JPH0740271B2 - Recording / searching method for chemical reaction information - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a method for recording and retrieving chemical reaction information, and more particularly, a method for recording and retrieving information on chemical reactions involving side reactions. It is about.

[Technical Background of the Invention] In recent years, with the development of computers, various methods have been proposed and are being used for recording structural information of chemical substances, particularly organic compounds. The amount of organic compounds and organic chemical reactions that have been studied and elucidated to date has reached enormous amounts. However, it is possible to effectively utilize this known information to search for known chemical substances or chemical reactions in a short time. Furthermore, it is desired to find a method for synthesizing a novel substance having desired properties. To that end, as a form of expression of chemical substances and chemical reactions, a computer can process (that is, a computer can make logical judgments) instead of a conventional chemical structural formula that makes it easy for an engineer to grasp the structural characteristics. ) It is required to develop and utilize forms of expression.

As a method of recording chemical substances, WLN (Wiswesser Linear)
Notation) and other linear notations are the typical ones, and details are given in, for example, WTWipke,
SRHeller, RJFeldmann, E.Hyde (Eds): “Computer
Representation and Manipulation of Chemical Inform
ation "(John Wiley and Sons, New York, 1974) [Wipke, Heller, Feldman, Hyde (eds.):" Computer representation and handling of chemical information "(John Willie and Sons)]. Join table (conn
ection table) is a list of, for example, the types of each atom in the structural formula of a chemical substance, the atoms of the partner that binds to it, the types of bonds, etc. There is an advantage that you can search in units.

Also, a method for recording information on the structural change (chemical reaction) of a chemical substance has been proposed, but a satisfactory expression method has not been known so far. For example,
As a method of recording information on chemical reactions, there is a method using a reaction code. Specifically, J.Valls, O.Scheiner: “C
hemical Information Systems ", E. Ash, E. Hyde (Eds),
(Ellis Horwood Limited, 1975) p.241-258 [bar,
Shiner: "Chemical Information System", Ash, Hyde, Ed. (Eris Hoawood Co.)], MA
Lobeck, Angew.Chem.Intern.Ed.Engl., 9, 578 (1970)
[Lovec, Angevante Chemie International Edition in English] and HJZiegler, J.Chem.Inf.Comput.Sc
i., 19 , 141 (1979) [Ziegler, Journal of the
Chemical Information and Computational Science]. This method has a drawback in that when a new chemical reaction is found, it cannot be recorded because the viewpoint of expressing the chemical reaction is fixed. Further, since the structural information of the chemical substance and the information of its change are recorded in separate forms, there is a drawback that effective information retrieval cannot be performed.

In addition, a recording method devised from the standpoint of designing a synthetic route for a chemical substance is also known. For example, EJCorey, RD
Cramer, WJHowe, J.Am.Chem.Soc., 94 , 440 (1972) [Cori, Cramer, Hohe, Journal of American Chemical Society], I.Ugi, J.Bauer, J.Braud
t, J.Friedrich, J.Gasteiger, L.Jochum, W.Schubert, Ange
w.Chem.Intern.Ed.Engl., 18 , 111 (1979) [Ugi, Bauer, Blaut, Friedrich, Gasteiger, Jocham, Schubert, Angevante Chemie International Edition in English] There is a way. However, this method is not suitable for recording individual chemical reactions.

Note that the present applicant has a method of recording and storing chemical reaction information by using an imaginary transition structure and / or a binding table, and various partial structures by performing graphic processing or arithmetic processing on the imaginary transition structure and / or the binding table. Patent applications have already been filed for the method for obtaining the compound, and the method for searching for the chemical reaction and the structure of substances involved in the reaction by using these methods (Japanese Patent Application Nos. 60-177345, 60-185386, 60-185386, 60-197463
No. 60-203690, No. 60-213184, No. 60-221087, etc.).

SUMMARY OF THE INVENTION It is an object of the present invention to provide a processing method for recording and retrieving main reaction information and side reaction information in a chemical reaction involving side reactions in association with each other. is there.

In particular, an object of the present invention is to provide a processing method for making it possible to mutually search and display and record information on chemical reactions including main reactions and side reactions by computer processing.

