1. Organic Pedagogical Electronic Network Reaction Monitoring using Mass Spectrometry Cornelia Flender and Richard Zare, Stanford University

2. Get a glimpse of the reaction! (1)Takáts, Z. et al. Science 2004, 306, 471–473 (2)Perry, R. et al. Angew. Chem. Int. Ed. 2011, 50, 250-254 Overview Desorption electrospray ionization (DESI) 1 is a mass spectrometry (MS) based tool that can be used to look in situ at what happens during the very first milliseconds of a reaction 2.

3. Shoot some droplets! Charged droplets of a reagent-containing solution are sprayed onto the catalyst, which was spotted on a surface at atmospheric pressure and room temper- ature. As the reagent hits the catalyst, the reaction is started and continues inside secondary microdroplets that are generated by the me- chanical impact of the spray. These secondary droplets are directed toward the inlet of a mass spectrometer. Reagent-sprayDroplets containing the reaction partners The secondary droplets evaporate in the heated transfer capillary to form gaseous ions which are then analyzed by the mass spectrometer.

4. The numbers are key! The resulting spectrum contains signals of all molecules contained in the mixture that were ionized under the conditions. The numbers in the graph correspond to the m/z value of the ion (mass/charge ratio). Normally the charge equals 1, but there can be doubly and multiply charges ions depending on the compound.

5. Check if what you put in is what you get out! Look at isotopic profile (example: ruthenium) Rhodamine measured Rhodamine simulated Simulate ion and calculate mass error (example: rhodamine) 1 2 mass error: -1.9 ppm (ideally within ± 5 ppm) Many elements (carbon, chlorine, many transition metals) have isotopes that will also give different signals in the spectrum. The abundances of the isotopes will be reflected in the intensity of the corresponding masses in the spectrum.

6. Capture transient reaction intermediates! We looked at a rhodium- catalyzed intermolecular amination reaction by spotting catalyst and substrate on the surface and spraying with nitrogen- source and oxidant 3. By DESI-MS we detected an intermediate of the reaction that is believed to have a lifetime on the order of micro- to milli-seconds. This intermediate had not previously been detected. This demonstrates the power of the interdisciplinary approach of using mass spectrometry based tools for reaction monitoring. (3) Perry, R. et al. Proc. Natl. Acad. Sci. 2013, 109, 18295–18299 Nitrene species

7. Problems 1.In what way does chlorine influence the mass spectrum of a molecule? 2.What is displayed on the x- and y- axis of a mass spectrum? 3.What does ‘accurate mass’ mean?