Chapter 6 Formal Report James Gallagher TA: Chris Gray Desk Number: 25E Course and section number:

203 sec 002 Introduction The purpose of this experiment was to successfully synthesize acetanilide from acetic anhydride and aniline, separating the acetanilide from acetic acid, and then recrystallizing and purifying the product to give a suitable yield. Recrystallization is a very useful method to isolate and purify a product and ensure that any impurities are eliminated from the final product. Each solid, pure organic compound has a defined crystalline structure; this lattice that forms allows only molecules of the same compound to fit into the lattice, thus keeping impurities out of the crystals and in the solution. (1) The crystal lattice is formed at the point of a nucleation by adding a seed crystal of the crude compound to begin the recrystallization. Recrystallization begins by choosing a suitable solvent; a solvent is acceptable for use when the product is not soluble when the solution is agitated. If it does dissolve then the product is too soluble in the solvent and would not be useful. If a solvent is determined to be a possibility then a small amount of solvent and product can be gently boiled for 30-45 seconds at a time to see if the solid dissolves in the hot solvent, the solution is then cooled and if crystals begin to form and are of high quality then that solvent is used. The process of recrystallization consists of adding the chosen solvent and crude product together and then this solution is heated until the solid dissolves, the solution is removed from heat and allowed to cool to room temperature to allow the crystals to form and create the crystal lattice, it is then placed on ice to finish the process, the crystals are then collected by use of vacuum filtration. If the crystals precipitate out as a liquid

and not as crystals this is known as oiling out, this is not favorable because the oil is a solvent for the impurities and thus if the oil freezes and forms crystals, the impurities will be in the crystals thus not giving a pure product. Through this process any impurities that may have been in the initial product are left in the solvent when the product is dissolved into the solution, when the product is recrystallized and vacuum filtrated it leaves behind the pure product. The mechanism for the reaction is as follows:

In the first step the nucleophilic (the aniline) is stealing the positive charge on the carbon to bond it to the nitrogen. When the nucleophile and electrophilic are bonded, the electronegative oxygen then breaks the bond to the carbon and the carbon breaks the bond to the other oxygen. The resulting amide and ketone then add electrons from the ketone oxygen to the amide to form acetanilide and acetic acid. (3) The synthetic reaction being performed in this experiment is a nucleophilic acyl substitution reaction and is performed by reacting acetic anhydride and aniline in water, this

reaction gives off heat and when the reaction is complete the products are acetanilide and acetic acid. (1) The crude acetanilide is then vacuum filtrated, after isolating the crude acetanilide a suitable recrystallization solvent was chosen as per the process described before. The crude acetanilide is then purified using recrystallization and further vacuum filtration. The pure crystals are analyzed by use of melting point, 1H NMR, and IR spectroscopy techniques to confirm the crystals are completely purified acetanilide.

Experimental Synthesis of Acetanilide: 2ml of aniline, 15ml of deionized water, and 3ml of acetic anhydride was stirred. This reaction was run for 30 minutes with a stir bar on medium speed, the resulting clear liquid was then poured into a vacuum filtration set up, the crystals were washed with 2ml of ice water and allowed to dry for 20 minutes, after drying was complete the crude acetanilide was weighed. A recrystallization solvent was then determined from four possibilities: water, ethanol, dichloromethane, and hexanes. A sand bath was set up to test the solvents; 0.5ml of water was added to a reaction tube, 0.5ml of ethanol to another tube, 0.5ml of dichloromethane to the next tube, and 0.5 ml of hexanes to the last tube. 50 mg of crude acetanilide was added to each tube and agitated, if the solid dissolved then the solvent was too strong for recrystallization. When a suitable solvent was found a boiling stick was added and then heated in the sand bath until the solution reached a gentle boil, after boiling for about a minute the tube was removed from heat and placed in ice water for two minutes. The solvents boiled were hexanes and water and it was determined from the crystals that water was the best solvent. A melting point determination was performed on the crude acetanilide using a MelTemp apparatus. The remainder of the crude acetanilide was added with 50ml of water and a glass stirring rod; it was then heated and stirred. Hot solvent was then added to put the

acetanilide in solution and stirred gradually; once the acetanilide was dissolved it was then allowed to cool to room temperature, the solution was then placed into an ice bath for 10 minutes to allow the crystals to form. The crystals were then isolated by vacuum filtration and the crystals were then allowed to dry, after drying the crystals were weighed. A melting point determination was performed on the pure crystals using a Mel-Temp. Two samples for 1H NMR and IR spectra were analyzed. Table 1. Melting point of Crude and Pure Acetanilide Type Crude Acetanilide Pure Acetanilide Melting Point 112C 116C

