Researcher

David Bulger

Obejective

To determine the solubility of DL-mandelic acid, trans-cinnamic acid, 4-phenylbutyric acid, L-ascorbic acid, acetylsalicylic acid and 4,4-azoxydibenzoic acid in various solvents using 1H NMR.

Procedure

DL-mandelic acid, trans-cinnamic acid, 4-phenylbutyric acid, L-ascorbic acid, acetylsalicylic acid, and 4,4-azoxydibenzoic acid were saturated in chloroform(except acetylsalicylic acid), tetrahydrofuran, methanol, hexanol, toluene, and diethyl ether by adding excess solute to solvent and sonicating solution for 30 min. Samples were then left to equilibrate at room temperature (usually 23.0 degrees Celsius). Supernatant liquid pipetted into NMR tubes and 20 uL of CHCl3 added with a microsyringe if CHCl3 is not the solvent. NMR runs performed on 300 MHz JEOL Spectrometer with 16 384 x_points, 8 scans, 45 degree pulse, and 4 second relaxation delay. Molarity calculated using Semi-Automated Measurement of Solubility (SAMS).

Results

The solubilities are calculated in ONSC-EXP072-sheet1, ONSC-EXP072sheet2, ONSC-EXP072sheet3, and ONSCEXP072sheet4.

Note: Solubility measurements will not be available until SAMS is adjusted to work with the .jdx format used in this experiment.
[Have you tried to resave the files according to AL's suggestion? To convert, open the spectrum file in JSpecView, then file -> export JCAMP-DX -> XY
You can get the standalone **JSpecView program from SourceForge** JCB] Thank you for the suggestion. I converted it as you explained and adjusted the solute and solvent ranges accordingly. However, SAMS was still unable to read it. (See NMR20_ASA_detSAMS in ONSC-EXP072sheet3) [This resaved spectrum looks like the phasing is way off JCB] You are right. When the file was converted, the phasing and shifts became distorted. The JSpecView program from SourceForge does not have phase correction. Besides, if the phasing were corrected, would SAMS be able to read it any better? [AL is working on fixing this - it looks like just another little glitch to be fixed and you can generate results from this experiment - SAMS has worked fine in experiments done on our Varian instrument and it should work for you as well JCB] AL explained that in order for the conversion to be right, the n=1 spectrum must be selected rather than the default of n=2. The n=2 spectra demonstrate the distorted phasing. SAMS is able to read the converted n=1 spectra. (See NMR23_DL-Ma_detS in ONSC-EXP072sheet3)
[OK it looks like you are getting your integrations now - but you need to fix several issues as you include all the rest:
1) You are significantly offscale - set the shift to the known value for the solvent - for example the **triplet in diethyl ether is at 1.13 ppm** You can change this directly in the JCAMP file via the offset - see AL for help if needed.
2) Your spectrum is inverted - again there is a setting in the JCAMP file to switch this
3) You are counting 4H in some entries in the spreadsheet for diethylether, which is correct for the methylene groups next to O but your ranges are wrong.
JCB] AL showed me how to set the shift and reverse the spectra. The ranges change with the conversion of the spectra and have to be redone each time the spectrum changes.

Sample Name
(Photo linked)
Spectrum
Solute
Solvent
Solubility (M)
NMR1

Acetylsalicylic acid
THF
(Impure Solvent)
NMR2
Spectrum_315
Acetylsalicylic acid
Methanol
1.32
NMR3

4,4-Azoxydibenzoic acid
THF
(Impure Solvent)
NMR4

L-Ascorbic acid
THF
(Impure Solvent)
NMR5
Spectrum_353
L-Ascorbic acid
CHCl3
insoluble
NMR6
Spectrum_361
4,4-Azoxydibenzoic acid
CHCl3
insoluble
NMR7

4,4-Azoxydibenzoic acid
Methanol
(Mislabeled)
NMR8

L-Ascorbic acid
Methanol
(Mislabeled)
NMR9
Spectrum_355
4-Phenylbutyric acid
CHCl3
4.04
NMR10
Spectrum_330
4-Phenylbutyric acid
Methanol
4.80
NMR11

4-Phenylbutyric acid
THF
(Impure Solvent)
NMR12
Spectrum_334
DL-Mandelic acid
Methanol
3.62
NMR13

