This isn't a regular blogpost. I've been incredibly busy with my research, so here's a synopsis, and a retrospective.
Fall '23
The remainder of the fall was spent in refining the bromination method, and the next step, a diazotization. That reaction failed miserably, and I began to study other avenues. My memories of this time are fuzzy, and my notes border insanity. I'm losing my marbles over this reaction. Too much precursor wasted, too many carcinogens synthesized. I'm told to stop, and rethink what I'm doing after a disastrous incident where I drain a brand new gas cylinder into the vacuum manifold in a dehydration step gone wrong. I pack my bags and head back home for break.
Spring '24
I struggle on with the synthesis. I got off to a rocky start, but I get some good precursors. I've nailed down the bromination step, and I realize I would need to re-think my synthesis pathway. I would synthesize a benzo-isatin following a patent and it went extremely well, unlike the failed diazotization. However, the following reduction of the benzo-isatin proved extremely difficult. The benzo-isatin derivatives I'm working with are cross-coupling and forming a brilliant blue. Wolff–Kishner reductions leave nothing but tar and 20+ compounds. Alternative syntheses with stronger methods cook the compound so hard that the bromine I have on the 8 position falls off. I become dejected, and progress slows to a crawl. I'm shotgunning methods, trying everything and anything to get something to stick to the metaphorical wall. Everything smells like the benzo-isatin, which has a light, pleasant, fruity odor. I smell like the benzo-isatin. I'm losing my marbles. At some point, my project is terminated. I take my final exams, and go home, leaving the lab and labwork behind me.
Summer '24
New synthesis! I'm working on a Shapiro reaction, trying to modify quinuclidinone to attach a sulfonated benzyl halide. The synthesis starts off well. Starting with the quinuclidinone, I prepare the compound with trisyl-hydrazine, which I also have to prepare beforehand. I then couple the trisyl hydrazine with the quinuclidinone, and then react the Shapiro precursor with n-BuLi. The reaction works, and I get a blood red intermediate, which I then add various compounds to get the aldehyde I want, and add a single carbon to the quinuclidinone. Things aren't working. I spend more time talking with friends than I do work. I stumble across an alternative method, synthesizing epoxides, and trying to react it with lithium-diethylamide. It seems promising, but it's the end of the summer by that point.
I switch to the other side, following patents to convert an sulfonated benzaldehyde into a benzyl alcohol, and the alcohol into a benzyl bromide, and then chlorinating the sulfonate. The work is simple, and can be done quickly and at scale. The reaction hits a roadblock though, as the chlorination step appears to be a stubborn reaction. Progress is promising, though at this point, the summer is over.
All the while, I've been saddled with another project. I can't divulge too much about the project, but what I can say, is that it becomes a massive time sink. I taught myself how to use an Agilent 6890N GC paired with an Agilent 5973 MSD (mass selective detector, aka a mass spectrometer.) I developed a GC method for solvent analysis, and I've refined my analytical techniques as practice for instrumental analysis in the fall. At the end of the summer, I inform the department chair of my work, and he is delighted with my results, though my PI informs him that sharing the results of this project is almost certainly unwise. I leave for home, leaving behind my mixed bag of a summer.
All the events above happen simultaneously, over the course of 10 weeks (end of may, through the first week of august).
Fall '24
I continue with the research I started over the summer. I re-analyze a lot of compounds, and determine which samples are good and which are garbage. I do some sample processing, and get back to work. I continue with my epoxide work until it fails. I'm becoming dejected, and I remember that there is another part to my project, the promising chlorination step. I attack the compound with progressively stronger chlorinating agents, and I get good results! The NMR looks like its working, and I'm looking forward to the end of the project. Ultimately though, the next step —protecting the sulfonate with neopentyl alcohol— did not work no matter how well chlorinated the starting substrate was. I went down a tangent involving a 2-in-1 chlorination step where the alcohol and sulfonate would be simultaneously chlorinated with a large quantity of thionyl chloride and DMF. It seemed to work, but never consistently enough to protect. Eventually, I gathered enough to protect, and the protection steps all failed. I became dejected once again, and I paused my lab work to study for my brutally hard upper division chem classes; Physical Chemistry I (Quantum Mechanics) and Instrumental Analysis. I aced the finals, and went home for break.
Retrospective.
Now, after winter break I return to W&M. New year, new research after all. I learned my lab's grant to the ACS-PRF was approved, and that my summer research project would be terminated. Two terminated projects, spanning a whole calendar year. I realize now that organic chemistry might not be for me, since I'm just not all that good with lab procedures, and more often than not i'm stuck with dead-end projects that never seem to work well. I feel like I was going places and getting nowhere over the summer, but now I feel like I was going nowhere and getting nowhere. I did find I have a knack for instrumental operation and maintenance, so I applied for a lab assistant job to fix and maintain instruments. I'm probably slowly pivoting my chemistry career away from pure synthesis into a more analytical and instrumental angle. I've been given a new, promising project to work on, but I'm probably going to put that work on the backburner as I chew on it slowly and steadily. I've got plenty of work to do for my upcoming honors thesis, as I prepare to apply for funding. I'm looking forward to an uncertain future, and maybe that's OK. I got lucky before, now I need to build a good foundation for a promising future.