ugi_exp52.JPG

Objective:


To form a Ugi product using piperonal, 5-methylfurfurylamine, Boc-Gly-OH, and t-butyl isocyanideto use for further cyclization. This is a scale up from experiment 52.

Procedure:


To four separate volumetric flasks was added piperonal (0.691 g, 4.6 mmol), 5-methylfurfurylamine (510uL, 4.6 mmol), Boc-Gly-OH (0.805 g, 4.6 mmol), and t-butyl isocyanide (520 uL, 4.6 mmol) and diluted to mark to approximately 10 mL with methanol. 40uL samples were removed and solvent evaporated to take NMR spectra of starting materials. In a separate Erlenmeyer flask were added piperonal and 5-methylfurfurylamine solutions and allowed to sit for approximately 3 hours. A 40uL sample was taken and placed under high vacuum to eliminate solvent. 1mL CDCl3 was added and NMR spectra was taken to confirm the formation of the imine. The Boc-Gly-OH solution was then added to the vial and shaken for approximately 30 seconds. Solution was allowed to sit for approximately 30 mins. A 40 uL sample was taken placed under high vacuum to eliminate solvent. 1mL of CDCl3 was added and an NMR spectra was taken of the reaction. The t-butyl isocyanide solution was then added to the solution and then monitored by NMR.

Results:


Starting Materials


Piperonal


HMR

5-Methylfurfurylamine


HMR

Boc-Gly-OH


HMR

Tert-butyl isocyanide


HMR

62A-Imine Confirmation (t=2hrs 49mins)


HMR

62B-Added Boc-Gly-OH (t=37 mins)


HMR

62C-Added Isocyanide


HMR

Crystals


62D - 198mg
62E - 760mg

X- Ray studies (Pseudo twinned crystals)
62E-Crystal1, 62E-Crystal-2
62E-Crystal analysis
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Discussion:

1. Proton Assignments for 62D:
singlets at 1.32ppm and 1.45ppm- t-butyl groups
singlet at 2.16ppm- methyl group of 5MFA
singlets at 4.18ppm and 4.43ppm- methylene groups of Boc-Gly-OH and 5MFA
broad singlets at 5.49ppm and 5.59ppm- amide protons
singlet at 5.74ppm- furan protons and chiral proton
doublet at 5.95ppm- methylene protons
multiplet at 6.75ppm- aromatic protons.

2. Proton Assignments for 62E
singlets at 1.32ppm and 1.45ppm- t-butyl groups
singlet at 2.16ppm- methyl group of 5MFA
singlets at 4.18ppm and 4.43ppm- methylene groups of Boc-Gly-OH and 5MFA
broad singlets at 5.49ppm and 5.58ppm- amide protons
singlet at 5.74ppm- furan protons and chiral protons
doublet at 5.97ppm- methylene protons
multiplet at 6.75ppm- aromatic protons


Conclusion:

The Ugi product was obtained in 41.3% isolated yield.

Log


2007-02-27


13:03 Prepared solutions of piperonal and 5-MFA. Removed 40uL samples, placed on high vac, added 1mL CDCl3 and took NMR spectra.
13:18 Mixed 5MFA and piperonal solutins together (pale yellow) in an Erlenmeyer flask.
16:07 Prepared Boc-Gly-OH solution. Removed 40uL sample and evaporated off solvent. Added 1mL CDCl3. Took NMR spectra.
16:20 Removed 40uL sample from reaction flask (62A). Evaporated off solvent , placed on high vac, and added 1mL CDCl3. Took NMR spectra. Noticed a tall peak for TMS reference point in spectra. 40uL may be too small for a sample. Imine peak was observed however. For future samples, larger amounts will be removed.
17:09 Added Boc-Gly-OH solution to reaction flask. Solution turned more yellow.
17:46 Removed 200uL sample from reaction flask (62B), evaporated off solvent, added 1mL CDCl3, took NMR spectra. Prep'd t-butyl isocyanide sol, removed 200uL sample, evaporated off solvent and took NMR. Added it to reaction flask.

2007-03-01


11:15 Noticed some small needles at bottom of reaction flask. Attempted "scratching" the flask to induce nucleation of crystals. The concentration may be too low for complete crystallization. If "scratching " isn't successful, will place solution on high vac to remove some solvent. Removed parrafin film covering flask.

14:30 Noticed white solid at bottom of Erlenmeyer flask.

2007-03-02

10:15 Noticed more white solid in the flask.
10:40 Removed 400uL sample from reaction (62C). Evaporated off solvent via high vac Took NMR spectra.
11:13 Filtered off crystals from reaction (62D) (198mg, m.p. 174C). Evaporated solvent down from filtrate, more crystals fell out of solution.

2007-03-06


12:00 Filtered off solvent via Hirsch funnel. Placed remaining crystals (62E) in round bottom flask. Placed crystals on high vac to evaporate any remaining solvent (760mg, 174C).

2007-03-07

10:52 Weighed out 10mg of 62D and 62E and placed them in an NMR tube. Added 800uL CDCl3. Took NMR spectra.

2007-12-07

17:20 Sent 62E for Crystallography studies

Tags

PiperonalInChI=1/C8H6O3/c9-4-6-1-2-7-8(3-6)11-5-10-7/h1-4H,5H2
5-methylfurfurylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
t-butyl isocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
Boc-Gly-OHInChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)
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-ugi052:InChI=1/C26H35N3O7/c1-16-8-10-18(35-16)14-29(21(30)13-27-24(32)36-26(5,6)7)22(23(31)28-25(2,3)4)17-9-11-19-20(12-17)34-15-33-19/h8-12,22H,13-15H2,1-7H3,(H,27,32)(H,28,31)