Exp094

Researcher
David Bulger

Objective
To verify the SAMS method with 2.80 M 4-phenylbutyric acid in THF.

Procedure
Made up a of 2.81 __M__ solution of 2-phenylbutyric acid in THF and used both SAMS and internal standard methods to measure concentration.

NMR
[|ONSCEXP094] This is the NMR spectrum of the 2.81 M 2-phenylbutyric acid in THF solution [|Raw JCAMP-DX file for ONSCEXP094]

Spreadsheet
[|ONSCExp094] This is the spreadsheet containing calculations.


 * [Where did you get the density values for the solvents? What do you mean by "standard deviation" in the pipette calibration calculations? BTW I am very pleased to see someone checking the accuracy of their pipetting; I think this is the first time in the whole project that this has been done. --BH]** The density values of the solvents were obtained from the [|SigmaAldrich database]. I used the excel STDEV function to calculate standard deviation values. The standard deviation gives how precise the measurement is and how many significant figures are allowed.


 * [I have never seen std dev used in this manner and cannot understand what any measure of variance might be telling us here. It cannot be related to precision, because you are comparing two measurements derived from entirely different methods. --BH]** You are right; std dev need not have been used.

[|ONSC094-IS] This is the spreadsheet containing SAMS and internal standard solubility data. media type="googlespreadsheet" key="rDet-iooN3i6f7nAMUHzAPw" height="400" width="900" media type="googlespreadsheet" key="rFMItWXH16wyO9UmLidr3Og" height="400" width="900"
 * [note that you can't use the aromatic range at all because you have a residual CHCl3 peak at 7.27 ppm JCB]** You are right. I did not notice the residual CHCl3 peak. It seems like the only peak without overlap is the carboxylic acid peak, which I changed the measurements to.

Pictures
Note: These pictures are compressed. Higher resolution photos are available. [|Exp94-01] [|Exp94-02] [|Exp94-03] [|Exp94-04] [|Exp94-05] [|Exp94-06] [|Exp94-07]

Comparison

 * Label || Concentration (__M__) ||
 * Known Concentration || 2.81 ||
 * SAMS Result || 1.75 ||
 * Internal Standard Result || 2.77 ||

Discussion
For the known concentration of 2.81 __M__ of 2-phenylbutyric acid in THF, SAMS measured the solubility to be 1.75 __M__. This is an error of about 37.7%. Using the internal standard method, the solubility was measured to be 2.77 __M__. This is an error of about 4%. Part of this error may be due to the expansion of solution during the experiment. This would cause the measured concentration values to be lower than the actual concentration as was observed.

Conclusion
With a 2.81 __M__ solution of 2-phenylbutyric acid in THF, SAMS appears to measure solubility with an accuracy of about 37.7% and internal standard method with an accuracy of about 4%. **[This is potentially a Big Deal, given the degree of reliance on the SAMS method throughout the project. Can you generalize from this to which other SAMS measurements might need to be re-validated using an internal standard? Why might integrating over the dissociable acid proton be giving rise to an apparent error? --BH]** The SAMS method is not expected to give 4% accurracy, but about 20-30%. This method of quick measurement of solubility has been utilized to generalize about how soluble one of the starting materials for a certain Ugi product would be in certain solvents. For example, a SAMS measurement of the solubility of 4-methoxyphenylacetic acid was 3.56M in THF. Using this information, a 1M solution could be easily made and potentially even a 3M solution (although not needed). Even if the actual solubility is closer to 2.9M, it still serves its purpose. However, the internal standard method does not take much longer and does seem to be more accurate, which is needed for border-line compounds like 4-phenylbutanoic acid. [**I don't think that this experiment proves very much either way - the NMR is very poor quality and the solvent peak overlaps with the reference compound. This should be redone with a reference compound that does not overlap with any peaks JCB]**

2009-05-19
10:26 Weighed three half-dram vials: A700 (2.417 7 g), B100 (2.430 9 g), C10 (2.418 3 g) 10:28 Added 700 uL of chloroform-d to A700 10:30 Weighed A700 (3.230 0 g) 10:31 Added 100 uL of THF B100 10:32 Weighed B100 (2.431 1 g) 10:33 Added 10 uL of 1,2-dichloroethane to C10 10:36 Weighed C10 (2.431 1 g) 13:05 Sonicator temperature is 23 degrees Celsius 13:06 Weighed 2-mL volumetric flask (18.120 4 g) **[Is this sample 94-1A, as per the spreadsheet ONSCExp094? --BH]** Yes, I had labeled it ONSC93-1A originally. However, I did not realize that this experiment would be Exp094. So on the spreadsheet I referred to it as 94-1A. 13:12 Added 2-phenylbutyric acid to volumetric flask and weighed (19.041 1 g) 13:19 Added THF up to 2-mL mark and weighed (20.093 2 g) 13:25 Parafilmed, supported with copper wire, and labeled (ONSC93-1A) 13:26 Photos ([|Exp94-01], [|Exp94-02]) 13:27 Began sonication (23 degrees Celsius) 14:02 Remove from sonicator 14:05 Sonicator temperature is 32 degrees Celsius 14:06 Photos ([|Exp94-03], [|Exp94-04]) - solution expanded past 2-mL mark **[Can you estimate the likely effect of this on concentration? Should you repeat the experiment because of this? --BH]** It would most likely lower the concentration measured in this experiment, which was observed. As the extent of the expansion was not measured, it would be difficult to accomodate for this in a repeat of the experiment. Although a repeat of this experiment would provide several more values that would help lead to a more accurate conclusion. 16:47 Photos ([|Exp94-05], [|Exp94-06]) 16:51 Labeled NMR prep vial (93-NA) 18:36 Added 700 uL of chloroform-d to 93-NA 18:38 Added 100 uL of solution from ONSC93-1A to 93-NA 18:39 Added 10 uL of 1,2-dichloroethane to 93-NA 18:39 Vortexed for 30 sec 18:40 Tranferred solution from 93-NA to NMR tube (93) 18:42 Photo ([|Exp94-07]) 18:43 Reparafilmed volumetric flask 21:00 Parafilmed NMR tube

2009-05-20
12:05 NMR of [|ONSCEXP094]