Not just another reaction database

Not just another Reaction Database
Aileen Day1, Valery Tkachenko1, Alexey Pshenichnov1, Leah McEwen2,
Simon Coles3, Richard Whitby3
1Data Science, Royal Society of Chemistry
2Physical Sciences Library, Cornell University
3Department of Chemistry, University of Southampton

RSC Archive – 480,000+ articles

Digitally Enabling RSC Archive

Article X-ray
Compounds
Reaction
Analytical Data
Text and References

The RSC data repository is under development, and
is intended to contain chemical data which supports
its publications.
A first version has been written which captures
compounds, data sources and properties domains.
Reactions are next…
RSC data repository
Compounds PropertiesData sources Reactions

• There are a lot of reactions databases already – many established with
many reactions
• This reactions database aims to capture reactions:
• in sufficient detail for someone else to reproduce
• in analogous ways to those captured in Electronic Lab Notebook
• with fully recorded processes, parameters and equipment in S88
process recipe [1] style
• raw characterization data linked to products
• which gave low yields or unintended products
• multistep reactions
• to fully record all reaction products (not just the target product)
• Guided by the aims of Dial-a-Molecule
RSC data repository - reactions
DetailScope

Dial-a-Molecule Roadmap
• To provide this
• In such a way
that others can
do this kind of
analysis
• For these to be a
potential source

RSC data repository – reactions domain
Reactions Substances Procedures Equipment
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
Parameters

• Reaction 1: Example of reaction text-mined
from RSC archive by NextMove with S88-
style procedure
• Reaction 2: Example From Will Dichtel’s
research group via Leah McEwen (ELN-style
reaction)
Reaction examples

Reaction 1: NextMove reaction text-mined
from RSC archive – original article

Reaction 1: NextMove reaction text-
mined from RSC archive – cml output
<?xml version="1.0" encoding="UTF-8"?>
<reactionList xmlns="http://www.xml-cml.org/schema" xmlns:cmlDict="http://www.xml-cml.org/dictionary/cml/" xmlns:nameDict="http://www.xml-cml.org/dictionary/cml/name/"
xmlns:unit="http://www.xml-cml.org/unit/" xmlns:cml="http://www.xml-cml.org/schema" xmlns:dl="http://bitbucket.org/dan2097">
<reaction>
<dl:source>
<dl:documentId>c3ra45871g</dl:documentId>
<dl:paragraphText>Diisobutylaluminium hydride (1.1 M in cyclohexane, 2.93 mL, 3.23 mmol) was added dropwise to the solution of 9 (500 mg, 1.29 mmol) and dichloromethane (20 mL) at −78 °C. The
reaction mixture was stirred at −78 °C for another 2 h, warmed up to rt, quenched with methanol (3 mL) and citric acid(aq) (w/w, 10%, 5 mL), concentrated. The residue was added with water (10 mL) and
extracted with dichloromethane (12 mL × 3). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The crude product was further purified by column chromatography (SiO2,
EtOAc–hexanes, 1 : 7; Rf 0.33) to give 10 (308 mg, 1.02 mmol, 79%) as a colourless liquid. [α]D20 −24.2 (c 1.1, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 0.04 (s, 3H), 0.07 (s, 3H), 0.85 (s, 9H), 1.34 (s, 3H), 1.44 (s,
3H), 2.16 (br, 1H), 3.68–3.81 (m, 3H), 4.16 (t, J = 13.8 Hz, J = 13.8 Hz, 1H), 4.59 (t, J = 6.6 Hz, J = 6.6 Hz, 1H), 5.22 (d, J = 10.7 Hz, 1H), 5.34 (d, J = 17.1 Hz, 1H), 5.90 (ddd, J = 7.2 Hz, J = 10.2 Hz, J = 17.2 Hz, 1H);
13C NMR (CDCl3, 75 MHz) δ 134.1, 118.4, 108.5, 79.5, 78.8, 70.8, 65.0, 27.8, 25.9, 25.4, 18.1, −3.7, −4.4. HRMS (ESI) calcd for [M + Na]+ (C15H30O4SiNa) 325.1811, found 325.1807.</dl:paragraphText>
</dl:source>
<dl:reactionSmiles>[H-
].C([Al+]CC(C)C)C(C)C.C([O:17][CH2:18][C@@H:19]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@@H:20]1[C@H:24]([CH:25]=[CH2:26])[O:23][C:22]([CH3:28])([CH3:27])[O:21]1)
(=O)C(C)(C)C>ClCCl>[C:33]([Si:30]([CH3:32])([CH3:31])[O:29][C@@H:19]([C@@H:20]1[C@H:24]([CH:25]=[CH2:26])[O:23][C:22]([CH3:28])([CH3:27])[O:21]1)[CH2:18][OH:17])([CH3:36])([CH3:35])[CH
3:34] |f:0.1|</dl:reactionSmiles>
<productList>
<product role="product">
<molecule id="m0">
<name dictRef="nameDict:unknown">10</name>
<dl:nameResolved>(R)-2-((tert-Butyldimethylsilyl)oxy)-2-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)ethanol</dl:nameResolved>
</molecule>
<amount dl:propertyType="AMOUNT" dl:normalizedValue="0.00102">1.02 mmol</amount>
<amount dl:propertyType="MASS" dl:normalizedValue="0.308">308 mg</amount>
<amount dl:propertyType="PERCENTYIELD" dl:normalizedValue="79">79%</amount>
<amount dl:propertyType="CALCULATEDPERCENTYIELD" dl:normalizedValue="79.1" units="unit:percentYield">79.1</amount>
<identifier dictRef="cml:smiles" value="C(C)(C)(C)[Si](O[C@H](CO)[C@H]1OC(O[C@H]1C=C)(C)C)(C)C"/>
<identifier dictRef="cml:inchi" value="InChI=1S/C15H30O4Si/c1-9-11-13(18-15(5,6)17-11)12(10-16)19-20(7,8)14(2,3)4/h9,11-13,16H,1,10H2,2-8H3/t11-,12+,13-/m0/s1"/>
<dl:entityType>definiteReference</dl:entityType>
<dl:appearance>colourless</dl:appearance>

