exp031_scheme.JPG

Objective

To monitor the Ugi reaction by C13 NMR and possibly isolate the Ugi product for cyclization.

Procedure

Ugi reaction will be made as proposed in 1996 Armstrong J. Am. Chem. Soc.with a 1M concentration for each component. TLCs of each starting material will be compared to a t=0 Ugi reaction and further subsequent times. If a decent C13 can be obtained, the time frame of each observation will be double the last observation (eg 15min, 30min, 1hr, 2hr, 4 hr, 8hr, etc). Kept all components at a 1:1:1:1 ratio. Under nitrogen in a round bottom flask (50mL) added methanol (2mL) and then phenylacetaldehyde by syringe(350µL, 3mmol), 5-methylfurfurylamine by syringe (330µL, 3mmol), and let that stir for 12 minutes. Next added Boc-Gly-OH (525mg, 3mmol) and benzylisocyanide (365µL, 3mmol). Continue to stir under nitrogen for over 24 hours. Video

Results

Characterization of Phenylacetaldehyde after Distillation

[0.25mL] HMR

Characterization of 31A over time

TLCs over 31 hours
[100mg per component in 1mL MeOH] C13MR after 2hours
[100mg per component in 1mL MeOH]C13MR after 5hours
[100mg per component in 1mL MeOH] C13MR after 30hours

Discussion

Between 2 and 5 hours, the CMRs are essentially the same. This is good because it means that we would be able to tell if significant change had taken place and validates that our 300 MHz instrument can take reproducible carbon spectra without locking at 1 M concentration (assuming that precipitate did redissolve) in methanol within 10 minutes. Note that there is a 2 ppm shift between the spectra; the methanol peak should be used to set the scale in the future. The relaxation delay was only 5 seconds, giving a large difference in peak height between quaternary and other carbons. Setting the relaxation delay to 30-60 seconds should give a spectrum with peak heights correlating to the amount of each component. This should take 1-2 h for the same number of scans.
The next spectrum taken after several days should tell us if anything happened.
Try to assign the peaks in the 150-200 range. You'll need to get some missing CMRs to do that. Next time get the CMR in MeOH with only the aldehyde then add the amine and take it before adding the acid and isonitrile so we can hope to see the imine peak.

Log

2006-10-13

1. Distilled phenylacetaldehyde under atmosphere, no vac 37-F1. HMR

2006-10-20

2.[11:48] Added the aldehyde and amine under nitrogen to round bottom flask in 2mL of methanol and let it stir for 12mins. Solution turned bright yellow and a precipitate formed and stuck to the flask.
3.[12:00] Added the acid and 1mL more methanol and the benzylisocyanide still under nitrogen stirring. The yellow precipitate was seen to dissolve back into solution with stirring. The solution became brown in color over time. Video (no heat was used) TLC in 1:1 MC hexanes was done but solvent line is the top of the plate.
4.[14:00] Acquired C13MR
5.[16:00] Acquired C13MR
6.[17:00] TLC in 1:1 MC hexanes was done

2006-10-21

7.[9:30] Attempted to get another C13 however the memory on the computer was full. Did not re-introduce the sample taken for NMR back into the flask. TLC in 1:1 MC hexanes was done. Solvent line is the top of the plate
8.[19:00] TLC in 1:1 MC hexanes was doen and nitrogen turned off. Solution was alowed to sit in flask.

Tags

Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2Phenylacetaldehyde, InChI=1/C8H8O/c9-7-6-8-4-2-1-3-5-8/h1-5,7H,6H2
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)
5-methylfurfurylamineInChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
ugi031:InChI=1/C29H35N3O5/c1-21-15-16-24(36-21)20-32(26(33)19-31-28(35)37-29(2,3)4)25(17-22-11-7-5-8-12-22)27(34)30-18-23-13-9-6-10-14-23/h5-16,25H,17-20H2,1-4H3,(H,30,34)(H,31,35)
DKP031: InChI=1/C17H18N2O3/c1-12-7-8-14(22-12)11-19-15(17(21)18-10-16(19)20)9-13-5-3-2-4-6-13/h2-8,15H,9-11H2,1H3,(H,18,21)