Solubility Determination Procedure for 4-Chlorobenzaldehyde in Non-Deuterated Chloroform by Proton NMR using a Sonicator

Researcher

David Bulger

Objective
To develop a procedure that can be implimented in determining solubility by proton NMR using 4-chlorobenzaldehyde in non-deuterated chloroform.

Materials and Instrumentation
A JEOL 300-MHz high resolution 5-mm probe NMR was used with no spin and no lock at 22.4 °C. Shimming was performed followed by three NMR runs while the spin was temporarily working at 12-13 Hz with 2.0600 g reagent grade non-deuterated chloroform in an NMR tube. Mass determinations were performed using a 0.1 mg accuracy Sortorius balance. Shimming was performed followed by three NMR runs while the spin was temporarily working at 12-13 Hz with 2.0600 g reagent grade non-deuterated chloroform in an NMR tube. Sonication was performed with a Branson 50/60 Hz Ultrasonic Cleaner.

Experimental
Chloroform (2.0601g; 1.3920 mL; 17.3 mmol) and 4-chlorobenzaldehyde (171.2 mg; 117.5 μL; 1.2 mmol) were added in various increments to a 5 mm NMR tube until solute precipitated and mixed by sonication for 1 min. This solution was then analyzed by 1H NMR.

Results
Identification of Peaks on Standard Spectrum (282):
Identification Spectrum.pdf

Decompressed/Corrected Spectra
NMR286
NMR284
NMR282
NMR280
NMR278
NMR276
NMR274
NMR272
NMR270
NMR268
Raw JCAMP-DX for NMR286
Raw JCAMP-DX for NMR284
Raw JCAMP-DX for NMR282
Raw JCAMP-DX for NMR280
Raw JCAMP-DX for NMR278
Raw JCAMP-DX for NMR276
Raw JCAMP-DX for NMR274
Raw JCAMP-DX for NMR272
Raw JCAMP-DX for NMR270
Raw JCAMP-DX for NMR268

Spreadsheet
Results Spreadsheet


Photos
300_MHz_NMR_1.JPG
300_MHz_NMR_2.JPG
300_MHz_NMR_3.JPG
300_MHz_NMR_4.JPG
NMR_Tubes.JPG
NMR_Caps.JPG
Sample_Preparation.JPG
Weighing_Table.JPG
Analytical_Scale_1.JPG
Analytical_Scale_2.JPG
Analytical_Scale_3.JPG
Sonicator_Detail.JPG
Empty_Sonicator_Back.JPG
Empty_Sonicator_Front.JPG
Sonicator_with_DI_Water.JPG
Computer_with_Delta.JPG
Pasteur_Pipet.JPG
Protonated_Chloroform.JPG
4-Chlorobenzaldehyde.JPG
Solid residue
Solid residue_close_up
4-chlorobenzaldehyde_side
4-Chlorobenzaldehyde_top
4-chlorobenzaldehyde_top_close_up

NMR
Solute Signal
Predicted (M)
Measured (M)
SE%
286
Hb
0.73
1.02
39
286
Ha
0.73
1.05
44
284
Hb
0.63
0.88
40
282
Hb
0.49
0.63
29
280
Hb
0.39
0.42
7
278
Hb
0.32
0.42
30
274
Hb
0.21
0.16
23
272
Hb
0.13
0.08
36
270
Hb
0.06
Undetectable
NA
268
Hb
< 0.06
Undetectable
NA
Table 1: Summary of Molarity Measurements.

Discussion
Since the JSpecView wasn't reading the JCAMP-DX Joint Committee on Atomic and Molecular Physical Data—Data Exchange) files correctly from the JEOL NMR, the orginal .jdx files were loaded into http://www.mylims.org, processed with automatic baseline correction, exported into XY data points in both ppm and hz, ppm XY data points were transferred into the NMR262new.jdx file replacing the XY data points, and the data info sections were changed to match the new spectra. However, intXY.php still can't read the file.

As in EXP016, the solution had not reached saturation when the NMR was taken. However, since some solute precipitated out at 0.81 M, the solubility of the compound is predicted to be less than 0.81 M. The concentrated solution predicated molarities were compared with those measured by SAMS (Table 1). However, the mean standard error was 31%, which is significantly greater than expected. The most concentrated solution analyzed by 1H NMR was predicted to be 0.73 M and measured by SAMS with the aromatic Hb signal to be 1.02 M (SE 39%) and with the aldehyde Ha signal to be 1.05 M (SE 44%). This may indicate a greater concentration of solute than was predicted, which would also mean a greater solubility. Still, this solubility measurement is very different from the 3.61 M measured in UCEXP209. As the solute showed glassy residue in the bottom of the bottle, this discrepancy may be due to some impurities in the solute.

