To determine the yield of the Ugi reaction involving phenanthrene-9-carboxaldehyde, furfurylamine, phenylacetic acid and butylisocyanide in benzene at ~0.4M concentration per component.


To a 0.4M solution (1.5mL) of phenanthrene-9-carboxaldehyde, phenylacetic acid and furfurylamine, butylisocyanide (0.6mmol, 62.7uL) was added. The solution was vortexed for one min. The concentration of the resulting solution was determined by SAMS using 100uL of the solution to obtain an HNMR.
The reaction mixture was left for 48h occasionally vortexed. The product precipitated was then centrifuged and washed with benzene (500uL x3) and dried under a vacuum desiccator and analyzed by HNMR. Yield 17%

[Add a spreadsheet for all the calculations relating to reactants and yield JCB]


Spreadsheet UCExp256
[The initial spectrum with the isocyanide is really clear JCB]


amount 51.2 mg 0.1mmol, 17% yield

Mother liquor

UCExp256A-2 - Ugi product conc - 0.05M; ~ 0.0125mmol (250uL supernatant)
Spreadsheet- A-2

Washing 1

UCExp256A-W1 - Ugi product conc - 0.06M (assuming the solution is only 750uL); ~0.045mmol

Washing 2

UCExp256A-W2 - Ugi product conc - 0.04M (assuming the solution is only 750uL); ~0.03mmol
Spreadsheet- W2

Washing 3

UCExp256A-W3 - Ugi product conc - 0.04M (assuming the solution is only 750uL); ~0.03mmol
Spreadsheet- W3


Stretching the assumptions farthest, I could possibly account for (0.1+0.125+0.045+0.03+0.03)= 0.33mmol for Ugi product formed which is a 55% conversion after more than two days of reaction time. Based on the kinetics it is expected that after 62.5h the reaction should be 88% complete, however in this case it is 63% complete. The discrepancy could be due to the fact that the reaction mixture clumps-up once a certain concentration of Ugi product precipitates out, which drastically reduces the interaction between the reactant molecules. Thereby changing the kinetics of the reaction. I am not sure what else could cause the observed sluggish behavior of the reaction.
[The NMRs of the washings are very helpful in determining how many washes are required for removal of all starting materials JCB]
The three washing are absolutely necessary to clean-up the product, apparent from the fact that after the third wash there are only traces of starting materials identifiable.


Although the reaction did achieve a 55% conversion, it did not produce a desired yield. Further investigation may be required to clear-up the causes/effect for the depreciated yield. However it confirms that benzene is not the solvent of choice for the reaction at 0.4M concentration.

Based on the model by Prof. Lang and Prof. Bradley, ethyl acetate is predicted to produce best results for the reaction on hand.


16:20 Weighed out phenanthrene-9-carboxaldehyde (2mmol, 412.5mg) and phenylacetic acid (2mmol, 272.3mg)
16:35 Weighed out furfurylamine (2mmol, 194.4mg) in to a 5mL volumetric flask. Pipetted out a small amount (~1.5mL) benzene in to the flask.
16:45 Transferred the aldehyde and the acid in to the volumetric flask. Vortexed the solution to mix the solution well
17:00 Made-up the solution to the 5mL mark and ensured a homogeneous solution was obtained by vortexing, sonicating and mixing for few minutes. This solution is labeled UCExp256-1A, the concentration of the solution is 0.4M / component.
17:30 Pipetted out DMSO-d6 (750uL) in to a 1 dram vial and added the freshly prepared 0.4M UCExp256-1A (100uL) to vial. Mixed by vortexing.
17:55 Transferred the DMSO-d6/UCExp256-1A solution to a clean and dry NMR tube.
19:00 Obtained HNMR of UCExp256-1A. The concentration of UCExp256-1A was confirmed to be 0.4M per component. The solution (UCExp256-1A) was left in the hood tightly sealed.
22:00 Pipetted out UCExp256-1A (0.6mmol per component, 1.5mL) in to a 1 dram screw-cap vial. (750uLx2)
22:20 Carefully pipetted out butylisocyanide (0.6mmol, 62.7uL) in to the vial. The reaction mixture is labeled UCExp256A-1. Vortexed the resulting solution for 1min.
22:25 Removed 100uL solution from UCEExp256A-1 and pipetted it out in to a clean vial with DMSO-d6 (750uL) and obtained HNMR of the solution.
The concentration of each component was again confirmed to be 0.4M.
23:00 The total volume of the reaction mixture in the vial is 1462.7uL (assuming volumes being additive). The vial was sonicated for 5min and left at room temp over-night.
15:10 Observed a small amount of precipitate in the vial UCExp256A-1.
15:10 Not a lot of ppt was observed, therefore sonicated the solution for 5min.
16:20 A whole lot of solid had formed in the vial..obviously an after effect of sonication /crystal induction
12:30 Vortexed the precipitate in the vial UCExp256A-1.
12:35 Centrifuged the reaction mixture and decanted the supernatant, only about 150-200uL (max 250uL) of the supernatant was obtained. The supernatant is labeled UCExp256A-2.
13:00 The residue from UCExp256A-1 was washed with benzene (750uL) three times consecutively. Each time the supernatant was separated from the reside by centrifuging the mix. The supernatant from the first, second and third wash was collected separately and labeled UCExp256A-W1, UCExp256A-W2 and UCExp256A-W3 . The residue collected after the three washings was labeled UCExp256A-3
13:45 The residue was set in a vacuum desiccator connected to high vac. Obtained 81.2mg 51.2mg (error in copying) UCExp256A-3, dry; a 17% yield.
16:20 Removed the residue UCExp256A-3 was removed from the vacuum.
16:350 In to five clean / dry vials pipetted out 750uL DMSO-d6. The vials were labeled similar to the previously collected residue, mother liquor and washing collection (UCExp256A-3, UCExp256A-2, UCExp256A-W1, UCExp256A-W2 and UCExp256A-W3 respectively)
16:40 In to the vials carefully pipetted out approximately 150-300uL (where ever possible) corresponding solid and the solutions.
17:50 Obtained HNMR of the the residue, mother-liquor, and the washings.