Reactions properties
[1] https://github.com/rsc-ontologies/rxno
[2] Carey, Laffan, Thomson and Williams hierarchy: DOI: 10.1039/B602413K
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
ParametersReaction is defined by:
• Reaction Smiles from textmining output
• NextMove’s NameRXN program
categorises reaction by:
• Named Reaction ontology ID and
name [1]
• Reaction Class and name [2]

Reaction 1: Reaction
Reactions
• Reaction SMILES: [H-
].C([Al+]CC(C)C)C(C)C.C([O:17][CH2:18][C@@H:19]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH
3:34])([CH3:32])[CH3:31])[C@@H:20]1[C@H:24]([CH:25]=[CH2:26])[O:23][C:22]([CH3:28])([CH
3:27])[O:21]1)(=O)C(C)(C)C>ClCCl>[C:33]([Si:30]([CH3:32])([CH3:31])[O:29][C@@H:19]([C
@@H:20]1[C@H:24]([CH:25]=[CH2:26])[O:23][C:22]([CH3:28])([CH3:27])[O:21]1)[CH2:18][OH:
17])([CH3:36])([CH3:35])[CH3:34] |f:0.1|
• ReactionClass: “9.7 Other functional group interconversion”
• Other Named Reaction: “9.7.61 Ester hydrolysis”
From Nextmove’s namerxn reaction output (software
source should be linked from Properties database)
As well as reaction SMILES we can store Reaction RXN, RD and ChemDraw files.

Reaction 1: Reaction reference
Reference
• URL: http://dx.doi.org/10.1039/c3ra45871g
• Title: "Diastereoselective vinylalumination for the synthesis of pericosine A, B and C"
• Description: Reaction text-mined by NextMove from RSC article with DOI:
10.1039/c3ra45871g
• Authors: Long-Shiang Li; Duen-Ren Hou
• Publication Date: 31/10/2013
• DOI: 10.1039/c3ra45871g
• Journal: RSC Advances
• Publication Type: Journal Article
Reference Details
• External Identifier: c3ra45871g: product 10
• Paragraph Text: Diisobutylaluminium hydride (1.1 M in cyclohexane, 2.93 mL,
3.23 mmol) was added dropwise …

RSC data repository – reaction components
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
Parameters
Reaction components define each reaction
and each component is:
• Defined as a
substance/compound/solution/mixture
• Assigned a reaction role is stored which
can take values Reactant/ Product/
Solvent/ Catalyst/ Intermediate/
ChiralAuxiliary
Text-mining identifies all compounds and solutions (indicated by
molarity) that play a role in each reaction and returns smiles, InChI,
reaction role, and amounts of each.

