Exp_179_Rxn_Scheme.JPG
Reaction Scheme

Objective

To synthesize a Ugi Product following the EXPLAN005 . The compound will contribute towards a library for Falcipain2 inhibitors.
This compounds was ranked 44 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

As described in Explan005
This reaction used Phenanthrene-9-carboxaldehyde, Aniline, 4-chlorophenyl acetic acid and t-butyl isocyanide
Phenanthrene-9-Carboxaldehyde (solid from Sigma-Aldrich)
HNMR
ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
179/44
Methanol
Phenanthrene-9-
carboxaldehyde
aniline
4-chlorophenyl acetic acid
t-butylisocyanide
N/A
Quantity
1500uL
0.5mmol, 103.1mg
0.5mmol, 45.6uL
(density=0.719g/ml)
0.5mmol, 85.3mg
0.5mmol, 56.3uL
(density=0.795g/ml)


Density information found on the Ugi Chemicals Page in Left Navigation Bar.

Results

Photos taken directly after all the components were charged and vortexed.
rank_44_day_1.JPG
179A




No dissolution could be achieved during the additions even with 30 minutes of vortexing as well as further dilution.

Discussion

This experiment is another example of the apparent amine-dependent solubility of the phenanthrene carboxaldehyde. One might hypothesize that the aromaticity of the aniline increases its stability and thus decreases its willingness to dissolve the phenanthrene-9-carboxaldehyde.

Conclusion

Experiment aborted because a clear solution was never obtained immediately after mixing all reagents or the addition of extra solvent. A further discussion of the apparent amine selective solubility of phenanthrene-9-carboxaldehyde is presented here.

Log

2008-03-03

16:00- Charged a vial with 1000 ul of methanol.
16:02- Weighed out the Phenanthrene-9-carboxaldehyde.
16:07- Weighed out the phenylacetic acid.
16:15- Added the aniline to the vial.
16:16 Vortexed vial 1 min
16:21- Added the phenanthrene-9-carboxaldehyde.
16:22-Vortexed vial 2 min
16:24- Added the 4-chlorophenyl acetic acid.
16:25-Vortexed vial 1 min, did not dissolve, moved on to next addition
16:26- Added the t-butyl isocyanide.
16:27-Vortexed 5 min, still no dissolution, made decision to add methanol to dilute it.
16:33-Added extra 500ul of methanol
16:34-Vortexed 5 min, still no dissolution
16:40-Concluded that no further dissolution possible.
16:45- A photo was taken (179A) to demonstrate insolubility.

Tags

phenanthrene-9-carboxaldehydeInChI=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
Aniline InChI=1/C6H7N/c7-6-4-2-1-3-5-6/h1-5H,7H2 InChIKey: PAYRUJLWNCNPSJ-UHFFFAOYAP
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) InChIKey: CDPKJZJVTHSESZ-UHFFFAOYAC
t-butyl isocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL
Ugi Product InChI=1/C3 ​4H31ClN2O2​/c1-34(2,3​)36-33(39)​32(30-22-2​4-11-7-8-1​4-27(24)28​ -15-9-10-1​6-29(28)30​)37(26-12-​5-4-6-13-2​6)31(38)21​-23-17-19-​ 25(35)20-1​8-23/h4-20​,22,32H,21​H2,1-3H3,(​H,36,39) InChIKey: KKLAGOLUKOTRAL-UHFFFAOYAS