4 Jan 2008

Buchwald/Hartwig amination

Lab Experiment

Submitted by Adam R. Johnson, Harvey Mudd College
Categories
Corequisites: 
Prerequisites: 
Course Level: 
Topics Covered: 
Subdiscipline: 
Description: 

I wanted a modern organometallic experiment showing the utility of Pd for coupling reactions.  Students attempted a variety of reaction conditions during the spring of 2007 and 2008.  Eventually,  we were able to get the reaction to work with a variety of primary amines (linear, cyclohexylamine) and t-butylamine.  Yields are not great (40-80%) and this experiment needs some optimization.  However, products were observed by GC-MS and NMR.

Equipment needs: 

This experiment is air-sensitive, but not enormously so.  The most sensitive reagent is the NaOtBu, which could be weighed in air in a pinch.  We use a glove box since we have one.  We store the Pd complexes under N2 after use.

 

Schlenk line, Ar balloons or glove box

Schlenk glassware, standard organic glassware

temperature controlled oil bath or heating mantle and thermometer.

Related activities: 
Implementation Notes: 

I usually turn off the students reactions after 18-24 hours, let them cool down, quench them with ether and store them in the 2-neck flasks until the following week where students work up the reaction and analyze by NMR and GC-MS.  We don't purify the compounds by column chromatography, but that could be added easily.

Time Required: 
1 to 2 3-4 hour lab sessions
Evaluation
Evaluation Methods: 

I would normally grade on purity and yield of the isolated compound, as well as experimental technique, but since we are still optimizing the conditions, I give students the benefit of the doubt.

Creative Commons License: 
Creative Commons Licence

Comments

The procedures included in this learning object have been used by multiple students over the past 3 years or so, and they generally work reasonably well.  I am attaching an updated lab manual page (called 2012 update above). The major change from before is that we weigh out the Pd, base, and phosphine in the glovebox and then assemble the reaction under an N2 line.  Storing the reagents in the glovebox gives us a more active catalyst and better coupling results.  We monitor the reaction by NMR and GC-MS to observe the coupled products.  In rare cases (with new Pd/Phosphine) we saw double coupling (minor product). We have not attempted to purify the crude reaction mixture; instead, students report NMR and GC yields and purities. 

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