DL-Mandelic acid
THF
(Impure Solvent)
NMR14
Spectrum_359
DL-Mandelic acid
CHCl3
0.10
NMR15
Spectrum_347
trans-Cinnamic acid
Methanol
1.32
NMR16

trans-Cinnamic acid
THF
(Impure Solvent)
NMR17
Spectrum_357
trans-Cinnamic acid
CHCl3
0.83

Sample Name
Photo
Spectrum
Solute
Solvent
Solubility (M)
NMR18
EXP072_18_(ASAHexanol)
NMR18_ASA_hex
Acetylsalicylic acid
Hexanol
insoluble
NMR19
EXP072_19_(ASAToluene)
NMR19_ASA_tol
Acetylsalicylic acid
Toluene
insoluble
NMR20
EXP072_20_(ASADiethylether)
NMR20_ASA_detS
Acetylsalicylic acid
Diethyl Ether
0.18
NMR21
EXP072_21_(LD-MaHexanol)
NMR21_DL-Ma_hex
DL-Mandelic acid
Hexanol
insoluble
NMR22
EXP072_22_(DL-MaToluene)
NMR22_DL-Ma_tol
DL-Mandelic acid
Toluene
insoluble
NMR23
EXP072_23_(DL-MaDiethylether)
NMR23_DL-Ma_detS
DL-Mandelic acid
Diethyl Ether
0.98
NMR24
EXP072_24_(AscHexanol)
NMR24_Asc_hex
L-Ascorbic acid
Hexanol
insoluble
NMR25
EXP072_25_(AscToluene)
NMR25_Asc_tol
L-Ascorbic acid
Toluene
insoluble
NMR26
EXP072_26_(AscDiethylether)
NMR26_Asc_det
L-Ascorbic acid
Diethyl Ether
insoluble
NMR27
EXP072_27_(44-AzHexanol)
NMR27_44-az_hex
4,4-Azoxydibenzoic acid
Hexanol
insoluble
NMR28
EXP072_28_(44-AzToluene)
NMR28_44-az_tol
4,4-Azoxydibenzoic acid
Toluene
insoluble
NMR29
EXP072_29_(44-AzDiethylether)
NMR29_44-az_det
4,4-Azoxydibenzoic acid
Diethyl Ether
insoluble
NMR30
EXP072_30_(4-PhbHexanol)
NMR30_4-phb_hexS
4-Phenylbutyric acid
Hexanol
0.50
NMR31
EXP072_31_(4-PhbToluene)
NMR31_4-phb_tolS
4-Phenylbutyric acid
Toluene
3.67
NMR32
EXP072_32_(4-PhbDiethylether)
NMR32_4-phb_det
4-Phenylbutyric acid
Diethyl Ether
4.13
NMR33
EXP072_33_(t-CinHexanol)
NMR33_Cin_hex
trans-Cinnamic acid
Hexanol
insoluble
NMR34
EXP072_34_(t-CinToluene)
NMR34_Cin_tol
trans-Cinnamic acid
Toluene
0.23
NMR35
EXP072_35_(t-CinDiethylether)
NMR35_Cin_det
trans-Cinnamic acid
Diethyl Ether
0.54




Discussion

[NMR1 of ASA and THF has lots of impurities and is not zeroed properly - see EXP069 for the THF range - also the proton count is not right JCB] You are right. I just recently figured out how to use the chloroform peak as a reference to get the spectra at the correct ppm. In future experiments, spectral shifts will be manually set using chloroform or the solvent [You don't need to add chloroform to zero the peaks - just look up the shift of the solvent you happen to be using - for example **methanol is 3.31 ppm** JCB] Good point.
Also, it appears that all the THF samples contain the same impurities. Therefore, the THF samples will not be included in the solubility measurements.

Conclusion

Acetylsalicylic acid was insoluble in hexanol and toluene and its solubility was measured to be 1.32 M in methanol and 0.18 M in diethyl ether. L-Ascorbic acid and 4,4-Azoxydibenzoic acid were measured to be insoluble in chloroform, hexanol, diethyl ether, and toluene. The solubility of 4-phenylbutryric acid was measured to be 4.04 M in chloroform, 4.08 M in methanol, 0.50 M in hexanol, 3.67 M in toluene, and 4.13 M in diethyl ether. DL-Mandelic acid was measured to be insoluble in hexanol and toluene, and soluble to 3.62 M in methanol, 0.10 M in chloroform, and 0.98 M in diethyl ether. Trans-Cinnamic acid was measured to be insoluble in hexanol, 1.32 M in methanol. 0.83 M in chloroform, 0.23 M in toluene, and 0.54 M in diethyl ether.

