Now that we are well in to the semester, Dr. Rizzo and I have been making a lot of progress with our synthesis. As mentioned in the prior post, our objective is to synthesize a variety of novel quaternary ammonium compounds that utlize a,w-diols, dihalides, polyethers, and naturally derived glycols covalently bound to 1,4-diazabicyclo[2.2.2]octane, otherwise known as DABCO.
The method of synthesis for these compounds include an activation of compounds bearing free hydroxyls sites followed by a covalent attachment of a free amine. Activation of the compound is done by a well-known procedure. What we have done is convert alcohols to an alkyl tosylates. The reason we do this is to generate a good leaving group. Once our compound has been activated, we follow up with covalent bond formation. The tosylated alcohol is then treated with a good nucleophile, like DABCO, which will readily undergo an SN2 reaction. An SN2 reaction is a bimolecular nucleophilic substitution. In this type of reaction, the lone pair of electrons from the nucleophile (DABCO), attacks an electrophilic center (our activated compound), and bonds to it, expelling the leaving group (the tosyl group). In other words, we are replacing our tosyl group with DABCO. The reason we want to substitute these groups is because we seek to synthesize a variety of novel quaternary ammonium compounds. Quaternary ammonium compounds have been found to yield the best results when tested against potassium ion channels. To date, I have modified about 20 compounds. A few of the compounds I have modified include, dulcitol, galactose, poly vinyl alcohol, and glycerol. Each of these structures bear free hydroxyl sites.
Thus far, I have been continuing synthesizing different compounds. Recently, I have been focusing on modifying amines. Amines are organic compounds that contain a basic nitrogen atom with a lone pair of electrons. The two specific amines I’ve been working with are N, N, N’, N’- Tetramethyl-1,3 Propane Diamine and N, N, N’, N’- Tetramethyl-1,6 Hexane Diamine. The synthesis of these compounds are a little different as they don’t know bear free hydroxyl sites. Therefore, instead, we treat the amines with a tosylated dabco compound. Upon reflux of the modified amine compounds, I observed color changes. The compounds went from a transparent solution to deep yellow/ brown. I allowed the compounds to continue reflux. Upon endpoint of reflux, I put the solutions on a rotavap to remove the solvent used. Unfortunately, the results yielded two, sticky, brown, syrup like solutions. Compounds of this consistency cannot be used for testing. So, I am currently redoing this synthesis. The second time around, I am synthesizing new tosylated dabco strings to treat with the amines. I am starting with 4-chloro-1-butanol and 3-chloro-1-propanol. These two structures have an alcohol group and a halide group. Upon dissolving in ethyl acetate, I am going to treat these compounds with dabco, which will substitute the halide group on the compounds. The new compounds now have an alcohol group and a dabco group. When these are treated with the amines, the alcohol group should react with the nitrogen on the amine, displacing the OH group, creating a quaternary ammonium ion. As of now, I have yet to treat the amines with my newly synthesized dabco compounds. I am hoping to yield better results the second time around. If not, I will reconsider the starting materials and method of synthesis. Perhaps I will try to synthesize a compound that isn’t as bulky.
More questions to consider are, what compounds will work the best? With a little background research and analysis of my data, hopefully we can gain a clearer understanding of the most beneficial compounds to synthesize. I am looking forward to continuing with my synthesis and am eager to see my results!