1 Reaction Searching in STN. 2 Main Files searchable for reactions in STN: Beilstein CASREACT ...

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Reaction Searching in STN

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Reaction Searching in STN

Main Files searchable for reactions in STN:

Beilstein CASREACT CheminformRX DJSMOnline PS Registry-CAPlus Synthline

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CASREACT

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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.

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• >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

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• 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

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Three File Segments• 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

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Journals

1985 Present1974

InfoChem

CAS

Patents

1991

Partial reaction coverage is provided from 1907-1985 via the reactions from InfoChem and INPI that could be algorithmically converted into CASREACT format.

~ ~

1907

INPI~ ~

Present1982 1991

~ ~

1907

~ ~

CAS

INPI

1985

InfoChem

Overview

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• Search terms in CASREACT include:

Structures for reactants/reagents and products in

the same query All reaction participants, most via CAS Registry

Numbers Reaction yields, number of steps, and additional

reaction notes

Overview

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• CASREACT records contain:

One or more searchable/displayable chemical

reactions All of the information contained in the associated

CAplus record

Overview

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Sample Record

Bibliographic Information (BIB)

AN 119:49291 CASREACTTI A new synthesis of pyrazolo[3,4-d]thiazolesAU Vicentini, Chiara B.; Veronese, Augusto C.;

Guarneri, Mario; Manfrini, Maurizio; Giori, PaoloCS Dip. Sci. Farm., Univ. Ferrara, Ferrara, 44100,

ItalySO Heterocycles (1993), 36(4), 857-63 CODEN: HTCYAM; ISSN: 0385-5414DT JournalLA EnglishCC 28-7 (Heterocyclic Compounds (More Than One Hetero

Atom))

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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.

NN N

S

RPh

eM

I NN

NH2

NHCSRPh

eM

II

Sample Record

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Indexing (IND)

ST pyrazolothiazole; aminopyrazolylthiocarboxamide diazotization photochem cyclizationIT 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

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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

MePh

NONH

NN

H *

A

PhCl

O

*

B(1)

Me

Ph

Ph

NONH

O

NN

*

YIELD 79%C

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

Me

Ph

Ph

NH

O

NN

NO

*

C(2)

Me

Ph

Ph

NH

O

NN

NH

H*

YIELD 87%G

Sample Record

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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

MePh

NH

NN

NOH * *

A

PhCl

O

*

B

2 STEPS

Me

Ph

Ph

NH

O

NN

NH

H

*

*

YIELD 87%G

Products from Step 2

Reactants from Step 1

Summary - Step 1

Summary - Step 2

Sample Record

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CASREACT Coverage

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

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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

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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

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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

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Reaction Search Terms

A variety of search terms can be used in CASREACT to:

Describe a reaction Focus a reaction search Focus a reaction answer set

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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

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


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Terms to focus a reaction search: Yield Number of steps CAS RNs for other reaction participants Reaction note

Terms to focus a reaction answer set: Document type Publication year Author Company name


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Ways for searching In CASREACT

Basic Index

Structures

Functional Groups

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Basic Index contains:

CAS Registry Numbers forCAS Registry Numbers for:

reagents, solvents, and catalysts

Single words fromSingle words from::

title, supplementary terms, abstract,

index terms,reaction note.

Basic Index

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=> 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

Basic Index

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Search Question:

Locate methods for converting the following thioamides to the corresponding nitriles:

R1, R2, R3, R4 = Anything, including hydrogen

Structures

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3. Upload the reaction query

2. Logon to STN and enter CASREACT

1. Build and save the reaction query

Structures

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5. Display the reactions

4. Run the reaction search

Structures

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• To build a Reactant => Product reaction query:

A Draw the structure diagramsB Specify the reaction featuresC Save the reaction query

Structures

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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

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B. Specify the reaction features1. Click on the Reaction button to activate the

reaction feature buttons on the vertical toolbar.To assign a Use the

Reaction direction Reaction Arrow Tool

Fragment role Reaction Role Tool

Bond that is changed/unchanged in the reaction

Reaction Site Tool

Mapping between an atom in the reactant and product

Reaction Mapping Tool

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B. Specify the reaction features2. To specify reactant and product, right click the Reaction

Arrow Tool and draw an arrow from the reactant to the product.

Structures

N

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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.

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.

Structures

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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

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C. Save the reaction query3. On the second save screen, click Save.

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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

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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

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Select the type of database in which you will do the search. Click OK.

NOTE - NOTE - The query will be uploaded as a reaction only in the reaction-The query will be uploaded as a reaction only in the reaction-searchable databases. In the other databases, the reactant and searchable databases. In the other databases, the reactant and product will be uploaded as separate structure queries.product will be uploaded as separate structure queries.

Structures

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When structure upload is completed, an L-

number is assigned to the structure reaction

query.

=>

Uploading r1.str

L1 STRUCTURE UPLOADED

Structures

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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.

SN

O

N

O

H

H H

H H

H H

H

Structures

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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:

Type of searchSSS CSS

Allows substitution at any open site in the query

Blocks substitution at any open site in the query

Scope of searchSAM FULL

Search a portion of the database (no cost)

Search the entire database (search fees apply)

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Running a reaction search involves three steps:

A. Run a SAMPLE search

B. Evaluate answers

C. Run a FULL search

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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

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=> 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)

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.

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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

RX(2) OF 5

NMe2

MeO

C N

S

CH

MeO

CN

32%

NaOH, Water

Structures

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=> S L1 SSS FULL

FULL SEARCH INITIATED 14:37:49 FILE 'CASREACT'




L3 7 SEA SSS FUL L1 (9 REACTIONS)

=> D SCAN


TI Mild and selective oxidations with polystyrene- bound diaryl selenoxide

HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1

RX(20) OF 27

MeO

C NH2

S

MeO

PhSe

O

+MeO

CNEtOH

NOTE: Polymer-bound selenoxide

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.

Structures

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TI A new, efficient one-pot preparation of nitriles from thiocarboxamides


RX(1) OF 4

MeO

C NH2

S

(step 1)

MeO

CN

70%

1. Me2N:CHO2SCl.Cl, CH2Cl22. Pyridine, CH2Cl2

Type "0" or "END" to exit from D SCAN.

Structures

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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=> D L3 1-7 FHIT

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Use this format To display

OCC The number of hit reactions in each answer

CRD All hit reactions for each answer in the compact format

FCRDREF (default) First hit reaction for each answer in the compact format,plus the reference

CRDREF All hit reactions for each answer in the compact format, plusthe reference

FHIT First hit reaction for each answer in the full format (Map,Diagram, and Summary - includes CAS RNs for eachparticipant)

HIT All hit reactions for each answer in the full format (Map,Diagram, and Summary - includes CAS RNs for eachparticipant)

BIB Full bibliographic information

ABS Abstract from printed Chemical Abstracts

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=> D L3 1-4 OCC L3 ANSWER 1 OF 7 CASREACT COPYRIGHT 2000 ACSNUMBER OF HIT REACTIONS 2NUMBER OF REACTIONS IN PATH 2NUMBER OF REACTIONS IN SPATH 2FIELD COUNTRX(4) 2 RX(5) 2 L3 ANSWER 2 OF 7 CASREACT COPYRIGHT 1998 ACSNUMBER OF HIT REACTIONS 1NUMBER OF REACTIONS IN PATH 1NUMBER OF REACTIONS IN SPATH 1FIELD COUNTRX(1) 2 o o o

OCC displays information about the "hits" in the answer. The first line shows the number of reactions that matched the search query.