Log

03.27.09 CST

16.06 - Vials filled with solvent and excess solute.[Define the names of the samples and how they correspond to each solute JCB] Names and corresponding solutes and solvents are now under results.
18.08 - Began sonication (21 degrees Celsius)
18.36 - Removed from sonicator (30 degrees Celsius)
18.36 - Left to equilibrate for 72 h 44 min

03.30.09

19.20 - Photos of equilibrated samples [give these a name - like ONSC072pic1 JCB] Pictures have been uploaded. Future picture will be given names like ONSC072pic1 etc. [ Did you notice the temp at this point? JCB] No, I did not check the temperature in the water bath, but the lab temp is usually around 23 degrees Celsius. I will check the temperature when I redo the CHCl3 NMR runs.
[You should only need one spectrum here per sample and use the solubility spreadsheet to calculate the solubilities directly JCB]
19.33 - NMR1a (autogain = 3; spectrum 301; 10 uL CHCl3 added) [Are you taking the NMR with the solid present or did you separate? Are you adding chloroform or CDCl3 JCB] Supernatant liquid that was separated from solid during equilibration was used and CHCl3 was added.
19.41 - NMR1b (autogain = 3; spectrum 302; 20 uL CHCl3 added)
19.46 - NMR1c (autogain = 3; spectrum 304; 40 uL CHCl3 added)
19.59 - NMR1d (autogain = 3; spectrum 312; 100 uL CHCl3 added)
20.16 - NMR2 (autogain = 1; spectrum 315; 20 uL CHCl3 added)
20.29 - NMR3 (autogain = 1; spectrum 317; 20 uL CHCl3 added) [If you added CHCl3 to a saturated CHCl3 solution you cant use the integrations to get the solubility. Adding CDCl3 would have been OK JCB JCB] You are right. I will have to redo the CHCl3 NMR runs without adding CHCl3. I can use the left over equilibrated samples.
20.44 - NMR4 (autogain = 2; spectrum 319; 20 uL CHCl3 added)
20.55 - NMR5 (autogain = 9; spectrum 321; 20 uL CHCl3 added)
21.10 - NMR6 (autogain = 9; spectrum 322; 20 uL CHCl3 added)
21.14 - NMR7 (autogain = 1; spectrum 324; 20 uL CHCl3 added)
21.21 - NMR8 (autogain = 2; spectrum 326; 20 uL CHCl3 added)
21.29 - NMR9 (autogain = 5; spectrum 328; 20 uL CHCl3 added)
21.43 - NMR10 (autogain = 2; spectrum 330; 20 uL CHCl3 added)
21.47 - NMR11 (autogain = 4; spectrum 332; 20 uL CHCl3 added)
21.58 - NMR12 (autogain = 2; spectrum 334; 20 uL CHCl3 added)
22:04 - NMR13 (autogain = 5; spectrum 336; 20 uL CHCl3 added)
22.17 - NMR14 (autogain = 9; spectrum 345; 20 uL CHCl3 added)
22.23 - NMR15 (autogain = 1; spectrum 347; 20 uL CHCl3 added)
22.28 - NMR16 (autogain = 4; spectrum 349; 20 uL CHCl3 added)
22.34 - NMR17 (autogain = 8; spectrum 351; 20 uL CHCl3 added)

03.31.09

17.51 - Room temperature checked (23.0 degrees Celsius)
18.00 - NMR5 (autogain = 9; spectrum 353; no CHCl3 added)
18.04 - NMR9 (autogain = 4; spectrum 355; no CHCl3 added)
18.16 - NMR17 (autogain = 8; spectrum 357; no CHCl3 added)
18.21 - NMR14 (autogain = 9; spectrum 359; no CHCl3 added)
18.26 - NMR6 (autogain = 9; spectrum 361; no CHCl3 added)
18.30 - Cleaned glassware
20.00 - Prepared samples 18-35 (solute and solvent added to vials)
21.30 - Began sonication (22.0 degrees Celsius)
22.00 - Removed from sonicator (31.2 degrees Celsius)
22.00 - Left to equilibrate

