Objective

To study the kinetics of a Ugi reaction in benzene by NMR; the Ugi product was first synthesized in UsefulChem Exp176, this will help correlate the solubility data for this compound with it rate of formation in benzene.
UCExp249-i.png

Procedure

OUTLINE OF WHAT IS TO BE DONE
Distill benzene over anhydrous calcium chloride.
Solution making
Dissolved phenanthrene-9-carboxaldehyde (103mg, 0.4994mmol) in benzene in a clean and dry volumetric flask. The concentration of this solution is 0.4994M
Dissolved phenylacetic acid (409mg,3mmol) in benzene a 1mL volumetric flask and made it up to the mark.
Added furfurylamine (8.9uL, 0.1007mmol) in to an NMR tube containing phenanthrene-9-carboxaldehyde (200uL, 0.1mmol, 0.5M in benzene)
Added a 3M phenylacetic acid solution in benzene ((33.4ul, 0.1mmol) to the NMR tube.
Added n-butylisocyanide (10.4uL, 0.1mmol) to the NMR tube.
Final volume of the reaction mixture: 0.2mL+0.0089mL+0.0335mL+0.00104mL=0.24334mL
Final concentration per component : 0.1mmol/0.24334mL= 0.41M

Results

DevelopingCrystals-after13h
Solid in the NMR tube-after 27h
Spreadsheet UCExp249-1- Aldehyde Change (aldehyde H)
SpreadsheetUCExp249-2 Imine Change (Imine H)
SpreadsheetUCExp249-3 Ugi Product formation Kinetics (methyl)
Plot of Imine Vs Ugi Change / Isocyanide depletion.
SAMS calculations for isocyanide
Kinetics for the depletion of the Isocyanide

HNMR of the Ugi product(UCExp176B) in benzene/benzene-d6
HNMR of the Ugi product (UCExp176B) in benzene/benzene-d6- with baseline correction using Varian software


UCExp249-Scatter-best fit

Discussion

There are two distinct methyl (next to a methylene) signatures (triplet) seen developing over entire range of the data collected; major peak 0.7-0.8ppm and a smaller triplet 0.6- 0.67ppm, these peaks appear to be in a 3:1 ratio. It may be possible that these peaks indicate the presence of two rotamers seen previously in an internal acetylene containing Ugi product (173G) from Exp173. However this had not been observed in any other Ugi products isolated so far, therefore this needs to be confirmed by repeating the kinetics run.
In order to determine the kinetics of the formation of the Ugi product, the methyl triplet (0.7-0.8ppm) and the isocyanide triplet (0.44-0.6ppm) have been used. The mmolar amount for isocyanide used-up was obtained by taking the initial amount added to be 0.1mmol at a 0.41M concentration. All peaks were then compared to the isocyanide methyl.
UCExp249-Isonitriledepletion.jpg
Figure1: Second order kinetics for isocyanide depletion during the course of the Ugi reaction in benzene at room temperature


It is evident from the plot of 1/[isocyanide[ Vs time, the reaction follows second order kinetics, and has a rate constant K= 6.2x10-3M-1 min-1.
At the time when solid was observed in the NMR tube (after 12h 22min) 0.55mmol of the Ugi product had been formed at a concentration of 0.23M. However the concentration of the Ugi product just before it came out was recorded at 0.18M (510min)
From the solubility studies of the Ugi product 176C, it is known that the product comes out of benzene at a 0.03M concentration. Therefore it appears likely that the starting materials and other impurities may be the cause for a dramatic increase in the solubility of the Ugi product.
[Were the crystals pure Ugi product? JCB] At the end of the reaction a very small amount of a yellow powder was isolated, UCExp249-4A, HNMR of the powder shows that the Ugi product was still contaminated with some impurities (0.942 ppm)
[Speculate about why this experiment turned out differently from EXP244 JCB] - I am not very sure what could have caused the furfuryl ammonium phenylacetate to precipitate out in Exp244 , it may be possible that the researcher in that experiment may have forgotten to add the isocyanide to the reaction mixture.
Note: All spectra have been base line corrected using Varian NMR software, therefore the solvent peak is distorted.