Structures

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=> D L3 1 CRD

L3 ANSWER 1 OF 7 CASREACT COPYRIGHT 2000 ACS

RX(4) OF 9

MeO

C NH2

S

MeO

CN

96%

TeCl4, Et3N, CHCl3

RX(5) OF 9

MeO

C NH2

S

MeO

CN

+

88%

OMeMeO

N

NS

8%

SeCl4, Et3N, CHCl3

CRD shows all hit reactions for an answer.

Structures

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=> D L3 1 FHIT


RX(4) OF 9 J ===> K

RX(4) RCT J 2362-64-3

RGT C 10026-07-0 TeCl4, D 121-44-8 Et3N

PRO K 874-90-8

SOL 67-66-3 CHCl3

MeO

NH

S

H**

*

J(4)

MeO

C N*

YIELD 96%K

REACTION SUMMARY

REACTIONMAP

REACTION DETAILS

Structures

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The FHIT and HIT formats are useful when you need

to see the CAS RNs for one or more of the reaction

participants.

Structures

54

=> D L3 1-3




RX(4) OF 9

MeO

C NH2

S

MeO

CN

96%

TeCl4, Et3N, CHCl3

REF: J. Chem. Res., Synop., (4), 152-3; 1995

RX(1) OF 4

MeO

C NH2

S

(step 1)

MeO

CN

70%

1. Me2N:CHO2SCl.Cl, CH2Cl22. Pyridine, CH2Cl2

REF: Indian J. Chem., Sect. B, 30B(11), 1065-6; 1991

RX(2) OF 5

NMe2

MeO

C N

S

CH

MeO

CN

32%

NaOH, Water

REF: J. Prakt. Chem., 330(5), 847-50; 1988

If a display format is not specified on the command line, STN uses the default format for the database to display the results.

Structures

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=> D L3 3 CRDREF ABSL3 ANSWER 3 OF 7 CASREACT COPYRIGHT 2000 ACS

GI

AB 4-MeOC6H4CN was obtained by treatment of 4- MeOC6H4CCl:NCH:N+Me2 ClO4- or 4-MeOC6H4CSN:CHNMe2

with base. 4-ClC6H4CN was similarly obtained from the pyrrolinium salt I and 3-morpholino-2-

phenylacrylonitrile from the iminium salt II. 3- Phthalimidopropionitrile was prepd. from N-(3-

phthalimidopropionyl) formamide and MeNHNH2.

C(SMe) NClN+

I-Me

I

ON+NCHPhCClClO4- II

RX(2) OF 5

NMe2

MeO

C N

S

CH

MeO

CN

32%

NaOH, Water

REF: J. Prakt. Chem., 330(5), 847-50; 1988

Structures

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1. To permanently change the default display format:=> SET FORMAT

ENTER FORMAT NAME OR (?):.MYRXN

ENTER FORMAT DEFINITION OR (?):TI CRDREF

SET COMMAND COMPLETED

2. Permanently change default to new format:=> SET DFORMAT PERM .MYRXN

SET COMMAND COMPLETED

Structures

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1 What types of products have been formed from the reaction of the following two starting materials?

R1 and R2 may be any ring or chain atom including hydrogen.

R3 may be ring or chain atom except hydrogen.

Skills Practice

58

1 Locate the requested information:

A. Build the query.

B. Test it with a SAMPLE search. Will the search run within system limits in the FULL database?

C. Run the search in the FULL database. How many documents were retrieved? How many total hit reactions were in the documents?

D. Display the Title (TI) and CRDREF information for all of the answers. How many different methods were reported for carrying out the conversion?

Skills Practice

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=> fil casreact=> Uploading C:\Program Files\stnexp\Queries\w9.str L1 STRUCTURE UPLOADED => dL1 HAS NO ANSWERSL1 STR

C NA N

H

H

H

C CC N N+

Ring, Chain

60

=> l1SAMPLE SEARCH INITIATED 06:38:14SCREENING COMPLETE - 142 REACTIONS TO VERIFY FROM 24 DOCUMENTS 100.0% DONE 142 VERIFIED 21 HIT RXNS 6 DOCSSEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED VERIFICATIONS: 2126 TO 3554PROJECTED ANSWERS: 6 TO 266 L2 6 SEA SSS SAM L1 ( 21 REACTIONS)

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=> l1 fullFULL SEARCH INITIATED 06:39:49SCREENING COMPLETE - 2571 REACTIONS TO VERIFY FROM 446 DOCUMENTS 100.0% DONE 2571 VERIFIED 531 HIT RXNS 137 DOCSSEARCH TIME: 00.00.01 L3 137 SEA SSS FUL L1 ( 531 REACTIONS)

=> d fhit

62

Ph

N

N

NNH

HH

* *

A

EtMe

NCC

ON **

F(2)

Me

Ph

NC

NN

N

NH

N

H

*** *

YIELD 70%G

63

Ac AcO

A CNNH

O

NH

H*

**

B

Ph

NCC N

H

**

* *

D

2 STEPS

NH

YIELD 32%E: CM 1

Ph

CN

NCN

N

N

O

H

H

**

* **

* **

*

**

YIELD 32%E: CM 2

64

1 Locate the requested information about the conversion of the following ketoximes to the corresponding ketones:

R = any non-hydrogen ring or chain substituent

Rings may have other rings fused to them

Any substitution at all open sites

Skills Practice

65

1 Locate the requested information:

A. Build the query.

B. Test it with a SAMPLE search. Will the search run within system limits in the FULL database?

C. Run the search in the FULL database. How many documents were retrieved? How many total hit reactions were in the documents?

D. Display the Title (TI) and CRDREF information for all of the answers. How many different methods were reported for carrying out the conversion?

Skills Practice

66

=> fil casreact => Uploading C:\Program Files\stnexp\Queries\w9.strL1 STRUCTURE UPLOADED => d

A

Me N

O H

A

Me O

67

=> l1SAMPLE SEARCH INITIATED 16:50:46SCREENING COMPLETE - 170 REACTIONS TO VERIFY FROM 35 DOCUMENTS 100.0% DONE 170 VERIFIED 10 HIT RXNS 5 DOCSSEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED VERIFICATIONS: 2618 TO 4182PROJECTED ANSWERS: 5 TO 234 L2 5 SEA SSS SAM L1 ( 10 REACTIONS)

68


69

=> d scan L3 71 ANSWERS CASREACT COPYRIGHT 2004 ACS on STN TI Application of Aryloximes as Solid-Phase Ketone Linkers

RX(11) OF 27

Me

PhO

CN OH

(step 1)

Ac

PhO

95%

1. R:94610-82-9, t-BuOK, DMF2. F3CCO2H, Water, MeOH

70

Precision ToolsLocate methods for converting the primary amine to a nitro group in the following types of compounds:

H2N–R–Cl => O2N–R–Cl

R = any type of carbocyclic ring system, e.g., benzene, cyclopentane, etc.

Any other substitution in addition to that shown in the structure is allowed

Structures

71

3. Test the query with a SAMPLE search

2. Logon to STN, enter CASREACT, and upload the

reaction query.

1. Build and save the reaction query.

Structures

72

• When many reactions of the same type are reported in a paper, generally only synthetically useful or structurally representative reactions are included in CASREACT.

• To maximize the retrieval of papers that may contain the types of transformations in which you are interested, make your structure query as broad as possible.

