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.

    What are the steps most chemists follow to do this successfully?

    • -Scour published literature for similar compound synthesis
    • -Determine the number of synthetic steps required to create your desired compound and likely synthetic yields with each step
    • -Determine the amount of each reagent needed for each reaction step
    • -Determine needed equipment to perform the synthesis, post-synthesis work-up, purification, and evaporation

    Once you have your raw materials, equipment, and synthetic pathway, your creative journey can begin.

    • -Synthesis
    • -Reaction monitoring with LC/MS, TLC
    • -Quench
    • -Liquid-Liquid extraction (typically aqueous extraction)
    • -Scavenge water with sodium (or magnesium) sulfate
    • -Evaporate to solid or oil
    • -Re-dissolve for purification
    • -Purify with chromatography
    • -Isolate purified compound from purification solvent
    • -Run next reaction step

    Synthesis is performed using any number ways – round bottom flasks and a water or oil bath, scintillation vials on a hot plate, or microwave reactor, Figure 1.



    Figure 1. Microwave used for organic synthesis (Biotage Initiator+)

    Since most reactions create not only the desired compound but also by-products, work-up/purification is usually required. Normally, extraction of the reaction mixture to remove either the product or impurities is performed, followed by evaporation and finally, actual purification.

    Synthesis work flow - phase sep + V10


    Figure 2. Typical work-up products include cartridge based extraction and drying tools (Biotage phase separators and drying cartridges) and a high-speed evaporator (Biotage V-10 Touch).

    Since the extraction process is rarely specific for a single compound further purification is needed. This step typically involves flash chromatography, a process which can be manual or automated and includes a column filled with a solid media and solvents to elute the different reaction mixture components at different rates. Today’s synthesis labs use automated purification equipment which includes not only the column and solvents but an ultra-violet (UV) detector to separate, detect, and isolate the reaction mixture’s compounds, even complex reaction mixtures, Figure 3.

    175C acetone RP 50-100% 12g Ultra C18 90mg

    Figure 3. Automated flash purification of a highly complex reaction mixture (Biotage Selekt with a Sfar flash column).

    Some automated flash purification systems have multiple detection options including both UV and either an evaporative light-scattering detector (ELSD) or mass detector. These optional detectors can help find hidden impurities or compounds not detectable by UV, Figure 4.

    ACS fall NP RxN mix Dalton 2000

    Figure 4. Automated flash chromatography with mass detection (Biotage Dalton 2000) can find hidden impurities.

    Once your product is purified, it can then be used as a reagent for the next synthesis step and the fun continues…

    Want to learn more about organic synthesis tools? We've got a specific breakdown on getting a flash chromatography system here:


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