Not a Ugi Product

As I mentioned previously, one of the objectives of our research is to determine the conditions required for precipitation of pure Ugi products. Until recently, every precipitate we obtained could be characterized as the expected product.

It looks like the situation is not so simple.

For example consider Khalid's attempt (EXP171) to make Ugi product 171 H:

A nice precipitate was obtained...



But it does not correspond to the expected product. For one thing the tosyl group is missing - no non-exchangeable protons past 7.0 ppm. It clearly has the 3,5-dimethoxybenzaldehyde and possibly the methylamine and 2,4,6-trihydroxybenzoic acid components. It is insoluble in all common solvents except for DMSO. Although I'm not completely satisfied with the integration of the H NMR, the MS seems to match an iminium salt:


If this is the case it may be because of the significantly increased acidity of ortho-hydroxybenzoic acids. 2,6-dihydroxybenzoic acid has a pKa of about 1.5 (Papadopoulos 1991), compared with benzoic acid's 4.2 value.

The problem may be with the isonitrile component TOSMIC. However, according to Chris Hulme, it should participate in Ugi reactions, even if it gives lower yields.

We'll just have to do more examples and see if a pattern emerges.