<![CDATA[jcbradley : RSS Feed]]> Elgg http://elgg.jfitzsimons.org/activity/user/jcbradley/summary/all/all/0 <![CDATA[EXP150]]> http://elgg.jfitzsimons.org/page/12 http://elgg.jfitzsimons.org/page/12 Jul 9, 2008 - 2:43pm

Objective

To synthesize a Ugi adduct from Phenanthrene-9-carboxaldehyde, benzylamine, Tert-butylisocyanide and Crotonic acid in methanol using Ugi 4CR following Explan005. This is a repeat of Exp143c.The target compound was ranked 155 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.

[The experiment is repeated because the Phenanthrene-9-carboxaldehyde which was used in the previous experiment (Exp143) was acquired as a liquid. The aldehyde used here was obtained from Sigma Aldrich as a solid- Mpt-100C.]

Procedure

To a one dram vial, charged with methanol (1 ml), benzylamine, phenanthrene-9-carboxaldehyde, crotonic acid and tert-butyl isonitrile (0.5mmol each) was added in that order. After each addition, the resulting solution was vortexed for 15 seconds (or more) and confirmed that a homogeneous solution had been obtained. The vial was capped tight and left at room temperature. After crystallization, the solution was decanted and the crystals were washed with methanol (3x 500uL) and dried under vacuum to obtain 150D in 58.5% yield.

Characterization of 150D: White powder;(fix spacing and other formatting issues and double check all values - 269.9 ppm is not even on the scale) H-NMR (external image delta.gif ppm ppm, CDCl3) 1.39 (s, 9H), 1.77 (d, 3H J 6.3Hz), 4.79 (d, 1H, J=17.9 Hz), 4.88 (d, 1H, J=17.9 Hz), 5.67 (s, 1H), 6.18 (d, 1H, J=15.0 Hz), 6.33-6.81 (m, 4H), 6.88-7.23 (m 2H ), 7.36-7.74 (m, 4H), 7.80 (d,1H J=7.3 Hz), 7.90 (s 1H), 8.09 (d 1H J 12.2 Hz), 8.51 (t 2H J 12.8Hz); 13C NMR (external image delta.gif ppm, CDCl3) 18.1, 28.6, 49.0, 50.6, 51.7, 57.6, 94.6, 122.2, 122.4, 122.9, 124.2, 125.8, 126.6, 126.68, 127.1, 127.2, 128.7, 129.3, 130.1, 130.2, 130.4, 130.7, 130.9, 137.3, 143.4, 168.0, 269.9 ; IR (KBr, 1/cm): v=3323.75, 3058.46, 2969.65, 1677.58, 1655.43, 1594.01, 1526.84, 1421.50, 722.23, 695.58; HRMS m/z calcd for C31 H32 N2 O2 : 465.254202 [M+H] found 465.2448; C31 H32 N2 O2 Na 487.236148 [M+Na] found 487.237610

Results

Phenanthrene-9-Carboxaldehyde (solid from Sigma-Aldrich)
HNMR
benzylamine
HNMR
Crotonic Acid
HNMR
tert-Butyl isocyanide
HNMR

Characterization of 150D

add all good spectra to the ChemSpider entry
HNMR
CNMR
MS (FAB)
HRMS
IR

X- Ray studies
150D-Crystal Structure
150D-Crystal analysis
To view the above file:
1.Right click, save to desktop
2. Download MERCURY or enCIFer from CCDC (free) install the program and view the file)

Conclusion

The Ugi product was obtained in 59% yield.

Log

2007-11-27

19:30- Charged a vial with 1ml of methanol and began to weigh out the crotonic acid and phenanthrene-9-carboxaldehyde.
19:40- Added 54.61 ul of benzylamine into the vial and vortexted for 15 seconds. A clear solution was achieved.
19:44- Added 103.1 mg of phenanthrene-9-carboxaldehyde to the vial and vortexed for one minute. The solution was light yellow and somewhat cloudy, and the sediment settled to the bottom of the vial. Therefore the solution was vortexed for another three minutes. The solid now went in to the solution, however a few oil like droplets were observed at the bottom of the vial. The solution homogenized upon standing.
20:10- Weighed out and added 43.0 mg of crotonic acid into the vial and vortexed for 30 seconds. The solution became clear.
20:25- Added 56.5 ul of tert-butyl isocyanide to the vial and vortexed for 30 seconds. The solution became cloudy with a few small flakes on the bottom of the vial. It was vortexed for a total of five more minutes before a clear yellow solution was obtained.
20:31 Obtained a picture of the vial (150A) remember to always label results so you can discuss them
20:35- The vial was left to sit at room temperature for a day.

2007-11-28

11:23 Moved the vial to another location and obtained a picture of 150B, still a clear solution..
12:18 Crystallization has started in.
13:29 Obtained another picture (150C)

2007-12-05

19:00 Decanted the clear solution from 150C in to another vial and washed the crystals with methanol (3x500uL), each time vortexing (how long?) the solution and just decanting the supernatant..(did not centrifuge because the crystals separated out from the supernatant easily)
19:30 Evaporated the methanol under high vac for half an hour.
20:20 Obtained 135.8mg of 150D.

2007-12-06

19:30 Obtained HNMR of 150D. (62.3mg / 623uL CDCl3)

2007-12-07

17:20 Sent 150D for Crystallography studies.

2007-12-08

12:30 Obtained IR of 150D. Pulverized 150D (~20mg ) with KBr (~200mg) (spectrograde ) using a tiny mortar-pestle, pressed the powder (mix) in to a pellet. Obtained an IR spectrum on a Perkin Elmer FTIR -Model: Spectrum One.
13:00 Submitted ~5mg of the sample (150D) for MS (FAB) analysis.

2007-12-14

14:09 Results from X -ray studies have come.


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
tert-butylisocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL
Crotonic Acid: InChI=1/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/f/h5H InChIKey: LDHQCZJRKDOVOX-UHFFFAOYAC
benzylamine InChI=1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2 InChIKey: WGQKYBSKWIADBV-UHFFFAOYAL
Ugi Product : InChI=1/C31H32N2O2/c1-5-13-28(34)33(21-22-14-7-6-8-15-22)29(30(35 ​)32-31(2,3)4)27-20-23-16-9-10-17-24(23)25-18-11-12-19-26(25)27/h5​ -20,29H,21H2,1-4H3,(H,32,35)/b13-5 InChIKey: PBZQTKRWYXTXIS-WLRTZDKTBU

 

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