exp054.gif

Objective

To synthesize a Ugi adduct(link) with 3,4-dihydroxybenzaldehyde, 5-methylfurfurylamine, tert-butylisocyanide and Boc-Gly-OH in deuterated methanol.

Procedure

Dissolved 3,4-dihydroxybenzaldehyde (2 mmol, 276 mg) and 5-methylfurfurylamine (2.2 mmol, 245 uL) in 4 mL CD3OD in a 4 mL volumetric flask, immediately transferred the contents to a 25mL Erlenmeyer flask, and removed 800 uL to obtain initial HMR spectra. The material used to obtain the H NMRs was returned to the Erlenmeyer, and the reaction was allowed to sit overnight without stirring to preform the imine. Boc-Gly-OH (2 mmol, 350 mg) was added to the mixture, and the reaction was swirled for approximately 30 seconds in order to dissolve the reagent. After approximately 15 minutes, t-butyl isocyanide (2 mmol, 226 uL) was added to the mixture and swirled for approximately 30 seconds. The progression of the reaction was monitored by H NMR.

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)

63A (after aldehyde and amine)
H NMR (t=2 min)
H NMR (t=18 min)
H NMR (t=42 min)
H NMR (t=20 h 12 min)
63B (after boc-gly)
H NMR (t=15 min)
63C (after isonitrile)
H NMR (t=26 min)
H NMR (t=33 min)
H NMR (t=46 min)
H NMR (t=1 h)
H NMR (t=3 h, 41 min)
H NMR (t=25 h 44 min) (Varian 500 MHz H NMR, TMS peak referenced wrong because it was too faint)

Spectral Overlays

Addition of isocyanide

Reaction Profiles


Discussion

  1. note effect of adding boc-gly on imine/aldehyde/amine ratios and link to other experiments that did or did not demonstrate similar behavior
  2. does it look like the Ugi product forms?

Conclusion

Log

2007-02-28

18:45 Dissolved 3,4-dihydroxybenzaldehyde in a minimal volume of CD3OD in a 4 mL volumetric flask. Added 5-methylfurfurylamine,
diluted to 4 mL, transferred to a 25 mL Erlenmeyer flask, swirled for 15 seconds, and immediately removed 800 uL for H NMR spectra (63A).
18:59 Obtained H NMR spectra of imine mixture 63A (t=2 min).
19:15 Obtained H NMR spectra of imine mixture 63A (t=18 min).
19:38 Obtained H NMR spectra of imine mixture 63A (t=42 min).

2007-03-01

15:08 Obtained spectra of imine mixture 63A (t=20h 12 min).
15:55 Added Boc-Gly-OH (63B).
16:10 Obtained H NMR spectra of mixture 63B (t=15 min).
16:20 Added t-butylisocyanide (63C).
16:46 Obtained H NMR spectra of mixture 63C (t=26 min).
16:53 Obtained H NMR spectra of mixture 63C (t=33 min).
17:06 Obtained H NMR spectra of mixture 63C (t=46 min).
17:20 Obtained H NMR spectra of mixture 63C (t=1h).
20:41 Obtained H NMR spectra of mixture 63C (t=3h 41 min).

2007-03-02

18:44 Obtained H NMR spectra of mixture 63C (t=25 h 44 min, on 500 MHz machine).

2007-03-03

17:07 A small amount of solid had formed in the flask.
17:30 Added 250 uL hexanes and 250 uL chloroform to the solution and put on ice in to attempt to draw more solid from the solution.
18:00 Suction filtered through a Buechner funnel, rinsed with a minimal amount of cold methanol, to yield white crystals. Allowed filter paper and solid to dry with suction.
18:30 The weight of the crude crystals (on tared filter paper) was determined to be 30 mg.

2007-03-25

22:00 Dissolved 63C in 1 mL CD3OD (didn't seem to dissolve), transferred 800 uL to a clean NMR tube.
22:20 Unable to obtain a good NMR, could not recover product, will attempt again in another experiment (exp106).


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)





external image exp054&js=1&rnd=0.9970695457207264