MIM_Research_Report

Objective
The original goal of my research was to discover the reason Evan Curtin had seen the creation of Benzoic acid rather than the expected n-[(e)-(4-chlorophenyl)methylene]aniline product. A couple of hypothesis for the creation of the acid product we developed, such as heating and aldehyde to amine reactant ratios.

After the correct procedure for the formation of the imine was established, I decided to test the solubility in at least 5 different solvent, so that the modeling software on the ONS wikispaces page would be able to determine approximate solubilities for this product in any solvent. The goal was to obtain solubilities of n-[(e)-(4-chlorophenyl)methylene]aniline in ethanol, acetonitrile, benzene, hexane, and THF. Once these were obtained it was also decided to test the solubility of the imine in the family of ethylene glycol polymers. To remove the interaction between the solute/solvent, and the deuterated solvent necessary for the NMR, a double chamber NMR tube was utilized.

Introduction
My name is Mark Mangir, and I am a senior chemistry major at Drexel University. Having a strong background in organic synthesis from my previous research with Dr. Papish of Drexel University, and my Co-op with the Wool group at the USDA, I took over the Imine synthesis project that had been started by Evan Curtin. Evan had begun this project with the goal to synthesize the Imine, but after multiple attempts, his experiments led him to conclude that his method did not only produce the desired imine, but it also produced a significant amount of Benzoic Acid. One of my goals is to test why this oxidation occurred. Possible sources seem to be either from the atmosphere or from the ethanol, possibly driven by the excess of amine or from heating the reaction mixture.

While Imine synthesis is a new procedure for me, the actual procedure is rather simple. Over the course of my research by far the most difficult problem I have face has been with obtaining usable spectra from NMR’s that have not been in functioning order. Once that difficulty was taken care of, the research went smoothly.

I have completed 4 sets of Imine preparations so far, and after my last preparation, the purity allowed me to take the sample I prepared and use it to test for the solubility of the desired Imine, which was on of the the goals of this project.

Experimental
**ONS EXP 227** First I tested sample of Trans-Cinnamic Acid (TCA) in ethanol and methanol, to test my ability to perform create a saturated solution and measure the solubility of a solute in a chosen solvent using the NMR SAMS method. I obtained a measurement of 1.1188M of ethanol and 1.3304M for methanol.

**Useful Chem EXP 276** Next I attempted to recreate Exp262 that was performed by Evan Curtin. The reaction was 4-chlorobenzaldehyde reacting with aniline in ethanol to form Benzalaniline. He performed this experiment, but he did not form the imine product he was expecting. Instead of the imine, the acid of the compound was formed. In addition of performing the 1:2 (Sample 2) aldehyde to amine ratio I did a 1:1 (Sample 1), 1:3 (Sample 3) and 1:4 (Sample 4), as well as a higher molar 1:1 (Sample 5). From these the fifth sample, the high molar 1:1, not all of the 4-chlorobenzaldehyde would go into the ethanol, so that sample was scrapped.

An NMR was taken of sample 1 (the 1:1 aldehyde to amine ratio) on the 300 MHz NMR in CDCl3 (mimexp267_2-8-12-in_CDCl3-sample_1.dx). The spectra obtained did not have a clear splitting pattern, and the peaks for the desired sample were located partially below the base line. Due to later experiences, it was determined that the NMR was out of spec, and this is what caused the problems in the obtained spectra.

Since the sample in ethanol had an indistinguishable splitting pattern, it was hypothesized that the ethanol in the sample was creating the difficulty. To solve this, sample 1 was dried by placing the sample in a round bottom flask and evaporating the sample on the rotovap. Our vacuum pump and water bath were out of service, so the house vacuum was attached to the rotovap, and it was evaporated at room temperature. Despite the vacuum the sample took over two weeks to dry. Once dry the sample was orange and feathery. An NMR was taken of this sample on the 500 MHz NMR in CDCl3 (mimEXP276_Dried_Sample_1.jdx). This spectrum had peaks that were indistinguishable within the range of 5.5-8.5 ppm. This also was determined to be an error due to incorrect calibration of the equipment.

