To monitor the formation of an imine using piperonal and 5-methylfurfurylamine in deuterated methanol.


In separate one dram vials was added piperonal (0.150g, 1mmol) and 5-methylfurfurylamine (111uL, 1 mmol) and diluted to approximately 1mL with deuterated methanol. NMR spectra were taken of the solutions (300 MHz) upon transfer to NMR tubes. The solutions were then combined in a separate vial and allowed to sit for 10 minutes. Spectra was taken of the mixture at evenly spaced intervals. To a separate one dram vial was added Boc-Gly-OH (0.175g, 1 mmol) and diluted to approximately 1mL with deuterated methanol. Spectra were taken of the solution and then it was added to solution of piperonal and 5-methylfurfurylamine. Reaction was monitored via NMR during spaced time intervals.


Imine Formation:

Starting Materials

5-methylfurfurylamine (HNMR) (d 6.0 furan H's, bs at 4.7 NH2, s at 3.6 CH2, s at 2.2 CH3)
5-methylfurfurylamine (CMR) (peak at 12 ppm CH3, peak at 39ppm CH2, peak at 116ppm 2- CH groups, peaks at 151 and 154- quaternary carbons)
Piperonal (HNMR) (s at 9.8- aldehyde proton, s btw 6.9-7.5 aromatic protons, s at 6.2, methylene protons)
Piperonal (CMR) (aldehyde peak at 191 ppm, quaternary carbons at 132, 149, &154 ppm, remaining aromatic carbons at 129, 106, 108 ppm, methylene dioxy carbons at 102ppm)

10 mins

HNMR-IF(T=10) (53.6% conversion to imine)

20 mins

HNMR-IF (T=20) CMR-IF (T=20) (62.9% conversion to imine)

40 mins

HNMR-IF (T=40) CMR-IF (T=40) (76.3% conversion to imine)

90 mins

HNMR-IF (T=90) CMR-IF (T=90)

172 mins

HNMR-IF (T=172) CMR-IF (T=172) (98.5% conversion to imine)

Addition of acid

Starting materials

HNMR Boc-Gly-OH (OH group at 5.1, t-butyl group at 1.5, methylene group at 3.7)
CMR Boc-Gly-OH (t-butyl group at 28ppm, methylene group at 41ppm, amide group at 158ppm, and carboxylic acid group at 172ppm)

10 mins

HMR-AA (T=10 min)

20 mins

HMR-AA (T=20mins)

30 mins

CMR-AA (T=30 mins)

40 mins

HMR-AA (T=40min)

45 mins

CMR-AA (T=45 mins)

83 mins

HMR-AA (T=83 mins)

90 mins

CMR-AA (T=90 mins)

180 mins

HNMR-AA (T= 180 mins)

185 mins

CMR-AA (T=185 mins)

Other Data
Imine Formation Spreadsheet


Based on the integration of the methyl and imine peaks in the NMR, there appears to be a mistake in the molar ratios of the amine and aldehyde (incorrect by a factor of 2). Despite this, the NMR data showed that imine formation was successful approximately three hours after the amine and aldehyde were added. This is significantly faster as compared with performing the experiment in CDCl3 as was done in a previous experiment.


Imine formation is much faster in a polar solvent.



11:25 Prepared solutions of 1M 5-methylfurfurylamine (pale yellow) and piperonal.
11:35 Took NMRs of starting materials.
12:40 Mixed solutions together in a separate one dram vial.
12:56 Took HNMR of solution (T=10 min).
1:05 Took HNMR and CMR of solution (T=20min).
1:35 Took HNMR and CMR of solution (T=40 min).
2:23 Took HNMR and CMR of solution (T=90 min).
3:45 Took HNMR and CMR of solution (T=172 min).


11:35 Prepared solution of 1M Boc-Gly-OH.
11:53 Took CMR and HNMR of Boc-Gly-OH.
12:50 Added Boc-Gly-OH to imine solution. Solution turned bright yellow.
13:00 Took HNMR of solution (T=10min).
13:10 Took HNMR of solution (T=20min).
13:20 Took CMR of solution (T=30min).
13:30 Took HNMR of solution (T=40 min).
13:35 Took CMR of solution (T=45 min).
14:13 Took HMR of solution (T=83min).
14:20 Took CMR of solution (T=90 min).
15:50 Took HMR of solution ( T=180 min)
15:55 Took CMR of solution (T= 185 min)


imine040 InChI=1/C15H15NO3/c1-11-2-4-13(19-11)9-16-7-6-12-3-5-14-15(8-12)18-10-17-14/h2-5,7-8H,6,9-10H2,1H3/b16-7+