Structures

73

Use this feature To retrieve

Variable groups(X ,M, A, Q, CY, CB,HY, AK)

Broadly defined groups of atoms

G-group A group of atoms that you specify (up to 20atoms)

Node Characteristicof Ring/Chain onchain atoms

Chain atoms that are parts of a ring or a chain

Bond Characteristicof Ring/Chain onchain bonds

Chain bonds that are in a ring or a chain

Leave the site open Any substitution at a position

Structures

74

Worksheet

Directions: Consider the amine => nitro query on the previous page. Which of the above features would you use to make the query as broad as possible?

HN

CbCl

H

ON

CbCl

O

Structures

75

=> FILE CASREACT

Uploading rx2.str


=> D L1

L1 HAS NO ANSWERS

L1 STR


HN

CbCl

H

ON

CbCl

O

Structures

76

=> S L1 SSS SAM






BATCH **COMPLETE**




Structures

77

=> D SCAN L2 3 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Preparation of benzimidazole phosphono-amino acids

useful as NMDA Antagonists


RX(2) OF 3NO2

Cl

NH2+

(step 1)

EtO OEtCH2(step 2)

OEt

OEt

NO2

Cl

NH CH2 P

O

95%

1. (EtO)2P(O)H, H2SO4, Water

Structures

78

L2 3 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Radioiodinated p-iodoclonidine. A high-affinity

probe for the .alpha.2-adrenergic receptor

L2 3 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Synthesis of the new pyrido[1,2-c]benzo-v-

triazinium system via valence bond isomerization


RX(12) OF 50O2N

Cl

Cl

NH2

CHO

O2N Cl

ClNH

64%

AcOCHO

RX(9) OF 22NO2

Cl

NH2

(step 1)

NO2Cl

N

76%

1. HCl, NaNO2, Water2. Pyridine

Structures

79

Worksheet

Directions: Look at the reactions retrieved in the SAMPLE search. How many of those reactions are the transformation of interest?

Neither one

Structures

80

6. Run the FULL search.

5. Test the modified query with a SAMPLE search

4. Add precision to the query, using map and site

tools.

Structures

81

Two tools are available for improving the precision of

reaction structure queries.

Use this tool When you need to specify that

Atom mappingAn atom in the reactant is thesame atom in the product

Reaction siteA bond is completelychanged, partially changed, orunchanged in the reaction

Structures

82

Atom MappingTo map atoms in a reaction query:

1. Click on the Atom mapping tool .

2. A mapping-type option box appears.

Select Manual Mapping. Click OK.

Structures

83

To map atoms in a reaction query:

3. Click on an atom in the reactant and the corresponding atom in the product.

Identical numbers indicate mapped atoms.

Structures

Atom Mapping

84

Mapping may NOT be used with

Shortcut symbols Variable groups G-groups Different elements, e.g. you cannot map C to N

Atom Mapping

Structures

85

Reaction SitesTo specify a reaction site in a reaction query:

1. Click on the Reaction site tool .2. Click on a bond in the query that you want

to specify as a reaction site.

3. A table of options appears. Select the desired option. Click OK.

Structures

86

To specify a reaction site in a reaction query:

4. Repeat Steps 2 and 3 for other bonds in the

structure.

5. Save the modified query.

Structures

Reaction Sites

87

• Over-specification of bond sites and atom Over-specification of bond sites and atom mapping may cause the loss of relevant answersmapping may cause the loss of relevant answers.

• Specify only the minimum requirements needed to Specify only the minimum requirements needed to

eliminate non-relevant answers.eliminate non-relevant answers.

Structures

88

For the search query in this example, oneone H–N and oneone O=N bond is specified as XC.

Bonds with site specifications on them have an asterisk (*) over the bond.

Reaction Sites

Structures

89

Determine the impact of the change you made with another SAMPLE search.

=> Uploading rx2b.strL3 STRUCTURE UPLOADED=> D L3L3 HAS NO ANSWERSL3 STR


HN

CbCl

H

ON

CbCl

O

Structures

90

=> S L3 SSS SAM






BATCH **COMPLETE**



L4 0 SEA SSS SAM L3(0 REACTIONS)

A SAMPLE search searches the same portion of the database each time, so you can easily see the impact of the changes you made.

Structures

91

=> S L3 SSS FULL


SCREENING COMPLETE -11605 REACTIONS TO VERIFY FROM 2604 DOCUMENTS




=> D SCAN


TI Functional group oxidation using sodium perborate


o o o

RX(7) OF 69Cl

NH2

NO2

Cl92%

R:90568-23-3, AcOH

Structures

92

=> D L5 1-7L5 ANSWER 1 OF 7 CASREACT COPYRIGHT 2000 ACS



o o o

RX(2) OF 6

Cl

Cl

NH2

NO2

Cl

Cl

38%

C:41867-66-7, K H persulfate, Me2CO

REF: Eur. J. Inorg. Chem., (12), 2319-2325; 1999NOTE: PHOSPHATE BUFFER USED

RX(3) OF 3

OMe

CO2HCl

H2N(step 1)

OMe

CO2H

O2N

Cl

60%

1. NaBO3, AcOH2. Water

REF: Eur. J. Med. Chem., 30(10), 757-62; 1995

The default format displays the first hit reactions and its associated reference.

RX(22) OF 83

PhCl C

ONH2

PhNO2

Cl C

O59%

H2O2, (CF3CO)2O, CH2Cl2

REF: J. Med. Chem., 33(8), 2296-304; 1990

Structures

93




RX(9) OF 14

O2NCl

NH2

(step 1)

NO2

O2NCl60%

1. NaNO2, HBF4, Water2. MeSO2Cl, THF

REF: J. Chem. Soc., Perkin Trans. 2, (6), 573-8; 1989

RX(7) OF 69Cl

NH2

NO2

Cl92%

R:90568-23-3, AcOH

REF: Tetrahedron, 43(8), 1753-8; 1987

RX(5) OF 16

CF3F3C

ClCl

S

O

O

S

NH2

O

O

NO2

CF3F3C

ClCl

S

O

O

S

O

O

86%

H2O2, H2SO4, Oleum

REF: Zh. Org. Khim., 23(3), 601-6; 1987

Structures

94

Many types of reaction structure queries

may be searched in CASREACT:

A + B => C (two reactants leading to a product)

A + B = > ? (two reactants going to any product)

A => ? (reactant going to any product)

? => B (any reactant going to a specific product)

Structures

95

Search Question:Locate methods for converting the two starting

materials shown below to the specified ether.

R = anything, including hydrogenBenzene rings may have other rings fused onto themAny substitution at all open sites

Structures

96

3. Save the query.

2. Specify reaction roles.

1. Build the structure for each participant.

4. Run the search.

Structures

97

To specify the reaction role for the structure fragment(s): 1. Click on the Reaction role tool .

A box explaining how to specify a reaction role is displayed. Click OK

Structures

98

To specify the reaction role for the structure fragment(s): 2. Click an atom in the structure for which you want to

specify a role.A menu of roles displays. Select the desired role. Click OK

Structures

99

To specify the reaction role for the structure fragment(s): 3. Repeat Step 2 for each fragment in the query.

Structures

100

Use as many of the reaction precision tools as needed to retrieve the desired types of reactions.

For this query, specify as XC the bonds from the benzene ring to X in one reactant from nitro-benzene ring to O in the product

Structures

(If you want you can also map the oxygen atom)

101

=> Uploading rx3.str


=> D L1

L1 HAS NO ANSWERS

L1 STR


X

NO2

O

X

O

NO2

X

Reaction roles do not display with the structures on STN.

