Exp109-1.JPG

Objective

To synthesize a Ugi adduct from benzaldehyde, 5-(Trifluoromethyl)-2-furylmethylamine , benzylisocyanide and Boc-Gly-OH in methanol using Ugi 4CR.

Procedure

A solution of benzaldehyde (106mg, 106uL, 1.04 mmol) and 5-(Trifluoromethyl)-2-furylmethylamine (167mg, 1.01mmol) was prepared in methanol-d4 in a 1mL volumetric flask to form an imine overnight. The next day a solution of Boc-Gly-OH(175 mg, 1 mmol), and benzylisocyanide (120uL, 1mmol) made up in a 1ml volumetric flask in methanol was added to the preformed imine. The product was filtered and washed with ice cold methanol (5mL).

Results

Benzaldehyde
H NMR (CD3OD)
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)]
5-(Trifluoromethyl)-2-furylmethylamine
HNMR Image
CNMR

109A
t = 3min
t = 4min
t = 11min
t = 37min
t = 44min
t = 1h15min
t = 2h 00min
t = 3h 4min
t = 17h 3min
109B
t = 10min
109C
HNMR
CNMR image
FAB MS
High Res
Low Res

Discussion

The NMR and MS data confirms the formation of a Ugi product -

Conclusion

A Ugi product was isolated in 31% yield.

Log

2007-06-24

14:00 Made up a solution of 5-(Trifluoromethyl)-2-furylmethylamine (167mg) in methanol-d4 in a 1ml volumetric flask, transferred the solution to an NMR tube and obtained HNMR and CNMR.
17:46 Added benzaldehyde (106uL, 1mmol) to the NMR tube containing 1M solution of the amine, this is 109A
17:49 Obtained HNMR of 109A (t = 3min)
17:50 Obtained HNMR of 109A (t = 4min)
18:01 Obtained HNMR of 109A (t = 11min)
18:23 Obtained HNMR of 109A (t = 37min)
18:30 Obtained HNMR of 109A (t = 44min)
19:01 Obtained HNMR of 109A (t = 01h15min)
19:46 Obtained HNMR of 109A (t = 02h)
20:50 Obtained HNMR of 109A (t = 03h 4min)

2007-06-25

10:49 Obtained HNMR of 109A (t = 17h 3min)
13:45 Made up a solution of benzyl isocyanide (120uL, 1mmol) and Boc-Glycine (175mg, 1mmol) in CD3OD (1ml)
13:49 Added the isocyanide and amino acid solution in the NMR tube containing 109A to form 109B
13:59 Obtained HNMR of 109B (t = 10min)
14:05 Soon after removing the NMR tube from the NMR instrument, solid particles started to develop in the NMR tube.

2007-06-26

19:20 Almost half of the NMR tube is now filled with the solid.

2007-06-27

17:25 After the entire nmr tube was filled with solid, the solid was forced out, washed with methanol, filtered through a sintered glass funnel. The obtained solid was air dried. The remaining mother liquor (109D) was saved to recover more product.
19:30 A white solid product 109C (170mg) [31.16% yield] was obtained.

2007-07-02

08:10 Obtained C NMR of 109C

Tags

[5-(Trifluoromethyl)-2-furylmethylamine InChI=1/C6H6F3NO/c7-6(8,9)5-2-1-4(3-10)11-5/h1-2H,3,10H2
Benzaldehyde InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H
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)
Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2
UgiExp109 InChI=1/C28H30F3N3O5/c1-27(2,3)39-26(37)33-17-23(35)34(18-21-14-15-22(38-21)28(29,30)31)24(20-12-8-5-9-13-20)25(36)32-16-19-10-6-4-7-11-19/h4-15,24H,16-18H2,1-3H3,(H,32,36)(H,33,37)