Exp047imineform.JPG

Objective

To monitor the formation of an imine, the first step in the Ugi reaction with 3,4-dihydroxybenzaldehyde and 5-methylfurfurylamine in deuterated methanol (CD3OD).

Procedure

1 mL of 1 M methanol-D4 solutions of 3,4-dihydroxybenzaldehyde (138mg, 1mmol) and 5-methylfurfurylamine (111uL, 1mmol) are prepared in separate 1 dram vials. 800uL of the solutions are used to obtain initial H NMR spectra. Then 400uL of each solution is transfered to a clean NMR tube and shaken vigorously for a few seconds. The formation of an imine is monitored by 300 MHz proton NMR.

Results

(*Spectra obtained on a Varian Inova 300MHz instrument, unless specified otherwise)
5-methylfurfurylamine
HMR
3,4-dihydroxybenzaldehyde
HMR
Reaction Mixture
t=3min
t=10min
t=14min
t=17min
t=20min
t=23min
t=26min
t=36min
t=47min
t=59min
t=66min
t=76min
t=86min
t=99min
t=112min
t=129min
t=148min
t=180min
t=208min
t=21h 50min
t=24h 36min
t=46h 27min
t=60h 36min

Kinetics - Excel Data Sheet

Overlays


Discussion

  1. The addition of the aldehyde shifts the methylene group next to the amine from 3.67 to 3.87 ppm. This is clearly due to the acidity of the phenolic groups since a similar shift is not observed for the dimethoxy derivative.(EXP054)
  2. At initial concentrations of 0.5M, the aldehyde and amine react too quickly within the first few minutes to get an accurate rate constant but using the points up to ~78% conversion an estimate of 1.043 E-1 /M*min can be obtained from the disappearance of the aldehyde peak at 9.65 and 2.559 E -1 /M*min from the disappearance of the amine methylene group at 3.87 ppm.
  3. Based on the available data with respect to the conversion of the aldehyde peak to the imine peak, the dimethoxy analog yielded a rate constant of 1.062 E -1 /M*min with ~20% conversion at t=4min (EXP046), and the methylenedioxy analog yielded a rate constant of 1.552 E -1 /M*min with ~50% conversion at t=10min (EXP043). The rate constant for the dihydroxy analog was calculated to be less than the other analogs with respect to aldehyde peak conversion, though was calculated to be twice the amount of the others with respect to amine peak conversion. Due to the higher calculated imine concentration at the time the initial NMR (55% at t=3min) was taken, the rate constant with respect to amine disappearance could be more probable to be applied to this reaction.
  4. The NMR after 60 hours shows disappearance of the 3.87 ppm peak indicating complete reaction of the amine but still some leftover aldehyde. Based on the integration of the aldehyde and imine protons, there was a 15% excess of aldehyde.

Conclusion

The imine formation using the dihydroxy analog initially proceeds at a very fast rate, then tapers off over a period of time. This experiment should be attempted with an excess of amine to see if product formation is reached faster.

Log

2007-01-20

14:03 - Prepared 1 M methanol-D4 solutions of 3,4-dihydroxybenzaldehyde and 5-methylfurfuylamine using separate 1mL volumetric flasks, then transferred 800 uL of each solution to a separate NMR tube via 100-1000 uL Eppendorf pipet, then capped.
17:10 - Acquired HMR for 5-methylfurfuryl amine
17:13 - Acquired HMR for 3,4-dihydroxybenzaldehyde
17:22 - Mixed the two solutions into a vial, shook vigorously for one minute. Transferred 800 uL of the mixture into a clean NMR tube via 100-1000 uL Eppendorf pipet.
17:25 - Obtained HMR (t=3min)
17:32 - Obtained HMR (t=10min)
17:36 - Obtained HMR (t=14min)
17:39 - Obtained HMR (t=17min)
17:42 - Obtained HMR (t=20min)
17:45 - Obtained HMR (t=23min)
17:48 - Obtained HMR (t=26min)
17:58 - Obtained HMR (t=36min)
18:09 - Obtained HMR (t=47min)
18:21 - Obtained HMR (t=59min)
18:28 - Obtained HMR (t=66min)
18:38 - Obtained HMR (t=76min)
18:48 - Obtained HMR (t=86min)
19:01 - Obtained HMR (t=99min)
19:14 - Obtained HMR (t=112min)
19:31 - Obtained HMR (t=129min)
19:50 - Obtained HMR (t=148min)
20:22 - Obtained HMR (t=180min)
20:50 - Obtained HMR (t=208min)

2007-01-21

15:12 - Obtained HMR (t=21h 50min)
17:58 - Obtained HMR (t=24h 36min)

2007-01-22

14:49 - Obtained HMR (t=46h 27min)

2007-01-23

14:58 - Obtained HMR (t=60h 36min)

Tags

3,4-dihydroxybenzaldehydeInChI=1/C7H6O3/c8-4-5-1-2-6(9)7(10)3-5/h1-4,9-10H
5-methylfurfurylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
imine InChI=1/C13H13NO3/c1-9-2-4-11(17-9)8-14-7-10-3-5-12(15)13(16)6-10/h2-7,15-16H,8H2,1H3/b14-7-