Conclusion
The solubility of the compound from the 4-Chlorobenzaldehyde bottle in chloroform was measured to be 0.73-0.81 M. The 0.73 M sample (NMR286) was measured by SAMS to be 1.02-1.05 M.

Log

12.12.08 CST

10.35 – Gradient shimming with deuterated chloroform.
11.00 – NMR run on sample three times at 13 Hz (EXP016).
11:15 – Spin cock valve problem (spin was turned off).
11.57 – Weighed empty NMR tube.
12.04 – Added chloroform.
12.05 - Weighed sample and sonicated for 1 min.
12.07 – NMR run - spin turned on, but not spinning (Spectrum_268.jpg, 1d_spectrum_268.jdx, 1d_spectrum_268.html).
12.15 – Weighed sample.
12.18 – Added 4-chlorobenzaldehyde and weighed.
12.19 – Sonicated for 1 min.
12.22 – NMR run - spin turned on, but not spinning (Spectrum_270.jpg, 1d_spectrum_270.jdx, 1d_spectrum_270.html).
12.25 – Weighed sample.
12.27 – Added 4-chlorobenzaldehyde and weighed.
12.28 – Sonicated for 1 min.
12.30 – NMR run - spin turned on, but not spinning (Spectrum_272.jpg, Spectrum_272_CHCl3_1.jpg, 1d_spectrum_272.jdx, 1d_spectrum_272.html).
12.33 – Weighed sample.
12.35 – Added 4-chlorobenzaldehyde and weighed.
12.36 – Sonicated for 1 min.
12.38 – NMR run - spin turned on, but not spinning (Spectrum_274.jpg, Spectrum_274_CHCl3_1.jpg, 1d_spectrum_274.jdx, 1d_spectrum_274.html).
12.40 – Weighed sample.
12.41 – Added 4-chlorobenzaldehyde and weighed.
12.43 – Sonicated for 1 min.
12.45 – NMR run - spin turned off (Spectrum_276.jpg, Spectrum_276_CHCl3_1.jpg, 1d_spectrum_276.jdx, 1d_spectrum_276.html).
12.48 – Weighed sample.
12.49 – Added 4-chlorobenzaldehyde and weighed.
12.51 – Sonicated for 1 min.
12.53 – NMR run (Spectrum_278.jpg, Spectrum_278_CHCl3_1.jpg, 1d_spectrum_278.jdx, 1d_spectrum_278.html).
12.56 – Weighed sample.
12.57 – Added 4-chlorobenzaldehyde and weighed.
12.59 – Sonicated for 1 min.
13.01 – NMR run (Spectrum_280.jpg, Spectrum_280_CHCl3_1.jpg, 1d_spectrum_280.jdx, 1d_spectrum_280.html).
13.04 Weighed sample.
13.05 – Added 4-chlorobenzaldehyde and weighed.
13.08 – Sonicated for 1 min.
13.10 – NMR run (Spectrum_282.jpg, Spectrum_282_CHCl3_1.jpg, 1d_spectrum_282.jdx, 1d_spectrum_282.html).
13.12 – Weighed sample.
13.13 – Added 4-chlorobenzaldehyde and weighed.
13.16 – Sonicated for 1 min.
13.18 – NMR run (Spectrum_284.jpg, Spectrum_284_CHCl3_1.jpg, 1d_spectrum_284.jdx, 1d_spectrum_284.html).
13.20 – Weighed sample.
13.21 – Added 4-chlorobenzaldehyde and weighed.
13.24 – Sonicated for 1 min.
13.25 – NMR run (Spectrum_286.jpg, Spectrum_286_CHCl3_1.jpg, 1d_spectrum_286.jdx, 1d_spectrum_286.html).
13.29 – Weighed sample.
13.30 – Added 4-chlorobenzaldehyde and weighed.
13.33 – Sonicated for 1 min.
13.35 – NMR run (Spectrum lost due to computer problems).
13.35 – Computer locked up (fuse blew).
14.30 – Solid residue observed in NMR tube.

1.16.09 CST

15.40 - Photos taken of equipment and reagents.

