Exp108-061407-2.JPG

Objective

To synthesize a Ugi adduct from benzaldehyde, furfurylamine, benzylisocyanide and Boc-Gly-OH in methanol using Ugi 4CR.

Procedure

A solution of benzaldehyde (212 uL, 2.09 mmol) and furfurylamine (FFA) (235uL, 2.66 mmol )was prepared in methanol-d4 in a 4mL volumetric flask to form an imine overnight. The next day a solution of Boc-Gly-OH(350 mg, 1.99 mmol), and benzylisocyanide (240uL, 1.97 mmol) made up in a 4ml volumetric flask in methanol was added to the preformed imine. The product was filtered and washed with ice cold methanol (5mL).
Characterization of 108C:tert-butyl 5-(benzylamino)-3-(furan-2-ylmethyl)-2,5-dioxo-4-phenylpentylcarbamate: Colorless Crystals; M.pt 146-148C; HNMR (external image delta.gif ppm, CDCl3) 1.43 (s, 9H), 4.18 (m, 2H), 4.43 (m, 2H), 4.48 (s, 2H), 5.46 (s, 1H), 5.68 (s, 1H), 5.94 (s, 1H), 6.09 (m, 1H), 6.30 (s, 1H), 7.10-7.50 (m 11H) 13C NMR (external image delta.gif ppm, CDCl3) 28.3, 42.5, 42.8, 43.6, 63.0, 79.5, 107.9, 110.3, 110.8, 127.4, 127.6, 128.6, 128.7, 129.6, 134.2, 137.7, 142.0, 149.5, 155.7, 169.0, 170.3; FAB HRMS: m/z 478.2366; calcd for C27H31N3O5 (M+H).


Results


Benzaldehyde
H NMR (CDCl3) - you also need spectrum in undeuterated methanol if you choose to monitor this way
C NMR
Furfurylamine
H NMR
C NMR
Boc-Gly-OH
H NMR
C NMR
Benzyl isocyanide
H NMR [CH2- 4.6 ppm (t) J=2.2Hz, aromatics- 7.3 - 7.4 ppm (broad multiplet)]
C NMR [CH2 (t)-46 ppm(J=28Hz), aromatics 127.9-134.5, Isonitrile Carbon (t)-157 ppm(J=22Hz)]

108A
t = 25min No deuterated solvent added.
t = 17h 18min (spectrum way off scale - set methanol CH3 peak)
108B
t = 20h 34min
t = 5 days
t = 1week
108C-1 (192mg)
HNMR (53mg / 800uL CDCl3) image
CNMR Image
FAB MS
High Res
Low Res

Discussion


A four component ugi reaction involving the imine of benzaldehyde and furfurylamine, and boc-glycine and benzyl isocyanide is only ~70% complete after one week, assuming the peak at 1.4 ppm (108B spectra) is the tert-butyl group.

Conclusion


The ugi product was successfully synthesized

Log

2007-06-14

19:35 Made up a solution of benzaldehyde and furfurylamine in methanol, in a 4 mL volumetric flask.This is 108A
2005 Obtained an H NMR of 108A by removing 800uL of 108A in an NMR tube....spectrum obtained without an addition of any deuterated solvent.

2007-06-15

12:53 Obtained H NMR of 108A (800uL) t = 17h18min
13:15 Made up a solution of benzyl isocyanide and Boc-glycine in a 4mL volumetric flask and added it to 108A, the preformed imine, this is 108B

2007-06-16

21:49 Obtained an H NMR of 108B (200uL in 600uL CD3OD)

2007-06-18

14:00 Left the reaction mixture in a refrigerator.

2007-06-19

15:00 Removed from the refrigerator.

2007-06-20

13:18 Obtained an H NMR of 108B (200uL/600uL CD3OD) (t = 5days)

2007-06-23

15:42 Obtained an H NMR of 108B (200uL/600uL CD3OD) (t = 1 week)

2007-06-24

14:20 The reaction mixture did not develop any solid (usually seen with similar reactants). The erlenmeyer flask containing 108B was placed in a dry ice-acetone bath for one hour.
15:30 No solid had appeared even after placing the reaction mixture in dry ice acetone bath (-70C).
16:00 This is when some of the solvent was evaporated off with a gentle stream of N2.
16:20 Solid had appeared in the erlenmeyer flask containing 108B.

2007-06-25

10:30 The solid was recrystallized from cold methanol (2ml). The product was dried under vacuum. The recovered mother liquor was saved for further crystallization (108D)
16:20 A dry 108C-1 was obtained (192 mg)- [20.4% Yield]
20:23 Obtained HNMR of 108C by dissolving 53mg in CDCl3 (800uL). HNMR

Tags

Benzaldehyde InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H
Furfurylamine InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2
Boc-Gly-OHInChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)
Ugiproduct108 InChI=1/C27H31N3O5/c1-27(2,3)35-26(33)29-18-23(31)30(19-22-15-10-16-34-22)24(21-13-8-5-9-14-21)25(32)28-
17-20-11-6-4-7-12-20/h4-16,24H,17-19H2,1-3H3,(H,28,32)(H,29,33)/i1-12,2-12,3-12,4-12,5-12,6-12,7-12,8-12,9-12,10-12,11-12,
12-12,13-12,14-12,15-12,16-12,17-12,18-12,19-12,20-12,21-12,22-12,23-12,24-12,25-12,26-12,27-12,28-14,29-14,30-14,31-16,32-16,33-16,34-16,35-16