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Bob Bickler


Recent Posts

What's the best way to scale-up flash chromatography?

April 25, 2023 at 4:00 PM / by Bob Bickler

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Flash chromatography is an integral part of the organic synthesis workflow. For most chemists, they make a compound once and then move on to the next synthesis. Sometimes, the synthesis needs to be scaled up and in those instances, its reaction mixture purification also needs scaling, especially if crystallization is not an efficient option.

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When should I use C18 rather than silica for flash chromatography?

April 11, 2023 at 3:00 PM / by Bob Bickler

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Flash chromatography is nearly ubiquitous within organic and medicinal chemistry labs. Most chemists, when the need arises to purify a reaction mixture, will use a silica column (aka normal-phase) for flash chromatography. This purification technique utilizes a column filled with silica and lipophilic solvents such as hexane, heptane, dichloromethane, and ethyl acetate. For polar and/or basic compounds, chemists will add methanol and a strong base (for basic compounds) to try the get their product to separate and elute.

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What should I use instead of DCM/MeOH flash chromatography for purification?

March 28, 2023 at 2:00 PM / by Bob Bickler

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While polar compound purification is frequently performed using a silica column and a DCM/MeOH solvent system, there is a need to reduce its use in chromatography for a number of reasons. First, dichloromethane (DCM) is categorized as a health hazard (neurotoxin[1]) and likely carcinogen (per the US EPA). If that isn’t a good enough reason, DCM is not environmentally friendly carrying a large carbon footprint and being a greenhouse gas[2].

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How to improve synthesis workflow by over 90%

March 14, 2023 at 2:00 PM / by Bob Bickler

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Synthesis workflow is the journey taken by chemists when creating a molecule. This journey can be like taking the interstate with no traffic lights and higher speed limits but usually this trip is more like taking backroads with slower speeds, stop signs, and sometimes detours. I believe most chemists prefer the highway rather than the local route but perhaps don’t have the infrastructure to get to their destination as efficiently as desired.

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How to create a reversed-phase step gradient

February 21, 2023 at 4:01 PM / by Bob Bickler

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Gradient elution in liquid chromatography (HPLC, flash chromatography) is the norm. There are two typical gradient types, the linear gradient, and the step gradient. Linear gradients are mostly used due to their relative simplicity but often lack the specificity needed to purify a specific compound to a desired percentage. That is where step gradient’s improved compound targeting can be beneficial. But how do you create a step gradient?

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What is the smallest amount I can purify using flash chromatography?

January 19, 2023 at 2:07 PM / by Bob Bickler

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Most often the question on loading is “how much can I purify” on a specific column size but once in a while I get the question above – what is the smallest amount I can purify? This is an interesting question, especially since flash chromatography is preparative chromatography technique used to purify large amounts of crude mixtures.

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Why is Solvent Evaluation by TLC Important for Good Flash Chromatography Results?

November 22, 2022 at 3:27 PM / by Bob Bickler

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Organic chemistry can be messy with not only the desired compound created but also myriad by-products. As synthetic chemists, our goal is to make these desired compounds in sufficient yield and purity to either create another compound or submit for evaluation by other departments. To purify these reaction mixtures, flash chromatography is the primary technique.

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How does a flash system’s internal volume affect gradients?

November 8, 2022 at 9:21 PM / by Bob Bickler

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For many years I have been publishing a blog on flash chromatography, especially related to its theory and application. It dawned on me today that one area I have not yet addressed is the impact of the flash system’s internal plumbing volume on a programmed gradient, so, here it is.

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How does an acidic pH affect reversed-phase chromatography separations?

November 1, 2022 at 2:19 PM / by Bob Bickler

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Chromatography is as much an art as it is a science. Between synthetic reaction products and natural products, the range of compounds requiring separation, purification, and isolation is broad and diverse creating challenges from time to time. Because of this diversity, not all chromatographic separations can be performed with a “neutral” solvent system – one without added pH modifiers or buffers.

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How should I make my linear gradient?

October 11, 2022 at 2:20 PM / by Bob Bickler

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Flash chromatography gradients need to provide as good of a separation between the target compound at its closest eluting by-products as possible in order to maximize product purity and load. Many chemists create methods based on a history with a compound class, knowing what has worked in the past. If no history with a synthetic compound class exists, then methods need developing.

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What is a step gradient and why should I use it?

September 27, 2022 at 2:07 PM / by Bob Bickler

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Most chemists I meet utilizing flash chromatography use linear gradients. These gradients are either very generic (X% to Y% over a certain time or volume) or can be complex with multiple slope changes and even isocratic holds. These complex gradients are often created during a purification to get the desired separation because the generic gradient does not provide enough separation for the target compound needing purification.

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How does acid concentration impact reversed-phase flash chromatography?

August 24, 2022 at 2:55 AM / by Bob Bickler

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Reversed-phase flash chromatography is extremely useful when purifying all types of compounds. Compounds that are charged or ionizable, however, typically need either a pH modifier (acid or base) or a buffer to better control compound retention, peak shape, and selectivity.

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How important is flow rate in flash chromatography?

August 9, 2022 at 1:54 PM / by Bob Bickler

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I often get questions from customers about the influence of flow rate on their flash chromatography. Typically, the questions are…

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Which solvents are best for terpene flash chromatography?

July 6, 2022 at 2:59 PM / by Bob Bickler

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Well, it’s spring as I write this, my favorite time of year, and the foliage is in various stages of bloom. I like the rebirth of nature and the floral aromas that emanate from the blooms. These botanical aromas are the result of the various terpenes and terpenoids in the plant which can be very different between species.

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How to maximize UV detection sensitivity in flash chromatography

June 21, 2022 at 4:11 PM / by Bob Bickler

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Automated flash chromatography has become an integral component of the workflows of both synthetic organic chemistry and natural product research. The most utilized chromatographic technique is normal-phase, which uses a polar stationary phase filled column (i.e. silica) and a mix of non-polar and moderately polar solvents, i.e. hexane or heptane and ethyl acetate (EtOAc), resp.

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How to isolate impurities from a reaction product

June 7, 2022 at 5:57 PM / by Bob Bickler

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Ensuring that the product of a reaction is pure is critical to that compound’s viability as a marketable entity. Impurities often require characterization if they are in excess of regulated limits. The isolation of these compounds can be quite challenging. 

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