Exp067-3.JPG

Objective

To cyclize the Ugi product obtained in Exp064 (64C-2) by an acid catalyzed transamidation reaction.

Procedure

Dissolved 55mg (0.109mmol) of the Ugi product 64C-2 from Exp064 in 500uL CDCl3. Then 500uL of trifluoroacetic acid was added to the above solution in the NMR tube (50% solution in CDCl3) and the reaction was monitored by NMR.

Results

Ugi Product 64C-2 in CDCl3 (from Exp064)
Benzylamine (20uL in 500uL CDCl3)
Benzylamine/TFA (20uL/ 500uL in 500uL CDCl3) [clear solution]

70A
t = 13min
t = 4h 17min
t = 8h 08min
t = 8h 52min CNMR
t = 8h 55min
t = 22h 27min
t = 24h 12min
t = 27h 44min
t = 31h 44min
CNMR Overnight
t = 48h 07min
70A-DEPT image (the peak at 55 ppm does not show up in CH, CH2 or CH3 - that is a problem - I think it should be CH as the benzylic chiral position)
70A-90 degree pulse
t = 51h 26min
70B HNMR
Kinetics for the disappearance of the methyl group at 2.1ppm

Discussion



The disappearance of the methyl group at 2.1ppm follows first order kinetics. The rate constant for loss of
2,5-dimethylene-dihyrofuran from the Ugi product was estimated to be 0.9x10-3 min-1

Over a period of time, the furan system is lost (seen consistently, as in Exp065, Exp067).
It is evident from the 70B HNMR that there is hardly anything interesting in the organic layer...the salt was washed away by water.
UCExp070-Kinetics.PNG
Figure- UCExp070-i -First order kinetics for the furfuryl cleavage of the Ugi product 064C.

Conclusion

The desired diketopiperazine was not produced and the furan group appears to have reacted in a clean conversion, unknown at this time.
The rate constant for the disappearance of methyl at 2.1ppm was estimated to be k = 0.9x10-3 min-1
This reaction is very similar 1,6-elimination observed in Exp091, where the rate constant was determined to be k = 1.2x10-3 min-1

Log

2007-03-16

12:00 Made-up a solution of 55mg ugi product (64C-2) in 500uL CDCl3 in an NMR tube,
12:05 Added 500uL TFA to the NMR tube.
12:18 Obtained HNMR (t = 13min)
16:22 Obtained HNMR (t = 4h 17min)
20:13 Obtained HNMR (t = 8h 08min)
20:57 Obtained CNMR (t = 8h 52min)
21:00 Obtained HNMR (t = 8h 55min)

2007-03-17

10:32 Obtained HNMR (t = 22h 27min)
12:17 Obtained HNMR (t = 24h 12min)
15:49 Obtained HNMR (t = 27h 44min)
19:49 Obtained HNMR (t = 31h 44min)

2007-03-18

12:07 Obtained CNMR (Overnight run)
12:12 Obtained HNMR (t = 48h 07min)
15:31 Obtained HNMR (t = 51h 26min)

2007-03-20

08:05 Decanted the 70A from the nmr tube in to a clean separatory funnel, rinsed the nmr tube with anhydrous chloroform (3mL), added to the separatory funnel. Added distilled water (5mL) to the separotory funnel, shook the funnel and let the organic layer separate from aqueous layer. Collected the brown bottom organic layer. The bottom layer was washed again with distilled water (5mL). After separation from the aqueous layer, the organic layer was dried using anhydrous MgSO4 (1g), filtered through a fluted filter paper which was futher rinsed with a small amount of anydrous chloroform.
9:10 The collected dry organic layer was set on a high vac to remove the solvent.
9:35 Dissolved the residue collected after vacuum drying (70B) in CDCl3 (1mL) and obtained HNMR.

Tags

ugi054:InChI=1/C30H37N3O7/c1-20-12-14-23(39-20)19-33(26(34)18-32-29(36)40-30(2,3)4)27(22-13-15-24(37-5)25(16-22)38-6)28(35)31-17-21-10-8-7-9-11-21/h7-16,27H,17-19H2,1-6H3,(H,31,35)(H,32,36)