Reaction Searching in STN • Main Files searchable for reactions in STN: • Beilstein • CASREACT • CheminformRX • DJSMOnline • PS • Registry-CAPlus • Synthline
Overview • CASREACT is an organic chemical reaction database produced by CAS. • CASREACT covers chemical reactions from the Organic sections of Caplus. • CASREACT contains displayable reaction schemes for, single - and multi-step, reactions. • CASREACT is updated weekly, with >600-1300 new reactions.
>10,000,000 reactions >4,000,000 single-step reactions >5,000,000 multi-step reactions >500,000 source documents >65,500 patents >341,500 journal articles Overview
From 1907-1985 Partial reactions coverage (InfoChem, INPI) From 1985-1991 All reactions in selected articles from a list of 106 journals in the organic CA sections From 1991-2002 Representative reactions from journals and patents in the organic CA sections From 2003 Extended to all reactions from selected articles in the 30 journals, which are richest in reaction information Representative reactions from the remaining journal articles and patents selected for CASREACT coverage Overview
Original CASREACT reactions Synthetically useful organic and organometallic reactions from CA sections 21-34 (1985-1990) Coverage expanded to sections 41, 7, and 16 in 1991- InfoChem/VINITI reactions Methods for preparing a variety of organic substances, including aliphatic, alicyclic, and heterocyclic compounds, natural products, and organometallics. Journals 1974-1991; Patents 1982-1991 INPI reactions (French Core Reactions Database) Proven synthetic methods for preparing primarily heterocyclic compounds, carbohydrates, and steroids. 1907-1985 Overview Three File Segments
Overview CAS INPI INPI ~ ~ ~ ~ ~ ~ ~ ~ Journals InfoChem 1974 1985 1991 Present 1907 Patents CAS InfoChem 1907 1982 1985 1991 Present Partial reaction coverage is provided from 1907-1985 via the reactions from InfoChem and INPI that could be algorithmically converted into CASREACT format.
Overview • Search terms in CASREACT include: • Structures for reactants/reagents and products in the same query • Allreaction participants, most via CAS Registry Numbers • Reaction yields, number of steps, and additional reaction notes
Overview • CASREACT records contain: • One or more searchable/displayable chemical reactions • All of the information contained in the associated CAplus record
Bibliographic Information (BIB) AN 119:49291 CASREACT TI A new synthesis of pyrazolo[3,4-d]thiazoles AU Vicentini, Chiara B.; Veronese, Augusto C.; Guarneri, Mario;Manfrini, Maurizio; Giori, Paolo CS Dip. Sci. Farm., Univ. Ferrara, Ferrara, 44100, Italy SO Heterocycles (1993), 36(4), 857-63 CODEN: HTCYAM; ISSN: 0385-5414 DT Journal LA English CC 28-7 (Heterocyclic Compounds (More Than One Hetero Atom)) Sample Record
Abstract (ABS) GI AB An efficient synthesis of pyrazolo[3,4-d]thiazoles I (R = Me, PhCH2, Ph) was achieved by treatment of N-(4-amino-5- pyrazolyl)thiocarboxamides II with sodium nitrite in acidic medium followed by irradn. with UV light. All of the BIB and ABS information from CAplus is searchable in CASREACT. Sample Record
Indexing (IND) ST pyrazolothiazole; aminopyrazolylthiocarboxamide diazotization photochem cyclization IT Ring closure and formation (photochem., of aminopyrazolyl)thiocarboxamides to pyrazolothioazoles) IT 23676-92-8 54621-93-1 RL: RCT (Reactant) (nitroso group redn. of) IT 148368-70-1P RL: RCT (Reactant); SPN (Synthetic preparation); PREP (Preparation) (prepn. and nitroso group redn. of) o o o All of the CAplus indexing information is searchable, except for the CAS RNs. Sample Record
RX(1) OF 10 A + B ===> C... RX(1) RCT A 52943-85-8, B 103-80-0 RGT D 144-55-8 NaHCO3 PRO C 148368-70-1 SOL 67-66-3 CHCl3, 7732-18-5 Water RX(2) OF 10 ...C ===> G … o o o Map - Letter placeholder for each reactant and product Diagram - Structures for reactants and products with broken/formed bonds are marked with an asterisk (*) Summary - CAS RNs and Role for each participant Sample Record
RX(5) OF 10 COMPOSED OF RX(1), RX(2) RX(5) A + B ===> G RX(1) RCT A 52943-85-8, B 103-80-0 RGT D 144-55-8 NaHCO3 PRO C 148368-70-1 SOL 67-66-3 CHCl3, 7732-18-5 Water RX(2) RCT C 148368-70-1 RGT H 7803-57-8 N2H4-H2O PRO G 148368-71-2 CAT 7440-05-3 Pd SOL 67-56-1 MeOH o o o Products from Step 2 Reactants from Step 1 Summary - Step 1 Summary - Step 2 Sample Record