The present invention provides at least one product from at least one starting material, the structure of the starting material and the product of the main chemical reaction that occurs with at least one side reaction, and the structure and the formation of the starting material of the side reaction. The structure of the substance is topologically overlapped with each other, and (1) the bond between the nodes commonly present in the starting material and the produced substance, (2) the bond between the nodes present only in the starting substance and (3) only the produced substance. To create a bond table of main reactions and side reactions each having a unique code that represents the bond between the nodes existing in each of them; a bond table of the main reaction and side reactions each having a unique code obtained in the above process To store the data in a recording medium attached to the computer; and by performing the processing in the computer by using the above-mentioned binding table stored in the computer, In recording and search for basic reactions information side reactions attendant comprising: step of searching in association with response and side reactions.

According to the method of the present invention, a binding table derived from an imaginary transition structure representing a main reaction and a side reaction of a chemical reaction involving a side reaction is given a unique code such as a number, and these codes are mutually indicated. By associating, recording, and searching,
Information about the main reaction or the side reaction can be derived at any time through the code.

When two or more reactions occur simultaneously in the reaction system (including cases where different reactions occur depending on the reaction conditions), the main reaction generally proceeds in a higher yield or proceeds easily. However, it may not be possible to unambiguously determine which is the main reaction, and in this specification, it is assumed that two or more reactions can occur in one reaction system. The distinction between reaction and side reaction is relative.

The above imaginary transition structure
s, hereinafter abbreviated as ITS) means the structural change of a substance involved in a chemical reaction, (1) a bond existing only in a starting material, (2) a bond existing only in a product, and (3)
A two-dimensional or three-dimensional structural diagram (figure) that is represented by distinguishing into three types of bonds that are common to both.
This structure diagram is easy for engineers to familiarize themselves with in accordance with the conventional structural formula and three-dimensional structure diagram of a compound,
In addition, the chemical reaction can be expressed in a form that can be easily understood.

Further, the connection table is a simple and clear list consisting of combinations of the types of nodes in a chemical reaction, the partner nodes that bind to the nodes, and the connections between these nodes, which are distinguished by being classified into the above three types. Yes, and this binding table allows chemical reaction information to be stored and stored in a recording medium without requiring a large capacity. In particular, the use of a binding table as a registration form facilitates the processing of information by a computer and facilitates the registration of chemical reactions, which facilitates the storage and management of such information.

In the above imaginary transition structure and bond table, a chemical reaction is basically expressed by a simple expression of a bond between a node (a node) composed of atoms, atomic groups, etc. and a node in a reaction system. The bond between them is represented by being distinguished into the above three types. Therefore, the imaginary transition structure and the binding table registered in the computer are not only chemical reactions, but also chemical substances involved in the reaction (starting substances and producing substances of the reaction, etc.)
It also includes information about.

In the present invention, when a chemical reaction simultaneously involves a side reaction in addition to the main reaction, a unique identification code is attached to each of the bond tables (and imaginary transition structures) of the main reaction and the side reaction, and these main codes are used. Reactions and side reactions are associated with each other. That is, the main and sub reactions can be associated with each other by attaching one code to the other, or by creating a comparison table such as a management table and previously associating the codes of each reaction together. .

Therefore, a person who wants to use the chemical reaction information can easily obtain not only one reaction information but also information about the accompanying reaction (sub-reaction or main reaction). Even when the chemical reaction is accompanied by side reactions, it is possible to derive information not only for one reaction but also for all other reactions that occur at the same time, and thus it is possible to comprehensively obtain information about the reaction system. This allows a comprehensive understanding of chemical reactions and reactivities of substances. Also, it becomes possible to search chemical reaction information from a wider angle,
Retrieval of reaction information becomes easier. Then, the availability and versatility of the reaction information can be improved.

The binding table (and the imaginary transition structure) associated with a unique code is recorded and stored in a computer, and can be further recorded on a blank sheet of paper or displayed on a screen such as a CRT. In addition, the main reaction and side reaction associated with each other are recorded and stored in a computer at once, on a recording paper, and in a CR.
Display and recording on T etc. can be performed.

Since information on chemical reactions can be efficiently searched in a short time based on a large number of registered reaction information, the time required for collecting and investigating information in individual research of engineers is shortened. , And increase the density of information that can be obtained, so that research can be advanced efficiently.

