Synthetic chemists continually seek ways to create novel compounds. Along the way they evaluate reagents, solvents, and reaction conditions giving rise to various reaction products and by-products.
Flash chromatography is a standard part of an organic chemist’s workflow. It is utilized after most reaction steps in order to remove most of the generated by-products and excess reagents.
The bane of organic synthesis for most chemists is purification rather than synthesis. Synthetic reaction mixtures are rarely devoid of impurities so some type of purification is necessary. Most often flash chromatography is used but for many chemists, it is less well understood than their chemical reaction and provides some level of anxiety.
In this post, I will summarize the five most important steps to creating a successful flash chromatography method and thus the anxiety associated with it.
The products of organic synthesis are designed with specific functional groups in order to possess desired properties. Depending on the compound’s functionality, it can be neutral, acidic, or basic as determined by a compound measurement called pKa or acid dissociation constant. Compounds with low pKa are typically acidic while those with high pKa tend to be basic. Compounds with a pKa near 7 are deemed neutral.
For most organic reaction mixture purifications the process is fairly straightforward. Use hexane/ethyl acetate or, for polar compounds, DCM/MeOH. But what do you do if this doesn't work and your compounds are basic organic amines?
In this post, I re-examine the options available to achieve an acceptable organic amine purification when typical separation methods are insufficient.
If you synthesize organic amine compounds, especially heterocyclic, secondary, or tertiary amines, you likely have encountered problems with their chromatography using silica columns. With the amine groups being basic and silica being acidic, there is a natural attraction between the two. This sometimes strong attraction often requires the use of a competing amine in the solvent system. Modification of the mobile phase with the addition of a solvent like triethyl amine can provide a successful purification. Often times the use of an amine-modified stationary phase can provide the needed conditions to avoid the acid-base interaction that can interfere with a successful flash chromatography purification.