following, we will use independently the term entered or acquisition.

  The data entry in step a) above may include the formulation of a request mentioning the reaction pattern concerned and the nature of the transformation that it wishes to undergo.

  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 formulating a request for 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.

  Data entry in step a) can still be done by formulating a request for transformation of at least one starting compound.

  In this case, the method may include analyzing the starting and ending compounds in order to identify the reactive and non-reactive reactive unit (s). 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 process according to the invention 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 input of the starting compound and the arrival compound can be done for example by drawing their structure, giving their name or an identifier referring to their structure.

  Data entry in 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.

  At least some of the reaction data recorded in the database has been acquired by reacting the reactivity probes. The latter have in their structure at least one reaction unit capable of being converted according to a catalytic chemical reaction, this reaction unit being for example chosen from those mentioned above.

  Reactivity probes can be natural or synthetic. It may especially be hydrocarbon molecules of low mass and may comprise from 30 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 thus be filled 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: ## STR2 ## C = C \; / C = 0; / C = N; Arp \ X - N = 0; and to this highly reactive unit, may be associated with at least one second unit, or even two other units, known on the other hand for a lower reactivity according to this same reaction, for example an aromatic ring or the nitrile function of a heterocycle. For example, for a given reactivity probe, it will be these less reactive patterns and their spatial arrangement which 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 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 COOH, CHO, CO, CONH2, carboimines functions, ...

  By way of non-limiting illustration of reactivity probes suitable for the invention, for example for evaluating the reactivity of a set of catalysts with respect to a hydrogenation reaction, mention may be made especially of those having the structures represented below:

O

NOT

  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 different reaction conditions, including the temperature of the reaction medium, the acidity, the pressure, the presence of solvents, the method of analysis, 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 present invention also relates, in another aspect, to a process for providing at least one catalyst that can be used to convert at least one reaction unit of at least one compound according to a given chemical reaction, characterized in that it comprises, in addition to steps a), b) and c) previously defined at least one step of providing the catalyst (s) thus selected.

  This supply step may, if necessary, include a step of manufacturing said catalyst.

  The present invention also relates, in another of its aspects, to a computer system that can be characterized in that it comprises means for: i) making it possible to formulate at least one request concerning a chemical transformation transforming at least one reaction unit of at least one compound, ii) identifying, in a database providing information on the reactivity of a set of catalysts with regard to reaction units listed in the database, a listed reaction pattern having a relationship with the transform, iii) select according to the listed reaction pattern identified in the database and the transformation to perform at least one catalyst having the required reactivity for the transformation and edit this catalyst.

  To edit, it is necessary to understand to display, to print, to record in a file, to transmit remotely or to deliver.

  The invention also relates to a method for selecting at least one catalyst that can be used for a given reaction, characterized in that the catalyst is selected as a function of the production yield of the reaction products assigned to at least one reactivity probe present in the database and transformed according to said reaction.

  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 Al203. 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 especially be made of the following catalysts: Pd / Al 2 O 3; PdBaSO4; Pd / CaCO3; Pd / PEI; Pd / CaCO3, PdIC; Pt / C; Ru / C; Re / C; Rh / C; Rh / Al2O3; 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.

  In this case, it is 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 guide the selectivity of the reaction between two functions. or via 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 a computer system making it possible to implement the invention, FIG. 2 is a block diagram illustrating various steps of an exemplary implementation of the method according to the invention; FIG. 3 schematically represents various entities of a database according to the invention; FIGS. 4 to 11 show examples of entities of the base, FIGS. 12 to 14 schematically represent examples of chromatograms, FIG. 15 represents a virtual chromatogram, FIG. 16 is an example of an algorithm of FIG. generation of a virtual chromatogram; FIG. 17 represents an example of a virtual chromatogram obtained during the execution of the algorithm of FIG. 16; and FIGS. 18 and 19 illustrate an exe mple selection of reaction media following the formulation of a query.

  A method according to the invention is advantageously implemented by means of a computer system which may comprise, as illustrated in FIG. 1, a computer server 1 connected by a network 2 to a user terminal 3. The network 2 is for example an Intranet or Internet network.

  The computer server 1 may also be connected to a data acquisition system 4, this system may comprise a manipulator arm and an analysis apparatus such as for example a gas or liquid phase chromatograph. This analysis apparatus provides data on each reaction medium after reaction, as will be explained below.

