Researcher

Khalid Mirza & Hai Truong

Objective

To study the effect of phenylacetic acid (PAA) concentration on the solubility of the Ugi product UC176 in benzene

Procedure

a) Make-up 0.1M, 0.2M, 0.3M, 0.4M and 1.0M phenylacetic acid solutions in benzene.
b) Saturate the solutions with the Ugi product UC176C (UC251-1C ) by first maintaining the resulting solution at 40C for 30min and then getting it to equilibrate at 25C for atleast 30 min.
c) Centrifuge the solution, separate the supernatants and obtain there HNMRs.
d) Measure the concentration of the Ugi product in each solution using SAMS


Results

Spreadsheet ONSCExp146-i



Discussion

At different concentrations of phenylacetic acid in benzene the solubility of the Ugi product 176C at 25C was estimated by HNMR by integrating the methyl peak of the Ugi product 0.8-0.9 ppm. The results are summarized in Table 146-i.

Table 146-i.
Sample number
Acid Conc (M)
Ugi productSolubility (M)
ONSCExp146-1A
0.94
0.20
ONSCExp146-2A
1.03
0.19
ONSCExp146-3A
0.39
0.14
ONSCExp146-4A
0.40
0.13
ONSCExp146-5A
0.20
0.11
ONSCExp146-6A
0.17
0.11
ONSCExp146-7A
0.09
0.10
ONSCExp146-8A
0.09
0.09
ONSCExp146-9A
0.07
0.07
ONSCExp146-10A
0.03
0.16
ONSCExp146-iv.jpg
Figure 1: Solubility of the Ugi product UC176C as a function of phenylacetic acid concentration in benzene

  • It appears that the solubility of the Ugi product UC176C is directly related the concentration of phenylacetic in the reaction mixture . The plot (Figure 1) of Ugi product solubility as a function of phenylacetic acid concentration shows a linear increase in the solubility of the Ugi product 176C with an increase in the concentration of phenylacetic acid in benzene.
  • However, at lower concentrations of phenylacetic acid (0.05M to 0.1M) there is steep increase in the solubility of the Ugi product. More data points up to 0.1M phenylacetic acid concentration may help confirm this effect.
  • Previous results (ONSCExp144) have been incorporated in the plot to account for the solubility of the Ugi product in benzene with no co-solutes.
  • Results from sample OSNCExp146-9A and 10A do fit the pattern in general, these samples are mislabeled, which is obvious from SAMS estimation of phenylacetic acid concentration. Therefore results from these samples have been discarded.
  • From the plot it is obvious that phenylacetic acid causes the Ugi product to be more soluble in the solution, thereby contributing to its relatively poor yield in a four component Ugi reaction in benzene. Assuming that phenylacetic acid is the major contributor for the enhanced solubility of the product, estimating its concentration in a Ugi reaction, could enable one to predict the concentration at which the product would precipitate out.
  • In the UsefulChem Exp249, its concentration just before the time when the Ugi product started to precipitate out was measured at 0.22M (both major and minor products) and 0.18M for just the major product. Concentration of phenylacetic acid at the time was estimated to be 0.187M (similar to butylisocyanide). Assuming a linear a change upto 0.1M acid concentration, the expected solubility for the Ugi product is estimated to be 0.098M, which is less than half its observed concentration (0.22M).
  • Therefore based on the above result, it is concluded that, know the concentration of just the acid (or any other component) by them themselves is not enough to explain the solubility of the Ugi product in benzene. There are obviously other component effects on its solubility.
Acid conc right
before product ppt

Observed Ugi product conc
right before precipitation

Estimated Ugi product
conc right before ppt

0.187M
0.22M
0.098

[How much supernatant was taken for these samples? - 200uL (Khalid).The peak shapes and signal to noise is poor in many places JCB]- What is the large peak at 3.4 ppm? JCB] - I guess it is the acid proton, I'm not quite positive.(Khalid)

Conclusion


Solubility of the Ugi product 176C linearly increases with an increase in the concentration of phenylacetic acid in benzene. However its solubility also depends on other components in the reaction.

Log

2009-11-09
13:00 Turned on the water/glycol bath of a heating/ cooling device and set the temperature to 40C.
15:00 Made-up following solution of phenylacetic acid (PAA) in benzene in one dram vials
883.0uL benzene +116.96uL PAA 136mg - 0.999M; solution 146A
953.6uL benzene + 46.39uL PAA: 54mg - 0.397M; solution 146B
964.4uL benzene + 35.22uL PAA :41mg - 0.301Ml; solution 146C
976.8uL benzene + 23.19uL PAA - 27mg - 0.198M; solution 146D
987.9uL benzne + 12.02uL PAA - 14mg - 0.103M; solution 146E
15:20 Placed Ugi product UC251-1C in to ten clean and dry half dram vial, labeled ONSCExp146-1 through ONSCExp146-10.
15:35 Pipetted out solution 146A (200uL) with a micropipette (100-1000uL) in to vials ONSCExp146-1 and ONSCExp146-2, vortexed the resulting solution and made sure some of the Ugi product remained undissolved. The vials were tightly parafilmed.
15:37 Pipetted out solution 146B (200uL) with a micropipette (100-1000uL) in to vials ONSCExp146-3 and ONSCExp146-4, vortexed the resulting solution and made sure some of the Ugi product remained undissolved. The vials were tightly parafilmed.
15:40 Pipetted out solution 146C (200uL) with a micropipette (100-1000uL) in to vials ONSCExp146-5 and ONSCExp146-6, vortexed the resulting solution and made sure some of the Ugi product remained undissolved. The vials were tightly parafilmed.
15:45 Pipetted out solution 146D (200uL) with a micropipette (100-1000uL) in to vials ONSCExp146-7 and ONSCExp146-8, vortexed the resulting solution and made sure some of the Ugi product remained undissolved. The vials were tightly parafilmed.
15:47 Pipetted out solution 146C (200uL) with a micropipette (100-1000uL) in to vials ONSCExp146-9 and ONSCExp146-10, vortexed the resulting solution and made sure some of the Ugi product remained undissolved. The vials were tightly parafilmed.
16:01 Placed the ten vials in the water/glycol bath at 40C.
16:47 Changed the temperature setting of the water/ glycol to 25C.
18:08 Removed the vials from the water/glycol bath.
18:15 Pipetted out DMSO-d6 in to ten clean and dry one dram vials labeld A-J.
18:20 Centrifuged the vials containing ONSCExp146-1 through ONSCExp146-10.
18:30 Pipetted out the supernatant in to one dram vials and obtained the solutions below
Supernatant source vial
DMSO-d6 vial
DMSO-d6 & supernatant solution
ONSCExp146-1
A
ONSCExp146-1A
ONSCExp146-2
B
ONSCExp146-2A
ONSCExp146-3
C
ONSCExp146-3A
ONSCExp146-4
D
ONSCExp146-4A
ONSCExp146-5
E
ONSCExp146-5A
ONSCExp146-6
F
ONSCExp146-6A
ONSCExp146-7
G
ONSCExp146-7A
ONSCExp146-8
H
ONSCExp146-8A
ONSCExp146-9
I
ONSCExp146-9A
ONSCExp146-10
J
ONSCExp146-10A
19:00 Transferred the above solutions in to ten clean and dry NMR tubes.
21:30 Completed obtaining HNMRs of the solutions.