In addition to these advantages, in the method of the present invention, by utilizing the information on the main and side reactions that are associated with each other, structural analysis of chemical substances and molecular design, which are greatly demanded by engineers involved in drug manufacturing, etc. (Molecular modeling),
Heuristic analysis of organic sy
nthesis) can be performed. Furthermore, partial structure search of chemical substances, structure-activity relationship, automatic structure determination of unknown compounds, and reaction mechanism and reaction product prediction of complex compounds under certain conditions (mechanisti
(c evaluation of organic reaction) etc. can be carried out within a sufficiently practical range in a short time.

[Structure of the Invention] In the method for recording / searching chemical reaction information involving side reactions according to the present invention, a bond between nodes exists only in the starting material, a bond that exists only in the produced material, and a common existence in both. The chemical reaction information, which is described as a bond table (and an imaginary transition structure) that is distinguished into three types of bonds, is attached with a unique identification code, and the main reaction information and side reaction information are The operation of associating with each other by the identification code is performed, whereby the main / sub reaction information is associated one-to-one with the identification code.

The method of the present invention will be described below by taking the reaction described in Org.Synth.Coll.Vol.V, P.459 as an example.

This chemical reaction is the main reaction: And side reactions: Includes two reactions consisting of

The imaginary transition structure (ITS) of each reaction can be expressed as follows, for example.

Imaginary transition structure corresponding to reaction formula 1: Imaginary transition structure corresponding to reaction formula 2: here, Represents the bonds that are commonly present in the starting material and the product, Represents a bond that is only present in the starting material, and the iii) symbol ... Represents a bond that is only present in the product material.

That is, the imaginary transition structure (ITS) is a two-dimensional or three-dimensional structure in which the structure of the starting material and the structure of the generated material are topologically overlapped and the bonds between the respective nodes are distinguished by the above three types i) to iii). The original structure. Note that "topologically superimposing" specifically means that the nodes appearing in the structure of the starting material and the nodes appearing in the structure of the produced material are matched and these structures are combined into one.

In the above imaginary transition structure (ITS), the nodes of the substances involved in the chemical reaction may be represented by the atoms contained in the original system (starting substance group) and the producing system (producing substance group) as a unit. , Or methylene group [nodes (1) and (3) in ITS1], methine group [above node (4),
(5)] may be represented by an atomic group unit such as a functional group. When expressing a chemical reaction, some of the nodes appearing in the original system and the producing system may be omitted.

Also, the distinction between the three types of bonds is not limited to the display by the symbols such as i) to iii) above, and may be displayed by simple characters such as numbers (1, 2, 3) or the color (black). , Red, green) and the like, any means may be used as long as the user can judge by the five senses and computer processing is possible.

In the following, i) a common bond to the starting material and the product Is called a "colorless bond" or a constant bond (par-bond), and ii) a bond that exists only in the starting material. Is called "out-bond", iii) The bond (symbol ...) that exists only in the product is called "in-bond", and the out-bond and the in-bond are collectively called. Are called "colored bonds", and these three types of bonds appearing in the imaginary transition structure are collectively called "imaginary bonds".

Specifically, Table 1 shows the types of bonds appearing in the imaginary transition structure. In addition, in Table 1, the numerical value on the side means an index of bond entry and exit.

In Table 1, for example, the bond represented by the symbol "..." Is a single in-bond and can be represented by a pair of numbers (0 + 1). Here, 0 means that there is no bond in the original system before the reaction, and +1 means that a single bond has occurred in the produced system after the reaction. Similarly, The bond represented by is a single out-bond and is represented by (1-1). There is a single bond in the original system before the reaction, but the single bond disappears in the production system after the reaction. It means that The bond represented by (2-1) is a double bond singly cleaved, It is written in.

Thus the type of bond is also a pair of numbers: (a, b)
[Where a is an integer that represents the bond multiplicity in the starting material, and b is an integer that represents the change in the bond multiplicity in the chemical reaction], and this can be represented by the “complex bond number” (complex bond number).
bond number) or “imaginary multipl”
icity). The comma (,) in the notation (a, b) may be omitted. According to this notation, even if the coupling multiplicity is two or more, it can be simply expressed. In addition, it is a particularly preferable method for recording and storing chemical reactions because it does not require much storage capacity and can be directly processed by a computer, and is an expression method that is preferably used when creating a binding table described below.