Reaction 1: compounds and solutions
Diisobutylaluminium hydride (1.1 M in cyclohexane,
2.93 mL, 3.23 mmol) was added dropwise to the
solution of 9 (500 mg, 1.29 mmol) and
dichloromethane (20 mL) at −78 °C. The reaction
mixture was stirred at −78 °C for another 2 h, warmed
up to rt, quenched with methanol (3 mL) and citric
acid (aq) (w/w, 10%, 5 mL), concentrated. The residue
was added with water (10 mL) and extracted with
dichloromethane (12 mL × 3). The organic layers were
combined, dried over Na2SO4, filtered and
concentrated. The crude product was further purified
by column chromatography (SiO2, EtOAc–hexanes,
1 : 7; Rf 0.33) to give 10 (308 mg, 1.02 mmol, 79%) as
a colourless liquid.
Solutions
• Diisobutylaluminium hydride
Compounds
• 9
• dichloromethane
• methanol
• citric acid
• water
• Dichloromethane
• Na2SO4
• 10
Ignored for now (only the name was
extracted in this pass) – in time
“Substances”
• SiO2
• EtOAc–hexanes
Reaction components: reactant , solvent, product
Other compound/substance used in procedure

Reaction 1: Reaction Components
Ordinal ReactionRole Compound Solution
1 Reactant 1.1 M solute:
Solvent:
2 Reactant
3 Solvent
4 Product

Reaction 1: Reaction rendering
Reaction
Solution: Diisobutylaluminium hydride
• Components:
When you click on it
• Solution Role: Solute; Molarity:
1.1M; Compound:
Diisobutylaluminium(1+) hydride:
• Solution Role: Solvent;
Compound: cyclohexane

RSC data repository – reaction runs
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
ParametersWhile the reaction information defines the
overall reaction, the details about each
specific instance of performing the reaction
are stored in reaction runs:
• stoichiometry table of each component
• labels of components
• amounts of components
• links to specific samples and sources
• results and yields of products.

Reaction 1: Reaction Run
Reaction Run
• Label: Preparation of lithium acetylide (phenylethynyl)lithium; Experiment Stage: Executed
• Stoichiometry Table Rows
Label Reaction
Component
Volume
(mL)
Mass
(mg)
Moles
(mMol)
Percentage
Yield (%)
Substance
State
Diisobutylalumini
um hydride
Reactant: 2.93 3.23 Liquid
9 Reactant 500 1.29 Solid
dichloromethane Solvent 20 Liquid
10 Product 308 1.02 79 Solid

RSC data repository – procedure
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
Parameters
For reactions to be fully reproducible and
queryable they are captured in a way
analagous to S88 process recipes [1]:
1. Break process down into a series of steps
(actions)
2. Define parameters at any level (for whole
experiment or for particular action)
3. Define equipment at any level (for whole
experiment or for particular action)
[1] https://en.wikipedia.org/wiki/ISA-88

S88-style procedures
Type of actions which can be assigned to procedure
steps
Action Types
Add Synthesize Wait Degass
Yield Wash Unknown Irradiate
Stir Extract Precipitate Mill
Remove Filter Partition Sample
Heat Concentrate Quench Reflux
Dry Cool Apparatus Action Transfer
Purify Dissolve Recover

S88-style procedures
Parameters that can be assigned to actions or
experiments
rate
speed pH
time
pressure
particle size
volume
weight
quantity
temperaturesample ID
Substance
Parameters Other Parameters
Can be time
dependent

Reaction 1: procedure steps
Diisobutylaluminium hydride (1.1 M in cyclohexane,
2.93 mL, 3.23 mmol) was added dropwise to the
solution of 9 (500 mg, 1.29 mmol) and
dichloromethane (20 mL) at −78 °C. The reaction
mixture was stirred at −78 °C for another 2 h,
warmed up to rt, quenched with methanol (3 mL)
and citric acid (aq) (w/w, 10%, 5 mL), concentrated.
The residue was added with water (10 mL) and
extracted with dichloromethane (12 mL × 3). The
organic layers were combined, dried over Na2SO4,
filtered and concentrated. The crude product was
further purified by column chromatography (SiO2,
EtOAc–hexanes, 1 : 7; Rf 0.33) to give 10 (308 mg,
1.02 mmol, 79%) as a colourless liquid.
Text mining breaks down procedure summary into steps:
<dl:reactionActionList/dl:reactionActions> dl:phraseTexts
• action="Add“: Diisobutylaluminium hydride (1.1 M in
cyclohexane, 2.93 mL, 3.23 mmol) was added dropwise to the
solution of 9 (500 mg, 1.29 mmol) and dichloromethane (20
mL) at −78 °C
• action=" Stir“: The reaction mixture was stirred at −78 °C for
another 2 h
• action="Heat“: warmed up to rt
• action="Quench“: quenched with methanol (3 mL) and citric
acid(aq) (w/w, 10%, 5 mL)
• action="Concentrate“: concentrated
• action="Add“: The residue was added with water (10 mL)
• action="Extract“: extracted with dichloromethane (12 mL × 3)
• action="Dry“: dried over Na2SO4
• action="Filter“: filtered
• action="Concentrate“: concentrated
• action="Purify“: The crude product was further purified by
column chromatography (SiO2, EtOAc–hexanes, 1 : 7; Rf 0.33)
• action="Yield“: to give 10 (308 mg, 1.02 mmol, 79%) as a
colourless liquid

