Reactants
Product
Reactants
Product

1,3,5-trioxane

formic acid

methylamine

n-butylisocyanide

Ugi product 1

1,3,5-trioxane

formic acid

methylamine

t-butylisocyanide

Ugi product 2

Researcher

Khalid Mirza

Objective

To synthesis Ugi products using a) formaldehyde (paraformaldehyde), methyl amine, formic acid and t-butylisocyanide; b) formaldehyde (paraformaldehyde), methyl amine and n-butylisocyanide in methanol

Procedure

Procedure using 1,3-5-trioxane
A solution of 1,3,5-trioxane (2mmol, 180mg) is dissolved in methylamine 2M in methanol (6mmol, 3mL) and formic acid (6mmol, 226uL). To one half of this three component solution (1.5mL) 1-butylisocyanide (3mmol,313uL) was added and to the remaining three component solution (1.5mL) t-butylisocyanide (1.5mmol, 340uL) was added. the two reactions were then left over night for the Ugi product precipitation.

Procedure using paraformaldehyde
A solution of paraformaldehyde (10mmol, 300mg), in 2M methyl amine in methanol (10mmol, 5mL) and formic acid (10mmol, 377uL) was prepared in a 2 dram vial. The solution was vortexed to ensure complete dissolution of the reagents. To one half of the three component solution (2.5mL) 1-butylisocyanide (5mmol, 523uL) was added and the to the remaining three component solution (2.5mL) t-butylisocyanide (5mmol, 565.5uL) was added. The two reaction mixtures were then left over night for the Ugi product precipitation.


Results

HNMR
UCExp260-1A


UCExp260-2A


Discussion

[You could also try aqueous formaldehyde, which worked fine with an excess here JCB]

Conclusion

Log

2010-12-18
17:00 Pipetted out methylamine (10mmol, 5mL, 2M in methanol) in to a glass vial, added paraformaldehyde (300mg=10mmol formaldehyde) to vial. Paraformaldehyde was obtained as a very fine white powder. It did not dissolve completely in to the methylamine/methanol solution. Vortexed the solution, yet was unable to dissolve it completely.
17:10 Pipetted out formic acid (10mmol, 377uL) in to the above solution. Vortexed it. The vial turned hot. The paraformaldehyde powder did not dissolve completely yet.
17:15 Set the vial to sonicate with the bath at room temperature.
18:17 Paraformaldehyde still insoluble in the reaction mixture.
18:20 Going to try the reactions with 1,3,5-trioxane.
18:30 Made-up a solution of 1,3,5-trioxane (6mmol, 180mg), methylamine (6mmol, 3mL, 2M solution in methanol) and formic acid (6mmol, 226uL) in a glass vial.
18:40 Pipetted out 1.5mL of this three component solution into another glass vial. To this solution added n-butyl isocyanide (3mmol, 313uL) and vortexed the resulting solution. This solution is labeled UCExp260-1. Note: n-butylisocyanide appears to have gone bad, when purchased it was a clear solution, now it has turned brick red..no change in its odor.[Hard to tell from color how much impurity present - it would be worth taking NMR of the isonitrile to see if it is at least >95% pure JCB]
18:45 To the remaining 1.5mL three component solution added t-butylisocyanide (3mmol, 340uL) and vortexed the resulting clear solution.[The clear solution at this point is the key - not the ability to make up a 2M solution of paraformaldehyde in methanol JCB] This solution is labeled UCExp260-2
18:50 Left the solution in the hood for the reaction to complete.
2010-12-20
13:00 No solid has precipitated out in either solutions.
[It might be worth taking an NMR of the crude mixture just to see if any Ugi product formed JCB]
2010-12-22
20:10 Obtained HNMR of the a small volume of sample UCExp260-1A and UCExp260-2A in CDCl3. It appears like sample UCExp260-2A has a slight dusting at the bottom of the vial.