Purifying your synthetic product efficiently in high yield with minimal impurities is every chemist’s goal. At discovery-scale, flash chromatography is the go-to purification technique as it is relatively simple and effective.
For most chemists, flash purification is a means to an end. In other words, it is a tool needed to purify and isolate one compound from a mixture of compounds so that the next reaction can occur with reduced by-product formation. Other than choosing between normal- or reversed-phase, there typically is not much thought put into cartridge selection, especially not related to stationary phase media porosity.
For most small molecules, this approach makes sense, but for larger molecules and very lipophilic compounds, factoring for media porosity should be included. In this post, I will discuss the impact media porosity can have on chromatographic performance.
For most organic and medicinal chemists, normal-phase flash chromatography is used to purify and isolate many types of organic compounds, most with some polar functional groups which help them retain on silica. However, some compound mixtures are water insoluble such as lipids, carotenoids, terpenes, tocopherols, polyaromatic and other hydrocarbons with minimal polar functionality. These lipophilic compounds do not retain well on silica and do not dissolve readily in water making them really difficult to separate.
In this post I will talk about a technique called non-aqueous reversed-phase chromatography that can be very effective at separating and purifying very lipophilic compounds.
Wouldn’t it be nice if your reactions only created your desired product? Of course the answer is yes, but that is not the reality of synthetic chemistry. Because our chemical reactions yield multiple components, they need work-up and purification to isolate the desired compound.