The sample was then washed with ethanol until all of the color had disappeared, leaving only white crystals. Then NMR samples were made from both the crystals (mimEXP276_Dried_Sample_2_washed.jdx), and the wash solution (mimEXP276_Ethanol_Wash_Solution.jdx). The NMR had been recalibrated between the last dried sample and these samples, so clear and distinct peaks were obtained. The dried sample seemed to be shifted due to the location of the ethanol peaks, but the peaks in the 6-8 ppm region seemed to match up with the acid peaks that Evan had obtained. The washed sample was not shifted, and it clearly contained both the acid peaks as well as the peaks for the desired Imine compound. It was determined that this reaction did work so a kinetic study would be performed to watch the formation of the product and the acid.

**Useful Chem EXP 277** This experiment was meant to be a kinetic study of the Imine reaction performed in EXP 276. The reaction was set up in 20mL test tube with a 1:1 ratio of aldehyde to amine, at the double the concentration of sample 1 from EXP 276. Unfortunately, the sample would not lock on the 300 MHz NMR, so the reaction was not monitored during the course of the reaction as planned. After one week, the finish sample was observed using the 500 MHz NMR (mimEXP277_reaction_mixture.jdx), and a clear spectrum was obtained, without any problem locking the sample. From this sample it was determined that both the acid and the imine were both present.

**Useful Chem Exp 278** Now that the reaction had been repeated at the 1:1 ratio, the effect caused by the amine concentration came back into question. Samples of 2:1 (Sample 1), 1:1 (Sample 2), and 1:2 (Sample 3) ratios of aldehyde to amine were prepared and run. NMR samples were taken after 15 minutes, after one hour, and then again after sitting overnight. One sample was prepared of each concentration, and the sample was mixed in CDCl3, so it is not a great representation of the actual speed of the reaction. All NMR were taken on the 500 MHz NMR in CDCl3.

It was clear from the NMR of sample one that the concentration of aldehyde dropped as the reaction proceeded. With each concurrent spectrum, the peak area of the aldehyde peak dropped significantly compared to the other peaks. The amine peak on the other hand did not have this correlation.

The other two samples showed similar results, only the aldehyde had completely disappeared by the 1 hour mark in both.

It was attempted to obtained dried samples of the Imine from these samples, but the experiment had been performed at such a low concentration that no product could be obtained, since it dissolved in the wash solution.

This experiment was a replication of EXP 278 at a higher concentration so that it would be able to obtained dried washed samples to use for solubility studies after this experiment is completed. The 1:2, 1:1, and 2:1 ratios of aldehyde to amine were performed in that order.
 * Useful Chem Exp 279 **

To test to see if the reaction worked, NMR spectra were taken of unwashed sample 2, washed sample 2, and the wash solution of sample two( mimEXP279_unwashed_precipitate_1-1.jdx, mimEXP279_washed_precipitate_1-1.jdx, and mimEXP279_filtrate_1-1.jdx). Once it was determined that the desired reaction had taken place, samples 1 and 3 were also washed and dried, and NMR were taken of all three dried samples. All NMR were performed on the 500 MHz NMR in CDCl3. spectra were: Sample 1- mimEXP279_washed_precipitate_1-2.jdx, Sample 2- mimEXP279_washed_precipitate_2-2.jdx, and Sample 3- mimEXP279_washed_precipitate_3-2.jdx.

All of the samples were pure imine product, so the procedure has been replicated, and found to be correct.


 * Conclusions**

At first it seemed that Evan's determination had been correct, and that this procedure produced Benzoic Acid in a significant quantity, as well as the desired Imine product. But as I became more proficient in the procedure, the acid, while still formed, was only an insignificant product of this reaction. It seems that some other factor forced the reaction towards the formation of the acid. It has been concluded that this driving force was not the concentration of the amine, since Exp 278 and 279 both ran 1:2 aldehyde to amine concentrations, same as Evan's, and only produced an insignificant amount of acid.

While no accurate determination has been made at this time, I have a couple of hypotheses. It could be heat in the reaction that had caused this acid product. The first two experiments I ran had been slightly heated by being left long enough in the sonicator that the water temperature had risen noticeably. Evan had also used the sonicator in his experiments to help the aldehyde dissolve into the ethanol. It is also possible that the excess of the imine helped drive the reaction in that direction. The 1:2 aldehyde to amine ratio products had consistently higher percentage of acid product, but still none nowhere near the amount recovered by Evan.