1.23.09 CST

20.30 - Photos taken of residue in NMR tube (Solid residue).

1.30.09 CST

16.50 - Photos taken of 4-chlorobenzaldehyde (4-chlorobenzaldehyde_side, 4-Chlorobenzaldehyde_top, 4-chlorobenzaldehyde_top_close_up)

References:

[1]http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TVT-3X9S1P9-9-1J&_cdi=5543&_user=5017369&_orig=search&_coverDate=09%2F30%2F1999&_sk=999439996&view=c&wchp=dGLzVtz-zSkzk&md5=13f1fdab933d1ee83d0ae2567ed5cbf4&ie=/sdarticle.pdf

Acknowledgements:

The author wishes to thank Dr. Robert Stewart for his advice throughout the course of the experiment and for the use of the NMR and other equipment, Dr. Jean-Claude Bradley for setting up the server for the interactive NMR spectra and the recommendation to use integration ratio comparision, Khalid Mirza for helping generate .html files to post on the server, and Dr. Antony Williams for his advice on improving the H NMR peaks.

Appendix


Spectra with screenshots
Spectra seem compressed like in the previous experiment. Thus, the following screenshot data will most likely be inaccurate and needs to be replaced by decompressed corrected spectra compatible with SAMS.
spec268
spec270
spect272
spec274
spec276
spec278
spec280
spec282
spec284
spec286
268Habc
270Habc
272Ha_a
274Ha_a
276Ha
278Ha
280Ha
282Ha
284Ha
286Ha


272Ha_b
274Ha_b








272Hb_a
274Hb_a
276Hb_a
278Hb_a
280Hb_a
282Hb_a
284Hb_a
286Hb_a


272Hb_b
274Hb_b
276Hb_b
278Hb_b
280Hb_b
282Hb_b
284Hb_b
286Hb_b


272Hc_a
274Hc_a
276Hc_a
278Hc_a
280Hc_a
282Hc_a
284Hc_a
286Hc_a


272Hc_b
274Hc_b
276Hc_b
278Hc_b
280Hc_b
282Hc_b
284Hc_b
286Hc_b
268Hd_a
270Hd
272Hd_a
274Hd_a
276Hd_a
278Hd_a
280Hd_a
282Hd_a
284Hd_a
286Hd_a
268Hd_b

272Hd_b
274Hd_b
276Hd_b
278Hd_b
280Hd_b
282Hd_b
284Hd_b
286Hd_b
268He1
270He1
272He1_a
274He1_a
276He1_a
278He1_a
280He1_a
282He1_a
284He1_a
286He1_a


272He1_b
274He1_b
276He1_b
278He1_b
280He1_b
282He1_b
284He1_b
286He1_b
286He2_a
270He2_a
272He2_a
274He2_a
276He2_a
278He2_a
280He2_a
282He2_a
284He2_a
286He2_a
268He2_b
270He2_b
272He2_b
274He2_b
276He2_b
278He2_b
280He2_b
282He2_b
284He2_b
286He2_b

