A 10-15 minute presentation on my research conducted in the chemistry department of Drexel University for students interested in participating in undergraduate research.

1. Using the Abraham Model to
Predict Organic Solubility to
Determine a
Recrystallization Solvent
Researchers’ Report
January 16, 2013
Matthew McBride
Undergraduate Chemistry Major
Drexel University
Bradley Research Group

2. Advantages of OpenNotebook
Science 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
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
(http://onschallenge.wikispaces.com/EXP324)

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
Allows the student to understand where an error was
made and how to avoid repeating the mistake
(http://onschallenge.wikispaces.com/EXP255)
(http://onschallenge.wikispaces.com/EXP229)

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

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
[William Acree](http://onschallenge.wikispaces.com/Benzoic+acid+-+Abraham)

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

12. 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)

13. 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)

14. 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
Dibenzalacetone
THF
(http://onschallenge.wikispaces.com/EXP308)
[Andrew Lang]

15. 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]

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

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

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

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

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

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

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

23. Solubility at Boiling
Cannot be too low or an impractical
recrystallization solvent
Developing a novel recrystallization method
using 1-octanol (boiling point: 195°C) and
then washing with pentane (boiling point:
35°C)
The ability to heat 1-octanol to higher
temperatures increases the yield of the
recrystallization

24. 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

25. 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
Uses phenanthrene-9-carboxaldehyde
(http://usefulchem.wikispaces.com/D-EXP022)
(http://www.chemspider.com/28190813)
[Andrew Lang]

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

27. 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]

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

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

30. 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)

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

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

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

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

35. 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

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