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.
Have you ever run flash column chromatography with mass detection (Flash-MS) and observed the total ion current or TIC increase during the purification only to find that there was no discernible compound contributing to the effect?
In this post I discuss how I came across this issue and the solution I found to work.
Synthetic organic chemistry is the genesis of new pharmaceutical and commercial chemical products. In short, it is based on the idea that two or more carbon-based compounds can be forced to react using heat, or other energy source, to create a new, novel product – but this we already know.
Many chemists today find they need to synthesize molecules at higher temperatures in order to force difficult reactions to proceed. Solvents such as DMF, DMSO, and NMP are commonly used in these reactions as they facilitate the use of the high reaction temperatures. However, the same attributes that make these chemicals attractive as reaction solvents make compound recovery from them very difficult, including flash column chromatography. These high boiling solvents are typically polar and pose a challenge if purification is to be accomplished with normal-phase silica.
Your choice of sample loading technique can, and likely will, affect the separation and purity of your targeted compound. While liquid loading is easy and often fit for purpose, it can provide some issues especially if large sample volumes are required relative to column size (> 1% of a column volume) or the dissolution solvent is too strong for the chosen purification method (e.g. injecting a methanol-solvated sample into a hexane/ethyl acetate mobile phase).