We're Gonna Ugi All Night!

Thus begins the CHEM254 lab manual for the week of April 7, 2008 at Dominican University:

“Ugi to the left, Ugi to the right. This is so fun, we’re gonna Ugi all night.”

As I discussed a few days ago, Brent has followed through in a big way in incorporating the UsefulChem project into his teaching lab:

This experiment represents the beginning of collaboration with the UsefulChem Bradley open notebook science group of graduate and undergraduate research at Drexel University. The goal of the UsefulChem project is to use the Ugi 4 component reaction to synthesize possible anti-malarial compounds. Open notebook science allows immediate dissemination of experimental results that invites advice and suggestions as well as complementary experiments that enhance and advance the project. We are going to reproduce some of the Drexel results as well as perform two complementary reactions that have not been done at Drexel.

The procedure is derived from our lab notebook with one interesting vortexing modification :)

Part I.
Add 0.33 g of your aldehyde to 8 mL methanol in a 20 mL scintillation vial.
Screw on a Teflon (green) cap on the vial. Vortex to mix and dissolve the aldehyde.
Add 1 mL of methylamine solution to the vial.
Vortex to mix. Sing the “Ugi song” while vortexing.
Obtain 0.34 g of the carboxylic acid. Add the carboxylic acid to the vial.
Vortex to mix.
Obtain 0.39 g of tosylmethylisocyanide. Add the tosylmethylisocyanide to the vial.
Vortex to mix.
Take a photo of your reaction mixture.
Label the vial and let the reaction mixture sit in the sealed vial.

By taking pictures his students can directly compare the progress of the reaction with our group. The questions for this lab are also excellent and may result in some useful ideas for my students to ponder (this may end up being a realistic way to foster chemistry crowdsourcing):

What could you do to isolate your product if after 7 days if there are no spontaneously formed crystals?

Refer to UsefulChem Experiment 171 . Which reaction most closely corresponds to our experiment? What were the results?

Consider the IR spectrum may reveal that there is unreacted isocyanide in your product mixture. Where does the isonitrile group appear in an IR spectrum? (Refer to appendix 2B in your textbook.)

Consider the possible 1H spectrum of your Ugi product. How many aromatic Hydrogens are there? How many methyl groups are there? Where would you expect to observe the methyl groups?

Consider the possible 13C spectrum of your Ugi product. How many aromatic Carbons are there? How many carbonyl carbons are there? How many methyl carbons are there? Where would you expect to observe the methyl carbons?

If you were given four different compounds for each type of Ugi reactant (16 compounds in all), how many different Ugi products could you attempt to make?

Safety Question: What is the safest way to transfer 1 mL of 2.0 M methamine in methanol from the stock bottle to your reaction vial? Give a reasonable explanation of your choice.

I also really like that he is exposing his students to some handy cheminformatics tools:

Look up “tosylmethyl isocyanide” in chemspider. What is the InChI code? What is an InChI code?

Since Brent and I started the discussion we have a few more precipitates involving the non-stinky tosylmethylisocyanide that may be suitable for his lab. Khalid has been doing some tedious but very necessary data checking and recording and the updated results are available on the Master Table of Ugi reactions.

There are currently 65 reactions, with 20 giving precipitates - and we are now including reactions where the starting materials fail to dissolve. Not all the precipitates have been characterized but they will be over time. In fact the Ugi product that Brent is trying to make in his lab for next week has not yet been fully characterized - all those phenolic groups seem to give rise to solubility issues in CDCl3.

That is a risk associated with using Open Notebook Science for a teaching lab. But it is also one that could pay off because his students could be contributing valuable results to an ongoing research project focussed on making anti-malarial compounds.