In addition to the imaginary transition structure, as shown in ITS1 and 2,
An identification code corresponding to the related information (referred to as “unit information item”) about the substance involved in the reaction may be attached.

Here, the substances involved in the reaction specifically mean a starting material, a produced material and a catalyst. The unit information items include molecular formula, name, weight, volume, number of moles, purity, physical properties (melting point, boiling point, specific gravity, etc.) of these substances, spectral information, stereochemistry, and in the case of produced substances, yield, etc. Means If the catalyst is not described in the ITS, the unit information item can include the catalyst.

The identification code for the unit information item is, for example, [-
Symbols such as 1], [−1], and [# 1] are used. Here, "-" is the starting material, "+" is the product,
“#” Means a catalyst, and serial numbers are attached when unit information items are associated with two or more types of starting materials (or produced materials or catalysts).

Specifically, the identification codes [-
1], [-2] and [+1] are added, on the other hand, as the unit information item of the starting material, the weight [500] g of maleic anhydride is associated with the code [-1], and the weight 100 g of allene is coded [-2]
Correspond to. In addition, compound 1 is added to the code [+1] of ITS1.
The corresponding yield of 19-23%, and the sign [+1] of 1ITS2 corresponds to the yield of compound 2 of 7-9%.

As shown in ITS1 and 2, this identification code is the node that is the core of the reaction in each substance (node (2) in Allen).
C, the node (5) CH in maleic anhydride, etc.) may be attached to the bond serving as the nucleus of the reaction.

Regarding the attachment of the identification code corresponding to the unit information item, Japanese Patent Application No. 62-30854 [February 12, 1987] filed by the present applicant.
Japanese application (1)] It is described in detail in the specification.

Further, with respect to the imaginary transition structure and the connection table, an operation of extracting a progenitor system and a generative system [respectively, "projection onto the progenitor system"
(Projection to the starting stage, abbreviated as PS), "Projection to the producer"
t stage, abbreviated as PP)], information on the structure of the starting material and the structure of the product can be obtained.

The PS operation, as shown below for ITS1 and ITS2, ignores the in-coupling (symbols ...) from the imaginary transition structure and out-coupling. Is an operation that regards a constant bond as a constant bond, and the PP operation is an operation that regards an incoming bond as a constant bond while ignoring an outgoing bond from an imaginary transition structure. For details of PS operation and PP operation, see Japanese Patent Application No. 60
-185386.

The identification code for the unit information item may be attached to the starting material and the product obtained by the PS and PP operations as described above, or may be associated with the PS and PP operations themselves.

A chemical reaction can also be represented as a connection table that contains information about each node, the node of the binding partner that binds to the node, and the binding between the nodes.

Tables 2 and 3 show the binding tables of the main reaction and the side reaction represented by the above reaction formulas 1 and 2, respectively.

As shown in Tables 2 and 3, the binding tables show the original system (starting substance group) and the producing system (producing substance group) involved in each reaction.
Is a list in which all nodes, all nodes connected to each node, and types of connections between these nodes are listed in the order of node numbers.

The binding table may also be provided with an identification code corresponding to the unit information item for the substance involved in the reaction. Second
In the table and the third table, the identification code (-1, -2, +1,) for each of the starting material and the produced material is attached to the node. Also in the case of attaching to the connection table, the identification code is not limited to these symbols as in the above, and it can be attached to a connection other than the node.

Note that it is possible to create a binding table based on the imaginary transition structure of the reaction, and conversely, if the binding table contains the position information of each node, the imaginary transition structure can be created from the binding table. . In other words, it can be said that the imaginary transition structure and the binding table form a one-sided relationship as a registration and display form of chemical reaction information. Input information regarding the position coordinates and the like of each node may also be written in the connection table.

Furthermore, ITS1, ITS2, ...
, Etc., on the other hand, the bibliography of the literature name, author name, reaction name, etc. describing the chemical reaction; and reaction conditions (temperature, time, atmosphere, reaction phase, enthalpy, presence of by-products, etc.) ), Purification conditions (distillation, steam distillation, recrystallization,
Information such as extraction) and information on prescriptions such as harmful poisons (also referred to as "bibliography / prescription items") are attached with symbols such as DATA1, DATA2, ... It is also possible to correlate the two by creating a comparison table such as the above and preliminarily correlating the codes of the both collectively.