Reaction 1: Example Reaction Step 1
Procedure Step
• Ordinal:1; Title: Add; Experiment Stage: Executed
• Description: Diisobutylaluminium hydride (1.1 M in cyclohexane, 2.93 mL, 3.23 mmol) was
added dropwise to the solution of 9 (500 mg, 1.29 mmol) and dichloromethane (20 mL) at −78
°C
• Type: “Add”
• Parameters:
• Substance: Stoichiometry Table Row for Diisobutylaluminium hydride
• Substance: Stoichiometry Table Row for 9
• Substance: Stoichiometry Table Rowfor dichloromethane
• Temperature:
• Value: -78C
<dl:reactionAction action="Add">
<dl:phraseText>Diisobutylaluminium hydride (1.1 M in cyclohexane, 2.93 mL, 3.23 mmol) was added dropwise to the
solution of 9 (500 mg, 1.29 mmol) and dichloromethane (20 mL) at −78 °C</dl:phraseText>
<dl:chemical ref="m1"/> <dl:chemical ref="m2"/><dl:chemical ref="m3"/>
<dl:parameter propertyType="Temperature" normalizedValue="-78">-78 °C.</dl:parameter>
</dl:reactionAction>
Underlined values are retrieved
from elsewhere in the repository
(so that if e.g. amounts are
updated, changes can be made in
one place and be picked up

Reaction 1: Example Reaction Step 2<dl:reactionAction action="Stir">
<dl:phraseText>The reaction mixture was stirred at −78 °C for another 2 h</dl:phraseText>
<dl:parameter propertyType="Time" normalizedValue="7200">2 h</dl:parameter>
<dl:parameter propertyType="Temperature" normalizedValue="-78">-78 °C</dl:parameter>
Procedure Step
• Ordinal:2; Title: Stir; Experiment Stage: Executed
• Description: The reaction mixture was stirred at −78 °C for another 2 h
• Type: “Stir”
• Parameters:
• Temperature:
• Value: -78C
• Time: 2 hours

Reaction 1: Example Reaction Step 3<dl:reactionAction action="Quench">
<dl:phraseText>quenched with methanol (3 mL) and citric acid(aq) (w/w, 10%, 5 mL)</dl:phraseText>
<chemical><molecule id="m4"> <name dictRef="nameDict:unknown">methanol</name></molecule>
<amount dl:propertyType="VOLUME" dl:normalizedValue="0.003">3 mL</amount>
<identifier dictRef="cml:smiles" value="CO"/> <identifier dictRef="cml:inchi" value="InChI=1S/CH4O/c1-2/h2H,1H3"/>
<dl:entityType>exact</dl:entityType>
</chemical>
<chemical><molecule id="m5"> <name dictRef="nameDict:unknown">citric acid</name></molecule> ….
</chemical>
Procedure Step
• Ordinal:3; Title: Quench; Experiment Stage: Executed
• Description: quenched with methanol (3 mL) and citric acid(aq) (w/w, 10%, 5 mL)
• Type: “Quench”
• Parameters:
• Substance:
• Label: methanol
• Compound:
• Volume: 0.003 L
• Substance:
• Label: citric acid
• Compound:
• Volume: 0.005 L

Reaction 2: ELN-style reaction
Example reaction from Cornell (Will Dichtel’s research group, via Leah
McEwen):
• Multiple “runs” of a reaction are performed, with different amounts, and
under different conditions
• Results, observations and product characterisations are stored for each
• This allows the run which gives rise to the best yield to be identified
• Currently the experient files are stored in a number of files (see below), but
this information is suitable to be stored in an Electronic Lab Notebook:
– SJH-01-227_Enotebook.docx (“notebook” which shows the details of a particular run
of a reaction – stoichiometry table (embedded Excel spreadsheet which does
calculations), actual quantities, notes of conditions and results and TLC images
embedded
– WeeklyReport_5_01_2014.docx (logs all runs of all reactions done during a particular
week – grouped by reaction, with reaction schema and observations noted)
– spectra files

