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


A 0.4M solution phenanthrene-9-carboxaldehyde, fufurylamine and phenylacetic acid was prepared in methanol and benzene in two 5mL volumetric flasks. In to three half dram vials 1.5mL methanolic solution was transferred (0.6mmol percomponent, 0.4M) and in to another three benzene solution was transferred. Following this butylisocyanide (0.6mmol) was pipetted out in to the vials. The reaction mixtures were vortexed and left for 72h. The precipitates were then centrifuged. The residue from vials 1-3 was washed with methanol (750uLx3) and the residues from vials 4-6 was washed with benzene (500uLx3). The products obtained subsequently were dried in a vacuum desiccator and analyzed by HNMR.


SAMS for supernatants

Kinetic Spreadsheet for benzene after 72h


In methanol the Ugi reaction yielded on average 65% yield and in benzene the yield was 30%. This was expected owing to co-solute effect of phenylacetic in benzene, which is not seen in methanol. The co-solute effect of phenylacetic acid increases the solubility of the Ugi product in benzene.

After 72h, in benzene the reaction is expected to 0.034M of the reactant remaining and 0.3658M (a 91.4% conversion) product formed. These numbers were estimated based on the rate constant for the reaction in benzene (UCExp249). However only 30% of the product was isolated. Obviously, the estimated kinetics do not take in to consideration the solubility effect and the phenylacetic acid- Ugi product interactions in benzene.
We know from ONSCExp157 the solubility of the Ugi product in benzene with phenylacetic acid co-solute at 0.4M was estimated at ~0.12M (0.1175M). Since over time as the reaction progresses, the effective concentration of phenylacetic acid is depleted and the concentration of the Ugi product increases, this should be reflected in the solubility trend as well, in essence the yield should be higher than (0.36-0.12), i.e, more than 60% and upto 80% assuming only 0.04M (8.5%) acid remains after 72h.
Similar results are expected even if the results from ONSCExp156 is used (the 3-component co-solute effect)
It may be possible that most of the product might have been lost during washing steps.
[I think that the fact that you did not get a precipitate after 2 days in benzene while in the past you got it after 13 hours strongly suggests something went wrong. Only NMR monitoring or NMRs of the mother liquor and washing could give you more information about that JCB]


Yields for the Ugi reaction in benzene and methanol have been successfully determined.


15:15 Weighed out furfurylamine (194.4mg, 2mmol) in to a 5mL volumetric flask.
15:20 Weighed out phenylacetic acid (272.3mg, 2mol) and phenanthrene-9-carboxaldehyde (412.3mg, 2mmol).
15:25 Transferred the solids in to the volumetric flask, pipetted out a small volume of methanol in to the flask tried to dissolve it. However not all solid dissolved. Therefore placed the solution on to a vortex then in to a sonicator with water bath at 25C and sonicated it for approximately ten min and made-up to the 5mL mark.
15:45 This homogeneous solution is 0.4M methanol solution of 3 components, labeled soln255-A.
18:52 Weighed out furfurylamine (194.2mg, 2mmol) in to 5mL volumetric flask.
19:00 Weighed out phenanthrene-9-carboxaldehyde (412.6mg, 2mmol) and phenylacetic acid (272.6mg, 2mmol)
19:15 Transferred the solids in to the volumetric flask, pipetted out a small volume of benzene in to the flask and dissolved by vortexing the flask. Made-up the solution to 5mL mark.
This is 0.4M benzene solution of 3 components, labeled soln255-B
19:50 Transferred soln255A and B in to two 2dram vials (for easy pipetting) and labeled six vials 1-6
20:03 In to vials labeled 1-3 transferred soln255-A (1500uL, 750u:x2) and in to vials 4-6 transferred soln255-B (1500uL, 750uLx2) and capped them off (0.6mmol per component)
20:08 In to each vial from 1 through 6, pipetted out butylisocyanide (0.6mmol, 62.7uL) and vortexed the solutions for ~15s each.The reaction mixtures are now labeled UCExp255-1A-1 through UCExp255-6A-1
20:35 Observed precipitation occurring in vial 1, obtained pictures UCExp255-IMG1 and UCExp255-IMG2
20:38 Therefor manually shaken for a few seconds. Soon after solution in vial 3 also formed precipitate.
21:10 However vial 2 did not show any precipitation for the next hour. Left the vials undisturbed.
19:39 Day 2- All three methanol solutions had precipitated out. However benzene solutions did not, therefore the solutions were sonicated for a few seconds and left undisturbed. Obtained a picture UCExp255-IMG3
18:35 All solutions at this time have precipitated out. Obtained a picture, UCExp255-IMG4. Solutions were first sonicated for a few min, then vortexed to mix them well.
18:55 The reaction mixtures in the vials were then centrifuged and the supernatants from each vial was carefully collected separately. The supernatants were labeled UCExp255-1B through UCExp255-6B.
19:30 The residues in vials 1 through 3 were washed with methanol (750uL x 3). Each time after adding methanol, the solution was vortexed to mix well, then centrifuged and the supernatant was separated in to a 1dram vial. These are mother liquors UCExp255-1C-3C
20:10 After washing the precipitates they were left in a vacuum desiccator.
20:20 The residues in vials 4 through 6 were washed with benzene (500uL x 3). Each time after adding benzene, the solution was vortexed to mix well, then centrifuged and the supernatant was separated in to a 1dram vial. These are mother liquors UCExp255-4C-6C The residues are labeled 1A thourgh 6A. Obtained picture of UCExp255-1A-6A, UCExp255-1B-8B and the UCExp255-1C-6C series, UCExp255-IMG5, UCExp255-IMG6 and UCExp255-IMG7
20:50 After washing the precipitates they were left in a vacuum desiccator.
22:45 Obtained HNMR of supernatants UCExp255-1B through UCExp255-6B in DMSO-d6.
22:30 The dried products were weighed.
Vial # 1 -- 199.3mg - now labeled UCExp255-1A2 - yield = 65.8%
Vial # 2 -- 197.1mg - now labeled UCExp255-2A2 - yield = 65.1%
Vial # 3 -- 201.1mg - now labeled UCExp255-3A2 - yield = 66.4%
Vial # 4 -- 89.9mg - now labeled UCExp255-4A2 - yield = 29.7%
Vial # 5 -- 92.5mg - now labeled UCExp255-5A2 - yield = 30.5%
Vial # 6 -- 87.6mg - now labeled UCExp255-6A2 - yield = 28.9%
23:30 Obtained HNMR of solids from UCExp255-1A2 through UCExp255-6A2

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