Specifically, DATA1 can be attached to the literature name of the reactions represented by the above reaction formulas 1 and 2, and this DATA1 can be attached to ITS1 and ITS2.

The correspondence with the bibliography / prescription items is described in detail in the specification of Japanese Patent Application No. 62-30855 [filed on Feb. 12, 1987 (2)] by the present applicant.

In this way, by attaching the identification code corresponding to the unit information item to the binding table and further associating it with the bibliography / prescription item, the chemical reaction information can be more comprehensively understood and used.

Next, the above-mentioned binding table is given a unique identification code for each reaction.

For example, in the reactions represented by the above reaction formulas 1 and 2, the number 001 is assigned to the ITS representing the main reaction and the binding table, and the number 002 is assigned to the ITS representing the side reaction and the binding table. The identification code may thus be a number that is simply a combination of numbers, or may be any number, letter, other symbol or combination thereof so long as it is computer readable. It is preferable to attach serial numbers to the series of main and side reactions.

The imaginary transition structure and the binding table of each reaction are associated with each other using these unique codes. Correspondence of reactions can be performed by, for example, attaching ITS1 number 002 as a side reaction to ITS1 and attaching ITS1 number 001 as a main reaction to ITS2. Alternatively, it is possible to make correspondence by creating a kind of reference table such as a management table in which these numbers are directly associated with each other.

In this way, by correlating a series of main reactions and side reactions with each other, if one reaction is found (hit) when retrieving chemical reaction information, the remaining that can occur in the same reaction system It is possible to derive the binding table (and imaginary transition structure) of all reactions (side reaction or main reaction) of.

As an example, when the above compound 1 is searched for as a search target, the main reaction (ITS1) is found (hit) by the association by the PS operation, and the ITS1 number 001 and the ITS2 number 002 are found.
A side reaction (ITS2) is obtained by associating with. Furthermore, the association of ITS2 with the PP operation revealed that compound 2 was a by-product. Then, from the identification code [+1] of ITS1 and ITS2, the yield of the main product is 19 to 23% and the yield of the by-product is 7 to 9%.

The binding table (and the imaginary transition structure) associated with each other by attaching the unique identification codes to each other may be registered in the computer by recording and storing them in the main storage device in the computer. Alternatively, the data may be recorded and stored via an appropriate recording medium (magnetic disk, optical disk, magnetic tape, etc.). When the management table is created, this management table is also recorded and saved separately.

These registered main and side reaction information can be immediately derived at any time based on the information of one reaction, and a series of reactions together or separately on various recording materials such as plain paper by an appropriate recording device. It can be recorded or displayed on a color CRT connected to a computer or electronic device (graphic display).

Claims (3)

[Claims] 1. At least one product from at least one starting material, the structure of the starting material of the main chemical reaction and the structure of the product, and the structure of the starting material of the side reaction, which are accompanied by at least one side reaction. Topologically overlapping with the structure of the product, (1) bond between nodes commonly present in the starting material and product, (2) bond between nodes present only in the starting material, and (3) product The main reaction and the sub-reaction binding table, each having a unique sign, that represents the bond between the nodes that exist only in each of them, is created; A step of recording and storing the table in a recording medium attached to a computer; and by performing a computer process using the above-mentioned recorded and stored combination table. Recording and search for basic reactions information side reactions including to incidental; step of searching in association with the main reaction and the side reactions. 2. A management table in which a unique code of the main reaction binding table and a unique code of the side reaction binding table are made to correspond to each other, and a correspondence table is created between the main reaction and side reaction binding tables. A method for recording and retrieving chemical reaction information, which is accompanied by a side reaction according to claim 1, including a step of adding. 3. A pair of numbers (a, b) [where a is an integer representing the bond multiplicity in the starting material, and b is a change in the bond multiplicity in a chemical reaction, as a bond between nodes in the bond table. The method for recording and retrieving chemical reaction information, which is accompanied by the side reaction according to claim 1, wherein the chemical reaction information is associated with the side reaction.