exp054.gif


Objective

To synthesize a Ugi adduct (link) with 3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, tert-butylisocyanide and Boc-Gly-OH in methanol, while preforming the inime via azeotropic distillation in chloroform to remove the water formed by imine synthesis step.

Procedure

Placed 3,4-dihydroxybenzaldehyde (276 mg, 2 mmol) and 5-methylfurfurylamine (245 uL, 2.2 mmol) into a 25 mL flask, and dissolved in 8 mL chloroform with stirring. The mixture was left to stir for for half an hour unheated. The flask was then hooked up to a distillation apparatus and allowed to distill through the use of a water bath. The residue was then placed under vacuum to dry for approx 1.5 h. The residue was then dissolved in 5 mL methanol, and Boc-Glycine (350 mg, 2 mmol) was added, and allowed to stir for 20 minutes, then t-Butyl isocyanide (226 uL, 2 mmol) was then added to the reaction.


Results

(*Spectra obtained on a Varian Inova 300 MHz instrument, unless specified otherwise)
3,4-Dihydroxybenzaldehyde
H NMR (CD3OD, from Exp047)
5-Methylfurfuylamine
H NMR (CD3OD, from Exp047)
Boc-Gly-OH
H NMR (CD3OD, from Exp054)
tert-Butylisocyanide
H NMR (CD3OD, from Exp052)
Preformed Imine 94A
H NMR

Overlays

Comparison of Imine formed in this experiment against that in Exp063.
H NMR Overlay

Discussion

1.) Chloroform was chosen as a solvent because of it's ability to form an azeotrope with water, and its lower boiling temperature than methanol as reaction solvent (97.3% CHCl3/2.7% H2O, BP 56.1C [see Ref 1].
2.) New peaks appear in the imine spectra taken from this experiment. The peaks can be explained as methanol (quint, 3.32d), water (s, 4.89d) and chloroform (s, 7.90d) [see Ref 2]. A few small shifts also take place in other peaks, and the reasons will be looked into.
Using 8 mL of chloroform, if distilled to completion, will azeotrope 0.216 mL water. The 0.036 mL of water expected to form through complete reaction should have been removed, unless water formation continued after the distillation. Based on the NMR, the peak area for water (4.89d) that is not water - what do you think it is? is 7.5 times the peak area for the imine (8.17d), so there is 3.75 times the concentration of water than the imine. What happens to the catechol OHs in the NMR?
3. Based on other successful Ugi reactions, what would you expect to happen after addition of the acid and isonitrile?

Conclusion



Log

2007-04-21

14:30 Mixed 3,4-dihydroxybenzaldehyde and 5-methylfurfurylamine into flask, dissolved in 8mL anhydrous chloroform. Allowed to mix thoroughly for 20 min.
15:00 Hooked up to distillation apparatus, placed in a water bath heated by a hotplate.
15:12 Ubergang temp. = 52C, first drop from condenser.
15:20 Continuous distillation temperature of 59 - 60C.
15:40 Temperature began to drop, removed reaction from heat and placed under vaccuum for 30 min (Dark brown, fluid tarry residue).
16:10 Reaction removed from vacuum, small sample 94A was removed via a pipette tip, and dissolved in 1 mL CD3OD, and 800 uL was used to obtain a spectra of the residue. Sample returned to vacuum.
16:15 H NMR Spectra obtained.
17:00 Removed reaction from vacuum, placed back above stir plate, added 5 mL MeOH to dissolve the sample.
17:10 Added Boc-Glycine. Reaction allowed to stir.
17:30 Added t-Butyl isocyanide. Reaction allowed to stir.

2007-05-04

14:32 Stopped stirring of reaction, loosened cap to allow solvent to evaporate

2007-05-06

13:35 Placed the semi-dry reacion into the dessicator to allow it to dry further.

2007-06-01

23:08 - Removed mixture from the dessicator. It had solidified into a tan solid. Broke up and ground the solid with a spatula, placed into a vial. Yielded 0.9815 g crude material.


References


1.) National Toxicology Program, Dept. of Health and Human Services, Chloroform. Accessed 2007-04-22.
2.) Gottlieb, H.E., et al. NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities. J. Org. Chem. 1997, 62, 7512-7515.


Tags

3,4-dihydroxybenzaldehyde InChI=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
tert-butylisocyanide 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)


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