Objective

To synthesize eight Ugi products with piperonal, furufylamine and boc-glycine acid with eight different isocyanides in methanol.

Procedure

A homogeneous solution of piperonal (10mmol, 1061.2mg), furfurylamine (10mmol, 883.7uL) and boc-glycine (10mmol, 1751.8mg) was made up in 5mL volumetric flask. The solution (500uL, 1mmol per component) was transferred in to eight labeld one dram vials. To each vial a unique isocyanide (1mmol) was added. The obtained solutions were vortexed for 10s each to ensure a homogeneous solution was obtained. The vials containing the reaction mixtures were left undisturbed overnight at room temperature.

Results

[CombiUgiResults needs Ugi SMILES -AL]
Pictures
IMGExp225-O
IMGExp225-1
IMGExp225-4
IMGExp225-5
IMGExp225-6
Spreadsheet

Discussion

Conclusion

[What is the outcome? JCB]

Log

2008-05-20
10:30 Weighed out piperonal (10mmol, 1061.2mg) in a 5mL volumetric flask, added a small amount of THF to it, to dissolve it, then pipetted out furfurylamine (10mmol, 884uL) in to it and vortexed the solution for 10s when it all turned homogeneous.
10:50 Added Boc-glycine (10mmol, 1751.8mg) to the volumetric flask and again vortexed it until the solution turned homogeneous. This solution is labeled 225-O. Obtained a picture of the solution (IMGExp225-O).
11:00 Labeled eight one dram screw cap vials 225-1, 225-2, 225-3, 225-4, 225-5, 225-6, 225-7 and 225-8. Transferred 500uL of 225-O in to each vial.
11:25 Added the following isocyanides to the corresponding vials. After the addition of the isocyanide to the vials they were vortexed for 10s and made sure a homogeneous solution was obtained. However vial 225-6 and 225-8 to which Tosylmethyl isocyanide and 2-chloro-6-methylphenyl isocyanide was added, did not clear-up after the isocyanide addition followed by vortexing. Obtained a picture of all the solutions. (IMGExp225-1). By the time isocyanide addition was complete, nucleation had already started in vials 225-1 and 225-4.
Sample Number
Isocyanide added
Amt of
isocyanide added(0.5mmol)
225-1
t-butylisocyanide
56.5uL
225-2
n-butylisocyanide
52.3uL
225-3
n-pentylisocyanide
63uL
225-4
cyclohexylisocyanide
62.2uL
225-5
benzylisocyanide
61uL
225-6
TOSMIC
97.6mg
225-7
Morpholinoethyl isocyanide
69uL
225-8
2-chloro-6-methylphenyl isocyanide
75.8mg
11:50 Vials labeled 225-6 and 225-8 were set in a sonicator.
12:10 Removed the vials from the sonicator...225-8 now had a homogeneous solution, however 225-6 still contained undissolved TOSMIC.
12:15 Obtained a picture of all the solutions (IMGExp225-4). Reaction mixtures in vials 225-1 and 225-4 had almost turned in to a solid ppt.
21:50 To vial 225-6 which contained undissolved TOSMIC, acetonitrile (250uL) was added. and vortexed for 25s, all the solid completely dissolved and a homogeneous solution was obtained.
22:00 Obtained another picture of all the solutions (IMGExp225-5). Now reactions vials 225-1, 225-2, 225-3, 225-4 and 225-8 have accumulated preciptates in them. Vial 225-8 has some fine needle likes crystals developing at the bottom of the vial.
2008-05-21
12:30 Obtained a picture of the solutions. (IMGExp225-6)
15:00 Needles formed in the vial 225-8 were not substantial enough to be isolated...because they were very few, hence the reaction reaction mixture in this vial will be dealt with later if more product / precipitate/ crystals are formed. Precipitates in vials 225-1, 225-2, 225-3, 225-4 and 225-5 were washed with methanol (500 x3). Each time after adding methanol (500uL) to a vial, it was vortexed for 30s. When the ppt at the bottom of the vial did not loosen-up then it was scratched out with a narrow spatula. Then the solution with methanol was vortexed again for 30s and then the solutions were centrifuged for 2min and then the supernatant was decanted out into another vial. This process of washing with methanol was repeated three times. The products obtained were left in a vacuum desiccator to dry.
18:00 Once the ppts dried off, they were weighed. Obtained;
225-1
Sample number
Weight of the product obtained
225-1

225-2

225-3

225-4

225-5