Exp084_03-29-07.JPG

Objective

To see if steric hindrance will prevent the formation of the imine between piperonal and aniline in CDCl3. The Ugi reaction of this imine with boc-gly and t-butyl isocyanide will then be attempted.

Procedure

Prepared solutions of piperonal(150.3 mg, 1 mmol, 2 mL CDCl3, 0.5 M) and aniline(91 uL, 1 mmol, 2 mL CDCl3, 0.5 M). Mixed aldehyde and amine solutions together in a 13 mL vial in the presence of 97(Ymg) 3A molecular sieves. Added 415 mg of MgSO4 to imine solution to remove water generated from reaction then filtered. Prepared a solution of Boc-Gly-OH(188.0 mg, 1.07 mmol, 2 mL CDCl3, 0.536 M) and tert-butylisocyanide(113 uL, 1 mmol, 2 mL CDCl3, 0.5 M) in 2 mL volumetric flasks. Added the two solutions in a 5 mL volumetric flask shook well and then added to imine solution.

Results

Characterization of Starting Materials

Piperonal(Used from same bottle in Exp076)
Aniline
Boc-Gly-OH
tertbutylisocyanide

Imine Formation

H NMR 1 hr 084A
H NMR 24 hrs 084B
H NMR 3 days 084C

Addition of Acid and Isocyanide

H NMR 2 hrs 084D

Overlays

ImineRxn overlay
UgiRxn overlay
Exp084 Excel

Discussion

  1. The imine reaction reaches completion after 24 hours where all of the amine (peaks 3.65 ppm and 4.05 ppm) is used up but about 1.5% extra aldehyde (peak 9.8 ppm) remains. The disappearing peaks from 1 hour to 24 hours at 1.20 ppm lies with the used up amine as they are present in the raw HMR of aniline. In the HMR of the raw starting aniline, the 1.20 ppm peaks seem to be an impurity. The increase in intensity of these peaks in the imine HMR after 1 hours (84A) is most likely due to an error of the Sun software or some other NMR glitch. Compared to Exp048 the reaction seems to be 25% fast at the 1 hour mark however the overall rate is still 8.0*10^-3 [1/M*min].
  2. The percentage of imine after three days is 99.85% which is relative to the amine. Since virtually all of the amine reacts in the three day period giving an extra 3.1% aldehyde concentration.
  3. Once the acid and isocyanide was added, the integration of the imine (8.3 ppm) after two hours decreases 97% relative to the percentage of the amine and the aldehyde increases 37% relative to the imine only. This means that the imine is being used up and reverting back to the aldehyde. In this experiment, almost 682mg of 3A molecular sieves and 415mg of MgSO4 was used to dry the imine solution. This means one of two things, either there is still a lot of water in the solution to reverse the imine reaction, or there are other reasons why the imine reverses significantly after the addition of the acid.
  4. There was no initial NMR taken after the addition of the acid and isocyanide and only the one taken after two hours so no kinetics and not relative concentrations can be determined. The imine decrease to 1.37% compared to that of the amine.
  5. There are new peaks surrounding the imine peak at 7.85ppm, 8.05ppm, 8.2ppm, and 8.6ppm after the addition of the acid and isocyanide. This means that the imine participated in other reactions besides the Ugi reaction. The crystalline Ugi product did not form possibly because of these side reactions that were for whatever reason more favorable however the peaks around 5.8 and 5.88 and 6.1ppm possibly correspond to one NH group, chiral proton, and furan protons. These results of the enantiomeric proton are consistent with other results from Exp052.


Conclusion

The imine was not reversed to the aldehyde and no crystalline Ugi product was formed however some of the Ugi product was formed compared to previous NMR were the Ugi product was isolated.

Log

2007-03-29

16:40 Prepared solutions of piperonal(150.3 mg, 1 mmol, 2 mL CDCl3, 0.5M) and aniline(91 uL, 1 mmol, 2m L CDCl3, 0.5 M).
17:30] Mixed aldehyde and amine solutions together in a 13 mL vial in the presence of 97(x mg) 3A molecular sieves. Solution was pale yellow.
17:52 Took 200uL of imine solution and added about 2 mL of CDCl3 to take an initial H NMR
18:40 Took H NMR 1 hr. 84A

2007-03-30

17:55 Took sample of imine solution and without diluting used for H NMR
18:15 Took H NMR 24.5 hrs 84B

2007-04-02

11:00 Took H NMR of imine solution 084C
11:52 Added 415 mg of MgSO4 to imine solution. Shook well and let sit for several minutes. Filtered solution into new 13 mL vial.
12:25 Prepared a solution of Boc-Gly-OH(188.0 mg, 1.07 mmol, 2 mL CDCl3, 0.536 M) and tert-butylisocyanide(113 uL, 1 mmol, 2 mL CDCl3, 0.5 M) in 2 mL volumetric flasks. Added the two solutions in a 5 mL volumetric flask shook well and then added to imine solution. Solution turned deep yellow to orange in color.
14:15 Took H NMR 84D

Tags

Piperonal InChI=1/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2
Aniline InChI=1/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2
t-butyl isocyanide InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
Boc-Gly-OH InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)