Guide to Separation Schemes

Step 1: Ask yourself which compounds are soluble in water at neutral pH. To determine this follow the general rules below.

a) For a given compound, if the ratio of carbon atoms to N-H, NH2, or OH groups is <> good bet that the compound is water soluble. Some examples:

b) If the compound is charged, then it is a good bet that the compound is water soluble. Some examples: c) Exceptions to Rule a, include compounds with very large dipole moments and <>

Step 2: Second, consider acid base chemistry that the compound can undergo. If you adjust the pH, can you form a salt, or reform a neutral compound from a salt. Knowing which compounds will and will not react when you are considering organic molecules is actually not terribly complicated. You just need to know approximate pKas for functional groups, and whether they will react with a strong or weak base, or an acid.

Carboxylic acids have a pKa around 5. This means that carboxylic acids can react with either a strong base like NaOH, or a weak base like NaHCO₃. This would form a carboxylic salt that would be soluble in water.

Alcohols generally have pKa’s around 17. Something with a pKa of 17 is not going to react with a strong base like NaOH. There is only one type of alcohol that can be deprotonated by NaOH-that is a phenolic alcohol. The pKa of a phenolic alcohol is significantly lower because of the aromatic ring, around 10. This is low enough to be deprotonated by NaOH, a strong base, but not by a weak base like NaHCO₃.

Amines have pKa’s around 35. They are bases, so they will not react with base. They can, however, become protonated by an acid to form the water soluble salt.

Neutral compounds remain soluble in organic solvents. Likewise if you do acid base chemistry that gets you back to the neutral compound it will no longer be soluble in water.

Step 3: Extraction is generally a preferred technique. If this cannot be used consider other methods.

a) Can a simple filtration be used? Is one a solid, and the other a liquid?

b) Is one of the compounds volatile? If the compound is low boiling it can be easily taken of by rotary evaporation. Some examples of volitle compounds are acetone, hexanes, ethyl acetate, methylene chloride, ethyl ether.

c) For remaining compounds, column chromatography would probably be a good choice. Column chromatography separates compounds based on polarity. An expert can separate almost anything on a column, even the most minor polarity differences.