CASREACT covers reactions used to prepare: Aliphatic compounds Alicyclic compounds Alkaloids, steroids, and carbohydrates Amino acids, peptides, and proteins Benzene and condensed benzene compounds Dyes and organic pigments Heterocyclic compounds Organometallic compounds (compounds with at least one carbon-metal bond) Terpenes and terpenoids CASREACT Coverage
p. 6 CASREACT does NOT cover reactions used to prepare: Inorganic compounds Coordination compounds with no carbon-metal bonds Polymers Surfactants and detergents CASREACT Coverage
p. 7 A variety of reaction types: Straightforward single-step and multi-step synthetic reactions Stereospecific syntheses Biologically mediated reactions, e.g., enzymatic conversions "Pot" reactions (multi-step reaction in which intermediates are not isolated) Failed reactions (if the intent was potentially synthetically useful) CASREACT Coverage
p. 7 Reactions typically not covered in CASREACT include: Conventional preparations for physiochemical or pharmacological studies Conventional methods of isotopic labeling Conventional methods for amino acid or carbohydrate coupling Reactions of compounds where there is no change in the atom connections in the reaction CASREACT Coverage
A variety of search terms can be used in CASREACT to: Describe a reaction Focus a reaction search Focus a reaction answer set Reaction Search Terms
Terms to describe a reaction: Structure diagrams for reactant/reagent and product A=>? What is made from this reactant? ? => B How is this product made? A=>B Reactant going to a product Reaction Search Terms • Functional groups appearing in the reactant/reagent and product Group that is formed in the reaction Group that reacts Group that does not participate in the reaction
Terms to focus a reaction search: Yield Number of steps CAS RNs for other reaction participants Reaction note Reaction Search Terms Terms to focus a reaction answer set: • Document type • Publication year • Author • Company name
Ways for searching In CASREACT • Basic Index • Structures • Functional Groups
Basic Index • Basic Index contains: • CAS Registry Numbers for: reagents, solvents, and catalysts • Single words from: • title, supplementary terms, abstract, • index terms,reaction note.
Basic Index => fil casreact => enzym? or biotransform? or yeast L1 18695 ENZYM? OR BIOTRANSFORM? OR YEAST => (enzym? or biotransform? or yeast)/nte L2 11368 (ENZYM? OR BIOTRANSFORM? OR YEAST)/NTE => d hit L2 ANSWER 1 OF 11368 CASREACT COPYRIGHT 2005 ACS on STN NTE biotransformation, enzymic, stereoselective, enantioselective (S-alc. in 99% ee), lipase PS-30 is immobilized on Celite 545
Structures Search Question: Locate methods for converting the following thioamides to the corresponding nitriles: R1, R2, R3, R4 = Anything, including hydrogen
Structures 1. Build and save the reaction query 2. Logon to STN and enter CASREACT 3. Upload the reaction query
Structures 4. Run the reaction search 5. Display the reactions
To build a Reactant => Product reaction query: Draw the structure diagrams Specify the reaction features Save the reaction query Structures
A. Draw the structure diagrams 1. Click on the Prepare Query button on the main STN Express screen to open the structure drawing screen. 2. Draw the structure for the reactant and the structure for the product in the same structure drawing window. Structures
B. Specify the reaction features 1. Click on the Reaction button to activate the reaction feature buttons on the vertical toolbar. Structures
B. Specify the reaction features 2. To specify reactant and product, right click the Reaction Arrow Tool and draw an arrow from the reactant to the product. Structures N
The role reactant/reagent is assigned to the structure at the beginning of the arrow and the role product is assigned to the structure at the end of the arrow. Structures NOTE: The role "reactant/reagent" is assigned instead of "reactant" because a compound may be considered to be a reactant in one paper and a reagent in others. To maximize the number of reactions retrieved, the broader role of reactant or reagent is assigned to the starting material.
