To synthesize a Ugi adduct from 3,4-dimethoxybenzaldehyde, Furfurylamine, tertbutylisocyanide and Boc-Gly-OH in methanol using Ugi 4CR. This reaction is a reaction redone Exp096


A solution of 3,4-dimethoxybenzaldehyde (veratradlehyde) (332 mg, 2 mmol) and furfurylamine(FFA) (234.8 uL, 2.2 mmol, 10% excess ) was prepared in methanol-d4 in a 2mL volumetric flask to form an imine. After two hours a solution of Boc-Gly-OH(350 mg, 2 mmol), and tert-butyl isocyanide(226 uL, 2 mmol) madeup in a volumetric flask in methanol-d4 was added to the preformed imine. The product was filtered and washed with ice cold methanol (5mL) - The mother liquor was saved until it formed crystals again.
C26H37N3O7; White solid; 1H NMR (external image delta.gif ppm, CDCl3) 1.34 (s, 9H), 1.45 (s, 9H), 3.76 (s, 3H), 3.87 (s, 3H), 4.22 (s, 2H), 4.48 (s, 2H), 5.49-6.12 (m, 5H) 6.71-6.88 (m, 3H), 7.20 (s, 1H) 13C NMR (external image delta.gif ppm, CDCl3) 28.3, 28.5, 42.0, 42.8, 51.6, 55.7, 55.8, 62.5, 79.5, 107.4, 110.4, 110.7, 112.6, 122.0, 126.7, 141.7, 148.9, 149.9, 150.0, 155.6, 168.7, 170.2; HRMS (FAB,m-nitrobenzyl alcohol): m/z calcd for C26H37N3O7 503.26, found 504.2725.


(Reactant NMRs from Exp054)
tert-Butyl isocyanide

t = 17min
t = 24min
t = 32min
t = 34mim
t = 35min
t = 37min
t = 44min
t = 46min
t = 49min
t = 54min
t = 01h 00min
t = 01h 03min
t = 01h11min
t = 01h 16min
t = 01h 20min
t = 01h 23min
t = 01h 46min CNMR
t = 01h 53min CHs only
t = 02h 01min
t = 02h 08min
t = 02min
t = 03min
t = 05min
t = 07min
t = 15min
t = 20min
t = 23min
t = 48min
t = 51min
t = 01h 00min
t = 02h 03min
104C (Batch-1 : 86.3mg, batch-2: 33.8mg) - you can't assume that 104C-2 is the same as 104C - need at least a separate HMR
C NMR C NMR (Image)
All CH's
Low Res
High Res


Ugi products obtained from veratraldehyde tend to be more powdery than crystalline and are relatively more soluble in methanol than there benzaldehyde counterparts.


A ugi product was successfully synthesized in 12% yield.



23:25 Madeup a solution of veratraldehyde and furfurylamine in 2 ml methanol-d4 in a volumetric flask to obtain 104A
23:42 Obtained H NMR of 104A (t = 17min)
23:49 Obtained H NMR of 104A (t = 24min)
23:52 Obtained H NMR of 104A (t = 27min)
23:57 Obtained H NMR of 104A (t = 32min)
23:59 Obtained H NMR of 104A (t = 34min)


00:00 Obtained H NMR of 104A (t = 35min)
00:02 Obtained H NMR of 104A (t = 37min)
00:09 Obtained H NMR of 104A (t = 44min)
00:11 Obtained H NMR of 104A (t = 46min)
00:14 Obtained H NMR of 104A (t = 49min)
00:19 Obtained H NMR of 104A (t = 54min)
00:25 Obtained H NMR of 104A (t = 01h 00min)
00:28 Obtained H NMR of 104A (t = 01h 03min)
00:36 Obtained H NMR of 104A ( t= 01h 11min)
00:41 Obtained H NMR of 104A (t = 01h 16min)
00:45 Obtained H NMR of 104A (t = 01h 20min)
00:48 Obtained H NMR of 104A (t = 01h 23min)
01:00 Made up a solution of Boc-Glycine and tert-Butylisocyanide in a 2 mL volumetric flask in 2 mL methanol-d4.
01:11 Obtained C NMR of 104A (t = 01h 46min)
01:18 Obtained DEPT of 104A (t = 01h 53min)
01:26 Obtained H NMR of 104A (t = 02h 01min)
01:33 Obtained H NMR of 104A (t = 02h 08min)
01:37 Added the previously made solution of Boc Glycine and tert-butyl isocyanide in methanol-d4 to 104A in a centrifuge tube, to obtain 104B, 800uL of 104B was transferred back into the tube and the changes were monitored.
01:39 Obtained H NMR of 104B (t = 02min)
01:40 Obtained H NMR of 104B (t = 03min)
01:42 Obtained H NMR of 104B (t = 05min)
01:44 Obtained H NMR of 104B (t = 07min)
01:52 Obtained H NMR of 104B (t = 15min)
01:57 Obtained H NMR of 104B (t = 20min)
02:00 Obtained H NMR of 104B (t = 23min)
02:25 Obtained H NMR of 104B (t = 48min)
02:28 Obtained H NMR of 104B (t = 51min)
02:37 Obtained H NMR of 104B (t = 01h 00min)
03:40 Obtained H NMR of 104B (t = 02h 03min)
04:20 Solid had started to appear in the solution in the centrifiuge tube, at this time the solution from the NMR tube was poured into the centrifuge tube and set on a sonicator for 30min.
05:30 Almost the entire the solution in the centrifuge tube had solidified / looked like a white cake.
06:00 Removed the solid from the centrifuge tube into a beaker and rinsed out the centrifuge tube with methanol (2ml). The product in the beaker was set on a sonicator again and the enitre solid dissolved into it within a couple of minutes.
06:30 The beaker was parafilmed and left in the hood for crystallization.
13:00 Solid had appeared in the beaker with no traces of any methaol.
13:30 The solid in the beaker was removed from the beaker by using ice cold methanol (5ml) and the solvent was removed by filtering through a sintered glass funnel.
15:00 Obtained the solid 104C (86.3mg) after air drying, the mother liquor 104D was saved for further crystallization.
20:10 Obtained H NMR of 104C by dissolving 25 mg in 800uL of CDCl3.


09:28 Obtained a C NMR of 104C from an overnight run.
16:20 After filteration of 104D, 104C-2 (33.8mg) of solid was obtained. Yield - 12%
The filtered mother liquor is 104E


15:42 Obtained DEPT of 104C


3,4-dimethoxybenzaldehyde InChI=1/C9H10O3/c1-11-8-4-3-7(6-10)5-9(8)12-2/h3-6H,1-2H3
Furfurylamine InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
tert-butyl isocyanideInChI=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)
Product InChI=1/C26H37N3O7/c1-25(2,3)28-23(31)22(17-11-12-19(33-7)20(14-17)34-8)29(16-18-10-9-13-35-18)21(30)15-27-24(32)36-26(4,5)6/h9-14,22H,15-16H2,1-8H3,(H,27,32)(H,28,31)