Structures

102

=> S L1 SSS SAM






BATCH **COMPLETE**




Structures

103

=> D SCAN


TI Polymer-supported bases in combinatorial chemistry: synthesis of aryl ethers from phenols and alkyl halides and aryl halides


RX(14) OF 15NO2

F

Cl

OH+

O2N Cl

O

73%

Pyrimidopyrimidine, MeCN

Structures

104

=> S L1 SSS FULL






Structures

105

=> D SCANL3 6 ANSWERS CASREACT COPYRIGHT 2000 ACSTI 3-(3-Aryloxyphenyl)-1-(substituted methyl)-s-

triazine-2,4,6-trione or -thiotrione herbicidal agents


(continued on next page)

RX(3) OF 6

MeO

NO2

FO

N

N

CH2

O

NH

C

O

O

+

Cl

Cl

OH

OMeNO2

Cl

Cl O

N NCH2

O NH

C

O

O

O

K2CO3, DMF

Structures

106


TI Synthesis of 2-alkoxy-5-nitrobenzamides by phase-transfer catalyzed nucleophilic substitution of 2-chloro-5-nitrobenzamides


RX(19) OF 19

NHBu-n

NO2

ClC

O

+

Cl

Cl

Cl

OH

NHBu-n

NO2Cl

Cl

Cl

O

C

O

Bu4N.Br, NaH, PhMe

NOTE: FAILED REACTION

Note how "failed reactions" display.

Structures

107

Precision tools are available in STN Express to focus on the desired types of reactions

To assign a Use the

Reaction direction Reaction Arrow Tool

Fragment roleReaction Role Tool

Bond that ischanged/unchangedin the reaction

Reaction Site Tool

Mapping between anatom in the reactantand product

Reaction Mapping Tool

Structures

108

1. Locate methods for carrying out the following ring-forming reaction:

Additional substitution is allowed at all open sites

Additional ring fusion is allowed

The bond can be single, double, or triple

Skills Practice

109

fragments assigned product role:containing 10fragments assigned reactant/reagent role:containing 1reaction site bonds:19-20:CC node mappings:7:11 8:10 9:18

110

=> Uploading C:\Program Files\stnexp\Queries\w9a.str L1 STRUCTURE UPLOADED => l1SAMPLE SEARCH INITIATED 05:24:29SCREENING COMPLETE - 99 REACTIONS TO VERIFY FROM 18 DOCUMENTS 100.0% DONE 99 VERIFIED 12 HIT RXNS 2 DOCSSEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED VERIFICATIONS: 1384 TO 2576PROJECTED ANSWERS: 2 TO 124 L2 2 SEA SSS SAM L1 ( 12 REACTIONS)

111


112

=> d fhit 2

Ph N

S

O

H

**

**

A

Ph

Br

O

H**

B(1)

Ph

Ph

O

S

N

***

*

YIELD 64%C

113

New compounds registered only from CASREACT

114

New compounds• Reaction participants not found in Registry were

given CASRN, Index Name, Structure

Only occurrence of this compound is in CASREACT

Patent interest: CASREACT has the relevant art

115

New compounds

=> casreact/lc(notp)(ca or caplus or caold)/lc L1 63411 CASREACT/LC(NOTP)(CA OR CAPLUS OR CAOLD)/LC => d 1-30 lc L1 ANSWER 1 OF 63411 REGISTRY COPYRIGHT 2005 ACS on STN LC STN Files: CASREACT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . => 408508-10-1L2 1 408508-10-1 => l1 and l2L3 1 L1 AND L2

116

In CASREACT there are two main ways for searching:

Structures

Functional Groups

117

Functional Groups

Create reaction queries using the functional group tool in STN Express

Search for broadly defined transformations using functional groups

Specify non-reacting functional groups

118

While structure queries could be created to search for broadly defined reactions, this approach may:

Not run to completion within system limits Take a long time to complete

Functional Groups

119

Consider using functional group queries when you:

Want an overview of current methods being used to carry out a broadly-defined transformation

Are not retrieving answers with a precisely defined structure query Are looking for a broadly defined transformation in the presence of a

non-reacting functional group Want a set on which you run a subset search

Functional Groups

120

Functional group terms are assigned to approximately 200 different structural groups in CASREACT. Groups are identified as:

Reacting functionalities Formed functionalities Non-reacting functionalities

Functional Groups

121

Functional groups are divided into terms for

Rings Functionalities

Functional Groups

122

Ring Terms

1,2-C3N2 1,3-C3O2 1,4-C5N2

1,2-C3NO 1,3-C3OS C2S

1,2-C3NS 1,3-C3S2 C3N

1,2-C3O2 1,3-C4N2 C3O

1,2-C3OS 1,3-C4NO C3S

1,2-C3S2 1,3-C4NS C4N

1,2-C4N2 1,3-C4O2 C4O

1,2-C4NO 1,3-C4OS C4S

1,2-C4NS 1,3-C4S2 C5N

1,2-C4O2 1,4-C4N2 C5O

1,2-C4OS 1,4-C4NO C5S

1,2-C4S2 1,4-C4NS C6N

1,3-C3N2 1,4-C4O2 C6O

1,3-C3NO 1,4-C4OS C6S

1,3-C3NS 1,4-C4S2

Functional Groups

123

Ring terms describe 5- and 6-membered rings with any type of bonding.

For example:The term 1,3–C3NS describes this type of ring

where the N and S are in the 1 and 3 positions and other rings may be fused to the structure.

Functional Groups

124

Functionality Terms

ACETAL HALOHYDRIN PHOSPHITE ACETYL HEMIACETAL PHOSPHONATE ACID HALIDE HETEROCYCLES PHOSPHONIUM ACYCLIC ALKENE HYDRAZIDE PHOSPHORUS YLIDE ACYCLIC KETONE HYDRAZINE PI-ALKENE ACYLMETAL HYDRAZONE PI-ALKYNE ALCOHOLS HYDROPEROXIDE PI-ALLYL ALDEHYDE HYDROXYLAMINE PRIMARY ALCOHOL ALKENES IMIDE PRIMARY AMINE ALKYL HALIDE IMINE PURINE ALKYNE IMINO ETHER QUATERNARY AMMONIUM ALKYNES ISOCYANATE S-O GROUP ALLENE ISONITRILE SE GROUP ALLYL ALCOHOL ISOTHIOCYANATE SECONDARY ALCOHOL ALLYL HALIDE KETAL SECONDARY AMINE AMIDE KETENE SELENIDE AMIDINE KETENIMINE SELENOL AMINE OXIDE KETONES SILYL AMINES LACTAM SILYL ENOL ETHER ANHYDRIDE LACTONE SULFENYL HALIDE ARYL HALIDE MESYL SULFIDE ARYLSULFONYL METAL ARENE SULFINATE AZIDE ENOL METAL CARBENE SULFINYL HALIDE AZINE METAL CARBONYL SULFONAMIDE AZIRIDINE METAL CYCLOPENTADIENYL SULFONE AZO METAL HALIDE SULFONYL HALIDE AZOXY METAL HYDRIDE SULFONYLOXY CARBAMATE METAL METAL BOND SULFOXIDE CARBONATE METAL NITROGEN SULFUR YLIDE CARBONATE DERIVATIVES METAL NITROSYL TE GROUP o o o

