To allow the imine reaction of tert-butylamine andpiperonal to go to completion in the presence of 3A sieves and then to add Boc-Gly-OH in a 1:1 ration of imine to acid. If very little to none of the imine is pushed back to the aldehyde then tert-butyl isocyanide will be added. This experiment will be compared to Exp048 and Exp051


Solutions of piperonal (603mg, 4.0 mmol in 2 ml MeOH-d4, 2 M) and tert-butylamine(420uL, 4.0 mmol in 2 ml MeOH, 2 M) were mixed in presence of 28x 3A sieves(~174mg). H NMR was taken at the start of the reaction and after 14.5hrs. Boc-Gly-OH(352mg, 2mmol) was added without the presence of sieves and changes were monitored by H NMR. 800uL of the same acid solution was added with 800uL of the imine solution in the presence of 16x 3A sieves(~100mg) for a little over an hour. 800uL of this solution was added to 800uL of tert-butyl isocyanide(226uL, 2mmol). Changes were monitored by HMR.


Characterization of starting materials


PartI - Imine Formation

14.5 hrs

Characterization of Part II - Addition of Boc-Gly-OH to imine soln w/o sieves


Characterization of Part II - Addition of Boc-Gly-OH to imine soln w/ sieves


Characterization of PartIII- Addition of t-butylisocyanide


Overlay1 - Pure starting materials
Overlay2 - PartI with piperonal and tert-butylamine
Overlay3 - PartII w/o sieves with piperonal, tert-butylamine, and Boc-Gly
Overlay4 - Part II w/sieves with piperonal, tert-butylamine, and Boc-Gly
Overlay5 - Part II 65mins, PartIII 2days and 6days and all starting materials
Exp058 Kinetics Excel


  1. Using the 9.7 peak for the aldehyde and the peak at 8.4 peak for the imine there is an 81% conversion of the aldehyde to the imine. Using the 1.15 peak for the amine and the 1.29 peak for the imine there is about 72% conversion of the amine after a 14.5 hour period. There is a 5.3% difference in concentration of the amine and aldehyde with an excess of amine after the 14 hour period. These percentages could be an equilibrium point but there is not enough data to determine this.
  2. The acid addition solution in part2 that had been mixed together in the presence of activated 3A sieves for an hour had a decrease in imine to 36% compared to the aldehyde.
  3. The sieves were tested before introduction into the reaction mixture by putting several in the palm of my hand and adding a few drops of water. The sieves generated ample heat to suggest they were properly activated. However because the mixture was not shaken enough over the 14 hour period the imine was still reverted back to the aldehyde.
  4. There are some peak shifts and small new peaks in the final HMR of part4 after the isocyanide was added over 6 days. The excel sheet also shows a peak growing around 5.9ppm which should correspond to the Ugi product. It is also becoming apparent that more peaks appear in the t-butyl region of the spectra. These and other peaks suggest side reactions occured. A picture of a general peak characterization is provided.


The imine reverted back to the aldehyde due to insufficient removal of water. Sieves should also be added prior to imine formation to remove water already present.



19:00] Prepared 2M solutions of piperonal and tert-butylamine in 2mL volumetric flasks with MeOH-d4.
21:00] Took piperonal HMR
21:10] Took tertbutylamine HMR
21:15] Pipetted 1.6mL of aldehyde with 1.6mL of amine into vial with 28x 3A sieves(174mg) which were activated in a crucible over a Bunsen burner for about 2mins. The concentration of the solutions is approximately 2M however redepositing of the aldehyde on the rim of the vial was observed suggesting that the MeOH-d4 had slighly evaporated. It can not be determined that the same thing happened to the tert-butylamine solution. Nothing was spilled.
21:20]Took 1minute HMR PartI A_06mins. Allowed solution to react over night. Substantial kinetic data will probably not be obtained.


11:00] Prepared a 1M solution of Boc-Gly-OH in MeOH-d4 using a 2mL volumetric flask. Also prepared a 1M solution of tert-butyl isocyanide using a 2mL volumetric flask.
11:58] Took HMR of imine solution that had been exposed to the sieves over night which was roughly 14.5hrs.
12:01] Took HMR of Boc-Gly-OH pure
12:12] After adding 600uL of acid to 800uL of imine solution, took HMR_1.5mins. This mixture was not exposed to the same or any additional sieves. Will add sieves to separate mixture later.
12:22] Took 10min HMR of acid/imine solution
12:32] Took 20min HMR of acid/imine solution.
18:20] Mixed 800uL of imine solution with 800uL of Boc-Gly-OH in the presences of 16x 3A sieves(~100mg)
18:48] Took 6hr 15min HMR of first imine/acid solution not treated with sieves.
19:15] Took 55min HMR of imine/acid solution that was treated with sieves.
17:25] Took 65min HMR of imine/acid solution that was treated with sieves.
17:25] Added 800uL of imine/acid solution that had been treated with 3A sieves with 800uL of 1M tert-butylisocyanide.
17:32] Took HMR of Ugi mix 1.5mins
17:40] Took HMR of pure tert-butylisocyanide
17:45] Took HMR of Ugi mix 14mins
18:10] Took HMR of Ugi mix 39mins
18:32] Took HMR of Ugi mix 51min
19:01] Took HMR of Ugi mix 80mins


15:05] Took HMR of Ugi mix after 45.5hrs of reacting


18:35] Took HMR of Ugi mix after 6days of reacting.
18:50] Took CMR of Ugi mix after 6days of reacting.


t-butyl isocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
imine: InChI=1/C14H13NO3/c1-10-2-4-12(18-10)8-15-7-11-3-5-13-14(6-11)17-9-16-13/h2-7H,8-9H2,1H3/b15-7-