Exp180_Rxn_Scheme.JPG
Reaction Scheme

Objective

To synthesize a Ugi Product following the EXPLAN005 with phenanthrene-9-carboxaldehyde, heptylamine, glacial acetic acid and n-butyl isocyanide. The compound will contribute towards a library for Falcipain2 inhibitors.
This compounds was ranked 40 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, n-Heptylamine, n-butyl isocyanide and Acetic Acid.
Phenanthrene-9-Carboxaldehyde (solid from Sigma-Aldrich)
HNMR
ID/ Lib Rank
Solvent
Aldehyde
Amine
Carboxylic Acid
Isocyanide
Ppt Yes/No
180/40
Methanol
Phenanthrene-9-
carboxaldehyde
heptylamine
Acetic acid
n-butylisocyanide
No
Quantity
1000uL
0.5mmol, 103.1mg
0.5mmol, 74.1uL
(density=0.777g/ml)
0.5mmol, 28.6uL
0.5mmol, 52.3uL
(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_40_day_1.JPG
180A
rank_40_day_2.JPG
180B


180A was taken directly after dissolution, and 180B was taken 24 hours after mixing.

Discussion

This experiment shows an example of the solubility of phenanthrene-9-carboxaldehyde. Since heptylamine is a fairly long-chain amine, it is less polar than the majority of the amines that have failed to dissolve the aldehyde such as propylamine, aniline, etc. Perhaps since phenanthrene-9-carboxaldehyde contains only one carbonyl group which is small in size compred to its phenanthrene group, that this makes it less polar than it needs to be to dissolve with the more polar amines. This explains why it would dissolve in heptylamine and not in propylamine.

Conclusion

No precipitate was obtained after 24 hours. 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.
16:05- Weighed out the Phenanthrene-9-carboxaldehyde.
16:18- Added the heptylamine to the vial.
16:19 Vortexed vial 1 min
16:21- Added the phenanthrene-9-carboxaldehyde.
16:22-Vortexed vial 2 min
16:30- Added the acetic acid.
16:31-Vortexed vial 1 min
16:32- Added the n-butyl isocyanide.
16:33-Vortexed 10 min until full dissolution occurred.
16:45- A photo was taken (180A).

2008-03-04

20:43 Solution was vortexed for one minute, then placed in the hydrosonicator for 1 minute.
20:45 A photo was taken to show that no precipitate was formed (180B).

Tags

n-butyl isocyanide InChI=1/C5H9N/c1-3-4-5-6-2/h3-5H2,1H3 InChIKey: FSBLVBBRXSCOKU-UHFFFAOYAR
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
n-Heptylamine : InChI=1/C7H17N/c1-2-3-4-5-6-7-8/h2-8H2,1H3 InChIKey: WJYIASZWHGOTOU-UHFFFAOYAD
Acetic Acid InChI=1/C2H4O2/c1-2(3)4/h1H3,(H,3,4) InChIKey: QTBSBXVTEAMEQO-UHFFFAOYAR
Ugi Product InChI=1/C2 ​9H38N2O2/c​1-4-6-8-9-​14-20-31(2​2(3)32)28(​29(33)30-1​9-7-5-2)27​ -21-23-15-​10-11-16-2​4(23)25-17​-12-13-18-​26(25)27/h​10-13,15-1​ 8,21,28H,4​-9,14,19-2​0H2,1-3H3,​(H,30,33) InChIKey: LTBVPTQRLGYDPE-UHFFFAOYAR