Conclusion

Rate of the Ugi reaction of phenanthrene-9-carboxaldehyde, furfurylamine, phenylacetic acid and n-butylisocyanide has been determine:
K= 6.2x10-3M-1 min-1. The reaction follows second order kinetics.
The Ugi product shows almost a ten fold increase in the solubility in benzene when present with its starting materials and intermediates. This possibly is a major cause for a decreased isolated yield of the product.


Log

2009-09-28

06:45 Weighed-out phenanthrene-9-aldehyde (103mg) in a clan and dry 1mL volumetric flask. Added benzene to it and dissolved the solid. Made-up the solution up to the 1mL mark. This is a 0.5M solution.
07:00 Pipetted out 200uL DMSO-d6 in to a co-axial insert NMR tube. Transferred 200uL of the 0.5M aldehyde solution in to a clean and dry NMR tube. Placed the coaixal insert with DMSO-d6 in it.
0.7:45 Obtained HNMR of the aldehyde solution (with d1=50). Performed a base line correction (bc) while processing the spectrum. UCExp249-aldeinundistilledbenzene
0:8:30 Observed impurity in the HNMR obtained. Therefore decided to distill benzene under CaCl2.
09:00 Placed 20g anhydrous calcium chloride and benzene (~25mL) in to a dry 100mL rb flask connected to a distillation assembly.
09:15 Started heating the liquid slowly (2 on the dial)
09:25 Solution started refluxing, about 2drop/sec
09:50 Increased heating (7 on the dial)
10:05 First drops of the distillate in the collecting flask. Temp 73C
10:10 Replaced the collecting flask with another clean and dry rb flask. (the 1st collecting flask had about 5mL of the distillate..this is discarded.
10:12 Started collecting in the second collecting flask, temp had increased to 78C.
10:20 Switched off heating.
10:25 Removed the collecting flask and immediately stoppered it. Accumulated about 10mL of the distillate
2009-09-29
10:00 To a clean NMR tube added 200uL of the 0.5M phenanthrene-9-carboxaldehyde solution. Placed a coaxial insert containing DMSO-d6 in to the NMR tube and obtained HNMR. (NMR ID) The solution is now labeled UCExp249-1A
11:03 Added furfurylamine (0.1mmol, 8.9uL) to the tube, mixed it for 10s and obtained HNMRs periodically. (time and HNMR ID)
19:30 Added phenyl acetic acid (33.4uL, 3M solution in benzene, 0.1mmol) to the NMR tube...the solution is now labeled UCExp249-2A. Obtained HNMRs periodically. (time and HNMR ID)
2009-09-30
Obtained HNMRs to monitor the reaction
2009-10-01
Obtained HNMRs to monitor the reaction
2009-09-02
06:35 After obtained an HNMR of the reaction mixture (UCExp249-2A) added n-butylisocyanide (0.1mmol, 10.4uL) to the NMR tube containing UCExp249-2A. The tube was shaken vigorously to mix the contents well. This solution is labeled UCExp249-3A
06:38 Soon after the addition of the isocyanide HNMR was obtained to monitor the conversion.
19:30 Obtained several HNMRs until now.[What are the names of the monitoring NMRs and when were they taken? JCB]- HNMR IDs and the time they were obtained are listed in the spreadsheet UCExp249-1- .
Observed crystals in the NMR tube after taking an HNMR at 742min.
Therefore further NMR analysis is stopped. Obtained a picture of the tube containing some crystals; DevelopingCrystals-after13h
2009-09-03
13:00 Entire solution in the tube had turned gel like solid...obtained another picture of the tube; Solid in the NMR tube-after 27h
2009-09-04
11:30 Added benzene (approximately 0.5mL) in to the NMR tube, vortexed it and transferred the contents in to a one dram vial. Rinsed the further with some more benzene (~100uL). Left the vials capped in to the hood for further crystallization.
2009-09-05
18:00 Only a small amount of solid had precipitated out at the bottom of the vial. Vortexed the vial and decanted the supernatant. Washed the ppt with 100uL benzene (x3). After the addition of benzene each time, the vial was vortexed thoroughly, centrifuged and the supernatant was decanted each time. The precipitate obtained after the wash was dried under vacuum..
22:00 Removed from vacuum and obtained only a very tiny amount of the yellow color solid..this is labeled 249-4A. Obtained HNMR of 249-4A.