ugicycmeoh.JPG

Objective

To cyclize a Ugi product to form a diketopiperazine via a boc-deprotected intermediate . This Ugi product was synthesized here.

Procedure

Prepared 10% HCl solution by adding 100uL concentrated (12 M) aqueous HCl to 1mL volumetric flask. Diluted to mark with deuterated methanol. Took NMR spectra. Added 50mg Ugi Product (62E) to NMR tube and monitored reaction via NMR spectra at specific intervals.

Results

10% HCl Solution
HNMR

62E
HNMR

10%HCl/ Ugi Product
HNMR

Reflux
TAR= 30min
HNMR

TAR= 90 min
HNMR

TAR= 150 min
HNMR

Discussion

1. The methyl group is still present at 2.2ppm.
2. It is hard to discern whether the boc group was lost even though a small peak at 1.6ppm begins to appear.
3. Some side reactions may be occuring with the appearance of new peaks at 1.29ppm - 1.38 ppm.
4. The doublets at 8.743 ppm and 4.477 point towards a clear 'Furfuryl cleavage'. This is the first time this type of cleavage has ever been observed in 10% HCl.- Khalid

Conclusion

The Ugi product did not cyclize.
Fufuryl cleavage observed for the first time in a tertiary amide.

Log

2007-03-23


11:20 Set temperature bath to 65C. Prepared 10% HCL solution.
11:32 Attempted NMR spectra. Had problems getting the NMR to lock and spin consistently.

2007-03-26


11:17 Prepared 800uL 10% HCl solution. Took NMR spectra. Set temperature bath to 65C.
12:01 Weighed out 50 mg of 62E and added it to contents of NMR tube.
12:15 Some problems with getting the crystals to dissolve. Added 20uL deuterated chloroform.
12:22 Crystals completely dissolved. Took NMR spectra.
12:46 Unable to get spectra until 12:37. Placed NMR tube in temperature bath. Bath temperature 60C.
12:52 Bath temperature 64C. Noticed condensation in the flask.
13:05 Bath temperature 70C. Reaction turned yellow.
13:30 Bath temperature 70C. Reaction turned orange. Took NMR spectra.
13:44 Bath temperature 70C. Returned reaction flask to temperature bath.
14:11 Bath temperature 70C. Took NMR spectra. Solution turned deep orange.
14:34 Bath temperature 70C. Placed NMR tube in bath.
15:30 Bath temperature 70C. Took NMR spectra. Solution turned red.

Tags

UgiproductInChI=1/C26H35N3O7/c1-16-8-10-18(35-16)14-29(21(30)13-27-24(32)36-26(5,6)7)22(23(31)28-25(2,3)4)17-9-11-19-20(12-17)34-15-33-19/h8-12,22H,13-15H2,1-7H3,(H,27,32)(H,28,31)
DKP065 InChI=1/C17H16N2O5/c1-10-2-4-12(24-10)8-19-15(20)7-18-17(21)16(19)11-3-5-13-14(6-11)23-9-22-13/h2-6,16H,7-9H2,1H3,(H,18,21)