Objective

To synthesize a Ugi adduct from
4-chlorobenzaldehyde, tosylmethyl isocyanide, 5-methylfurfurylamine, and salicylic acid in methanol using Ugi 4CR following Explan005. The target compound was ranked 16 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) 5-methylfurfurylamine, 4-chlorobenzaldehyde, salicylic acid and tosylmethyl 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
158/16
Methanol
4-chlorobenzaldehyde
5-methylfurfuryl amine
Salicylic Acid
tosylmethyl isocyanide
no
Quantity
1000uL
0.5 mmol, 70.3 mg
0.5mmol, 55.7uL
(density=0.997g/ml)
0.5mmol, 69.06mg
0.5mmol, 96.6 mg


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

Results


5 min after mixing
all components
(158A)

One day after mixing
all components
(158B)

Exp158day1.jpg
Exp158day2.JPG

Discussion




All results are recorded Master Table and Workflow Tables.

Conclusion


After the vial set out at room temperature for a day and was sonicated, no Ugi product was formed.

Log

2008-01-17

16:55- Charged a vial with 1 mL of methanol.
17:01- Started to weigh out 4-chlorobenzaldehyde.
17:06- Started to weigh out salicylic acid.
17:10- Started to weigh out tosylmethyl isocyanide.
17:15- Added the 5-methylfurfurylamine to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:17- Added the 4-chlorobenzaldehyde to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:19- Added the salicylic acid to the vial and vortexed for 15 seconds. A clear solution was obtained.
17:22- Added the tosylmethyl isocyanide to the vial and vortexed for one minute. A clear solution was obtained.
17:25- A photo was taken after all of the components were mixed. The solution was left to sit for a day at room temperature.

2008-01-18
17:33- Took picture of the vial. No precipitate has formed yet. The solution was very dark green
17:35- Put the vial into the sonicator for ten minutes.
17:45- Removed the vial from the sonicator. No precipitate has formed.

Tags


4-chlorobenzaldehyde
tosylmethyl isocyanide InChI=1/C9H9NO2S/c1-8-3-5-9(6-4-8)13(11,12)7-10-2/h3-6H,7H2,1H3 InChIKey: CFOAUYCPAUGDFF-UHFFFAOYAC
5-methylfurfurylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3 InChIKey: YSEAGSCGERFGBL-UHFFFAOYAH
salicylic acid InChI=1/C7H6O3/c8-6-4-2-1-3-5(6)7(9)10/h1-4,8H,(H,9,10) InChIKey: YGSDEFSMJLZEOE-UHFFFAOYAQ