SJH-01-227_Enotebook.docx
SJH-01-227_Enotebook.docx
Actual quantities
SJH-01-223 0.1009 g
Benzaldehyde 0.0554 g
Cu(OTf)2 0.0055 g
TFA 0.030 mL
EQ FW MMOL g d mL Reagent
1 756.95 0.132 0.100 SJH-01-223
6 206.24 0.793 0.163 Benzaldehyde
0.1 361.67 0.013 0.005 Cu(Otf)2
3 114.02 0.396 0.045 1.49 0.030 TFA
Conc in line 1 (M): 0.100 1.321 DCE
1 1063.36 0.132 0.140 Theoretical Yield
SJH-01-227 11/4/2014
SJH-01-223 and Cu(OTf)2 was transferred to a 5mL RBF with
a reflux condenser with a schlenk adaptor and put under a N2
environment. The benzaldehyde was dissolved in
dichloroethane and this solution was added via syringe to the
RBF reaction flask. The flask was then placed in a 100°C oil
bath and TFA was added via Hamilton microsyringe. The
reaction stirred or 30 min.
When complete, the reaction was washed with sat.
NaHCO3(aq) and extracted three times with DCM. The
organic fractions were collected and dried with MgSO4,
filtered and solvent was removed under vacuum. The
product was purified on SiO2 column chromatography (3:7
DCM:Hexanes).
The product was isolated as a light yellow solid
0.0963 g (68% Yield).
Reaction run -
stoichiometry
table
Procedure, parameters,
substance parameters,
equipment
Procedure-
results
Reaction database
Procedure - results

WeeklyReport_5_01_2014.docx
Date NB Page Type Comments
12/7/2013 SJH-01-211 0.015g Did a prep plate purification an isolated ~0.002g from my top band.
HNMR is tricky, not sure if I made it. Did not see anything on MALDI
(graphite, no matrix, or 2,5 dihydroxy benzoic acid). GCMS shows a
peak, retention time 13.01 min with m/z = 202. I don’t know what this
mass equates to.
1/11/2014 SJH-01-227 0.100 Isolated 0.0963g. ASAP does not show significant surface area (20ish)
Flourescence does not change much but UV absorption does blue shift
after benzannulation.
2/12/2014 SJH-01-227 2D high temp NMR is much more simplified than previous 2D NMRs. I
haven’t yet gotten a chance to look through them and process the
spectra. The 13C looks significantly simplified as well with 24 signals.
Ivan has a partial assignment finished and we think we’ve figured out
where the proton on the central benzene ring is. For a more complete
assignment he said he or Tony would help me set up a band specific
HMBC and HSQC to help solve some of the ambiguities in the NMR. He
was using the low temp NMR to solve.
2/26/2014 Set up a band specific HMBC and HSQC for this with the help of Tony
last night. The HMBC does not have good sensitivity for some reason.
Tony is going to talk to Ivan about this and we should be able to get it
next week.
3/26/2014 SJH-01-298 0.150 Was going to run this reaction last night but I opened the flask under
vacuum instead of nitrogen and SM got sucked up into the hose. I
extracted out the compound best I could. I’ll need to repurify but I
should be able to do this reaction today.
3/26/2014 SJH-01-298 0.1417g Isolated 0.1235g of final product. 62%Y. Confirmed by MALDI and NMR
Working on Structural assignments with Ivan.
Experiment observations mostly – stored
in Procedure results

• Files that would probably go into spectra bucket of data repository:
– SJH-01-227.jdx or SJH-01-227_jcamp.jdx (IR spectrum files - same content)
– SJH-01-227_22-145C.jdx (1H NMR spectrum)
– SJH-01-227-RT-2D.jdx (2D 1H NMR spectrum)
• Other files which might be processed (to extract e.g. store peak assignment values into the data repository so that they can be exported):
– SJH-01-227_DCM_rsw.rsw or SJH-01-227_DCM_rtf.rtf (UV-VIS-NIR peaks in text file – nearly the same as each other)
• Other files (we think duplicates of the above):
– SJH-01-227.spa (binary file)
– SJH-01-227_csv.csv (text, but with no headers)
– SJH-01-227_grams.spc (binary file)
– SJH-01-227_mattson.ras (binary file)
– SJH-01-227_nicolet.nic (binary file)
– SJH-01-227_pcir.ird (binary file)
– SJH-01-227_spa.spa (binary file)
– SJH-01-227_spectacle.irs (binary file)
– SJH-01-227_tiff.tiff and SJH-01-227_wmf.wmf (image files of the same spectrum)
– SJH-01-227_DCM_baseline.csw (UV-VIS-NIR, binary file)
– SJH-01-227_DCM_bsw.bsw (UV-VIS-NIR spectrum, binary file)
– SJH-01-227_DCM_csv.csv (might be able to do something with this – UV?)
– SJH-01-227_DCM_dsw.dsw (UV-VIS-NIR spectrum, binary file)
– SJH-01-227_DCM_grams.spc (UV-VIS-NIR spectrum, binary file)
– SJH-01-227_DCM_gsw.gsw (UV-VIS-NIR spectrum, binary file)
– SJH-01-227_DCM_msw.msw (UV-VIS-NIR spectrum, binary file)
Other spectra files Spectra database ultimately
(but Procedure Results Files
for now)
Procedure
Results files
Use this as an interim example