Functional Groups

125

Functionality Terms

o o o CARBOXY DERIVATIVES METAL PHOSPHINE TERTIARY ALCOHOL CARBOXYLATE METAL SULFUR TERTIARY AMINE CARBOXYLIC METALLOCARBOCYCLE THIOACETAL CEPHEM MU-CARBONYL THIOAMIDE CHLORAMINE NITRILE THIOCARBONYL CYANAMIDE NITRILE OXIDE THIOCARBOXY CYANATE NITRITE THIOCYANATE CYANOHYDRIN NITRO THIOKETAL CYCLIC ALCOHOL NITRONE THIOL CYCLIC ALKENE NITROSAMINE THIONE CYCLIC KETONE NITROSO THIOPHENOL CYCLOPROPYL NITROXIDE THIOUREA DIAZO NULL TRIAZENE DIAZONIUM O-QUINONE TRIHALIDE DIENE ORGANOMETAL UNSATD ACID DIIMIDE ORGANOMETALLICS UNSATD ALDEHYDE DISULFIDE ORTHO ESTER UNSATD AMIDE ENAMINE OXIME UNSATD ESTER ENOL OXONIUM UNSATD KETONE ENOL ETHER P-N GROUP UNSATD NITRILE ENYNE P-O GROUP UNSATURATED ACID EPISULFIDE P-QUINONE UNSATURATED ALDEHYDE EPOXIDE P-S GROUP UNSATURATED AMIDE ETHER PENAM UNSATURATED ESTER GEM-DIHALIDE PEROXIDE UNSATURATED KETONE GLYCOL PEROXY ACID UNSATURATED NITRILE GUANIDINE PEROXY UREA HALIDES PHENOL VIC-DIHALIDE HALOFORMATE PHOSPHATE VINYL HALIDE

Functional Groups

126

Search Question:

Locate methods for converting a nitroso group to a primary amine.

Functional Groups

127

3. Upload the reaction query.

2. Logon to STN and enter CASREACT.

1. Build and save the functional group reaction

query.

Functional Groups

128

5. Display the results.

4. Run the reaction search.

Functional Groups

129

• Functional group queries are created in the structure drawing window of STN Express.

• Building a functional group query is accomplished in four steps:

a) Select the functional groups for the query

b) Assign reaction roles to functional groups

c) Do mapping

d) Save the query

Functional Groups

130

Click on the Functional Group button .

In "functional group mode" the current atom box changes to functional group terms, and all structure drawing tools are inactive.

Functional Groups

131

Click on the current atom box. An alphabetical listing of all functional group terms and their definitions appears:

RC = the atom can be in a ring or chainCON E2 = only 2 connections on the atomCSE = Chain Single Exact bondCDE = Chain Double Exact bond

Functional Groups

132

Click on the name of the desired functional group and select Single Use or Multiple Use. Click at the position on the structure drawing screen where you want to position the functional group.

Functional Groups

133

Repeat Step 3 for each functional group in the query.

Functional Groups

134

1. Click on the Reaction role tool .

2. Click on the functional group to which you want to assign a role. A box with all of the functional group roles appears.

Functional Groups

135

Select the role that applies to the functional group. Click OK.

3. Click on the next functional group and repeat Step 2 for it.

Functional Groups

136

Functional Groups

137

Use the Atom MappingAtom Mapping Tool to guarantee that at least one atom from the reacting group appears in the formed group. Atom map numbers appear on the screen

1 1

Functional Groups

138

Save the functional group query using the same procedure used to save a structure query.

Functional Groups

139

Functional Groups

140

• Proximity can be changed depending on the desired precision:– (L) proximity does not require mapping between

reacting functional groups and forming functional groups

– (S) proximity requires that at least one atom in the reacting functional group also be in the forming functional group

141

Upload the query

=> FILE CASREACT

=> QUE (NITROSO/FG.RXN (S) PRIMARY AMINE/FG.FORM)

L1 QUE (NITROSO/FG.RXN (S) PRIMARY AMINE/FG.FORM) The functional group query is converted to a 'text'

query when you save it.

The 'text' query includes search fields:

Reacting functional groups (/FG.RXN) Formed functional groups (/FG.FORM) The (S) operator which maps one atom from the

reacting group to an atom in the product group

The uploaded "text" query is assigned an L-number.

Functional Groups

142

For a functional group query, as with any other text

query, you cannot specify a search type (SSS/CSS)

or a search scope (SAM/FULL).

Run the search

=> S L1

562 NITROSO/FG.RXN

13296 PRIMARY AMINE/FG.FORM

L2 78 (NITROSO/FG.RXN (S) PRIMARY AMINE/FG.FORM) Each answer to a functional group

search is a document record containing one or more reactions that match the specified transformation.

Functional Groups

143

Display the results

=> D SCAN


TI Reactions of trimethyl- and triethylaluminum with 2,4,6-tri-tert-butylnitrosobenzene


RX(1) OF 2

Bu-t

t-Bu

t-Bu

NO

(step 1)

Bu-t

t-Bu

t-Bu

NH2+

20%

Bu-t

t-Bu

t-Bu

N

CH2O

+

25%

Bu-t

t-Bu

t-Bu Me

N OH+

28%

Bu-t

t-Bu

t-Bu Me

NHO

18%

1. AlMe3, THF2. Water

Functional Groups

144


TI [7-15N]guanosine-labeled oligonucleotides as a nuclear magnetic resonance probe for protein- nucleic acid interaction in the major groove


TI Process for the reductive halogenation of aromatic nitro or nitroso compounds to haloaromatic amines


RX(2) OF 15

15N ONH2

NH

ONH2N

15NH2NH2

NH

ONH2N

Na2(S2O4), Water

RX(1) OF 4N O

F

NH234%

NH2+

34%

Pb, HF

Functional Groups

145

Search Question:

Find out more about this D SCAN hit:

TI A new and efficient method for the selective reduction of nitroarenes: use of ammonium sulfate- sodium borohydride

RX(11) OF 13N O NH2

90%

1. NaBH4, (NH4)2SO4, EtOH2. Water, Et2O

Functional Groups

146

3. Display the resulting answer in more detail.

2. Search the answer L-number AND word/TI.

1. Select a unique word from the title.

To display a D SCAN answer in more detail

Functional Groups

147

=> S L1 AND NITROARENES/TI 562 NITROSO/FG.RXN 13296 PRIMARY AMINE/FG.FORM 78 (NITROSO/FG.RXN (S) PRIMARY AMINE/FG.FORM) 69 NITROARENES/TIL3 1 L1 AND NITROARENES/TI

=> D L3 1 BIB ABSL3 ANSWER 1 OF 1 CASREACT COPYRIGHT 2000 ACSAN 123:338641 CASREACTTI A new and efficient method for the selective reduction of nitroarenes: use of ammonium sulfate- sodium borohydrideAU Gohain, Sujata; Prajapati, Dipak; Sandhu, Jagir S.CS Reg. Res. Lab., Assam, 785 006, IndiaSO Chem. Lett. (1995), (8), 725-6

o o o

Functional Groups

148

o o oCODEN: CMLTAG; ISSN: 0366-7022DT JournalLA EnglishGI

AB Nitroarenes I (R = NO2; R1 = e.g., 4-Cl, 2-, 4- CO2H, 4-Ac, 4-cyano, 3-vinyl) were selectively and rapidly reduced to 75-90% corresponding amino compds. I (R = NH2) using (NH4)2SO4-NaBH4. This method is typically complete in 30 min and shows no byproducts usually seen using other methods.

