The overall goal of this methodology is to synthesize suitable X-ray monocrystals of 3, 5-lutidine N-oxide dehydrate in shorter reaction time using inexpensive and easy-accessible reagents to yield a novel solvated supramolecular structure. This method can help answer key questions in the synthetic organic and inorganic chemistry field such as how to synthesize noble aromatic compounds, and et-see-cic compounds and perioding dare-ee-batics. The main advantage of this technique is that it uses solvents and materials that are more accessible and generally found in a research laboratory.
We first have the idea for this method when we were in search of an optimal route to obtain 3, 5-lutidine N-oxide as an intermediate of 2-aminopyridine-3, 5-dicarboxylic acid. First, place on open 100 milliliter round bottom flask containing a magnetic stir bar on a magnetic stir plate in a fume hood. Add 29.8 milliliters of glacial acetic acid, 5.82 milliliters of 3, 5-dimethylpyridine and five milliliters of 35%hydrogen peroxide to the flask.
Stir the reaction mixture at an inner temperature of 80 degrees Celsius for five hours. After the reaction is complete cool the flask to 24 degrees Celsius with ice. Once cooled, connect the flask to a high-vacuum distillation unit for 90 to 120 minutes to remove excess acetic acid.
Following this, add 10 milliliters of distilled water to the flask, and concentrate the mixture to remove trace acetic acid. Dissolve the isolated viscous and transparent product in 20 milliliters of distilled water. Then use a potentiometer to adjust the pH to 10 with sodium carbonate.
Next, carefully add the solution to a 250 milliliter separation funnel. Extract the solution five times with 250 milliliters of chloroform. Recover the product containing organic layer and dry it over sodium sulfate for a maximum of 30 minutes.
After filtering off the sodium sulfate remove the solvent under reduced pressure with a high-vacuum distillation unit to afford of a very hygroscopic, clear, beige, crystalline powder. Now, dissolve 4.3 grams of the crystalline powder in 50 milliliters of cold HPLC grade diethyl ether. Vacuum filter the solution to remove any trace of solid starting material or dust.
Then pour the filtrate into a glass Petrie dish and store at four degrees Celsius to slowly evaporate the solvent. After two days, check that clear, colorless crystals are obtained. Then measure the melting point, which should be in the range of 310 to 311 Kelvin.
Next, isolate the 3, 5-lutidine N-oxide dehydrate crystals by decantation for X-ray analysis. Finally, dissolve 0.01 grams of the 3, 5-lutidine N-oxide dehydrate crystals in 0.4 milliliters of deuterated chloroform for proton and carbon NMR analysis. The signal at 2.28 ppm in the proton NMR spectrum of 3, 5-lutidine N-oxide dehydrate corresponds to the six equivalent hydrogen atoms of the two methyl groups in the three and five positions.
The signals at 7.9 ppm and 6.9 ppm represent protons C and A respectively. These hydrogens are at the higher frequency than the methyl hydrogens because they are closer to the electron-withdrawing oxygen atom. In the carbon spectrum of 3, 5-lutidine N-oxide dehydrate the signals for the carbons closer to the oxygen atom show frequency separation between their signals of 1300 hertz and 200 hertz.
The methyl carbons do not show any change. The ORTEP diagram shows two molecules of water surrounding the asymmetric 3, 5-lutidine N-oxide dehydrate which are believed to stabilize the N-O bond. There is a significant stabilizing Pi type O-N back donation reflected in a calculated bond order higher than one and number of electron lone pairs on the oxygen atom lower than 36.
While attempting this procedure it's important to remember that this protocol uses solvents and materials that are easily obtainable and generally found in any research laboratory.
