exp19a.JPG


Objective

To produce a diketopiperazine by a Ugi synthesis and cyclization using piperonal, 5-methylfurfurylamine, Boc-Gly-OH, and benzylisocyanide using the protocol described here with the modification that THF will be used instead of 1,2-dichloroethane in the cyclization step. This compound is not an anti-malarial target but is a close analog of the product that we wish to make once the catechol aldehyde is obtained.

Procedure

Methanol (20 mL), piperonal (73.75mg, 0.49 mmol), Boc-Gly-OH (85.85 mg, 0.49 mmol), 5-methylfurfurylamine (55µL, 0.49 mmol), and benzylisocyanide (60µL, 0.43 mmol) were added to a 50 mL Erlenmeyer flask. The flask was stoppered and the mixture was stirred for 24 hr, then evaporated on rotovap and high vacuum.

Results

Characterization of 26A

-- Picture of setup with a colorless solution, right after stirring was started.
-- TLC of 26A against piperonal and benzylisocyanide in 1:1 methylene chloride to hexanes. Left to right: piperonal, benzylisocyanide, and 26A (Picture under UV light).

Characterization of 26B

-- H-NMR, C13-NMR
-- TLCs of 26B in pure methylene chloride and 2% methanol.

Characterization of 26B-F1

-- H-NMR, C13-NMR , C13-NMR 30s relaxation
-- MALDI (not enough sample?)
-- mass: 131.9 mg

Discussion

-- HNMRs of starting materials: piperonal, Boc-Gly-OH, 5-methylfurfurylamine and benzylisocyanide.
-- C13-NMRs of startinng materials: piperonal, Boc-Gly-OH, 5-methylfurfurylamine (pending) and benzylisocyanide.

The CMRs of 26B and 26B-F1 are almost identical. The peak at 190 ppm in 26B was suspected to be a glitch, which is confirmed by its absence in 26B-F1. The strong peak at 175 ppm in both CMRs of 26B-F1 is not present in 26B. If it were a glitch it would not be expected to show up in both spectra.

Conclusion


Log

2006-08-30

1. 14:53) Mixed chemicals and started stirring at room temperature, stir setting 3. The solution was colorless. The 5-methylfurfurylamine and the benzylisocyanide were added by using a 500 microliter GC syringe.

2006-08-31

2. 14:53) Stopped stirring the solution, which is now a yellow color.
3. 14:58) Rotovap solution at 60C.
4. 16:10) Sample was taken off rotovap.
5. 16:24) Sample was put on high vacuum at 1.1 mmHg for 10 hours to get 26A. Mass of 26A is 254.4 mg.

2006-09-01

6. Ran TLC of 26A against piperonal and benzylisocyanide in 1:1 methylene chloride to hexanes.
7. 5 mL of methanol was added to the sample (26A).

2006-09-27

8. 15:01) Evaporated the methanol by nitrogen for 2 hours.
9. 17:10) Put solution on high vac for 1.5 hour to get 26B 191.1 mg.

2006-10-04

10. Ran TLC of 26B against piperonal and benzylisocyanide in 3:1 methylene chloride to hexanes (Picture).
11. Ran TLC of 26B in pure methylene chloride (Picture).

2006-10-04

12. Ran TLC of 26B in 2% methanol and 4% methanol.

2006-10-10

13. Flash chromatography (28.5g silica) was done on 26B with methylene chloride then 2% methanol in methylene chloride and one fraction 26B-F1 was collected.
14. 26B-F1 was rotovaped for 45 minutes.

2006-10-11

15. 14:30) 26B-F1 was put on high vac for 45 minutes. The mass of the crude product was 131.9 mg.

Tags

Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2
PiperonalInChI=1/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2
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
ugi019:InChI=1/C29H33N3O7/c1-19-10-12-22(38-19)17-32(25(33)16-31-28(35)39-29(2,3)4)26(21-11-13-23-24(14-21)37-18-36-23)27(34)30-15-20-8-6-5-7-9-20/h5-14,26H,15-18H2,1-4H3,(H,30,34)(H,31,35)
DKP019InChI=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)