Sonderamine

  One ordinary lab day in the Fall of 2024, I desperately needed a multi-necked round bottom flask for a reaction. I strolled about the lab and scoured for the piece I needed in each oven we had. The glassware was too small, too big, or had too few necks. After many minutes, I finally found my flask... by a recently used sink. For the average person, they might think: "Just wipe off the water?" or "go ahead and use it, it's fine :p." In the field of organic chemistry, water present on any level (atmospheric too) will almost always RUIN any hopes and dreams of a successful reaction. You have a water-sensitive product? It will degrade in the air before you can purify it. Your reagents will hydrolyze in the air? Without a sealed inert atmosphere, the reaction will never initiate to begin with.

  With no luck of magically finding a similar but dry round bottom, I cleaned and dried the only found piece per lab procuedure. I cheerfuly went about rinsing it with acetone, soap and water, and subsequently acetone once more. Then, as if I'm saying goodbye to someone, I placed it in the oven and shut the door in its face. Per procedure, around a couple hours needed to be alloted for complete dryness. Knowing this full well, I yapped with a close friend for a bit before returning to my desk.

  As the time ticked by, I wrote down yields, scavenged for literature reactions on SciFinder and analyzed proton NMRs. As I finish up my notebook work, I look up to only see its been about an hour (It really felt like 2 hours though). Typically time is not a concern, but as the day was ending and my friend was planning on departing from lab, I needed to get the reaction started. If I delayed until tomorrow, it will only push back my research to the weekend or beyond... Looking to find a quick solution, I walked over to the otherside of my lab and obtained a bunsen burner. I then fetched my partially dried round bottom flask and brought it over.

  Assuming this will be a quick and easy glassware flaming, I began arranging the apparatus. The bunsen burner connects to a neoprene tube, and the tube attaches firmly to a gas inlet. My friend sat merely 10 meters away, and we began chatting some more during the process. With heat resistant gloves on and everything in place, I began the flame drying process. Unexpectedly, after supposedly turning on the propane line, nothing seemed to be igniting from a lighter I had. It was being held right above above where gas should be exiting from! I rapidly tried over and over again with no results. Thinking maybe not enough gas was being pushed through, I increased the flow rate by slightly turning the gas lever. Again, no ignition! Now hearing a loud rush of something from the tube, my friend and I looked at each other. I began to fear there was a gas leak somewhere in the tubbing and I quickly turned the lever in the opposite direction. Still, I heard this gurgling "rushing" sound...

WOOOOSSSSHHHHHHHH

  A jet of water comes screaming out of the bunsen burner. It rises into the air like a fountain. Myself and the benchtop are sprayed with water, but thankfully none of it spalshes on any reagents. Confirming the "gas" lever, which turned out to be the water line, was still closed, I allowed the flow to quiet down and come to a halt. The flow continued but it began to linearly decrease. My friend, who was peacefully working away at her desk, witnessed the jet and came rushing over thereafter. She hurridly turned the lever completely to the opposite position (open again!), thinking it hadn't been closed yet since the water was still flowing... Suddenly, the bunsen burner, now a Bunsen Fountain^TM (pretty good name, right?) roared to life again and spewed even more water than before. The tubing then broke off from the inlet due to the immense water pressure. In a split second, our bodies were coated with a blast of water before the water line was finally shut off for good.

  My friend and I looked at each other and began laughing hysterically in our damp lab coats. Tears were in our eyes; we couldn't believe what just occurred. I began to clean up the mess I had created. A true and obvious lesson was learned that day... Read your labels.

  Reducing agents. Countless scientists have heard them, many have used them. Organic II students learn you can use sodium borohydride (NaBH₄) and LAH (LiAlH₄) for carbonyls (R₂-C=O) reduction and such. But, what about reducing other functional groups? Well, another reducing agent called sodium cyanoborohydride (NaBH₃CN) is right at our doorstep. It specializes in reducing imines (R₂-C=N-R) to amines (R₂-C-N-R₂), and has been crucial in countless syntheses for medicinal compounds, such as Zoloft. For decades, reductive amination has proven its utility time and time again in both industrial and academic settings. It has saved untold numbers of hours that may have been spent following less efficient pathways. Despite this, my journey with sodium cyanoborohydride, and reductive amination as a whole, can be described as tumultuous at best.

  Upon boarding my research lab two years ago and becoming familiarized with synthetic techniques, I boldly pursued a project of my own whilst being an undergraduate student. To begin my study, I had to synthesize a particular substrate over 2-3 steps. First step? Messy but good yield. Second step? Incredibly clean and phenomenal yield. Third step... this would define my troubles. In that third reaction step, I had to transform a ketone (R₂-C=O) to either a primary or secondary amine; seems simple. I followed a procedure advised from my previous mentor and waited till the reaction completed. I TLC'd it... hm... just starting material and impurities. After running it a second time and NMRing it, no significant product still. So I thought to myself, "a little troubleshooting will fix this; I'm a scientist." Little did I know, it would be a titanically large amount of troubleshooting which lay ahead. From that April (2024) to April of this year (2026), I tried a multitude of solvents, temperatures, catalysts, acids (at small eq. to promote imine formation), reducing agents, and amine sources. In addition, I took proton NMRs of the reagents I worked with, dried them on 1 mbar vacuum lines, and even vacuumed distilled a suspicious bottle of cyclohexylamine. -78 degrees Celsius? Nothing. What about 110 degrees Celsius at reflux for a week? Try again man. I consulted with my PI, talked with other research students, and scoured various pieces of literature. Even digging into obscure, all-Chinese patents and all-Russian articles, I found myself stuck in a persistent loop of synthetic hell.

  This cycle continued into my Spring '26 semester... During which, my PI was describing a story of how attempting left-field reactions--even with little hope of it working--gave him surprisingly great results during his PhD program. Carrying this sentiment, I decided to dig deeper and I subsequently came across some inconspicuous French patents that deviated somewhat from my usual synthetic pathway. One of them contained a compound somewhat similar to my own substrate. But, I never discovered this source when looking through SciFinder all of the previous times before... better late than never I thought to myself. When I attempted the procedure, I threw in some less-precious starting material and didn't expect much. It was a microwave reaction at 130 degrees Celsius for 5 minutes. Why would this return product considering my week long reflux reaction never gave any tangable results? Well... despite all personal expectations, the reaction proceeded until completion as indicated via TLC. I hurridly rushed to my fumehood to work it up. I had a slurry of emotions in my head; pessimistic doubt, reinforced by countless failed reactions, and euphoric excitement, emerging due to my hope for long-awaited results. I then purified it via column chromatography and sat down at my desk with both ¹³C and ¹H NMRs of my compound. After completing my analysis, I became overwhelmed with relief and gratitude. Two years have led up to this moment; just days away from the official anniversary since the first unsuccessful amination.

  I FINALLY DID IT! I MADE MY COMPOUND!!!! and so can you traveler...