Previous Questions
[Identify which peak you integrated in the spreadsheet and what the integration values were that you used to make your ratios - where do you expect the chloroform peak to appear? Put in the spreadsheet the equation you used to calculate molarity. JCB] The peak analyzed for 4-chlorobenzaldehyde was the largest aromatic peak (Ha) at around 10 ppm on the spectra integrated to chloroform C13 H. The identification spectrum below shows how the peaks were labeled. I just realized that molarity cannot be calculated without volume of solution, since the solute is in a solid state. Weight percent will be used instead.
[Can you also upload the JCAMP-DX format on the wiki until I have an account set up for you on our server? If you don't know how to do that can you at least upload the FID? For your approach the ability to interactively access the NMR spectra is particularly useful. Also check out the general comments page for instructions relating to JEOL JCB] Thank you for setting up the server for the JCAMP files. The links to the server for the various spectra are listed below under interactive spectra.
[I believe that you need to define in detail exactly how you are intending to do the calculations in order to determine the solubility. This would be of value to anyone wishing to repeat the work. ChemSpiderman]
The calculation for comparing the integration ratios is as follows: grams unsaturated solute/ (NMR solute area 1/ NMR C13 area 1) = grams saturated solute/ (NMR solute area 2/ NMR C13 area 2). The calculation for weight percent is as follows: wt% = (100%) * (solute mass [g])/ (solution mass [g]).
[Since you are measuring the weights as well as the integrations you should be able to compare the predicted and observed integrations JCB] That is a great idea. I will try it in future experiments.
As solid residue was observed at 6.29 wt%. [How did you calculate this number? JCB] I do not think the volume of the solution cannot be determined with a solid solute. Before, I was converting the grams solute to milimeters solute using its density. I have changed it to weight percent now. As the solute had trouble dissolving, the solute was further examined. It was found to be highly oxidized and nearly insoluble. There is a hard white substance in the bottom of the 4-Chlorobenzaldehyde container (4-chlorobenzaldehyde_side, 4-Chlorobenzaldehyde_top, 4-chlorobenzaldehyde_top_close_up). This explains the problems associated with the NMR measurements. As the spin cock valve was not working following the shimming, the spin was turned off for the NMR runs. Shimming before each run with spin turned on may improve the accuracy of the readings.
[Your conclusion should at least directly address the objective: what do you calculate for the solubility of 4-chlorobenzaldehyde in chloroform? How does that number compare to what others have found? JCB]
The solubility of 4-chlorobenzaldehyde was not determined by this experiment as the sample was found to be nearly insoluble, most likely due to the oxidation of the air-sensitive sample prior to the experiment.
[You're doing a tremendous number of calculations here but you don't have to in order to answer the key question - can you trust the ratio of the aldehyde peak to the chloroform main peak? Just for spectrum 286 what weight ratio do you predict based on Ha/Hd and how close is that to the amounts you measured? JCB]
[Oxidation of 4-chlorobenzaldehyde is a possibility but does the NMR of spectrum286 show any evidence of that? What would be the oxidation product and how would that manifest in the NMR spectrum? JCB] One possible oxidation product is 4-chlorobenzoic acid. The predicted spectrafor 4-chlorobenzoic acid is pretty much the same as 4-chlorobenzaldehyde without the aldehyde peak at ~10 ppm. Both show a doublet of doublets between 7.5 and 8.0 ppm. Also, the chloroform peak's downfield lorenzian tail is in that region. Since there is an aldehyde peak at ~10 ppm, some 4-chlorobenzaldehyde was present. Any oxidation products could change the solubility.[If you have some 4-chlorobenzoic acid in there it is not much because your aldehyde and aromatic peaks integrate well in a 1:2 ratio - also the aromatic peaks would be similar for the acid but not identical JCB] Reference #1 shows many possible products that result from air and light exposure. Many of the chlorohydroxybenzaldehydes have spectra similar to 4-chlorobenzaldehyde. I agree that the aldehyde and aromatic peaks 1:2 integration ratio demonstrates the low concentration. Some of the upfield peaks increased as the solute was added. Some of these may be attributed to the oxidation products. For example, 4-chloro-3-hydroxybenzaldehyde has a predicted peak at around 2.15 ppm. The observed peak at 2.15 ppm also increased as the solute was added.
As the relative standard deviation was 37.1%, the precision was not sufficient for a sulubility curve. This method requires greater precision for it to produce a clear solubility curve. A solubility curve requires a large amount of NMR runs. It would be more efficient to compare integration ratios with a saturated solution. The solution needs to be sonicated longer to make sure it completely dissolves.
[All of your measurements depend upon the integration values but I cannot reproduce your ratios. For example for spectrum 286, taking the ratio of the peak at 10.38 ppm (integration 481250) to the large peak at 8.14 ppm (integration 5750000) I get a ratio of 0.084, which is very different from your reported ratio of 0.23 - how can you explain the difference? Do you expect chloroform to appear at 8.14 ppm? JCB] Please refer the scan of the print out of the integration of spectrum 286, Spectrum_286.jpg. Rather than manually integrating as I am with future spectra, this spectrum was integrated by the computer using Delta. The peak at ~7.4 (the tallest peak) on the print out, ~8.14 on the interactive spectrum, was taken to be the chloroform peak and set to be the norm equal to one. [8.14 ppm is way off for the chloroform peak - you need to properly adjust the scale before uploading spectra JCB] The difference might be accounted to manual integration rather than the automatic integration. It looks to me like the computer integrated one of the aromatic peaks with the chloroform peak.[That's exactly the point I was trying to get across - you cannot trust automated integrations for this type of analysis - and for everyone to understand exactly how you measured the integrations you should provide screenshots of the JSpecView displays JCB] From now on, I will calculate the integration ratios with the JSpecView displays and take screenshots to show exactly how I calculated the integration.