Objective

To synthesize a Ugi adduct (wrong link) from Phenanthrene-9- carboxaldehyde, tert-butyl isocyanide, benzylamine, and crotonic acid in methanol using Ugi 4CR following Explan005. This is a repeat of Exp143c.The target compound was ranked 155 in the DEXP014-V1B file from D-EXP014. The purpose of this experiment is to synthesize an anti-malarial compound based on the inhibition of falcipain-2, as described in this summary post.

[The experiment is repeated because Phenanthrene-9-carboxaldehyde which was used in the previous experiment was acquired as a liquid. The aldehyde used here was obtained from Sigma Aldrich as a solid- Mpt-100C]

Procedure

To a one dram vial, charged with methanol (1mL) benzylamine, phenanthrene-9-carboxaldehyde, crotonic acid and tert-butyl isocyanide (0.5mmol each) was added in that order. After each addition, the resulting solution was vortexed for 15 seconds and confirmed that a homogeneous solution had been obtained. The vial was capped tight and left at room temperature for 1 day.


ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
156/155
Methanol
Phenanthrene-9-
carboxaldehyde
benzylamine
Crotonic acid
tert-butylisocyanide
Yes
Quantity
1000uL
0.5mmol, 103.1mg
0.5mmol, 56.6uL
(density=0.981g/ml)
0.5mmol, 43.0mg
0.5mmol, 56.5uL
(density=0.735g/ml)


Density information found on the Sigma-Aldrich website (www.sigmaaldrich.com)

Results


5 min after mixing
all components (156A)

One day after mixing
all components (156B)

Exp156day1.JPG
Exp156day2.JPG

Discussion




The experiment was repeated because Phenanthrene-9-carboxaldhyde which was used in the previous experiment was obtained as a liquid, the HNMR of the liquid does not correspond to the NMR of the compound purchased from Sigma-Aldrich.

All results are recorded Master Table and Workflow Tables.

Conclusion


After one day a precipitate was obtained - analysis by NMR pending to confirm Ugi product.

Log

2008-01-11

17:22- Weighed out the Phenanthrene-9-carboxaldehyde.
17:30- Weighed out the crotonic acid.
17:39- Charged a vial with 1 ml of methanol.
17:42- Added the benzylamine to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:44- Added the phenanthrene-9-carboxaldehyde and vortexted for 6 minutes before the solution was no longer cloudy. The solid went into the solution.
17:48- Added the crotonic acid and vortexed for one minute before the solution was not longer cloudy. A clear solution was obtained.
17:50- Added the tert-butyl isocyanide and vortexted for one minute. A clear solution was obtained.
17:55- A photo was taken after all of the components were mixed. The solution was left to sit for a day at room temperature.

2008-01-12
17:45- The solution precipitated white crystals. A photo of the vial was taken.

Tags


Phenanthrene-9- carboxaldehyde InChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13(11)15-8-4-3-7-14(12)15/h1-10H InChIKey: QECIGCMPORCORE-UHFFFAOYAE
tert-butyl isocyanide InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL
crotonic acid InChI=1/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/b3-2 InChIKey: LDHQCZJRKDOVOX-NSCUHMNNBH
benzylamine InChI=1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2 InChIKey: WGQKYBSKWIADBV-UHFFFAOYAL