04.03.09

15.47 - Photos of Samples 18-35
16.58 - NMR18 (autogain = 1; NMR18_ASA_hex; 20 uL CHCl3 added)
17.10 - NMR19 (autogain = 2; NMR19_ASA_tol; 20 uL CHCl3 added)
17.18 - NMR20 (autogain = 2; NMR20_ASA_det; 20 uL CHCl3 added)
17.30 - NMR21 (autogain = 1; NMR21_LD-Ma_hex; 20 uL CHCl3 added)
17.38 - NMR22 (autogain = 2; NMR22_LD-Ma_tol; 20 uL CHCl3 added)
17.46 - NMR23 (autogain = 2; NMR23_LD-Ma_det; 20 uL CHCl3 added)
17.57 - NMR24 (autogain = 1; NMR24_Asc_hex; 20 uL CHCl3 added)
18.09 - NMR25 (autogain = 2; NMR25_Asc_tol; 20 uL CHCl3 added)
18.16 - Room temperature checked (23.0 degrees Celsius)
18.21 - NMR26 (autogain = 2; NMR26_Asc_det; 20 uL CHCl3 added)
18.28 - NMR27 (autogain = 1; NMR27_44-az_hex; 20 uL CHCl3 added)
18.38 - NMR28 (autogain = 2; NMR28_44-az_tol; 20 uL CHCl3 added)
18.44 - NMR29 (autogain = 2; NMR29_44-az_det; 20 uL CHCl3 added)
18.53 - NMR30 (autogain = 1; NMR30_4-phb_hex; 20 uL CHCl3 added)
19.01 - NMR31 (autogain = 2; NMR31_4-phb_tol; 20 uL CHCl3 added)
19.13 - NMR32 (autogain = 3; NMR32_4-phb_det; 20 uL CHCl3 added)
19.24 - NMR33 (autogain = 1; NMR33_Cin_hex; 20 uL CHCl3 added)
19.35 - NMR34 (autogain = 2; NMR34_Cin_tol; 20 uL CHCl3 added)
19.46 - NMR35 (autogain = 2; NMR35_Cin_det; 20 uL CHCl3 added)
19.54 - Room temperature checked (23.0 degrees Celsius)

References

[1] Bradley, Jean-Claude. Semi-automated measurement of solubility using NMR. 3 March 2009. 4 April 2009. http://usefulchem.blogspot.com/2009/03/semi-automated-measurement-of.html

[2] Mirza, Khalid, Tchakounte, Cedric. Verifying the concentrations of 0.25M 4-pyrenebutanoic acid solution and 1.25M crotonic acid solution in DMSO by HNMR. 7 March 2009. 4 April 2009. http://onschallenge.wikispaces.com/Exp067

Solubility of Acetylsalicylic Acid in Organic Solvents
Solubility of Acetylsalicylic Acid in Diethyl Ether (solubility data viewer)
Solubility of Acetylsalicylic Acid in Methanol (solubility data viewer)

Solubility of 4-Phenylbutyric Acid in Organic Solvents
Solubility of 4-Phenylbutyric Acid in 1-Hexanol (solubility data viewer)
Solubility of 4-Phenylbutyric Acid in Chloroform (solubility data viewer)
Solubility of 4-Phenylbutyric Acid in Diethyl Ether (solubility data viewer)
Solubility of 4-Phenylbutyric Acid in Methanol (solubility data viewer)
Solubility of 4-Phenylbutyric Acid in Toluene (solubility data viewer)

Solubility of Mandelic Acid in Organic Solvents
Solubility of Mandelic Acid in Chloroform (solubility data viewer)
Solubility of Mandelic Acid in Diethyl Ether (solubility data viewer)
Solubility of Mandelic Acid in Methanol (solubility data viewer)

Solubility of Cinnamic Acid in Organic Solvents
Solubility of Cinnamic Acid in Chloroform (solubility data viewer)
Solubility of Cinnamic Acid in Diethyl Ether (solubility data viewer)
Solubility of Cinnamic Acid in Methanol (solubility data viewer)
Solubility of Cinnamic Acid in Toluene (solubility data viewer)

Solubility of Ascorbic Acid in Organic Solvents

Solubility of Azoxydibenzoic Acid in Organic Solvents

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 lab, Dr. Jean-Claude Bradley for his helpful comments throughout the course of the experiment, Dr. Andrew Lang for his help with SAMS, and Dr. Hal Reed for the use of the department camera for the second series of measurements.

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