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Objective

To synthesize a Ugi adduct from benzylamine, phenanthrene-9-carboxaldehyde, 4-chlorophenyl acetic acid and n-butyl isocyanide in methanol using Ugi 4CR following Explan005. The target compound was ranked 18 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.

Procedure

To a one dram vial, charged with methanol (1mL) and benzylamine, phenanthrene-9-carboxaldehyde, 4-chlorophenyl acetic acid and n-butyl isocyanide (0.5mmol each) was added in that order. After each addition, the resulting solution was vortexed for at least 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
159/18
Methanol
Phenanthrene-9-
carboxaldehyde
benzylamine
4-chlorophenyl acetic acid
n-butyl isocyanide
Aborted
Quantity
1000uL
0.5 mmol, 103.12 mg
0.5mmol, 54.6uL
(density=0.981g/ml)
0.5mmol, 85.30 mg
0.5mmol, 52.28 ul
(density=0.795g/ml)


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


Results


5 min after mixing
all components (159A)

One day after mixing
all components (159B)

Exp159day1.JPG
Exp159day2.JPG

(159C)

Exp159C.JPG


Discussion


All results are recorded Master Table and Workflow Tables.
[So it looks like you get a clear solution when the phenanthrene-9-carboxaldehyde is mixed with benzylamine in methanol JCB]

Conclusion


After one day a precipitate was obtained but the solvent was evaporated without washing - aborted and to be repeated.

Log

2008-01-18

16:03- Started to weigh out the phenanthrene-9-carboxaldehyde.
16:09- Started to weigh out the 4-chlorophenyl acetic acid.
16:14- Charged a vial with 1 mL of methanol.
16:16- Added the benzylamine to the vial and vortexed for 15 seconds. A clear solution was obtained.
16:20- Added the phenanthrene-9-carboxaldehyde to the vial and vortexed for 5 minutes until a clear solution was obtained.
16:26- Added the 4-chlorophenyl acetic acid to the vial and vortexed for 15 seconds. A clear solution was obtained.
16:30- Added the n-butyl isocyanide to the vial and vortexed for 15 seconds. A clear solution was obtained.
16:33- Took a photo of the vial and left it to sit for 24 hours at room temperature.

2008-01-19
16:38- Took a photo of the vial after one day. A most of the liquid in the vial precipitated into a solid.

2008-02-08
15:34- Vortexed the product in the vial for 15 seconds. No solvent was visible.
15:36- Added 500 ul of methanol to the vial and vortexed for 15 seconds. The solvent remained over the solid.
15:40- Sonicated the vial containing undissolved solid and methanol on top for 1 min, then vortexed it for 15 sec. At this time the solid packing at the bottom of the vial mixed well with the solvent and a pasty mixture covered the walls of the vial.
15:43- The vial was then emptied onto a clean watch glass.
15:45- The vial was rinsed with 250 ul of methanol, and then the contents were emptied onto a watch glass.
15:47- A photo was taken (159C) of the watch glass and empty vial. The methanol will evaporate so the product can be weighed.


Tags

benzylamine InChI=1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2 InChIKey: WGQKYBSKWIADBV-UHFFFAOYAL
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
4-chlorophenyl acetic acid InChI=1/C8H7ClO2/c9-7-3-1-6(2-4-7)5-8(10)11/h1-4H,5H2,(H,10,11)
n-butyl isocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3 InChIKey: FSBLVBBRXSCOKU-UHFFFAOYAR