  The computer server 1 comprises or can access conventional data storage means and in particular may be able to communicate with other computers, by the network 2 or by other networks.

  The terminal 3 is for example a PC type computer connected by a telephone or other link to the network 2.

  According to one aspect of the invention, the server 1 is arranged to allow in a first step 6, as illustrated in FIG. 2, the acquisition of data relating to the chemical transformation to be performed, to interrogate in a second step 7 a relational database 5, whose entities 5a to 5g have been shown schematically in Figure 3, and allow editing, in a third step 8, at least one catalyst having a utility to perform the transformation.

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

  FIG. 4 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 comprises a 5b entity called Tbl PartComp which contains information concerning the name and the state of the bonds of each reactive functional group of the 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 index of reactivity Level, 0 may mean that there is no linkable to be 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 inform 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, besides 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. 6, a primary key ID, the ID or Reagent identifier (s) 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 5y Reagent and 5g Catalyst tables, partially represented in FIGS. 7 and 8.

  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. 9 and 10.

  The constituents of each well of a given plate are analyzed by liquid or gas phase chromatography and the Chromato entity makes it possible to preserve the information of each chromatographic injection which corresponds to the result of a reaction.

  FIGS. 12 to 14 show three examples of chromatograms obtained by reacting the same reactivity probe in three different reaction media, which made it possible to detect the presence of 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 the entity 5a and the name Naine 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. 10, 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 the Table Result partially shown in Figure 11.

  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 5e entity, 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.

  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 can make it possible to assign to each signal, a compound, automatically on a large number of signals and to facilitate the analysis of the result of the reaction for a new catalyst or different operating conditions, since there is not to proceed to the chemical analysis of the compounds whose retention times coincide appreciably with those of the compounds already analyzed.

  A very schematic example of a virtual chromatogram, constructed from the signals of the chromatograms of FIGS. 12 to 15, has been represented in FIG.

  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 T1 is initialized to 0.

  For each signal W of the list C thus read, of retention time Tc, 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 T, of the signal W of the list C being read is greater than T1 and smaller than the retention time Tb of the signal X of the list B being reading less Tm.

  If not, we go to step 53 during which we assign the value Tb + Tm to the variable T1 and read the next signal X from the list B, 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 Te is greater than T1 and the retention time Te 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 greater than T1.

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

  Then, in step 57, the next signal W of list C is played, with corresponding retention time Tc and T1 is initialized to zero. In the next step 58, it is checked that the list C is not finished and if this is the case, we return 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. list B generated previously.

  At each peak of a chromatogram may be associated, as can be seen in FIG. 12, a provisional time range 60 which, in the case of FIG. 12, 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 13.

  The database 5 may be queried to respond to requests for the listed reaction patterns.

  FIG. 18 shows an extract of a data field from the database 5, each line of which contains information concerning the transformation efficiency of two reaction units whose names are given in the columns labeled Fct Group 1 and Fct Group 2d in the presence of a reaction medium whose identifier is carried in the column titled Medium. On either side of the name of the reaction pattern are the state of the bonds. The same number to the left and right of the name of the reaction pattern means that it has not changed. For example, decreasing one unit means that there has been a reduction. The number 2 indicates, for example, that the reaction unit is still susceptible to reduction. The number 0 indicates for example that there has been a break in bond and therefore the reaction pattern is no longer likely to undergo a new reduction step. The number 1 indicates that the compound is likely to be transformed and in particular reduced depending on the nature of the connection. In the example of the first row of the table of FIG. 18, it should be understood that the Arylcetone reaction unit has not reacted and that the 1-alkylalkene reaction unit has only very slightly reacted, since this reaction unit is remained unchanged at 99.4%.

  In the example of the third row of the table, the Aryliodium reaction unit was reduced with a yield of 5.28%, the iodine having been replaced by hydrogen.

  A request concerning two reaction units present within the same reaction medium may be formulated, indicating for each reaction unit whether it is desired that it reacts or not.

  The request may for example be formulated so as to seek the reaction media which allow the reduction of an Arylbromide reaction unit without reducing an Arylketone reaction unit.

