This is a question I asked myself while I have been studying synthesis variables to see what, if any, impact each variable has on reaction product yield and purity. For this post, I evaluated the order in which I added reactants and solvent.
Most chemical reactions take place in liquid form since compounds in solution are more likely to interact with each other, especially when heated. Reaction solvent choice varies based on reagent solubility and reaction temperature requirements. Because many reactions today require high temperatures, solvents such as dimethylformamide (DMF) and dimethylsulfoxide (DMSO) are frequently used. However, just because a reaction solvent has the proper reagent solubility and/ or a high boiling point does not mean it should be used. Why? Well, as we will show in this post, the solvent itself can alter synthetic efficiency by changing reaction kinetics as well as the number and type of by-products.
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.
Many microwave assisted organic synthesis (MAOS) reactions use polar solvents such as alcohols, DMF, DMSO, because they absorb and transfer microwave energy very efficiently. However, the downside of using polar, microwave absorbing solvents is that they can interfere with normal-phase flash chromatography.
In this post, I discuss why dry loading can be advantageous when purifying polar-solvated reaction mixtures.
"50% of my time as a Ph.D. was spend baby-sitting columns," stated Dr. László Kürti during our interview in February. Keep reading to find out more about how his team was able to increase their productivity by implementing Automated Flash Purification into their lab work.
Have you heard about Biotage® V-10 Touch? If you're struggling with rapidly drying samples dissolved in either aqueous or organic solvents, or evaporating HPLC fractions from purification and high boiling point solvents from synthesis, or simply if you would like to access a novel dry down onto silica technique for easier dry load capabilities, then you are in the right place! Just keep reading...
OK. We get it. You aren’t a molecule factory. Creating the right target molecule as soon as possible in order to keep your pharmaceutical research project moving isn’t easy or routine. Frankly, organic chemistry is hard and unpredictable. As Professor Gilbert Stork said, “Unless the molecule is very simple, it is not possible to go into the lab and make it within a short period of time.” His ‘Rule of Seven’ meant that, “however long you think a synthesis will take, multiply it by seven”.1
Organic reactions are generally inefficient, which means that crude reaction mixtures require work-up and purification to remove by-products and unreacted starting materials and/or catalysts. The goal in pharmaceutical research is to isolate the target compound with required purity and yield to be able to progress to the next synthetic sequence or biological testing with confidence. But the process of purification is viewed by synthetic chemists as a ‘means-to-an-end’ and the more rapidly and reliably the purification step can be performed the better. Easy enough to state, but hard to achieve when you need to be certain of purity and yield in a single, rapid purification attempt. As we will see here, flash column chromatography can help you achieve this.