He has been extremely patient with me over the past two years and has been a constant source of encouragement and guidance whenever things have not gone as I had planned. Without his guidance on laboratory techniques and his constant criticism of my work, none of this research would have been possible. They have supported me in my academic endeavors over the past four years and I am eternally grateful for their love and support.
The aim of this study is to investigate the synthesis of a diamino dovetail with a methine connector. The next step is to create an oxime that is later reduced to an amine [5]. Due to time constraints, the creation of the oxime was the furthest step achieved.
Nevertheless, the trials of this study provide valuable insight into the feasibility of creating the intended dovetails. If ultimately successful, these dovetails could provide further insight into future research on PBI binding to G-quadruplex DNA.
INTRODUCTION AND BACKGROUND
Such multiple ionic charges can increase the solubility as well as the DNA binding ability of the PBI [1]. Swallowtails are long alkane chains that are joined to the rest of the molecule at the center chain; one is shown in Figure 1.2. One of the possible explanations for the difficulty in purification may be due to the PBI nitrogen being attached to a methylene instead of the bulkier methine of a normal dovetail.
In terms of TLC, dibenzylamine tails are better for the reaction due to the polarity of the molecule. When analyzing the 1H NMR spectra of the two tails, the dibenzylamine tails are easier to follow due to the phenyl hydrogen creating peaks in the aromatic region between 7 ppm and 8 ppm and the methylene hydrogens creating simple single peaks between 3 ppm and 4 ppm create. Nucleophilic substitution occurs when a nucleophile, an electron donor species, attacks the back of the electrophile, an electron acceptor species, and replaces a leaving group that was previously attached to the electrophile.
In the SN2 substitution, a final attack of the nucleophile occurs and the leaving group leaves. Because iodide ions from sodium iodide displace alkyl chlorides or bromides. Through procedures from each of the aforementioned journals and proposals, thin-layer chromatography and nuclear magnetic resonance spectroscopy.
For the purposes of this research, proton NMR, abbreviated 1H NMR, was used to determine the structures of the target molecules in each reaction.
EXPERIMENTAL PROCEDURES
The residual oil was taken up in chloroform (4.50 mL) and washed with saturated aqueous sodium bicarbonate (2.60 mL) and brine (2.60 mL). A small sample of the remaining oil was dissolved in deuterated chloroform and analyzed by proton NMR. The residual oil was taken up in chloroform (10 mL) and washed with saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL).
The residual oil was purified by flash column chromatography using 7:3 hexanes/ethyl acetate as elution solvent and a yield of 6% was obtained. Procedure for SN2 substitution involving 1,3-dichloroacetone and dibenzylamine using the Finkelstein reaction and potassium carbonate. The mixture was filtered via vacuum filtration and the solid was washed with acetonitrile (10 mL).
The resulting oil was taken up in chloroform (10 mL) and washed with a saturated aqueous solution of sodium bicarbonate (5 mL) and brine (5 mL). The resulting mixture was concentrated using a rotary evaporator and the residue partitioned between 5% aqueous sodium bicarbonate and hexanes. After partitioning, the organic layer was dried over magnesium sulfate and filtered by vacuum filtration.
RESULTS AND DISCUSSION
In my work, the reaction was scaled down to the micromolar scale in order to save materials and facilitate the preparation. It is possible that most of the lost yield can be attributed to the column. Due to the reactivity of iodoacetone, dibenzylamine readily displaced iodine by SN2 substitution and precipitated KI due to the presence of K2CO3 in the reaction mixture.
By replacing acetone, a polar, aprotic solvent, with acetonitrile, another polar, aprotic solvent, it is safe to say that the rate in acetonitrile will be very similar to the rate of the reaction in acetone. The purpose of the water in the second set of conditions was to stop a possible side reaction of enamine formation from a ketone and a secondary amine. Since water is a side reaction product, it was thought that the presence of water would cause the SN2 reaction instead of the enamine reaction.
In both sets of conditions, triethylammonium chloride was expected to precipitate from the solution. With the lack of precipitate in the THF-water reaction, it is possible that another reaction occurred due to the presence of water in the solution. None of these values match the chemical shifts of the starting material, and it appears that several by-products have formed in the solution.
Similar to the THF-water reaction, shifts in these spectra do not correspond to the predicted shifts of 1,3-bis(dibenzylamino)propan-2-one. After running the reaction under both sets of conditions several times, I came to the conclusion that both reactions did not form 1,3-bis(dibenzylamino)propan-2-one. These two reactions may form the previously proposed enamine, or the presence of the second chlorine on the acetone may cause problems in the reaction that do not allow the targeted SN2 reaction to occur.
After the many failures of reaction III, efforts were shifted to the hopeful success of reaction IV. When reaction IV was first attempted, the reaction was only allowed to last two hours due to the results of reaction II. This was evident from the odor of 1,3-dichloroacetone in the round-bottom flask after rotary evaporation and the appearance of chemical shift peaks consistent with 1,3-.
Using the entire product formed in reaction IV, reaction V gave some interesting results. Before partitioning with sodium bicarbonate and hexanes, the product had to be dissolved in a solvent.
CONCLUSION
The only caveat I have with this reaction is the use of HCl to dissolve the RedAl products during workup. The use of a strong acid could protonate our target amine, which would end up causing the amine to remain in the aqueous layer upon extraction. After the creation of the amine, the next step would be the creation of the target molecule for this research.
With the knowledge gained so far and more time in the future, I am confident that the target molecule of this research can be created with the hope of answering questions regarding the complexity of PBI binding to G-quadruplex DNA. Synthesis of Donor-σ-Perylenebisimide-Acceptor Molecules Having PEG Dovetails and Sulfur Anchors.” Journal of Organic Chemistry.
