Blog #2: The Arduous Task of Synthesis

In my previous post, I described one of the challenges of scientific research: science takes a very long time to come to fruition. After just a week in the lab, I realized how much work is involved in just one step of a reaction. Another challenge of scientific research, particularly in chemistry, soon became apparent to me as well: it’s really hard to see what’s going on. What I mean is that, I may run a reaction using milligrams of a solid and microliters of a liquid, and those amounts can be very hard to collect, isolate, and sometimes even see.

After finishing my first profluorophore, I began making my second. The synthesis of this molecule had 5 steps (thus 4 intermediate compounds), the first of which took place in the microwave; even though my research focus changed after my original proposal, I still did work with the microwave quite a bit. It took some work to perfect the microwave synthesis for the first step of the reaction, but after a few days I had figured out the correct temperature, time, and power input to complete the first step. The next step took a little more than a day, as I had to run the reaction for about 8 hours and then perform a series of steps to make the compound as pure as possible.

These extra steps are often what makes organic synthesis a time-consuming challenge. For example, after allowing the compounds to react, I have to perform an “extraction,” which effectively removes all of the non-organic products from my reaction mixture. Then, after removing the solvent from my mixture via rotary evaporation, I perform column chromatography by running my organic product through a column full of silica gel and collecting it in several test tubes. The goal of the silica column is to separate the organic molecules (such as the product and any other molecules that didn’t reactant fully) ¬†into separate test tubes based on their polarity. Then, I perform thin layer chromatography on the test tubes by “spotting” some liquid from each tube on a silica plate, placing the plate in solvent, and allowing the solvent to separate the spots, which I can see under UV light. At that point, I can try to determine which compounds are in each test tube, collect the test tubes with my product, remove the liquid via rotary evaporation again, and then prepare my product to be analyzed by nuclear magnetic resonance (NMR). If all goes well, I will have a clean NMR spectrum which clearly shows what my product is. But, if the spectrum is too messy, I have to back up a few steps and try to recover my compound. ¬†After all of that, I can move on to the next step.

What I’m trying to emphasize here is that chemical research, especially organic synthesis, takes a long time, as there are so many steps involved to just get from one molecule to another. So, whenever I would get a really nice NMR spectrum, or my product yield would be really high, I was ecstatic because my hard work had paid off. I spent the majority of my summer making my second profluorophore, and as more time went by, I was able to perform the steps I described above even more quickly and efficiently.