Hydrogenation (atmospheric pressure) with Pd/C

1. Put a catalyst, a solvent, and a substrate into a reaction vessel.
CAUTION! Pd/C is flammable. To avoid a fire:
1. A fire distinguisher beside you.
2. Fill the reaction vessel with Ar.
3. Put Pd/C first (a vapor of the solvent can cause a fire).
4. Collect the powder paper used in weighing Pd/C in specialized bottles. Paperto ‘the bottle for paper’ (the left bottle in the right photo).
5. Remove O2 from the solvent by sonication or Ar bubbling (if necessary).
6. Reduce the pressure moderately (water aspirator is recommended) when
you replace air/Ar with H2.
7. The reaction and workup should be conducted inside a hood.
TIPS solvent effect: Generally, protic solvents (ROH, AcOH, etc.) accelerate the hydrogenation rates.
TIPS stirring speed: The hydrogenation proceeds faster as the reaction mixture is stirred faster.
• Typical substrates: C–C double/triple bonds, benzyl ethers/esters, Cbz, N3, NO2, epoxides.
1/5

2. Fill the reaction vessel with H2 gas.
To make the vessel full of H2, repeat around 10 times “aspirate the gas inside => let H2 gas inside”.

~ 10 cycles

CAUTION! H2 gas is explosive. To avoid a fire/explosion:
1. Excess H2 gas should be discharged into a hood.
2. Reduce the pressure moderately (water aspirator is recommended).
3. You must not add another amount of Pd/C, even if you replace H2 with Ar in advance (H2 mayremain in the solvent). Filter Pd/C out, evaporate the solvent, and try hydrogenation from thebeginning again when the reaction did not finish.
4. The reaction and workup should be conducted inside a hood.

2/5

TIPS You should prepare double-layered balloons to keep H2 inside for longer time.

H2 easily pass through a single
layer of a rubber balloon.

H2 stays longer inside with adouble-layered balloon.

One balloon put intoanother with a spatula.

You can keep H2 for 6~12 hours (my feeling) with double-layered balloon.
TIPS You can use 2 balloons when you try a large-scale hydrogenation (theright photo).
*Water aspirator is too weak to reduce sufficiently the pressure in a large flask:a benchtop pump is better then.
TIPS You can use beach balls (= vinyl balloons) instead of rubber balloons.
H2 stays longer inside beach balls than inside double-layered rubber balloons.
If you are concerned about H2/air exchange, you can try beach balls.
*Rubber balloons have tension, and can apply more pressure of H2 to thereaction mixture than beach balls. This characteristic is a trade-off.
TIPS MS is useful when TLC gives no information whether hydrogenation finishes or not.

3/5

3. Removal of Pd/C — Celite filtration
CAUTION! Pd/C adsorbing H2 is more flammable than new Pd/C. You must not dry it out.
You detach the balloon and release H2 into a hood, then replace the gas inside with Ar. After that you remove
Pd/C from the reaction mixture by Celite filtration.
*Chlorinated solvents (CH2Cl2, CH3Cl) are nonflammable. They are safe when you wash Pd/C on Celite.

Glass filter

funnelThe waste Celite containing Pd/C is collected in specialized bottles in the same
way as paper adsorbing Pd/C. Celite to ‘the bottle for Celite’ (the right bottle inthe right photo).

4/5

4. Appendix
Starting Material

ProductPd/C

Pd/C(en)

Pd/Fib

Pd/PEI●

alkynesalkanes●●●azidesamines●●●olefins

alkanes●●●

Ar–NO2

Ar–NH2

●

●

●

Ar–X

Ar–H

●

●

Ar–NH-Cbz

Ar–NH2●●

R–CO2Bn

R–CO2H●●

R–NH–Cbz

R–NH2●

epoxidesalcohols●

R/Ar–OBn

R/Ar–OH●

R/Ar–OTBS/OTES

R/Ar–OH●

en: ethylenediamine, Fib: fibroin, PEI: polyethyleneimine; cf. http://www.wako-chem.co.jp/siyaku/product/chemical/kouso/pdf/4.pdf

5/5