ESI docx example – synthetic procedure
Synthesis of 17: 16 (0.101 g, 0.132 mmol) and Cu(OTf)2 (0.006 g, 0.01 mmol) were added to a round-bottom
flask under a N2 atmosphere. In a separate vial, 2 (0.155 g, 0.753 mmol) was dissolved in C2H4Cl2 (1.3 mL) and
transferred to the reaction flask. CF3CO2H (0.030 mL, 3 equiv) was added to the reaction mixture, which was
refluxed at 100 °C for 1 h. The reaction mixture was washed with saturated NaHCO3 (15 mL) and extracted with
C2H4Cl2 (3 x 5 mL). The organic fractions were collected, dried (MgSO4), and filtered to give a dark red solution.
The solvent was removed, and the product was purified by column chromatography (SiO2, 30:70 CH2Cl2 :
hexane) to yield 17 as a pale yellow powder (0.096 g, 68% yield). 17: 1H NMR (500 MHz, CDCl3): δ 8.15 (d, 2H),
8.13 (s, 1H,), 7.98 (s, 1H), 7.95 (s, 2H), 7.92 (d,2H), 7.88 (d, 1H), 7.87 (d, 1H), 7.84 (d, 1H), 7.80 (s, 1H), 7.69 (t,
2H), 7.64 (d, 2H), 7.57 (t, 2H), 7.56 (s, 2H), 7.54 (s, 2H), 7.54 (d, 2H), 7.45 (t, 1H), 7.44 (t, 2H), 7.40 (t, 2H), 7.39 (t,
1H), 7.38 (t, 1H), 7.34 (t, 1H), 6.88 (t, 4H), 6.88 (t, 2H), 6.80 (s, 2H), 6.77 (d, 4H), 6.70 (d, 1H), 6.50 (t, 1H), 6.39
(d, 2H), 6.24 (t, 2H), 6.22 (s, 1H), 6.11 (s, 2H), 6.04 (s, 1H). 13C NMR (125 MHz, CDCl3) δ 141.47, 141.10, 140.85,
140.42, 140.32, 140.20, 140.10, 139.60, 139.45, 139.37, 139.16, 139.03, 138.72, 138.28, 138.07, 133.28, 133.04,
132.96, 132.90, 132.64, 132.37, 131.60, 131.41, 131.19, 131.17, 130.72, 130.48, 130.28, 129.87, 129.85, 129.57,
129.30, 129.16, 129.11, 128.35, 128.21, 128.08, 128.04, 127.86, 127.72, 127.47, 126.85, 126.65, 126.50, 126.32,
126.25, 126.17, 126.08, 125.98, 125.84. IR (solid, ATR) 3051, 2925, 2131, 1947, 1590, 1488, 1444, 1415, 1318,
1274, 1180, 1133, 1074, 1018, 950, 882, 870, 809, 771, 743, 720, 697 cm-1. HRMS (DART) calcd for [C84H56
+]
1064.4376, found 1064.4348.
Reaction runs database - stoichiometry table, reaction results and procedure – S88

Reaction 2: Reaction, ReactionFile and Reference
Reaction
• ReactionFile: SJH-01-227.cdx
• FileType: ReactionFileType.CDX
• ReactionSMILES:
C1(C#CC2=C(C3=CC=CC=C3)C=C(C=CC=C4)C4=C2)=CC(C#CC5=C(C6=C
C=CC=C6)C=C(C=CC=C7)C7=C5)=CC(C#CC8=C(C9=CC=CC=C9)C=C(C=C
C=C%10)C%10=C8)=C1.O=CC1=CC=CC=C1C#CC2=CC=CC=C2>[O-
]S(=O)(C(F)(F)F)=O.[O-
]S(=O)(C(F)(F)F)=O.[Cu+2].OC(C(F)(F)F)=O.ClCCCl>C%11(C%12=C(C=C
(C=CC=C%13)C%13=C%12)C%14=C(C%15=CC=CC=C%15)C=C(C=CC=C
%16)C%16=C%14)=CC(C%17=C(C=C(C=CC=C%18)C%18=C%17)C%19
=C(C%20=CC=CC=C%20)C=C(C=CC=C%21)C%21=C%19)=CC(C%22=C(
C=C(C=CC=C%23)C%23=C%22)C%24=C(C%25=CC=CC=C%25)C=C(C=C
C=C%26)C%26=C%24)=C%11|f:3.4.5|
Limiting
Reactant
compound
Reactant compound
Reactant compound
Solvent compound
Solvent compound
Product compound
• Components:

Reaction 2: Reference
• ELN: Reaction SJH-01-227
• Authors: Sam Hein; William R. Dichtel; Leah McEwen
• URL: http://www.eln.com/cornell/dichtel/SJH-01-227
• Publication date: 12th February 2014
• PublicationType: PublicationType.ELN
• Reference Details: Reaction SJH-01-227
Reference

Reaction 2: Planned reaction run
Reaction
• Reaction Run: Reaction SJH-01-227 dated 2/12/2014; FailedReaction: false; Experiment Stage: Planned
• Stoichiometry Table:
Label Reaction Component Substance Amounts Comments
SJH-01-223 Role: Limiting Reactant
Compound
Molecular Mass: 756.95
State: Solid Equivalence: 1
Moles: 0.132 mMol
Mass: 0.1 g
benzaldehyde Role: Reactant
Compound
Moles: 0.293 mMol
Mass: 0.163 g
Cu(OTf)2 Role: Reactant
Compound
State: Liquid
Purity: 98%
Source: 283673-5G, Sigma Aldrich
Equivalence: 0.1
Moles: 0.013 mMoles
Mass: 0.005 g
DCE Role: Solvent
Compound
State: Liquid
Purity: 99-100%
Source: 283673-5G, Sigma Aldrich
Volume: 1.321 mL Concentration in
line 1: 0.1 M
TFA Role: Solvent
Compound
Density: 1.49 g/ml
State: Liquid
Purity: 99%
Source: T6508-500mL, Sigma Aldrich
Equivalence: 3
Moles: 0.396 mMol
Mass: 0.045 g
Volume: 0.030 mL
SJH_01_227 Role: Product
Compound
Moles: 0.132 mMol

S88 process standard approach
Process
Process
Stage
Process
Stage
Process
Stage
Process
Operation
Process
Actions
Experiment Synthesis stage Preparation / Reaction
/ Work up / Isolation
Heat / Cool /
Dose / Stir etc.
S88 allows procedure steps (process actions) to be grouped
into “process operations”:
We allow “Procedure Steps” to be nested and have seeded the following
procedure step types to assign to procedure steps for these parent operations:
S88 process operation/Procedure. StepTypes.Title
Preparation
Reaction
S88 process operation/Procedure. StepTypes.Title
Work up
Isolation

Reaction 2: Planned procedure
Procedure
• Title: Reaction SJH-01-227 dated 2/12/2014; Failed Reaction: false; Experiment Stage: Planned; Link to ReactionRun
• Procedure Steps:
Ordinal Parent Title Description ParameterSubstances Parameter Equipment
1 Reaction
2 Reaction Add Add SJH-01-223 (0.1 g, 0.132 mmol)
to a 5 mL round bottom flask with a
reflux condenser with a schlenk
adaptor
• SJH-01-223
stoichiometry table row
• round bottom
flask
• Volume=5mL
• Type=Apparatus
• reflux condenser
• schlenk adaptor
3 Reaction Add Add Cu(OTf)2 (0.005 g, 0.013 mmol)
and put under a N2 environment
• Cu(OTf)2 stoichiometry
table row
• N2 environment
4 Reaction Dissolve Dissolve the benzaldehyde (0.163 g,
0.791 mmol) in DCE (1.3 mL).in a
vial
• Benzaldehyde
• DCE stoichiometry table
• vial
5 Reaction Transfer Transfer this solution via syringe to
the reaction round bottom flask
• syringe
• round bottom
flask

If there are differences between the planned and executed reaction or
procedure then both versions of the following can be stored and
flagged as having an ExperimentStage field as Planned or Executed:
• Reaction run
• All corresponding stoichiometry table rows
• Procedure and for each
• All corresponding Procedure Steps and ParameterValues and
ParameterTimes
• Results and requested user inputs can be recorded and linked the
relevant procedure or step of the Executed Procedure
Reaction/Procedure Planned and
Executed Experiment Stage

Reaction 2: Reaction run (Executed and Planned)
Reaction
• Reaction Run: Reaction SJH-01-227 dated 2/12/2014; FailedReaction: false; Experiment Stage: Planned
• Stoichiometry Table
Reaction
• Reaction Run: Reaction SJH-01-227 dated 2/12/2014; FailedReaction: false; Experiment Stage: Executed; Link to Planned
reaction run
• Stoichiometry Table
By default, the executed version is shown, but the
planned version can be accessed via clicking on a link
Links to actual amounts of reactants/reagents used
Links to planned amounts of reactants/reagents used