R

R1

I

Functional Groups

149

Search Question:

Locate methods for converting a primary alcohol to an aldehyde in the presence of a non-reacting secondary alcohol.

Functional Groups

150

The secondary alcohol is assigned a non-reacting role.

1 1

Only the reacting group is mapped to the product.

Functional Groups

151

Functional GroupsSave it then click on:

152

=> FILE CASREACT

=> QUE SECONDARY ALCOHOL/FG.NON (L) (PRIMARY ALCOHOL/FG.RXN (S) ALDEHYDE/FG.FORM)

L1 QUE SECONDARY ALCOHOL/FG.NON (L) (PRIMARY ALCOHOL/FG.RXN (S) ALDEHYDE/FG.FORM)

=> S L1 19805 SECONDARY ALCOHOL/FG.NON 35627 PRIMARY ALCOHOL/FG.RXN 14977 ALDEHYDE/FG.FORML2 217 SECONDARY ALCOHOL/FG.NON (L) (PRIMARY ALCOHOL/FG.RXN (S) ALDEHYDE/FG.FORM)

Functional Groups

153

=> D SCANL2 217 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Selective oxidation of primary hydroxy groups in primary-secondary diols


RX(1) OF 1

(CH2)5 MeMe

OH

HO

(CH2)5 MeMe

CHO

OH

82%

Bu4NCl, NaOCl, Me4-piperidoxyl, NaHCO3, KBr, CH2Cl2, Water

Functional Groups

154

L2 217 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Total synthesis of (+)-compactin by a double Michael protocol


RX(78) OF 409 - 3 STEPS

Me

HOOH

H

H

Si(Pr-i)3

Me

OHC OH

H86%

1. Pivaloyl chloride, Pyridine2.1. (i-Pr)3Si O3SCF3, Et3N, CH2Cl22.2. LiAlH4, Et2O3.1. (COCl)2, DMSO, CH2Cl23.2. Et3N

NOTE: 2) (99%/99%)

Functional Groups

155

L2 217 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Prostanoid and related compounds. Part II. Synthesis of biologically active 6-azaprostacyclin derivatives


RX(6) OF 69

OMeHO

HON

O O

H

H

OMe

OHC

HON

O O

H

H

NOTE: Pfitzner-Moffatt reagent

Functional Groups

156

When a reaction is entered into the CASREACT database, the most precise functional group term that applies to a structure group is assigned. Broader functional group terms are not also assigned.

Example: For this structure:

The functional group term ENOL is assigned, but the terms SECONDARY ALCOHOL and ACYCLIC ALKENE are not.

Functional Group Classes

H

Functional Groups

157

Use class terms, which encompass specific functional group terms for that class, to search for all specific functionalities in a broader functional group.

Class Terms

Alcohols Carboxy derivatives

Alkenes Halides

Alkynes Heterocycles

Amines Ketones

Carbonate derivatives Organometallics

Functional Groups


158

ALCOHOLS ALLYL ALCOHOLCYANOHYDRIN CYCLIC ALCOHOLENOL GLYCOL HALOHYDRIN

HEMIACETAL HYDROXYLAMINEPHENOL PRIMARY ALCOHOLSECONDARY ALCOHOL TERTIARY ALCOHOL

ALKENES ACYCLIC ALKENECYCLIC ALKENE

ALKYNES ALKYNE ENYNE PI-ALKYNE

AMINES AMINE OXIDE AZIRIDINE CHLORAMINE CYANAMIDE ENAMINE

HYDROXYLAMINEIMINE PRIMARY AMINE SECONDARY AMINETERTIARY AMINE


Functional Groups

159

CARBONATEDERIVATIVES

CARBAMATE CARBONATE GUANIDINE

HALOFORMATE THIOUREA UREA

CARBOXYDERIVATIVES

ACID HALIDE AMIDE AMIDINE ANHYDRIDECARBOXYLATE CARBOXYLIC HALOFORMATE

IMIDE LACTAM LACTONE PEROXY ACIDPEROXY ESTER THIOAMIDE THIOCARBOXY

HALIDES ACID HALIDE ALKYL HALIDE ALLYL HALIDEARYL HALIDE CHLORAMINE GEM-DIHALIDE HALOFORMATE

METAL HALIDE SULFENYL HALIDE SULFINYL HALIDE SULFONYL HALIDE TRIHALIDEVIC-DIHALIDE VINYL HALIDE

Functional Groups


160

HETEROCYCLES 1,2-C3N2 1,2-C3NO 1,2-C3NS 1,2-C3O21,2-C3OS 1,2-C3S2 1,2-C4N2 1,2-C4NO 1,2-C4NS 1,2-C4O2 1,2-C4OS1,2-C4S2 1,3-C3N2 1,3-C3NO 1,3-C3NS 1,3-C3O2 1,3-C3OS 1,3-C3S21,3-C4N2 1,3-C4NO 1,3-C4NS 1,3-C4O2 1,3-C4OS 1,3-C4S2 1,4-C4N2

1,4-C4NO 1,4-C4NS 1,4-C4O2 1,4-C4OS 1,4-C4S2 1,4-C5N2 C2S C3N C3O C3S C4N C4O C4S C5N C5O C5S C6N C6O C6SAZIRIDINE CEPHEM EPISULFIDE EPOXIDE PENAM PURINE

Functional Groups


161

KETONES ACYCLIC KETONE CYCLIC KETONE O-QUINONEP-QUINONE

ORGANOMETALLICSACYLMETAL METAL ARENE METAL CARBENE METAL CARBONYLMETALCYCLOPENTADIENYLMETAL HALIDE METAL HYDRIDE METAL METAL BOND METAL NITROGEN

METAL NITROSYL METAL PHOSPHINE METAL SULFUR METALLOCARBOCYCLEMU-CARBONYLORGANOMETAL PI-ALKENE PI-ALKYNE PI-ALLYL

Functional Groups


162

Search Question:

Locate methods for converting secondary alcohols or cyclic alcohols to ketones.

Functional Groups

163

To search all relevant functional group terms in one step, combine the terms using the OR feature.

After

Selecting the functional groups Assigning the roles Mapping reactants to the product

Functional Groups

164

Click on the OR operator button and draw a box around the terms to be ORed.

1

1

1

Functional Groups

Cyclic alchools

Secondary alchools

1

Ketones1

1

165

=> FILE CASREACT=> QUE KETONES/FG.FORM (S) (SECONDARY ALCOHOL/FG.RXN OR CYCLIC ALCOHOL/FG.RXN)L1 QUE KETONES/FG.PRO (S) (SECONDARY ALCOHOL/FG.RXN OR CYCLIC ALCOHOL/FG.RXN)

=> S L1 52307 KETONES/FG.PRO 30715 SECONDARY ALCOHOL/FG.RXN 2207 CYCLIC ALCOHOL/FG.RXNL2 6586 KETONES/FG.PRO (S) (SECONDARY ALCOHOL/FG.RXN OR CYCLIC ALCOHOL/FG.RXN)=> D SCANL2 6586 ANSWERS CASREACT COPYRIGHT 2000 ACSTI Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide

Functional Groups

166

RX(4) OF 57

(CH2)7 (CH2)7Me

OH

N

O

(CH2)7 (CH2)7Me

O

N

O

67%

Martin's reagent, CH2Cl2

NOTE: STEREOSELECTIVE

Functional Groups

167

HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1L2 6586 ANSWERS CASREACT COPYRIGHT 2000 ACSTI An enantiodivergent route to .alpha.-cuparenone utilizing chiral cyclopentenol having a latent meso structure


