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Does high performance flash column chromatography require high performance TLC for method development?

November 25, 2020 at 4:34 PM / by Bob Bickler


Higher performance flash columns are becoming all the rage these days.   Chemists are using them for challenging as well as for routine purification.   As a result, I am often asked, "do I need high-performance TLC plates for method development?"

In this post I will explain why the answer is no.

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When should I add acid to my detector make-up solvent when using mass-directed flash chromatography?

November 20, 2020 at 2:57 PM / by Bob Bickler

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Increasingly, organic and medicinal chemistry labs use mass-directed flash chromatography to isolate synthesized compounds. Mass-directed flash chromatography benefits are many, including collecting only the targeted molecule(s) in the reaction mixture. This approach simplifies compound purification since you know what you have made and it's associated mass.

However, there are mass detection nuances that can be challenging. One of these is to know when an acid should be added to the mass detector’s make-up solvent to protonate targeted molecules. In this post, I will provide some insight on this topic.

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In-line Scavenging Simplifies Flash Column Chromatography Reaction Mixture Purification

November 20, 2020 at 2:55 PM / by Bob Bickler


I am always grateful for the feedback I get from my blog readers.  Today's blog is in response for multiple requests for tips on purifying complex mixtures and suggestions for alternative sample loading techniques.

In this post, I will attempt to address both, to some degree anyway, with a single example using a scavenger resin.

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Can reversed-phase chromatography compound elution volume/time be predicted?

November 18, 2020 at 9:26 PM / by Bob Bickler


When developing reversed-phase flash chromatography methods it is important to understand the impact that a change in solvent ratio has on compound retention and, therefore, separation performance. Unlike normal-phase chromatography where you can optimize separations using TLC and a wide variety of solvents and solvent ratios, reversed-phase limits you to 3 to 4 solvents, including water, using either HPLC or small flash columns for method development. Those solvents include:

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Invest 10 minutes on TLC and save a day of grief

November 13, 2020 at 1:17 PM / by Bob Bickler


Flash column chromatography is used by between 20 and 40 thousand organic synthesis chemists worldwide, an amazing number. For most of these chemists flash chromatography is an important part of their daily workflow but allocating time for good method development is often not considered, which can lead to less than ideal purification results.

In this post I focus on how allocating just 10 minutes on thin-layer chromatography (TLC) for method development can save you a lot of grief later on.

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Why is my UV baseline changing during flash column chromatography?

November 6, 2020 at 8:15 AM / by Bob Bickler


A baseline that rises or drops when using flash chromatography with a UV detector can be a problem, especially if you are trying to collect compounds with poor detectability or that exist in low quantities.

In this post I will talk about the causes and solutions for a rising (or even dropping) baseline.

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