ugi_exp52.JPG

Objective:

To obtain the Ugi product formed when using 5-methylfurfurylamine, Boc-Gly-OH, t-butyl isocyanide, and piperonal.

Procedure:


To four separate vials was added piperonal (0.150 g, 1 mmol), 5-methylfurfurylamine (111 uL, 1 mmol), Boc-Gly-OH (0.175 g, 1 mmol), and t-butyl isocyanide (113 uL, 1 mmol) and diluted to approximately 1 mL with deuterated chloroform. This was used to take the NMR spectra of the starting mateials. To four separate vials was added piperonal (0.150 g, 1 mmol), 5-methylfurfurylamine (111 uL, 1 mmol), Boc-Gly-OH (0.175 g, 1 mmol), and t-butyl isocyanide (113 uL, 1 mmol) and diluted to approximately 1 mL with methanol.400uL samples were taken and solvent was evaporated off using hgh vacuum. 1mL CDCl3 was added and NMR spectra were taken of each. In a separate scintillation vial were added piperonal and 5-methylfurfurylamine solutions and allowed to sit for approximately 3 hours. A 400uL sample was taken and solvent was evaporated off using high vacuum. 1mL CDCl3 was added and NMR spectra was taken to confirm the formation of the imine. The Boc-Gly-OH solution was then added to the vial and shaken for approximately 30 seconds. Solution was allowed to sit for approximately 30 mins, 400uL sample was taken, solvent evaporated off, and an NMR spectra was taken of the reaction. The t-butyl isocyanide solution was then added to the solution and then monitored by NMR after evaporation of solvent using high vacuum..

Results:


Starting Materials

Piperonal

HNMR, CMR

5-Methylfurfurylamine

HNMR, CMR


Boc-Gly-OH

HNMR, CMR

Tert-Butyl Isocyanide

HNMR, CMR

Imine Formation (59A)

HNMR, CMR

Addition of Boc-Gly-OH (59B)

HMR

Addition of tert-Butyl Isocyanide (59C)

HNMR, CMR

Crystals (59D)

74mg, m.p.174C
HNMR, CMR


Discussion:

1. Proton Assignments (59D):
a. t-butyl groups (s at 1.43ppm and 1.31ppm)
b. methyl group of 5MFA (s at 2.15ppm)
c. methylene groups of Boc-Gly-OH and 5MFA (singlets at 4.4ppm and 4.2ppm)
d. amide protons (singlets at 5.47ppm and 5.7ppm) It was proven in experiment 52 (exp052) that one of the amide protons is hidden in the peak at 5.7ppm by adding methanol d4 to the NMR tube.
e. furan protons (singlet at 5.7ppm)
f. methylene group of piperonal (doublet at 5.9ppm)
g. aromatic protons (multiplet at 6.7ppm)

2. At this time it is hard to make accurate assignments of the CMR of the Ugi product without 2D NMR such as HETCOR or DEPT.

3. The HMRs and CMR of 59B and 59C are inconclusive because of the methanol peak that is seen at ppm. There is also a shimming problem with the reference peak. This is possibly due to an unsuccessful evapoation of solvent under vacuum.

Conclusion:

The Ugi product was formed based on the HNMR of the crystals (59D). This experiment shows that this particular method is reproducible for obtaining the Ugi Adduct. It may be useful to do a more in-depth kinetcs study of the last step. This may explain why the crystals took four days to form in this experiment as opposed to 24hrs in experiment 52 (exp052).

Log:


2007-02-07

12:40 Prepared 1M solutions of 5-MFA and piperonal. Took NMRs.
13:03 Mixed solutions together (pale yellow).
16:02 Prepared 1M solution of Boc-Gly-OH. Took NMR spectra of Boc-Gly-OH.
16:28 Took 400ul sample from reaction flask and took NMR spectra to confirm imine formation (59A).
17:32 Confirmed imine formation. Added Boc-Gly-OH (solution turned a deeper hue of yellow.
17:55 Prepared 1M solution of t-butyl isocyanide.
18:04 Took NMR spectra of t-butyl isocyande.
18:42 Removed 400uL sample from reaction vial. Took NMR spectra (had problems getting the NMR to shim correctly). Saw huge (relatively) peak at 3.2ppm compared to imine and aldehyde peak (59B).
18:48 Added t-butyl isocyanide.

2007-02-08

11:50 Took 800uL sample of reaction (59C). Got white solid after placing sample in high vacuum. Took NMR spectra.

2007-02-13

10:36 Noticed formation of crystals at the bottom of the flask.

2007-02-22


12:04 Emptied out contents of reaction flask into centrifuge tube and rinsed flask with methanol. Placed tube in centrifuge and allowed it to run for approximately 30 seconds. Removed liquid from top and flushed under nitrogen to get rid of remaining solvent. Took mass of crystals remaining, 136mg.

2007-02-23


12:30 Weighed out 74mg of crystals and dissolved in 1mL chloroform (59D) for NMR characterization. Took NMR spectra.
13:00 Took melting point of crystals, 174C.

Tags

PiperonalInChI=1/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2
5-methylfurfurylamineInChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
t-butyl isocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
Boc-Gly-OHInChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)
imine:InChI=1/C14H13NO3/c1-10-2-4-12(18-10)8-15-7-11-3-5-13-14(6-11)17-9-16-13/h2-7H,8-9H2,1H3/b15-7-ugi052:InChI=1/C26H35N3O7/c1-16-8-10-18(35-16)14-29(21(30)13-27-24(32)36-26(5,6)7)22(23(31)28-25(2,3)4)17-9-11-19-20(12-17)34-15-33-19/h8-12,22H,13-15H2,1-7H3,(H,27,32)(H,28,31)