Ether, ethyl acetate, hexane and
You can simply dilute your reaction with more solvent and then
wash with water.
Ether is not as polar as the others, so look out for polar
compounds that may choose to remain in the aqueous layer.
Dichloromethane should be avoided for environmental reasons, but
for small scale extractions it may be preferred.
Tricky Reaction Solvents:
When you have to mix solvents
for an aqueous workup, complications can occur.
Acetonitrile: Soluble in water. If convenient, remove
solvent before workup to avoid losing polar products. If product
is very nonpolar, partition between hexanes and water and carry
out aqueous extraction. On small scale, you can dilute with a lot
of the extraction solvent, and washed several times. Acetonitrile
will partition into the aqueous layer
Alcohols: Miscible with both water and organic solvents,
alcohols do not cooperate during the typical aqueous workup.
Remove the solvent by rotoevaporation first.
THF and Dioxane: These ethers are water soluble. If diluted
sufficiently with extraction solvent, and washed several times,
they will partition into the aqueous layer. However, sometimes
product goes along with them, and sometimes emulsions form. It is
safer to remove THF by rotoevaporation before workup if practical,
especially for large scale procedures. Dioxane is high boiling,
usually making rotoevaporation impractical.
Aromatic solvents: These are very nonpolar and will usually
stay in the organic layer. Benzene is miscible with water and can
lead to emulsion formation. It should be either removed by
rotoevaporation before workup, or diluted well with the extraction
solvent before washing with water.
DMF or DMSO: Very polar and high-boiling solvents that are
difficult to remove. If your product is not dangerously polar,
dilute with lots and lots of water before extracting with a
nonpolar solvent. Then thoroughly wash the organic layer with
Rule of Thumb (see all): For 5 mL of DMF or DMSO, use 5 X 10 mL of water during the aqueous wash. This should remove all of the DMF or DMSO.
Two aqueous washes to remove DMF:
1. 5% LiCl (aq)
2. 0.5 N HCl
Boc groups will survive the dilute HCl wash. TMS groups may not. (submitted by Bill Spencer, Albany Molecular Research, Inc.)
Amine solvents (pyridine, di- and trialkylamines): Amines
will partition into the organic layer during a typical aqueous
workup. However, they become water soluble if you
Wash the organic layer several times with dilute HCl
solution. The protonated amine will partition into the aqueous
layer. For use with acid stable target compounds only.
Wash the organic layer several times with 10% copper sulfate
(aqueous and blue). The copper-complexed amine will partition
into the aqueous solution, which turns purple. Continue to wash
with the copper sulfate solution until no color change is
Rule of Thumb (see all):
For 5 mL of an amine solvent, use 5 X 10 mL
of the 10% aq. CuSO4 solution during the aqueous wash. This
should remove all of the amine.
Magnesium sulfate: Fast, always works, but kind of messy.
Sodium Sulfate: convenient for small scale drying- it is
very easy to filter. You should start with a clear organic layer
(washed with brine, and not poured into a wet flask). Drying
takes longer than for magnesium sulfate. Sit it over the drying
agent ~15 minutes for dichloromethane, ~30 minutes for ethyl
acetate. It does not work well for ether.
Celite: Sometimes it is useful to filter small scale
reactions through Celite to remove trace water.
Miscellaneous Tricks and Advice
Azeotropes: Often traces of a high boiling solvent or other impurity
can be removed
from a product or reaction mixture by concentration of a solution of the compounds
an appropriate solvent. This works because higher boiling solvents often
lower boiling solvents, forming an easy to remove binary distillate. For an
table of azeotropic mixtures, see The Chemists Companion.
Pyridine: repeated (2-3 times) concentration of a reaction mixture
pyridine from heptane, cyclohexane, or toluene.
Water: organic compounds are conveniently dried by concentration
on the vacuum pump) by concentrating the compound to be dried from benzene or
especially tolunne. This technique is also useful for removal of water from
organic hydrates (eg. NMO) by concentrating the compound from toluene 1-3
times followed by drying in a vacuum dessicator.
To pull aqueous soluble organics out of the aqueous phase when CH2Cl2, EtOAc, Et2O, etc. don't work.
(submitted by Bill Spencer, Albany Molecular Research, Inc.)
If you think your product may be volatile (possible if MW is below
250), see How to Handle Difficult Compounds. If solvent is slow
to evaporate, consider heating the bath- but be careful, some
compounds decompose upon heating.