Exp164_Rxn_Scheme.JPG
Reaction Scheme

Objective

To synthesize a Ugi adduct from aniline, phenanthrene-9-carboxaldehyde, phenyl acetic acid and n-butyl isocyanide in methanol using Ugi 4CR following Explan005. The target compound was ranked 20 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 aniline, phenanthrene-9-carboxaldehyde, phenyl 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
164/20
Methanol
Phenanthrene-9-
carboxaldehyde
aniline
phenyl acetic acid
n-butyl isocyanide
Aborted
Quantity
1500uL
0.5 mmol, 103.12 mg
0.5mmol, 45.6uL
(density=1.022g/ml)
0.5mmol, 68.08 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 (164A)


Exp164A.JPG




Discussion


All results are recorded Master Table and Workflow Tables.

Conclusion

This Ugi reaction failed to dissolve, possibly due to the apparent selective solubility of phenanthrene-9-carboxaldehyde as discussed here.

Log

2008-01-24

15:37- Charged a vial with 1 ml of methanol.
15:39- Started to weigh out the phenanthrene-9-carboxaldehyde
15:45- Started to weigh out the phenylacetic acid.
15:49- Added the aniline to the vial and vortexed for 15 seconds. A clear solution was obtained.
15:52- Added the phenanthrene-9-carboxaldehyde to the vial and vortexed for 6 minutes. No clear solution was obtained.
15:59- Added the phenylacetic acid and vortexed for 5 minutes. No clear solution was obtained.
16:08- Added the n-butylisocyanide and vortexed for 5 minutes. No clear solution was obtained.
16:15- Added another 0.5 ml of methanol to the vial and vortexed for one minute. There was no change in the vial and no clear solution.
16:17- Vortexed for 5 more minutes. No clear solution was obtained.
16:25- Took a photo of the vial. This experiment needs to be aborted, because the components did not all go into solution.

Tags

aniline InChI=1/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2 InChIKey: PAYRUJLWNCNPSJ-UHFFFAOYAP
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
phenyl acetic acid InChI=1/C8H8O2/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,9,10) InChIKey: WLJVXDMOQOGPHL-UHFFFAOYAR
n-butyl isocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3 InChIKey: FSBLVBBRXSCOKU-UHFFFAOYAR
Ugi adduct InChI=1/C3 ​4H32N2O2/c​1-2-3-22-3​5-34(38)33​(31-24-26-​16-10-11-1​9-28(26)29​ -20-12-13-​21-30(29)3​1)36(27-17​-8-5-9-18-​27)32(37)2​3-25-14-6-​ 4-7-15-25/​h4-21,24,3​3H,2-3,22-​23H2,1H3,(​H,35,38) InChIKey: UBRMSVUGUNBCHK-UHFFFAOYAX