  FIG. 19 shows two result lines corresponding to this request. It can be seen that the reaction mediums 356 and 391 make it possible to reduce the ArylBromide unit, since the reactivity index has been increased from 1 to 0, while leaving the Arylketone reaction unit unchanged, in total for the reaction medium 356 and with a yield of 96.36% for the reaction medium 391. Knowledge of the reaction medium allows to go back to the catalyst present therein.

  Returning to FIG. 2, the acquisition of data in step 6 can be done for example by the terminal 3 after connection to the server 1 and, where appropriate, identification of the user by an access code. The user may himself be a computer system programmed to search for relevant information on a computer network.

  The reaction to be performed can be entered on a keyboard or by means of a mouse, for example on the terminal 3, or in the form of an image file or the like, and the data entered can notably comprise the starting compound (s). , and the desired compound (s) on arrival.

  The next step 7 may involve decomposing the compounds involved in the reaction into reaction units and identifying the reaction units that undergo transformation and, where appropriate, those that are preserved. This decomposition can be performed automatically by a computer system and in particular the server 1, so as to allow the internal formulation to the computer system 6 of a request containing the identity of the reaction units concerned and for each of them, the variation of the reactivity index, in order to obtain from the database the name or names of the appropriate catalysts.

  For example, in the case where the reaction is a hydrogenation of a compound of formula I as follows: (n the computer system can identify two reaction units, namely an ethylenic bond and a brominated carbon bond.

  Reaction units related to these, present on reactivity probes, are listed in the database 5.

  For example, probe # 1 below has the brominated carbon linker reaction unit and probe # 2 is the ethylenic linker reaction unit.

probe n 1

NOT

  probe No. 2 The database 5 contains information on the reactivity of the catalysts listed, in particular the conversion yield, for each of the reaction units of the probe in question.

  For example, the reactivity of several catalysts with respect to the conversion of the reaction units was tested for each of the two probes, being reported hereinafter in Table I for probe No. 1 and in Table II for probe No. 2. It can be seen that the Pd / C, Pt / C, Pd / Al 2 O 3, Pd / BaSO 4, Pd / CaCO 3, Pd / CaCO 3 Pb and Ir / CaCO 3 catalysts are effective in reducing the ethylene bonding unit and the same Pd / Pd catalysts. C, Pd / Al2O3, Pd / BaSO4 for the reduction of the brominated carbon bond of the bromide unit.

  Table I (Probe No. 1) Table II (Probe No. 2) Catalyst Reduction carbon-bromine bond Er203-Pt / C-Pt / C, AcOH-Pd / C 100% Pd / Al2O3 100% Pd / BaSO4 100% Pd / CaCO3 - Pd / CaCO3.Pb - Pd / Poly - Ni / SiO2.Al 2 O 3 Ru / C - Re / C - Rh / C - Rh / Al 2 O 3 - Ir / C - Ir / CaCO 3 - Catalyst Reduction Ethylenic Linkage Er203 1% Pt / C 97% Pd / C 99% Pd / Al2O3 100% Pd / BaSO4 96% Pd / CaCO3 96% Pd / CaCO3.Pb 100% PdIPoly 1% Ni / SiO2.Al203 1% Ru / C 15% Re / C 1% Rh / C 70% Rh / Al 2 O 3 23% Ir / C 8% Ir / CaCO 3 95% Table III below shows a close correlation between the predictive reactivity data acquired using the reactivity probes and the reactivities. experimentally verified by carrying out the hydrogenation of the compound of formula I with the seven previously identified catalysts.

Table III

  Catalyst Probe 1 Probe 2 Compound I Compound I Reduction Reduction Reduction reduction bond bond bond carbon-ethylenic carbon-ethylenic bromine bromine Pd / C 1% 1% 1% 1% PdBaSO4 1% 1% 70% 1% Pd / Al2O3 1% 1% 1% 1% Pt / C 0 1% 0 1% Pd / CaCO3 0 1% 30% 1% Pd / CaCO3.Pb 0 1 0 40% Ir / CaCO3 0 1% 0 100% Note: 1 = 100% yield 0 = <5% of the yield The computer system 1 makes it possible to know the catalyst or catalysts capable of carrying out the desired transformations for the identified reaction units.

  In the case where several catalysts are suitable, a single effective catalyst can be edited according to, for example, criteria such as the commercial availability of this catalyst or the cost of the catalyst.

