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    Bob Bickler


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    Can reaction solvent choice impact synthesis results?

    June 30, 2020 at 5:21 PM / by Bob Bickler posted in Synthesis, microwave

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    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.

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    When should I use an amine-bonded silica for flash chromatography?

    May 8, 2020 at 8:30 PM / by Bob Bickler posted in Amine, Chromatography Fundamentals, Sfär, Media and Resin, Normal Phase

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    Flash chromatography is a standard part of an organic chemist’s workflow. It is utilized after most reaction steps in order to remove most of the generated by-products and excess reagents.

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    How do I scale-up my reversed-phase flash chromatography method?

    April 27, 2020 at 2:53 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Scale-Up

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    Scaling up reversed-phase flash chromatography methods is often necessary as reaction scale increases. This is especially true when other non-chromatographic purification techniques do not work or meet purity and/or yield needs.

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    5 Steps to successful flash chromatography

    April 20, 2020 at 10:15 AM / by Bob Bickler posted in Amine, Chromatography Fundamentals, Reversed-phase, Solvents, Media and Resin, Loading Techniques, Normal Phase, Pillar Page

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    The bane of organic synthesis for most chemists is purification rather than synthesis. Synthetic reaction mixtures are rarely devoid of impurities so some type of purification is necessary.  Most often flash chromatography is used but for many chemists, it is less well understood than their chemical reaction and provides some level of anxiety.

    In this post, I will summarize the five most important steps to creating a successful flash chromatography method and thus the anxiety associated with it.

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    Does a longer flash column really provide better purification?

    April 17, 2020 at 9:30 PM / by Bob Bickler posted in Chromatography Fundamentals, Sfär, Scale-Up, Cost, Normal Phase

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    This is an interesting question that I am asked from time to time. There does seem to be two camps in which chemists reside – one believing longer and thinner columns provide better separations and the other preferring shorter and fatter columns to do the same chromatography.

    Which is right? That is a question I will try to answer based on my own data.

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    Understanding silica – why matching TLC and flash silica is important for good flash column chromatography

    April 15, 2020 at 12:00 PM / by Bob Bickler posted in Chromatography Fundamentals, Solvents, Sfär, Media and Resin, Normal Phase

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    Recently, I posted an article explaining why high performance TLC plates are not needed for method development for high-performance flash chromatography.  Based on some excellent feedback, I see a need to discuss silica chemistry and its impact on chromatography.

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    How and when to insert an isocratic hold in flash column chromatography

    April 13, 2020 at 7:00 PM / by Bob Bickler posted in Chromatography Fundamentals, Solvents

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    For many chemists using generic linear gradients and even gradients based on TLC the purification results often are not selective enough to separate all of the compounds in their mix.  This is especially true if your target has a closely eluting impurity. One method used to try and increase resolution is the use of an isocratic hold or gradient pause during purification.

    In this post I examine the use of the isocratic hold to determine how well it works and when/if it should be inserted into a gradient method.

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    How do I remove an annoying MS TIC background?

    April 10, 2020 at 2:52 PM / by Bob Bickler posted in Chromatography Fundamentals, Troubleshooting and Optimization, Sfär, Detector, Normal Phase, V-10, Isolera

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    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.

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    How does an alkaline pH affect normal-phase flash chromatography separations?

    April 7, 2020 at 6:25 PM / by Bob Bickler posted in Amine, Chromatography Fundamentals, Solvents, Sfär, Normal Phase, Isolera

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    The products of organic synthesis are designed with specific functional groups in order to possess desired properties. Depending on the compound’s functionality, it can be neutral, acidic, or basic as determined by a compound measurement called pKa or acid dissociation constant. Compounds with low pKa are typically acidic while those with high pKa tend to be basic. Compounds with a pKa near 7 are deemed neutral.

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    How does reversed-phase flash chromatography compare to prep HPLC?

    March 26, 2020 at 2:42 PM / by Bob Bickler posted in Reversed-phase, Green, Sfär, Selekt, HPLC

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    For medicinal chemists, maximizing the synthetic yield of their newly created intermediate compound is their priority. More times than not, flash chromatography is used to purify these intermediate compounds to at least 80% purity. Final compounds, however, not only require high yield but maximum attainable purity, typically in excess of 95%. For this purity level, chemists will either send the reaction mixture to an in-house prep HPLC lab or perform their own preparative HPLC compound purification, if it is available in the lab.

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    What is the Chemistry Behind Reversed-Phase Flash Chromatography?

    February 25, 2020 at 4:18 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Sfär

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    In my previous post, I talked about the "Chemistry Behind Normal-phase Flash Chromatography", the most common form of liquid-solid chromatography. In this post, I focus on reversed-phase flash chromatography and how it differs from normal-phase.

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    What is the Chemistry Behind Normal-Phase Flash Chromatography?

    February 11, 2020 at 3:44 PM / by Bob Bickler posted in Chromatography Fundamentals, Normal Phase

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    Our clientele at Biotage have interesting and diverse backgrounds from highly skilled synthetic chemists, to experts in natural product chemistry, to those who are just beginning they journey with chemistry. What I have learned over my 40+ year career in the “art” of chromatography is that for many of these fine folks there is a lack of understanding about chromatographic principles. This lack of understanding, I believe, is only due to their core study curriculum where separation science is used as a tool during lab work but the principles behind why a mixture’s components separate (or do not separate) perhaps are not effectively explained, understood, or studied.

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    When should I choose APCI or ESI for my flash column chromatography?

    February 11, 2020 at 3:16 PM / by Bob Bickler posted in Detector, Isolera

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    Mass spectrometers today are typically available with either Electrospray Ionization (ESI) or APCI (Atmospheric Pressure Chemical Ionization) sources.  That’s really nice but, how do you know which source will work best when purifying your sample?

    In this post I attempt to provide some guidance to selecting the ionization source best suited to your sample types.

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    When should I use a pH modifier in flash column chromatography gradient?

    February 11, 2020 at 3:15 PM / by Bob Bickler posted in Chromatography Fundamentals

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    Have you ever experienced compound tailing or streaking on your TLC plate or flash chromatography results and wondered what in the world is going on here? Well, there can be multiple reasons for this problem including poor mass-transfer kinetics, secondary solute-sorbent interactions, or unstable compound chemistry.

    In this post, I will discuss one technique that has been shown to work time and time again to address the issue.

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    How can I modify my flash chromatography method to separate chemically similar compounds?

    February 11, 2020 at 3:13 PM / by Bob Bickler posted in Chromatography Fundamentals, Reversed-phase, Solvents, Sfär, Selekt, Media and Resin, Normal Phase

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    The challenges organic, medicinal, and natural product chemists face are many: from designing reactions, to optimizing synthesis, work-up / extraction, and purification / isolation of the desired compound or compounds. Among those issues related to purification / isolation is the common problem of separating compounds with similar chemistry that either co-elute or separate poorly.

    In this post I will discuss some tips on how to "resolve" this issue (yes, pun intended).

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    What do I do if a 2-solvent gradient will not separate my sample?

    February 11, 2020 at 3:12 PM / by Bob Bickler posted in Chromatography Fundamentals, Solvents, Troubleshooting and Optimization, Normal Phase, Isolera

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    Usually, a 2-solvent or binary gradient will separate your desired compound from the by-products and impurities. Sometimes though, you can encounter a mixture in which some compounds co-elute and are not separable with any binary gradient you try.

    I encountered this situation recently while trying to purify a lavender essential oil and have dedicated this post to how I solved the problem. 

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