newugi.JPG

Objective

To accomplish the Ugi reaction and cyclization to a diketopiperazine using veratraldehyde,
5-methylfurfurylamine, N-t-BOC glycine and benzylisocyanide using the protocol described here. The target diketopiperazine is not predicted to be active but is a close analog of the product that we wish to make once the catechol aldehyde is obtained.

Procedure

To a small vial added methanol (2 ml), Veratraldehyde (3,4-dimethoxybenzaldehyde)
(0.5 mmol 82.8mg), benzylisocyanide (0.5 mmol, 60µl), Boc-Gly-OH (0.5 mmol, 87.7mg) and 5-methyl furfuryl amine (0.5 mmol, 56µl).The mixture was stirred for 24hr and evaporated. A solution of Acetylchloride (3ml) in Methanol (27ml) was added to the product and set aside for 27 hours it was then rotovaped and set on high vac. The product was taken up in dichloromethane, washed with water, dried over anhydrous MgSO4 and evaporated again.

Results

Characterization

1. Initial precipitation
2. TLC of 22AVs the starting materials
3. TLC of 22BVs the starting materials
4. HNMR of 22B.

Discussion

From the NMR of 22B it is clear that there is a substantial amount of unreacted aldehyde (9.9 ppm). The yellow precipitate which was obtained initially might well have been that of the aldehyde which precipitated out because of insufficient amount of solvent methanol (2mls) used.

Conclusion

Experiment aborted, because apparently insufficient amount of methanol was used.

Log

2006-08-17

1. 16:40] Mixed chemicals and started stirring
2. After about one hour the reaction changed color and looked like a yellow precipitate.

2006-08-18

3. 16:45] Stopped stirring, a yellow precipitate (22A) obtained. The precipitate is soluble in excess solvent (methanol).
4. A TLC of 22A Vs all the starting materials is run using 1:1 MeCl2 and Hexanes.

2006-08-21

5. 13:38] 30mls of a 10% solution of Acetyl chloride in Methanol (prepared by adding 3mls of Acetyl chloride to 27mls of methanol) ) was added to 22A. (this generates anhydrous HCl in MeOH)

2006-08-23

6. 16:30] 22A was rotovaped and set on high vac for 30 mins. It was taken up in MeCl2 and washed with water, dried over anhydrous MgSO4, rotovaped, and set under high vac for 2 1/2 hrs to obtain 22B (47.1mg).

2006-08-23

7. A TLC of 22B was obtained in 1:1 MeCl2 / Hexanes, also a HNMR of 22B was obtained.

Tags

Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2
VeratradehydeInChI=1/C9H10O3/c1-11-8-4-3-7(6-10)5-9(8)12-2/h3-6H,1-2H3
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
ugi022: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)
DKP022 InChI=1/C18H20N2O5/c1-11-4-6-13(25-11)10-20-16(21)9-19-18(22)17(20)12-5-7-14(23-2)15(8-12)24-3/h4-8,17H,9-10H2,1-3H3,(H,19,22)