RX(5) OF 113

Me

Me Me

Me

Ph

OO

O

OH

H

H

Me

Me Me

Me

Ph

OO

O

O

H

H

96%

Martin's reagent

Functional Groups

168

Summary Functional group terms can be used to search for broadly defined transformations

Functional groups terms are available for

Reactants

Reagents Products

Functional groups are identified as Reacting functionalities

Formed functionalities Non-reacting functionalities

Functional Groups

169

Functional group queries are easily created in the structure drawing window of STN Express

"Class terms" can be used to search for broad classes of functional groups

Search relevant functional group terms in one step by combining them with the OR operator

Functional Groups

Summary

170

1. Locate reactions in which sulfides are converted to sulfones.

2. Locate reactions in which acyl halides are converted to alcohols in the presence of non-reacting primary amines.

3. Locate reactions in which hydrazines are used to prepare the following type of diazoles:

Skills Practice

171

=> fil casreact => que SULFIDE/fg.rxn (L) SULFONE/fg.form L1 QUE SULFIDE/FG.RXN (L) SULFONE/FG.FORM => l1 26225 SULFIDE/FG.RXN 6113 SULFONE/FG.FORML2 3557 SULFIDE/FG.RXN (L) SULFONE/FG.FORM

1

172

=> d fhit L2 ANSWER 1 OF 3557 CASREACT COPYRIGHT 2004 ACS on STN RX(7) OF 692 ...AC ===> AF...

RX(7) RCT AC 5651-88-7 RGT AG 37222-66-5 Oxone PRO AF 2525-40-8 SOL 67-56-1 MeOH, 7732-18-5 Water

PhS CH2 C CH

AC(7)

PhSOO

C CH

**

YIELD 93%AF

1

173

=> d fcrdref L2 ANSWER 1 OF 3557 CASREACT COPYRIGHT 2004 ACS on STN

RX(7) OF 692

PhS CH2 C CH Ph S CH2

O

OC CH

93%

Oxone, MeOH, Water

REF: Heterocycles, 62,, 583-618; 2004

1

174

=> fil casreact => que PRIMARY AMINE/fg.non(L)(ACID HALIDE/fg.rxn(S)ALCOHOLS/fg.form) L1 QUE PRIMARY AMINE/FG.NON(L)(ACID HALIDE/FG.RXN(S)ALCOHOLS/FG.FORM) => l1 14761 PRIMARY AMINE/FG.NON 36978 ACID HALIDE/FG.RXN 123464 ALCOHOLS/FG.FORML2 3 PRIMARY AMINE/FG.NON(L)(ACID HALIDE/FG.RXN(S)ALCOHOLS/FG.FORM)

2

175

=> d fhit 2 L2 ANSWER 2 OF 3 CASREACT COPYRIGHT 2004 ACS on STN RX(1) OF 1 A ===> B RX(1) RCT A 39878-87-0 RGT C 16940-66-2 NaBH4 PRO B 56613-80-0 SOL 110-71-4 (CH2OMe)2

Ph

ClNH2

O

**

HCl

A(1)

Ph

NH2O

H

H **

*

YIELD 87%B

2

176

3

=> fil casreact => que 1,2-C3N2/fg.form L1 QUE 1,2-C3N2/FG.FORM => l1L2 6679 1,2-C3N2/FG.FORM

177

3

=> Uploading C:\Program Files\stnexp\Queries\fg6.str

chain nodes :1 2 chain bonds :1-2 exact/norm bonds :1-2 Match level :1:CLASS 2:CLASS fragments assigned reactant/reagent role:fragments assigned reactant/reagent role:containing 1containing 1L3 STRUCTURE UPLOADED

178

3

=> l3 full subset=l2FULL SUBSET SEARCH INITIATED 11:06:28SCREENING COMPLETE -55237 REACTIONS TO VERIFY FROM 5883 DOCUMENTS 100.0% DONE 55237 VERIFIED 47288 HIT RXNS 4821 DOCSSEARCH TIME: 00.00.01 L4 4821 SEA SUB=L2 SSS FUL L3 ( 47288 REACTIONS)

179

3

=> d fhit L4 ANSWER 1 OF 4821 CASREACT COPYRIGHT 2004 ACS on STN RX(12) OF 23 Y + Z ===> A...

MeMe

OO

H

**

**

Y

NNH

N

H

H

* *

*

Z(12)

Me

Me NN

N

****

A

180

3

=> d fhit 2 L4 ANSWER 2 OF 4821 CASREACT COPYRIGHT 2004 ACS on STN RX(4) OF 8 O + P ===> Q

EtO

OEt

Ph

P NO

NH

H

H*

*

O

Ph

Ph

NC

S

SCN * ***

P(4)

EtO OEt

PhPh

NC

P

N

O

N

NH

S

H**

**

**

YIELD 50%Q

181

Refining Results

In this section, you will learn to:

• Restrict results to reactions with yields above a given value• Restrict results to single-step reactions • Specify that a specific catalyst, reagent, or solvent is present or not

in the reaction• Include reaction note information in the refinement

182

Several reaction search fields are available for refining reaction search results.

When you want to Use this search field

Restrict results by yield /YD

Restrict results by number of steps /NS

Require/eliminate a specific reactionparticipant using its

CAS RN and

Reaction role

Solvent

Catalyst

Reagent

Reactant

Reagent or Reactant

Product

Not a product

/SOL

/CAT

/RGT

/RCT

/RRT

/PRO

/NPRO

Specify terms from the reaction NOTE Basic Index

Refining Results

183

Use these fields to refine the reactions in answer sets from:

Structure searches Functional group searches

Since each answer in CASREACT may contain more than one reaction, you must use the (L) operator to apply the refinement to the "hit" reactions in the answer set.

Refining Results

184

Yields are reported for many, but not all, reactions in CASREACT. Yields are whole number percent values, e.g., 75%. They may be searched as numeric ranges, e.g., YD>80 for yield greater than 80%. To isolate reactions without yields, use the term NON/YDT.

Refining Results

185

Helpful Hint

Use (L) to require that one of the products in the hit reaction have the specified yield. In reactions with more than one product, the specified yield may apply to a product other than the "hit" product.

If you retrieved the reactions using a Structure search query CAS RN for the product

Then use the (A) operator to specify that the yield applies to the hit product.

Refining Results

186

The number of steps in a reaction is searched as a numeric range, e.g., 1/NS for single-step reactions.

Helpful Hint

'Pot' reactions are considered to be single-step reactions.

Refining Results

187

Reaction participants can be specified by a:

CAS RN (Solvents and catalysts can only be specified with CAS RNs) Registry L-number

Refining Results

188

To specify the role the CAS RN plays in the reaction, use one of these fields:

Use this field To specify this role

/SOL Solvent

/CAT Catalyst

/RGT Reagent

/RCT Reactant

/RRT Reagent or Reactant

/NPRO Not a Product

/PRO Product

189

Examples

Use this strategy If you want to

=> S L1 (L) 7440-05-3/CAT Limit the hit reactions in L1 to thosecatalyzed by palladium (7440-05-3)

=> S L1 (L) ANY/CAT Limit the hit reactions in L1 tocatalytic reactions

=> S L1 (L) 64-19-7/NPRO Limit the hit reactions in L1 to those inwhich acetic acid (64-19-7) is sometype of starting material

=> S L1 (NOTL) 108-24-7/RRT Eliminate the hit reactions from L1where acetic anhydride (108-24-7) isused as a reactant or reagent

Refining Results

190

The NOTE field contains additional information about the reaction that cannot be specified in the reaction diagram via a structure or CAS RN, e.g.,

Safety information

RX(17) OF 46 - 2 STEPS

OMeNO2

NO2O2N

ClNH2

NH2

NH2

H2N

H2N

1. NH3, MeOH2. Pd, H2, MeOH

NOTE: 1) explosive compd.