  For example, if the Pd / Al2O3 and Pd / C catalysts are suitable and only the Pd / Al2O3 catalyst is available from a company queried by the computer system, then only this catalyst is edited in response to a request from a user . The catalyst may, where appropriate, be addressed to the user or even be manufactured on demand. If necessary, the catalyst can be addressed with a particular packaging facilitating the performance of tests.

  The computer system can publish, in addition to the catalyst structure, its name, cost, efficiency, and specificities in terms of selectivity.

  In the example just given, the responses to requests made by the user are provided by the server 1, but it is not beyond the scope of the present invention when the computer system is reduced to a single computer on which runs an application. In this case, the application can for example be downloaded to a remote site or present on a computer medium such as for example an optical disk and be loaded on the computer.

  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 (16)

  A method of selecting at least one catalyst useful for the chemical conversion of at least one reaction unit, 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 unit to be transformed, b) identify in a database providing information on 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 unit related to the unit to be converted, c) selecting in the database as a function, on the one hand, of the listed reaction unit thus identified and, on the other hand, of the transformation to be carried out at least a catalyst having the required reactivity for the transformation.   2. Method according to claim 1, characterized in that the reaction unit is chosen from: C = C; / C = C CH = C; CH = C; CH C \; X 0 N CH 2 N (CH 2 O; CH 2 X; j = N-C N; N = C 0 / C = O; C 1; N = N; N = 0; 0 0 \ 0; X JN    O P \; % P with X representing a halogen atom.   3. Process according to claim 2, characterized in that the database contains for each listed catalyst information concerning the reaction medium in which it has been tested for its catalytic activity.   4. Method according to any one of the preceding claims, characterized in that for at least part of the reaction units listed in the / \ = O; O-Si \ 24 2865819 database, are associated with each pattern listed information, to qualify the status of the links associated with it.   5. Method according to the preceding claim, characterized in that the link state is an integer ranging from 0 to 3.   6. 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.   7. Process according to any one of the preceding claims, characterized in that the conversion takes place during a chemical reaction chosen from the halogenation, reduction, hydrogenation, oxidation, hydrolysis, dehydration, esterification, acidic or basic catalytic reactions, metallocatalytic multicomponent reactions, trimerization reactions, and heterocycle formation reactions.   8. Process according to any one of the preceding claims, characterized in that the conversion is chosen from: reduction of imine to amine, cleavage of a CN or benzyl CO bond, reduction of a halide, reduction of a nitro function to amine, nitrile to amine, amide reduction, reduction of an alkynic unit, reduction of a ketone to alcohol, reduction of a ketone to alkane and cutting of an ether unit.   9. Method according to any one of the preceding claims, characterized in that the acquisition of the data in step a) comprises the formulation of a request mentioning the relevant reaction pattern and the nature of the transformation that is desired to put him through.   10. Process according to any one of the preceding claims, characterized in that the transformation is formulated by indicating the variation of the bond state of the functional groups to be transformed or stored at each reaction unit resulting from the transformation or the reaction. difference in the state of the bonds in the reaction pattern considered between the states before and after transformation.   11. Method according to any one of the preceding claims, characterized in that the data acquisition comprises the formulation of a request concerning the transformation and / or non-transformation of at least two different reaction units.   2865819 12. Process according to any one of the preceding claims, characterized in that in the case 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 compound Initially, the request is to select a catalyst capable of performing the transformation of the first pattern with a sufficient yield while leaving the second intact, or at least by transforming it sufficiently little.   13. Method according to any one of the preceding claims, characterized in that the acquisition of data in step a) is carried out by formulating a request for transformation of at least one starting compound, the method comprising the analyzing the starting and ending compounds to identify the reactive and non-reactive reactive unit (s).   14. Process according to any one of the preceding claims, characterized in that it comprises: the decomposition of a starting compound involved in a reaction in different substructures, the identification of the reaction unit or units to be converted and, where appropriate, the identification of the reaction unit (s) to be preserved.   15. 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 method of analysis, 16. A method for providing at least one catalyst that can be used to convert at least one reaction unit of at least one compound according to a given chemical reaction, characterized in that it comprises, besides the steps a), b) and c) defined in claim 1 at least one step of supplying the catalyst (s) thus selected, and in particular the manufacture of said catalyst.