Objective

To synthesize and fully characterize 11 Ugi products which are known to ppt out from the reactions run in THF.

Characterization
C35H47N3O4:UCExp247-1A White solid; 1H NMR (external image delta.gif ppm, 500MHz, CDCl3) 0.4-0.51 (m, 3H), 0.6-0.8 (m, 5H), 1.0-1.2 (m, 4H), 1.21-1.45 (m, 5H), 1.46 (2, 9H), 1.55-1.75 (m, 2H), 1.9-2.0 (m, 2H), 3.0-3.2 (m, 1H), 3.28-3.42 (m, 1H), 3.85-3.95 (m, 1H), 4.0-4.1 (m, 1H), 4.11-4.23 (m, 1H), 5,59 (bs, 1H), 5.65-5.75 (m, 1H), 6.78 (s, 1H), 7.55-7.75 (m, 4H), 7.85-7.95 (m, 3H), 8.69 (d, 1H, J=8.3H), 8.76 (d, 1H J=8.3H); yield %

C33H43N3O4:UCExp247-2A: White solid; 1H NMR (external image delta.gifppm, 500MHz, CDCl3) 0.38 (t, 3H, J=7.3Hz), 0.47-0.62 (m, 1H), 1.02-1.14 (m, 3H), 1.16-1.26 (m, 1H), 1.32-1.40 (m, 2H), 1.47 (s, 9H), 1.55-1.62 (m, 1H), 1.63-1.72 (m, 2H),1.88-2.03 (m, 2H), 2.98-3.12 (m, 1H), 3.25-3.40 (m, 1H), 3.85-3.96 (m, 1H), 4.01-4.10 (m, 1H), 4.12-4.20 (m, 1H), 5.5-5.75 (m, 2H),6.76 (s, 1H), 7.61-7.67 (m, 2H), 7.68-7.75 (m, 2H), 7.86-7.94 (m, 3H), 8.69 (d, 1H J=8.3Hz), 8.75 (d, 1H, J=8.3Hz)

C33H43N3O4 UCExp247-5A White solid; (external image delta.gifppm, 500MHz, CDCl3) 0.37 (t, 3H, J=7.3Hz), 0.43-0.45 (m, 1H), 0.69-0.86 (m, 2H), 1.03-1.15 (m, 3H), 1.16-1.27 (m, 1H), 1.31-1.39 (m, 2H), 1.46 (s, 9H), 1.54-1.62 (m, 1H), 1.62-1.71 (m, 2H), 1.89-2.03 (m, 2H), 3.03-3.15 (m, 1H), 3.29-3.44 (m, 1H), 3.84-3.95 (m, 1H), 4.01-4.09 (m, 1H), 4.1-4.23 (m, 1H), 5.59 (bs, 1H), 5.69 (bs, 1H), 6.76 (s, 1H), 7.59-7.76 (m, 4H), 7.83-7.95 (m, 3H), 8.69 (d, 1H, J=8.3Hz), 8.76 (d, 1H J=8.3Hz)

C32H37N3O5: UCExp247-6A White solid; (external image delta.gifppm, 500MHz, CDCl3) 0.91 (t, 3H, J=7.3Hz), 1.27-1.38 (m, 2H), 1.4-1.55 (m, 11H), 3.33 (ddd, 1H, J=7.3Hz, 5.8Hz, 6.8Hz), 3.37-3.46 (m, 1H), 4.21-4.35 (m, 2H), 4.44 (d, 1H, J=17.5Hz), 4.63 (d,1H, J=17.5Hz), 5.59 (s, 2H), 5.79-5.85 (m, 1H), 6.75 (s, 1H), 6.87 (s, 1H), 7.51-7.57 (m ,1H), 7.58-7.66 (m, 2H), 7.67-7.73 (m, 2H), 7.74-7.78 (m, 1H), 7.84-7.89 (m, 2H), 8.645 (d, 2H, J=8.3Hz)

C32H37N3O5: UCExp247-7A White solid; (external image delta.gifppm, 500MHz, CDCl3) 1.41 (s, 9H), 1.47 (s, 9H), 4.20-4.35 (m, 2H), 4.47 (d, 1H, J=17.5), 4.65 (d, 1H, J=17.5), 4.81 (s, 1H), 5.50-5.55 (m, 1H), 5.60 (bs, 2H), 7.51-7.56 (m, 1H), 7.57-7.66 (m, 3H), 7.67-7.73 (m, 1H), 7.74-7.79 (m, 1H), 7.83-7.94 (m, 2H), 8.61-8.68 (m, 3H)

C30H37N3O4: UCExp247-8A White solid; (external image delta.gifppm, 500MHz, CDCl3) 1.03-1.19 (m, 3H), 1.29-1.41 (m, 2H), 1.46 (s, 9H), 1.56-1.63 (m, 1H), 1.64-1.74 (m, 2H), 1.90-1.98 (m, 1H), 1.98-2.05 (m, 1H), 2.76 (s, 3H), 3.87-3.96 (m, 1H), 3.96-4.11 (m, 2H), 5.59 (bs, 1H), 5.73 (m, 1H), 6.84 (s, 1H), 7.59-7.66 (m, 2H), 7.67-7.74 (m, 2H), 7.83-7.92 (m, 3H), 8.68 (d, 1H, J=8.3Hz), 8.75 (d, 1H, J=8.3Hz)

