Objective

To synthesize 176B, 150D and 148B



Procedure


To a one dram vial, charged with phenanthrene-9-carboxaldehyde, methanol (0.5mL) and amine, carboxylic acid and an isocyanide (1mmol each) was added in that order. After each addition, the resulting solution was vortexed. After the addition of all the components, the vials were placed in a sonicator for 10min when clear solution were obtained. These solutions were left at room temperature for Ugi product precipitation.

Results

UCExp251-i
UCExp251-ii

UCExp251-2B-1-motherliquor (only usable mother liquor NMR)
SAMS for the concentration of the Ugi product UCExp251-2C in the mother liquor
Isolated products HNMR
UCExp251-1C
UCExp251-2C
UCExp251-3C
Baseline corrected Isolated product HNMR
UCExp251-1C
UCExp251-2C
UCExp251-3C
M.P UCExp251-1C- 184-186C

Discussion

[What is the concentration of the Ugi product in the mother liquor using SAMS? JCB]
SAMS estimation suggests that the concentration of the Ugi product UCExp251-2C in the mother liquor is 0.06M. It is also known that the solubility of the Ugi product in methanol is 0.6M. This lead us to believe that there is a very insignificant effect of the impurities on the solubility of this Ugi product in methanol at room temperature.

From the HNMR of UCExp252-1C it appears that there is still a small amount of phenanthrene-9-carboxaldehyde remaining. [can you report a rough estimate? JCB]

Conclusion

Log


2009-11-01
13:00 Weighed out phenanthrene-9-carboxaldehyde (1mmol, 206mg) in to three one dram vials labeled 251-1, 251-2 and 251-3.
13:10 Pipetted out methanol (500uL) in to each vial.
13:15 Added furfurylamine (1mmol, 88.4uL) to vial 251-1. Vortexed the solution for 15s...solid did not dissolve.
13:20 Added benzylamine (1mmol, 109.2uL) to vial 251-2. Vortexed the solution for 15s...solid did not dissolve.
13:25 Added heptylamine (1mmol, 148.3uL) to vial 251-3. Vortexed the solution for 15s...solid did not dissolve.
13:30 Weighed out phenylacetic acid (1mmol, 136mg), added it to vial 251-1 already containing the aldehyde and furfurylamine..vortexed the contents for about 15s, the color of the ppt turned deep yellow, but it remained heterogeneous.
13:35 Weighed out crotonic acid (2X) (1mmol, 87mg). Added 1mmol of the acid to vial 251-2, vortexed it for about 15s, unable to obtain a clear solution..
13:45 The vials at this stage were left in the sonicator with water bath at 25C.
13:50 Removed vial 251-1 from the sonicator, at this time there was still some amount of solid at the bottom of the vial.Then pipetted n-butylisocyanide (1mmol, 104.6uL) in to the solution. Vortexed the resultant solution for 10s and placed it back in to the sonicator.
13:55 Removed vial 251-2 and 251-3 from the sonicator, there was still some solid at the bottom of the vials. Pipetted out t-butylisocyanide (1mmol, 113.1uL) in to both the vials. Vortexed them for 10s and placed them back in to the sonicator.
14:00 Solution in vial 251-1 had turned completely clear...removed it from the sonicator and left it on the bench.
14:20 Solutions in vial 251-2 and 251-3 now clear-up completely. Removed them from the sonicator and placed them next to 251-1, however unfortunately, solid had already started to ppt out from 251-1, even before a picture could have been taken...
14:22 Obtained a picture of the solutions, one with solid in it and the other containing clear solutions, UCExp251-i
15:00 All the vials at this time have developed precipitates in them. Obtained a picture of the vials containing solid products in them, UCExp251-ii
17:20 Vials 251-1, 251-2 and 251-3 were vortexed for 1min, and centrifuged, supernatant was obtained vial 251-2 only, the other two vials contained relatively dry ppts.
18:00 The supernatant/ mother liquor from vial 251-2 was carefully decanted in to a clean NMR tube (obtained approximately 100uL), added CDCl3 (600uL) and obtained an HNMR of the mother liquor UCExp251-2B-1.
18:10 Pipetted methanol (500uL) in to the three vials, vortexed them until, the solid mixed well with methanol.
18:25 Centrifuged the vials, separated out the supernatants; ones from vial 251-1 and 251-3 are now labeled UCExp251-1B-1, UCExp251-3B-1.The supernatant from 251-2 was collected separately; UCExp251-2B-2.
18:50 Obtained HNMR of UCExp250-1B-1 and UCExp250-3B-1; the mother liquors. UCExp251-1B-1-motherliquor
UCExp251-3B-1-motherliquor
19:30 To the ppts obtained after removing the supernatant more methanol (500uL) was added and the solutions were vortexed and centrifuged. The supernatant from each vial was collected in to the previously used vials which contained UCExp251-1B,UCExp251-2B-2 and UCExp251-3B. The process of washing with methanol was repeated another 2 times.
20:00 Lastly, the obtained white powdery residues were left in a desiccator connected to a house vac for over night drying.

2009-11-03
11:00 Removed from the desiccator and and obtained UCExp251-1C, 386mg, (from UCExp251-1B); yield: 76.5%
Obtained UCExp251-2C, 299mg (from UCExp251-2B), yield: 64.3%
Obtained UCExp251-3C, 333mg (from UCExp251-3B), yield: 70.4%
2011-02-05
17:20 Obtained melting point of UCExp251-1C- 184-186C