Researcher: Khalid Mirza



To synthesize the Ugi product 176C(UC) in ethyl acetate.


A 0.37M solution of phenanthrene-9-carboxaldehyde, furfurylamine and phenylacetic acid is prepared in ethyl acetate. Butylisocyanide is pipetted (0.63mmol) out in to the three component solution (1.7mL). The reaction is left to undisturbed with occasional sonication in order to felicitate precipitation. The solid is then washed with ethyl acetate and dried under vacuum. 24% yield.


UCExp257-1 Spreadsheet
Reaction monitor Spreadsheet
[Why are you using the 5.52 starting range to quantify the Ugi product in the mother liquor with an assignment of 1H? JCB] - I thought this was one of the furan protons of the product, based on a) all furan protons in the reactants including the imine appear above 6ppm (eg, 3comp HNMR). b) In HNMR of the Ugi product UCExp257-1C, a similar signal appears at 5.64ppm. Apart from these, since a Passerini product cannot contain any furan protons, this appeared to be a reasonable peak to quantify the Ugi product. Also I added two other values in the spreadsheet - Khalid.

Precipitate in the vial after 23h
Picture #1
Picture #2
UCExp257-1C Ugi product 176C
UCExp257-1B Mother Liquor
Spreadsheet UCExp257-1B
UCExp257-W1 first wash
UCExp257-W2 second wash
UCExp257-W3 third wash
Spreadsheet three washings

Yield Spreadsheet


After 22.5h 30% of butylisocyanide had been converted to the Ugi product.
[great - it will be interesting to see the 72h yield - we predict very little Ugi product will get washed away JCB]
Based on the amount of butylisocyanide remaining it is estimated that the reaction was 60% complete after 73h, however only 24% of the Ugi product was isolated. Possible causes include a side reaction (eg. a three component Passerini reaction, a reaction which excludes the amine) which does not yield a Ugi product, although in a very small amount, less than 5%...

Total Conversion to Ugi product = 37% and 64% of which was isolated as pure solid and 36% was lost during washing steps and separation of mother liquor.

It was expected that ethyl acetate would behave more like methanol based on its polarity (dipole moment- MeOH 1.78, EtOAc-1.78). However it is possible that the protic nature of methanol plays a role in accelerating the Ugi reaction. It may also be interesting to use binary solvent system, such that one solvent is known to accelerate the reaction (methanol) and the other desirable solubility properties (EtOAc)


Ethyl acetate does not exhibit the desired characteristics of a good solvent to carry out the Ugi reaction.
The reaction was very slow, though from solubility perspective it turned out to be a good solvent. It could possibly be used during the washing steps.


11:20 Weighed out furfurylamine (0.75mmol, 72.8mg) phenanthrene-9-carboxaldehyde (0.75mmol, 155mg), phenylacetic acid (0.75mmol, 102mg) in to a 2mL volumetric flask and diluted with ethyl acetate. The solution was made-up to the 2mL mark to obtain a 0.37M solution. This solution is called UCExp257-3comp.
12:30 Obtained an HNMR of the UCExp257-3comp (100uL).
13:45 Weighed out butylisocyanide (0.6375mmol, 53mg) in to a clean one dram screw cap glass vial.
14:00 Pipetted out UCExp257-3comp (1.7mL) in to the vial. The reaction mixture is labeled UCExp257-1A. Total volume of the solution in the vial remaining is 1200uL (0.37M per component)
14:01 Vortexed UCExp257-1A for 15s.
14:02 Removed 500uL solution from UCExp257-1A and pipetted it in to a clean dry NMR with a co-axial insert containing DMSO-d6.
15:15 Obtained HNRMs until 75min in to the reaction.
15:40 Observed cloudiness develop in the vial UCExp257-1A.
15:50 Placed the vial and the NMR tube in sonication.
15:55 Removed from sonication.
16:30 Observed a cloudy ppt in NMR tube as well.The turbidity however goes way when shaken vigorously
11:30 Observed some more precipitate in the vial and the NMR tube, sonicated the vial and the tube for five minutes.
12:36 Obtained an HNMR of the solution in the NMR tube.
12:55 The solution in the vial by now had clumped-up in to a solid mass, therefore vortexed it for few seconds and obtained a picture of the vial containing the reaction mixture.
2010-03-14 (Day light time change)
16:10 Vortexed UCExp257-1A for a few seconds and centrifuged the reaction mixture.
16:15 Separated the supernatant, mother liquor by carefully pipetting out ~ 350uL, labeled UCExp257-1B. (73h15min in to the reaction)
16:20 Pipetted out ethyl acetate (500uL) in to the residue to wash it. Vortexed, centrifuged and separated the first wash supernatant. The supernatant is labeled UCExp257-W1.
16:35 Repeated the washings another two time. Each time the supernatant was collected separately in to a one dram vial and labeled UCExp257-W2 and UCExp257-W3 respectively.
16:45 The residue collected after the washing was left in a vacuum desiccator to evaporate traces of ethyl acetate remaining.
19:10 Obtained dried, off white powder in the vial. This is labeled UCExp257-1C (44.4mg, 24% yield)
19:15 Transferred 300uL from UCExp257-1C, UCExp257-W1, UCExp257-W2 and UCExp257-W3 in to four one dram vials containing CDCl3 (700uL), vortexed the resulting solution. These solutions were pipetted out in to clean/dry NMR tubes. Capped the tubes and saved them in refrigerator for HNMR acquisition.
12:30 Obtained HNMRs of the solution previously prepared