Video of this presentation can be found here: http://www.youtube.com/watch?v=-rNGkmNTdLc. This talk was given as an oral presentation at the ACS 244th National Meeting held in Philadelphia, PA on August 20, 2012. This talk examined the advantages of being an undergraduate student in a research group using Open Notebook Science. Additionally, this talk examined how to use solubility tools to choose a recrystallization solvent and to plan a reaction synthesis.

1. Leveraging Open Notebook
Science for solubility and
melting point predictions for
optimizing reactions and
recrystallizations
CINF
ACS Symposia #244
Philadelphia, PA
Matthew McBride
Undergraduate Chemistry Major
Drexel University
Bradley Research Group
August 20, 2012

2. Advantages of ONS for
Undergraduate Research
Gain organization skills and learn how
to properly present experiments
Receive timely feedback and corrective
input
Documentation of a student’s
contribution to a project

3. Organization and Presentation
Updating the log the day the experiment is performed
requires a student to keep an organized record of the
lab work
(http://onschallenge.wikispaces.com/EXP324)
Eliminates long term reliance on handwritten notes
and allows the log to be recorded when the
experiment is still fresh in the student’s memory

4. Organization and Presentation
Teaches a student how to identify the critical
elements of an experiment
(http://onschallenge.wikispaces.com/EXP321)

5. Correction and Input
Using ONS allows the student to receive needed
advice and guidance from the mentor directly on the
experiment’s page
(http://onschallenge.wikispaces.com/EXP255)
(http://onschallenge.wikispaces.com/EXP229)
Allows the student to understand where an error was
made and how to avoid repeating the mistake

6. Documentation
Allows a student’s work and contribution to a project
to be documented
(http://onschallenge.wikispaces.com/list+of+experiments)
Provides graduate schools with the ability to view
exactly what research an applicant has conducted

7. Solubility
Important when choosing a
recrystallization solvent
Accurate solubility predictions for a
compound allows the optimal solvent to
be used

8. Preferred Solvent
Characteristics
Does not react with the compound
being recrystallized
High solubility at boiling point, but low
solubility at room temperature
A boiling point that allows for easy
drying of the product
Miscibility with water

9. Predicting Solubility with
Abraham Descriptors
Five descriptors for each solute and each solvent
The descriptors for over 80 solvents, including some
ethanol/water mixtures, are known
Descriptors for a solute can be experimentally
determined by measuring the solubility in 5 solvents
Descriptors for a solute can be predicted using AD
Model003
Using the solute descriptors, the solubility in any of
the solvents with known descriptors can be predicted
(http://onschallenge.wikispaces.com/Benzoic+acid+-+Abraham) [William Acree]

10. Solubility Predictions
Using ONS Webservices, can list the predicted
solubility for a compound
Trans-dibenzalacetone
(www.chemspider.com/55
5548)
Solvent Model003 AD Measured Experimental BP
(M) (M) (M) (°C)
(http://showme.physics.drexel.edu/onsc/models/solventselector.php?csids=555548)
[Andrew Lang]

11. Solubility Curves
Using a melting point, temperature dependent
solubility curves are generated
Assumes that at the melting point the compound is
miscible with the solvent
Solubility in Ethanol (Concentration M vs. Temperature °C)
[Andrew Lang] (http://showme.physics.drexel.edu/onsc/models/solventselector.php?csids=555548)

12. Measuring Solubility
Surprisingly difficult. Must be sure the solution is at
saturation, while avoiding supersaturated solutions
(http://usefulchem.blogspot.com/2010/07/general-transparent-solubility.html)

13. Temperature Controlled Shake
Flask Method
Add solute to the vials with the solvent and allow to
shake in the 25°C water bath
(http://onschallenge.wikispaces.com/e
xp324)

14. Temperature Controlled Shake
Flask Method
Measure the solubility using HNMR
Need to take two consecutive measurements without
the solubility changing to confirm the solution is
saturated
(http://onschallenge.wikispaces.com/EXP311)

15. Measuring Solubility with NMR
Compare integration of solute and solvent peaks in
saturated solutions using google app scripts
1.5M Saturated solution of dibenzalacetone in THF
THF
Dibenzalacetone
(http://onschallenge.wikispaces.com/EXP308)
[Andrew Lang]

16. Benefits of Solubility
Curves
These temperature dependent solubility
curves allow a solvent with the greatest
difference between solubility at room
temperature and at the boiling point to
be used
Reduces reliance on only recrystallizing
in solvents listed in literature
Optimizes the process of choosing a
recrystallization solvent
[Andrew Lang]

17. Example
The solvents used to recrystallize compounds in
organic teaching labs can be improved
Trans-dibenzalacetone
(http://showme.physics.drexel.edu/onsc/reactionattempts/advancedsearch.php?compound=&solvent=&reactiontype
=&researcher=Matthew+McBride)
Aldol condensation between two molecules of
benzaldehyde and one molecule of acetone
[Andrew Lang]

18. Dibenzalacetone
First recrystallized in ethyl acetate in 1906
(Straus and Ecker, Ber. 39, 2988 (1906))
Recrystallized in ethyl acetate in Organic Syntheses

19. Organic Teaching Labs
Many recrystallize in ethyl acetate
(http://classes.kvcc.edu/chm230/MIXED%20ALDOL%20CONDENSATION.pdf)
(http://www.xula.edu/chemistry/documents/orgleclab/Aldol_notes.pdf)
Is there a different solvent that could be used?

