Objective

To ascertain the solubility of 4-chlorophenylacetic acid in methanol and THF by NMR spectroscopy using 2 different methodologies
In using two different methodologies, 2 concepts are being studied or verified. A test to determine if the internal standard being used is at all having an effect on the formulated solutions. Second, to test the accuracy of the SAMS method.

Procedure

Saturated solutions of 4-chlorophenylacetic acid were prepared in acetonitrile, DMSO, and ethanol. In order to do so, a few crystals of the solute were added to an NMR tube, then a Pasteur pipette was used to add a droplet of the solvent. A capillary tube was also prepared containing deuterated chloroform. The capillary tube was then carefully placed within the NMR tube. The NMR tube was then sonicated, using a Branson 1510 instrument, for 30 minutes. Proton NMR readings of the solutions were obtained using a 500MHz instrument.

Modified Procedure:

  1. Saturated solutions of 4-chlorophenylacetic acid were prepared in methanol and THF. In order to do so, crystals of the solute were placed directly into an NMR tube, then 100μL of solvent was added to the NMR tube. The NMR tube was briefly vortexed in-between additions of the solute. Once solute was seen to no longer go into solution, the NMR tube was sonicated, using a Branson 1510 instrument, for 10 minutes. Solutions were then left to equilibriate. A capillary tube was prepared containing D-6 acetone, which was then carfeully placed within the NMR tube. Proton NMR readings of the solutions were obtained using a 500MHz instrument of both the NMR tube containing the capillary tube and without.
  2. Saturated solutions of 4-chlorophenylacetic acid were prepared in methanol and THF. The solutions were prepared by mixing together the solute and 300μL of the solvent into a vial. With subsequent additions of solute, with bouts of vortexing. Once the solutions showed excess of solute, the vials were sonicated, using a Branson 1510 instrument, for 10 minutes. Solutions were then left to equilibriate. 100μL of the supernatants were micropipetted out and then dissolved into NMR tubes containing 600μLof deuterated chloroform (CDCl3). Proton NMR readings of the solutions are obtained with the use of a 500MHz instrument.


Results

Sample
Methodology
Solvent
Solute
HNMR
HNMR Raw Data
Solubility (M)
1
no capillary tube
Methanol
4-chlorophenylacetic acid
HNMR-1
4-clphenylacetic acid-methanol.jdx
7.44
2
no capillary tube
THF
4-chlorophenylacetic acid
HNMR-2
4-clphenylacetic acid-THF.jdx
4.1
3
with capillary tube
Methanol
4-chlorophenylacetic acid
HNMR-3
4-clphenylacetic acid-methanol-capillary.jdx
8.07
4
with capillary tube
THF
4-chlorophenylacetic acid
HNMR-4
4-clphenylacetic acid-THF-capillary.jdx
4.24

Spreadsheet





Discussion

This experiment was carried out to determine if the use of an internal standard had any effect on the formulated solution. Based on the solubility results, it can be concluded that there is not a big difference (there is a slightly significant difference in the methanol results, but this is most likely attributable to some experimental error and not the method per se). Therefore, the SAMS method is accurate in determining solubilities.

Also, upon comparison of the NMR spectra from both methods, it is observed that the NMR tube without the capillary produces a better quality spectra. Having the capillary within the NMR tube acts to slightly interfere with the spectra scan.

Conclusion

The solubility of 4-chlorophenylacetic acid has been determined in methanol and THF. The data obtained in this experiment shows that 4-chlorophenylacetic acid is capable of making 2M solutions for the Ugi product.

There is no need to isolate the internal standard from the solution reaction. The SAMS method is as accurate and produces better spectra than the other method.

Log

(includes Observations)

2009-04-3

17:56 Ambient temperature in the room recorded to be 26⁰C
17:58 Cleaned and sterilized a spatula with acetone, and evaporated it off in an oven.
18:02 Added 300μL of methanol to a vial labeled "methanol".
18:04 Added 300
μL of THF to a vial labeled "THF".
18:06 Added 4-chlorophenylacetic acid solute to the "methanol" vial, vortexing in-between additions, till the solute visibly collected at the bottom of the vial. The vial was then parafilmed.
There were many additions of solute, appears to be highly soluble in methanol.
18:12 Added solute to the "THF" vial, vortexing in-between additions, till the solute was clearly visible at the bottom of the vial. Parafilmed the cap.
18:19 Vortexed both vials for 1 minute.
18:21 Sonicated both vials for 10 minutes.
18:32 Left the vials to equilibriate for another 10 minutes.
19:00 Cleaned 2 NMR tubes with acetone, and evaporated it off in an oven.
19:03 Made saturated solutions of the solute in methanol directly in a NMR tube labeled "73-M-Cap" in red pen, and another saturated solution in the other NMR tube labeled "73-THF-Cap", by adding solute to 100μL of solvent and vortexing in-between additions till solute began to collect at the bottoms of the tubes.
19:07 Sonicated both NMR tubes for 10 minutes.
19:08 Added more solute to the "methanol" vial, because no recrystallization was seen to occur after the equilibriating process
; vortexing in-between additions till solute again collected at the bottom of the vial.
19:12 Placed the vial in the Sonicator for 10 minutes.
19:18 Let the NMR tubes equilibriate.
19:22 Left the "methanol" vial to equilibriate for 10 minutes.
19:27 Added more solute to the "73-M-CAP" NMR tube, because no solid was seen to recrystallize after the equilibriating process. Vortexed the NMR tube briefly, and placed the tube back into the Sonicator for 10 minutes after some solute was seen to collect.
19:39 Left the NMR tubes to equilibriate.
20:35 2 NMR tubes and caps were cleaned with acetone, then evaporated solvent off in oven.
20:38 Micropipetted 100μ
L of the supernatant from the "methanol" vial into a NMR tube labeled "73-M-NoCap" in green pen
20:40 Micropipetted 100μ
L of the supernatant from the "THF" vial into a NMR tube labeled "73-THF-NoCap" in green pen.
20:42 Added 600μ
L of deuterated chloroform to both NMR tubes and briefly vortexed.
20:49 D-6 acetone was added to a capillary tube using a syringe.
21:09 Proton NMR readings were obtained using a 500MHz instrument.



References

[[http://oru.edu/cccda/sl/solubility/ugidata.php?solute=4-chlorophenylacetic acid&solvent=methanol|Solubility of 4-chlorophenylacetic acid in methanol]] (Solubility data viewer)
[[http://oru.edu/cccda/sl/solubility/ugidata.php?solute=4-chlorophenylacetic acid&solvent=THF|Solubility of 4-chlorophenylacetic acid in THF]] (Solubility data viewer)



Compound
Inchi Key
Inchi
4-chlorophenylacetic acid
CDPKJZJVTHSESZ-UHFFFAOYAC
InChI=1/C8H7ClO2/c9-7-3-1-6(2-4-7)5-8(10)11/h1-4H,5H2,(H,10,11)
Methanol
OKKJLVBELUTLKV-UHFFFAOYAX
InChI=1/CH4O/c1-2/h2H,1H3
THF
WYURNTSHIVDZCO-UHFFFAOYAI
InChI=1/C4H8O/c1-2-4-5-3-1/h1-4H2