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.


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.


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


-- 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.




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.


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.


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).


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.


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).


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


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.


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


Benzylisocyanide InChI=1/C8H7N/c1-9-7-8-5-3-2-4-6-8/h2-6H,7H2