Refining Results

191

Reaction conditions

RX(6) OF 12

Pr-nPh

PhCH2 O CO

O

OPh

PhOH

O

O80%

Lipase

NOTE: enzymic

RX(17) OF 19 - 2 STEPS

AcO

AcO

OAc

OMe

O

O

AcOOAc

AcOOMe

BrO

C

O

47%

1. Pd, H2, MeOH2. Bromosuccinimide, Perbenzoic acid, CCl4

NOTE: 2) photochem.

Refining Results

192

Failed reactions

Participants not indexed via CAS RNs

RX(3) OF 5

Br BrCH2 CH2SiH2 SiH2

OMe

NSiH2SiH2

MeONH2, Et3N

NOTE: Failed reaction

RX(3) OF 47

(CF2)3 CF3S

O

HO(CF2)3 CMe2F3C S CH2

O

O

CH

60%

Isopentadiene

NOTE: Petroleum ether

Refining Results

193

Helpful HINT

Individual words from the NOTE are in the Basic

Index and may be searched. Use truncation and synonyms for best results when

searching NOTE words.

Example:

=> S L1 (L) PHOTOCHEM?

Refining Results

194

Refining Results

NS N

OO

Find reactions: With yield > 50% Using solvent CHCl3

Catalyzed

195

Refining Results=> fil casreactL1 STRUCTURE UPLOADED => dL1 HAS NO ANSWERSL1 STR

NS N

OO

196

Refining Results


197

Refining Results

=> l2(a)yd>50 272798 YD>50L3 3 L2(A)YD>50 => d fhit L3 ANSWER 1 OF 3 CASREACT COPYRIGHT 2003 ACS RX(4) OF 9 J ===> K

MeO

NH

S

H**

*

J(4)

MeO

C N*

YIELD 96%K

198

Refining Results=> l2(l)yd>50 272798 YD>50L4 3 L2(L)YD>50 => l2(l)67-66-3/sol 17914 67-66-3/SOLL5 1 L2(L)67-66-3/SOL

RX(4) RCT J 2362-64-3 RGT C 10026-07-0 TeCl4, D 121-44-8 Et3N PRO K 874-90-8 SOL 67-66-3 CHCl3

199

Refining Results=> l2(l)any/cat 123302 ANY/CATL6 2 L2(L)ANY/CAT => d fhit

RX(1) RCT A 2362-64-3 RGT C 7664-41-7 NH3 PRO B 874-90-8 CAT 7632-00-0 NaNO2

200

Me

CH2

CH

N

OH Me

CH2 N0-9 0-9

Locate syntetic methods for converting the following aliphatic aldoximes to nitriles

Skills Practice

201

=> fil casreact => que OXIME/fg.rxn (S) NITRILE/fg.form L1 QUE OXIME/FG.RXN (S) NITRILE/FG.FORM => Uploading C:\Program Files\stnexp\Queries\react.str. . . . . . . . . . . . . . fragments assigned product role:containing 6fragments assigned reactant/reagent role:containing 1reaction site bonds:4-5:CC node mappings:4:9


202

=> l1 8112 OXIME/FG.RXN 11370 NITRILE/FG.FORML3 855 OXIME/FG.RXN (S) NITRILE/FG.FORM => l2 full subset=l3FULL SUBSET SEARCH INITIATED 03:24:57SCREENING COMPLETE - 2142 REACTIONS TO VERIFY FROM 668 DOCUMENTS 100.0% DONE 2142 VERIFIED 83 HIT RXNS 49 DOCSSEARCH TIME: 00.00.01 L4 49 SEA SUB=L3 SSS FUL L2 ( 83 REACTIONS)

203

=> d fhit L4 ANSWER 1 OF 49 CASREACT COPYRIGHT 2004 ACS on STN RX(39) OF 50 BM ===> B

RX(39) RCT BM 110-69-0 RGT C 5470-11-1 H2NOH-HCl, D 124-63-0 MeSO2Cl PRO B 109-74-0 CAT 1344-28-1 Al2O3 NTE green chem.-no solvent

Pr-nNHO

H

**

*

BM(39)

CH3C N*

YIELD 95%B

204

Find reactions concerning carbonilations of aromatic systems

Skills Practice

205

=> fil reg => carbon monoxide/cnL3 1 CARBON MONOXIDE/CN => fil casreact=> l3/nproL10 6536 L3/NPRO

206

=> Uploading C:\Program Files\stnexp\Queries\saguatti2.str chain nodes :4 5 6 ring nodes :1 2 3 . . . . . .normalized bonds :1-2 2-3 fragments assigned product role:containing 1reaction site bonds:2-4:CCL13 STRUCTURE UPLOADED

207

=> l13 full subset=l10FULL SUBSET SEARCH INITIATED 03:56:36SCREENING COMPLETE - 48032 REACTIONS TO VERIFY FROM 5937 DOCUMENTS 100.0% DONE 48032 VERIFIED 303 HIT RXNS 74 DOCSSEARCH TIME: 00.00.01 L15 74 SEA SUB=L10 SSS FUL L13 ( 303 REACTIONS)

208

=> d scan L15 74 ANSWERS CASREACT COPYRIGHT 2004 ACS on STN TI Manufacture of aromatic aldehydes

RX(1) OF 1

C O- +CH O

Benzene, C:129648-41-5

NOTE: photochem.

209

N N

O O

S

This reagent has been cited? Who sells it in Italy?

Skills Practice

210

=> fil reg=> c11h8n2o2s/mf and nc=1 and nrs=2 and 2 c5n/ea L1 3 C11H8N2O2S/MF AND NC=1 AND NRS=2 AND 2 C5N/EA => l1 and casreact/lc and chemcats/lc L2 2 L1 AND CASREACT/LC AND CHEMCATS/LC => d scan

211

L2 2 ANSWERS REGISTRY COPYRIGHT 2003 ACSIN Carbonothioic acid, O,O-di-2-pyridinyl ester (9CI)MF C11 H8 N2 O2 S

OCO

SNN

L2 2 ANSWERS REGISTRY COPYRIGHT 2003 ACSIN 2(1H)-Pyridinone, 1,1'-carbonothioylbis- (9CI)MF C11 H8 N2 O2 S

C

S

NN

OO

212

=> l2 and pyridinone 18237 PYRIDINONEL3 1 L2 AND PYRIDINONE => fil chemcats => l3 and italyL4 1 L3 AND ITALY => d hitCOMPANY INFORMATION SIGMA-ALDRICH S.r.l.Via Gallarate, 154Numero Verde: 167-827018Milano, 20151 Italy Phone: 39 2 3341 7310Fax: 39 2 3801 0737Email: [email protected] Registry No. (RN): 102368-13-8

1 Reaction Searching in STN. 2 Main Files searchable for reactions in STN: Beilstein CASREACT ...

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