C. Save the reaction query 1. Click the Save button . The Save Query As dialog box appears. 2. In the File Name: entry box, type a name for the query. Click Save. Structures
C. Save the reaction query 3. On the second save screen, click Save. Structures
1. Logon to STN by clicking the Logon button . You are placed in the HOME file on STN. 2. Use the FILE command to enter a reaction database. * * * * * * * * * * STN Columbus * * * * * * * * * * * FILE 'HOME' ENTERED AT 16:01:49 ON 16 NOV 2000 => FILE CASREACT Structures
1. Start the structure uploading process by clicking the Upload Structure Query button . 2. Choose the name of the structure to upload. Click Open. Structures N
Select the type of database in which you will do the search. Click OK. Structures NOTE - The query will be uploaded as a reaction only in the reaction-searchable databases. In the other databases, the reactant and product will be uploaded as separate structure queries.
When structure upload is completed, an L- number is assigned to the structure reaction query. => Uploading r1.str L1 STRUCTURE UPLOADED Structures
Option: Verify the reaction query online Display the uploaded reaction and verify that it corresponds to the reaction you wish to search. => D L1 L1 HAS NO ANSWERS L1 STR Structure attributes must be viewed using STN Express query preparation. Structures
The SEARCH command is used to run a reaction search. The command line needs three pieces of information: 1. The L-number of the uploaded reaction query. 2. The type of search you want to perform: 3. The scope of the search: Structures
Running a reaction search involves three steps: A. Run a SAMPLE search B. Evaluate answers C. Run a FULL search Structures
The SAMPLE search is a no-cost way to: 'Test' your query to make sure it will run within system limits Verify that the types of answers retrieved are the types of answers you want Structures
=> S L1 SSS SAM SAMPLE SEARCH INITIATED 14:37:13 FILE 'CASREACT' SCREENING COMPLETE - 2 REACTIONS TO VERIFY FROM 2 DOCUMENTS 100.0% DONE 2 VERIFIED 1 HIT RXNS 1 DOCS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED VERIFICATIONS: 2 TO 124 PROJECTED ANSWERS: 1 TO 79 L2 1 SEA SSS SAM L1 (1 REACTIONS) Structures The search is projected to complete in the full database. Each answer contains one or more reactions that match the query. Each answer is a document record.
In CASREACT the no-cost D SCAN feature shows the: Title of the publication First hit reaction in a condensed form => D SCAN L2 1 ANSWERS CASREACT COPYRIGHT 2000 ACS TI Nitrile-formamide chloride adducts. X. Formation of nitriles by base-induced fragmentation of N- acylamides and their heteroanalogous derivatives ALL ANSWERS HAVE BEEN SCANNED Structures
=> S L1 SSS FULL FULL SEARCH INITIATED 14:37:49 FILE 'CASREACT' SCREENING COMPLETE - 24 REACTIONS TO VERIFY FROM 15 DOCUMENTS 100.0% DONE 24 VERIFIED 9 HIT RXNS 7 DOCS SEARCH TIME: 00.00.02 L3 7 SEA SSS FUL L1 (9 REACTIONS) => D SCAN L3 7 ANSWERS CASREACT COPYRIGHT 2000 ACS TI Mild and selective oxidations with polystyrene- bound diaryl selenoxide HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 Structures D SCAN randomly selects answers from the answer set for display. The FULL search retrieved 7 documents containing a total of 9 reactions that match the query.
HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 L3 7 ANSWERS CASREACT COPYRIGHT 2000 ACS TI A new, efficient one-pot preparation of nitriles from thiocarboxamides HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 Structures Type "0" or "END" to exit from D SCAN.
Many display formats are available in CASREACT to view additional information from an answer. To use the display formats with the DISPLAY command, enter in any order: Format name L-number of the answer set Answer numbers Example: To display answers 1-7 from L3 in the FHIT format, enter => D L3 1-7 FHIT Structures
=> D L3 1-4 OCC L3 ANSWER 1 OF 7 CASREACT COPYRIGHT 2000 ACS NUMBER OF HIT REACTIONS 2 NUMBER OF REACTIONS IN PATH 2 NUMBER OF REACTIONS IN SPATH 2 FIELD COUNT RX(4) 2 RX(5) 2 L3 ANSWER 2 OF 7 CASREACT COPYRIGHT 1998 ACS NUMBER OF HIT REACTIONS 1 NUMBER OF REACTIONS IN PATH 1 NUMBER OF REACTIONS IN SPATH 1 FIELD COUNT RX(1) 2 o o o Structures OCC displays information about the "hits" in the answer. The first line shows the number of reactions that matched the search query.