Label Reaction Component Actual Amounts (Planned values) State Comments
Compound
Mass: 0.1009 g
Moles: 0.133 mMol
Equivalence: 1
Solid
Compound
Mass: 0.0554 g
Moles: 0.269 mMol
Equivalence: 2.02
Solid
Compound
Mass: 0.0055 g
Moles: 0.015 mMoles
Equivalence: 0.11
Solid
DCE Role: Solvent
Compound
Volume: 1.321 mL Liquid Concentration in
line 1: 0.1 M
TFA Role: Solvent
Compound
Density: 1.49 g/ml
Volume: 0.030 mL
Mass: 0.045 g
Moles: 0.396 mMol
Equivalence: 2.97
Liquid
Compound
Mass: 0.0963 g; Moles: 0.0906 mMol
Equivalence: 0.679 (planned: 1)
Yield: 67.9%
Solid
Click to see added sample information (see next slide)
Label Reaction Component Planned Amounts State Comments
Compound
Equivalence: 1
Moles: 0.132 mMol
Mass: 0.1 g
Solid
Compound
Equivalence: 6
Moles: 0.293 mMol
Mass: 0.163 g
Solid
Compound
Equivalence: 0.1
Moles: 0.013 mMoles
Mass: 0.005 g
Solid
DCE Role: Solvent
Compound
Volume: 1.321 mL Liquid Concentration i
line 1: 0.1 M
TFA Role: Solvent
Compound
Density: 1.49 g/ml
Equivalence: 3
Moles: 0.396 mMol
Mass: 0.045 g
Volume: 0.030 mL
Liquid
Compound
Equivalence: 1
Moles: 0.132 mMol
Mass: 0.140 g
Solid
Reaction 2: Stroichiometry table (Executed and Planned)

Reaction 2: Sample information of product (for executed version)
Sample
• Label: SJH_01_227
• OriginalDateAcquired: 17:00:00 02/12/2014
• SubstanceState = Solid
• SampleAmounts:
• Mass: 0.0963 g at TimeStamp: 17:00:00
02/12/2014
• SubstanceSource:
• Reaction:
• Reaction Run: Reaction SJH-01-227 dated
2/12/2014
• Stoichiometry Table Row Product : SJH_01_227
• Compound:
• Characterisations:
• Appearance: “light yellow solid” at
DateMeasured: TimeStamp: 17:00:00 02/12/2014

Reaction 2: Procedure (planned and executed values)
Procedure
• Title: Reaction SJH-01-227 dated 2/12/2014; FailedReaction: false; Experiment Stage: Planned; Link to ReactionRun
• Procedure Steps
Procedure
• Title: Reaction SJH-01-227 dated 2/12/2014; FailedReaction: false; Experiment Stage: Executed; Link to Planned Procedure;
Link to ReactionRun
• Procedure Steps
Links to planned ReactionRun and Procedure Steps
Links to executed ReactionRun and Procedure Steps

Ordinal Parent Title Description ParameterSubstances Parameter Equipment
1 Reaction
2 Reaction Add Add SJH-01-223 (0.1 g, 0.132 mmol)
to a 5 mL round bottom flask with a
reflux condenser with a schlenk
adaptor
• SJH-01-223
• round bottom
flask
• Volume=5mL
• Type=Apparatus
• schlenk adaptor
table row
• N2 environment
vial
• Benzaldehyde
• vial
• syringe
• round bottom
flask
Reaction 2: Procedure Steps (Executed version)
Ordinal Parent Title Executed Description ParameterSubstances Parameter Equipment
1 Reaction
2 Reaction Add Add SJH-01-223 (0.101 g, 0.133
mmol) to a 5 mL round bottom flask
with a reflux condenser with a
schlenk adaptor
• SJH-01-223
• round bottom
flask
• Volume=5mL
• Type=Apparatus
• schlenk adaptor
table row
• N2 environment
vial
• Benzaldehyde
• vial
• syringe
• round bottom
flask
All values that are retrieved from stoichiometry table
rows are automatically updated with Executed rather
than Planned values

• We have shown how this reactions database captures reactions:
• in sufficient detail for someone else to reproduce
• in analogous ways to those captured in Electronic Lab
Notebook
• with fully recorded processes, parameters and equipment in
S88 process recipe [1] style
• raw characterization data linked to products
• which gave low yields or unintended products
• multistep reactions
• to fully record all reaction products (not just the target product)
Conclusions

Because of all this being captured and linked…
Compounds
Mixtures
Solutions
Samples
Reaction runs Steps
Parameters

• We have shown 2 examples:
• Reaction 1: Example of reaction text-mined from
RSC archive by NextMove with S88-style procedure
• there are 31,000 more of these to be validated and
imported
• Reaction 2: Example From Will Dichtel’s research
group via Leah McEwen (ELN-style reaction)
• Consider pipeline for population direct from ELNs
• Develop reactions user interface, API, and
import/validation platform
Future work

Thank you
Email: tkachenkov@rsc.org
Slides:
http://www.slideshare.net/valerytkachenko16

Not just another reaction database

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