C36H36N2O3: UCExp247-10A White solid; (external image delta.gifppm, 500MHz, CDCl3) 0.98-1.18 (m, 2H), 1.29-1.45(m, 2H), 1.56-1.63 (m, 1H), 1.64-1.71 (m, 2H), 1.73 (s, 3H), 1.88-1.96 (m, 1H), 1.97-2.05 (m, 1H), 3.86-3.97 (m, 1H), 4.00 (s, 2H), 4.50 (d, 1H, J=17.5Hz), 4.61 (d, 1H, J=17.5Hz), 4.87-4.90 (m, 1H), 5.16-5.20 (m, 1H), 5.70 (d, 1H, J=7.8), 6.95 (s, 1H, 7.20-7.40 (5H), 7.49-7.56 (m, 1H), 7.57-7.64 (m, 2H), 7.65-7.71 (m, 1H), 7.81-7.91 (m, 3H), 8.59-8.69 (m, 2H).

Results

Spreadsheet of reactions
Pictures
UCExp247-IMG-i
UCExp247-IMG-ii
UCExp247-IMG-iii
UCExp247-1A
UCExp247-2A
UCExp247-3A
UCExp247-5A
UCExp247-6A
UCExp247-7A
UCExp247-8A
UCExp247-10A
HNMR
HNMR
HNMR
HNMR
HNMR
HNMR
HNMR
HNMR
CNMR
CNMR
CNMR
CNMR
CNMR
CNMR
CNMR
CNMR

IR


IR
IR
IR


Discussion


Conclusion

Log

2009-08-02
12:30 Made-up 1.5M solution of phenanthrene-9-carboxaldehyde by dissolving the solid aldehyde (2.8g, 13.57mmol, 2.30mL) in THF (6.75mL)
13:00 Made-up a 3M solution of Boc-glycine by dissolving the solid acid (2.5g, 14.27mmol, 2.157mL) in THF (2.5999mL)
13:20 Made-up a 3M solution of phenylacetic acid by dissolving the solid acid (0.8g, 5.875mmol, 0.6872mL) in THF (1.2713mL)
13:45 Labeled 11 one dram vials 247-1 to 247-11
14:00 Pipetted out phenanthrene-9-carboxaldehyde solution (666.7uL, 1.5M in THF) in to the vial labeled 247-1 to 247-11
14:15 Pipetted out corresponding amine in to the vials (see spreadsheet for the name and volume added), vortexed the vials for 15s each.
14:30 Pipetted out boc glycine solution (333.4uL, 3M in THF) in vials 247-1 to 247-8, vortexed the vials for 15s each.
14:35 Pipetted out phenylacetic acid solution (333.4uL, 3M in THF) in vials 247-9 to 247-11, vortexed the vials for 15s each.
14:55 Pipetted out corresponding isocyanide in to the vials (see spreadsheet for the name and volume added), vortexed the vials for 15s each.
15:03 Obtained a picture of the reaction mixtures in the vials- UCExp247-IMG-i
16:40 Vial 247-3 had formed a solid ppt in it. Obtained a pic of the vials, UCExp247-IMG-ii
16:55 Vortexed all the vials for 15s each.
17:00 Pipetted out THF (500uL) in to vial 247-3 and vortexed and mixed the contents thoroughly.
17:05 Centrfuged vial 247-4 and separated the supernatant from the residue--collected the supernatnat separately
17:10 Repeated the THF (500uL) was of 247-3 another two times and collected the supernatant each time in to the previously collected supernatant. The combined supernatant is now labeled 247-3B
17:15 The residue obtained was set under a high vac for the solvent to evaporate.
2009-08-03
10:30 Removed 247-3 from the high vac and obtained 247-3A (xx mg, yield xx%)
11:55 Off the remaining ten reactions, 8 have formed precipitates, obtained a picture of the vials- UCExp247-IMG-iii
12:10 To the vials which had ppts (247-1, 274-2, 274-4, 247-5, 247-6, 247-7, 247-8 and 247-10) THF (500uL) was added. The vials were then vortexed to homogenize the solution. The vials were then centrifuged for about 2-3min. The supernatant was separated from the reside and the clear supernatant were collected and labeled accordingly as 247-1B to 247-8B and 247-9B.
15:45 THF wash repeated another two times (total of 3) and the obtained residues from the vials were left in the high vac to dry. Sample vials 246-6 and 247-7 yielded a very small amount of the solid after the wash.
16:00 Vials 247-9 and 247-11 did not form ppt even after 24h..the reactions in the vials is therefore aborted.
2009-08-04
12:20 Removed the vials from the desiccator and obtained dry powders...all vials contained white powder except vial 247-6 and 247-7 which were off-white. The products obtained after drying are labeled 247-1A, 247-2A, 247-3A, 247-4A, 247-5A, 247-6A, 247-7A, 247-8A and 247-10A.
13:00 The mother-liquors (247-#B series) from THF wash had evaporated off completely (they were left open in a fume hood). The residues were washed with methanol (3x 1mL) and the solid obtained after the wash was left to dry in a desiccator on a high vac.
18:00 Submitted a small portion of each sample from series 247-#A for mass analysis.