20. SmartPhone App
This app predicts the recrystallization yields of any
compound in different solvents using the solubility
curves:
(http://onschallenge.wikispaces.com/recrystallization)
Provides experimental and predicted values for
melting point and LogP
[Andrew Lang]

21. SmartPhone App
Enter compound identification (SMILES, CSID,
name…etc), and desired parameters
(http://onschallenge.wikispaces.com/rec
ation)
[Andrew Lang]

22. SmartPhone App
Lists solvents and their predicted recrystallization
yield
(http://onschallenge.wikispaces.com/recrystalliz
ation)
Prediction is generated by the temperature
[Andrew Lang]

23. Comparison
Ethyl acetate (predicted yield of 69%) vs ethanol
(predicted yield of 91%)
Ethyl acetate 2.06M
0.62M
Ethanol
1.1M
0.09M
(http://showme.physics.drexel.edu/onsc/m
odels/solventselector.php?csids=555548)
[Andrew Lang]

24. Solubility at Boiling
Cannot be too low or an impractical
recrystallization solvent
Example: Dibenzalacetone in hexane
(predicted yield of 90%)

25. Hexane
0.3M
(http://showme.physics.drexel.edu/onsc/models/solventselector.php?csids=555548)
[Andrew Lang]
Too insoluble at the boiling point
To recrystallize 1 gram of product (4 mmol), would
need approximately 13 mL of hexane

26. Designing reactions using
solubility
These solubility tools can be used to
choose a solvent for a reaction
Finding a solvent in which the reactants
are soluble, but the product is insoluble.
This allows the product to be recovered
by a simple filtration

27. Example
Derivatives of dibenzalacetone may be synthesized
by altering the aldehyde used
From a library of derivatives, the following compound
was the top hit for the docking site of Taxol
(http://usefulchem.wikispaces.com/D-EXP022)
(http://www.chemspider.com/28190813)
Uses phenanthrene-9-carboxaldehyde [Andrew Lang]

28. Search Literature
Perform a Reaxys© search to determine availability of
synthesis procedures
No results

29. Synthesis Planning
Desire a solvent that the aldehyde is soluble
in, but the product is not
The product was predicted as having very low
solubility (<0.000M) in all solvents
NaOH used as the catalyst, so needs to be
soluble in the solvent
(http://showme.physics.drexel.edu/onsc/models/solventselector.php?csids=281908
13) [Andrew Lang]

30. Synthesis Planning
NaOH is soluble in methanol, so check aldehyde
solubility
Phenanthrene-9-carboxaldehyde
(http://www.chemspider.com/708
06)
Model003 AD Measured Experimental BP
Solvent (M) (M) (M) (°C)
(http://showme.physics.drexel.edu/onsc/models/solventselector.php?csids=70806)
[Andrew Lang]

31. Synthesis Planning
Conclusion: Using methanol as the
reaction solvent should allow the
aldehyde be dissolved into solution, but
will cause the product to precipitate

32. Synthesis
Created an approximately 0.016M
solution of phenanthrene-9-
carboxaldehyde in methanol
Added acetone and then a large excess
of NaOH (catalyst) to the reaction
mixture
Stirred mixture without heat over two
days
(http://usefulchem.wikispaces.com/EXP286)

33. Product
Reaction mixture:
(http://usefulchem.wikispaces.com/EXP286)

34. Crude Product
Following suction filtration: 0.0834 g of yellow
crystals
(http://usefulchem.wikispaces.com/EXP
286)

35. Recrystallization
Used benzene
(http://usefulchem.wikispaces.com/EXP286)
Melting Point: 264-265°

36. HNMR
Spectrum of product (http://www.ch
emspider.com/
28190813)
Benzene peak in
CDCl3
16Hz Trans Coupling
(http://usefulchem.wikispaces.com/EXP286) [Andrew Lang]

37. Summary
Open Notebook Science provides
advantages to an undergraduate
researcher
Measured and predicted solubilities can
be used to optimize recrystallizations
Predicted solubilities can be used to
plan the synthesis and optimize the
recovery of the product

38. Further Information
http://onschallenge.wikispaces.com/
http://usefulchem.wikispaces.com/
http://onswebservices.wikispaces.com/