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Objective

To obtain a simple Ugi adduct under aqueous conditions.

Procedure

To a 100 ml round bottom flask added 25mls of 1M LiCl solution (1.05g/25ml of water), formaldehyde 37% w/w, (100 µl), tert -butylamine (105µl, 1.0 mmol ) 2-morpholin ethyl isocyanide (140µl, 1.0mmol ) and Boc-Gly-OH (0.175 mg, 1.0mmol). The mixture is stirred for 4h.The product is then taken up in methylene chloride dried over MgSO4 (anhydrous), rotovaped and evaporated under high vacuum .

Results

Characterization of 28A

1. A TLC of t-butyl amine and formaldehyde could not be obtained because the components are so volatile that as soon as they were spotted on the plate they disappeared and a run in methylene chloride / hexanes (1:1) showed nothing except the isocyanide. (Boc-Gly-OH being UV inactive).
2.A HNMR of 28A was obtained in CDCl3 (500MHz Varian Inova).
3. A TLC was run in methylene chloride against the isocyanide and the amine (not visible because of its volatile nature), under UV lamp , stained with ninhydrin (heated).
4. C-13 NMR of 28A (300MHz Varian Inova) is unusable - too much noise.

Discussion

The choice of this isonitrile may be problematic for the way that this reaction was worked up because it results in a Ugi product which is an amine. Since the aqueous layer was not made basic, it is possible that much of the Ugi product stayed in the aqueous later as a carboxylate salt, especially since only one wash was done. It was not possible to get a good C NMR of the little material obtained as the crude product 28A and the experiment was aborted.

Conclusion

Most material was not extracted into the organic layer. Rendering the aqueous layer basic during extraction may help in the future. However, this is problematic for phenolic products. The use of basic isonitriles is not suitable for the Ugi synthesis of our target compounds.

Log

2006-09-07

1. 15:22] Added all the components to a round bottom flask (using a 500µl syringe for liquids), started stirring at room temperature. Solution was clear.
2. 19:22] Stopped stirring and added 25ml of methylene chloride, the solution is remained clear.
3 19:55] Dried the obtained methylene chloride layer with Sodium Sulfate, filtered, rotovaped and set on high vac to obtain 28A (23.8mg).

Tags

Formaldehyde InChI=1/CH2O/c1-2/h1H2
2-morpholin ethyl isocyanideInChI=1/C7H12N2O/c1-8-2-3-9-4-6-10-7-5-9/h2-7H2
Boc-Gly-OHInChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)
tert -butylamineInChI=1/C4H11N/c1-4(2,3)5/h5H2,1-3H3
ugi027:InChI=1/C19H36N4O5/c1-18(2,3)23(16(25)13-21-17(26)28-19(4,5)6)14-15(24)20-7-8-22-9-11-27-12-10-22/h7-14H2,1-6H3,(H,20,24)(H,21,26)