Hydrogenation using palladium on carbon and ammonium formate is my favorite reaction to perform, because:

  • It typically doesn’t take more than 10 minutes to get the reaction going, from weighing out the starting materials until the first promising bubbles appear.
  • Almost any solvent is good. I prefer low-boiling alcohols; methanol or ethanol.
  • No special glassware or equipment necessary. Grab a round bottom flask or a test tube, and you’re good to go. Air and water, no problemo.
  • Once the actual reaction gets going, it can be quite entertaining/dramatic for a brief couple of seconds. Woosh! Done.
  • No fancy ligand or anything alike is needed. Just good old, uncut palladium(0). (No manuscript for Journal of Organometallic Chemistry, though.)
  • I love the concept of ammonium formate as the hydrogen source. Weighing out exactly 6.0 equivalents of hydrogen is easy peasy, when you deal with a solid.
  • Nitro groups, imines, nitriles, aryl (pseudo)halides, ketones – you name it – all tend to give spot to spot conversion to their reduced counterparts. Even benzylic alcohols can give up the hydroxy group, if you crank up the temperature high enough.
  • Work-up is a dream. Filter, evaporate, done.

So – which one is yours?

 

13 Responses to My favorite reaction

  1. KarlDCollins says:

    Mine is still the first experiment of my PhD. Knoevenagel condensations in water.

    Benzaldehyde, Meldrum’s acid, H20, 60 deg for 2h.

    Cool to room temperature and filter off your alkylidene product.

    Easy as pie.

  2. tuky tuky says:

    Agreed, highly recommendable reaction. Two issues though: 1 – upon heating, part of your ammonium formate sublimates into the condenser. 2 – the side product, ammonia, will cleave base sensitive groups. Beware!

  3. pi* says:

    Dr Freddy – do you have a reference to a good review on this reaction, perhaps in the context of complex molecule synthesis?

    • drfreddy says:

      Unfortunately, I can’t say I do. For me, I think it started with a method in a ’90s Synthesis paper about reducing Ar-NO2 to Ar-NH2 with Pd/C and ammonium formate (can’t seem to find it now), and I soon realized, as did many with me, that this could be extended to lots of other functional groups.

      If you have the time, I recommend searching through old Synthesis issues. Lots of examples to be found. A quick and dirty search yielded:

      Synthesis 2003, 2023-2026. (DOI: 10.1055/s-2003-41024)
      Synthesis 2003, 2467-2469. (DOI: 10.1055/s-2003-42410)
      Synthesis 1988, 91-95. (DOI: 10.1055/s-1988-27478)

  4. Brandon says:

    Boc protection of amines, using TEA/MeOH(/H2O). Works beautifully, and the only purification is prolonged time on the Hi-Vac.

  5. milkshaken says:

    NaH2PO2 also works well as a hydrogen source with Pd-C in EtOAc-water biphasic mix (don’t ask) at room temp. Had some success using it for selective dehalogenation.

  6. GW FTW says:

    So did you realize that the first to do transfer hydrogenation this way was a certain Nobel Laureate who also discovered the vinylic hydrogen substitution reaction, carbonylations to form esters and the Sonogashira reaction before Sonogashira (oh and also used Boron before Suzuki)

    http://www.udel.edu/chem/heck/

  7. GW FTW says:

    Some of those achievements might be obscure enough for the Mega Chemist Challenge

  8. Caroline says:

    Super easy reaction right, you just need to be extra carefull when you filter off on large scale !!!!!!!!!!
    Or you need to find a way to stop the evolution of hydrogen from the formate + palladium …. almost had a fire once !!!!

  9. Chelsea says:

    This has always been a favorite of mine too, but I had my first fire with it yesterday! The ammonium formate usually dissolves nicely for me in MeOH, but I had a stubborn chunk that didn’t want to dissolve and I sonicated it like I would for any stubborn solid dissolution. Turns out that sonication accelerates the process for forming hydrogen. When I added the Pd/C, the reaction flashed and a huge flame shot out of the round bottom. NEVER SONICATE AMMONIUM FORMATE IN SOLUTION!!

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