This table shows the two melting points of both crude acetanilide and pure acetanilide for easier comparison. Table 2. Yield and percent recovery Crude Yield Purified yield Percent Recovery of acetanilide 38.10% 2.57% 11.52%

This table compares the crude yield of the acetanilide and the percent recovery of the pure acetanilide from the crude acetanilide. Table 3. Solubility of acetanilide in known recrystallization solvents Solvent Water Dissolves acetanilide No Crystal description Abundant, stick to sides of tube and form proper lattice Crystals form but do not form a good lattice N/A N/A

Hexanes

No

Dichloromethane Ethanol

Yes Yes

This table compares the different solvents that were considered for recrystallization and their interactions with acetanilide. Results and Discussion The solvent chosen for the experiment was water, water did not dissolve the acetanilide and when the solvent was boiled gently with the acetanilide and then cooled, crystals were formed and they were of a higher quality then the crystals formed by the hexane solvent. The hexane did not produce good crystals and as such was not a good solvent to use. The dichloromethane and ethanol dissolved the acetanilide at room temperature which means the acetanilide is too soluble and would not make a good solvent. The water solvent was able to recrystallize the acetanilide perfectly and there was no problems encountered while using it. It was found through 1H NMR and melting point determination that the product is pure acetanilide. On the NMR spectrum it has the characteristic peaks of acetanilide such as a peak at 8.0 for the NH group, 3 peaks at 7.45, 7.29, and 7.162 representing the ortho-hydrogen, the meta-hydrogen, and the para-hydrogen respectively, and a distinct peak for the methyl groups. The spectrum has an acetone spike because the acetone used to clean the NMR tube did not dry all the way and as such found its way into the solution of acetanilide and d-chloroform. The melting point of acetanilide as determined by the Material Safety Data Sheet on www.sciencelab.com is 114.3C, (2) the melting point of the crude acetanilide was determined at 112C and the melting point of the pure acetanilide was determined at 116C making 114.3C fall within the range of the two melting points. In the IR spectra the characteristic peaks of aromatic hydrogens at 3136.04 and 3058.97 and a primary amide peak at 3292.64 shows that the acetanilide was purified and was properly characterized.

During the vacuum filtration in the first procedure to isolate the crude acetanilide a piece of filter paper was not placed in the Buchner funnel and so most of the product ended up in the flask and could not be retrieved and as such a lower yield was obtained. From the lower yield of crude acetanilide there was a much lower yield of pure acetanilide crystals and the crystals formed very slowly but were of high quality, the crude percent recovery of 38.10% and the pure percent recovery of 2.57% show that a much lower yield was obtained due to the mistake of not placing the filter paper. The crystals that formed during the recrystallization took a long time to form however they were very colorful and according to the IR spectra, NMR spectra, and melting point they were pure acetanilide crystals. This shows that recrystallization is a very suitable method for isolating and purifying a substance even with a below average yield.

Conclusion The synthesis of the acetanilide was moderately successful in the sense that the acetanilide was synthesized correctly, but the mistake of not adding filter paper led to a much lower yield. The procedure was very straightforward with the aniline, acetic anhydride, and water being added to a flask and stirred. After 30 minutes the reaction was complete and the acetanilide was synthesized, normally around 2g is the expected yield however only 753 milligrams was synthesized in this experiment. The crude acetanilide, while it was abundant was very impure and as such needed further isolation and purification by use of recrystallization. The solvent chosen was water and it proved to be the best solvent for the recrystallization of acetanilide because when the four solvents were tested water had the best looking crystals and crystal lattice. When the recrystallization of the acetanilide was complete the crystals that formed

were very colorful and abundant for the lower yield that was obtained. The water was easy to heat up and is very abundant so it was easy to perform the acetanilide recrystallization in water. When the melting points were determined it gave a good range of 112C for the crude and 116C for the pure crystals which confirms that the acetanilide was pure. The NMR spectra and IR spectra showed the characteristic peaks of acetanilide and the spectras were properly annotated at the aromatic hydrogens, the amide peak, and the methyl groups. Observing all of this data shows that the acetanilide was synthesized, and purified through use of recrystallization, the only problem that was encountered was the lower yield and this is reflected in the low percent recovery of crude acetanilide, the only consequence of this lower yield was less crystals but the crystals themselves were of high quality and were able to determine a melting point, and give accurate 1H NMR and IR spectras to prove the purity of the acetanilide.

References (1) Bortiatynski, Jackie. "Purification of Acetanilide by Recrystallization." Lab Guide for Chemistry 203: A Life Science Experience in the Organic Chemistry Laboratory (2013): 169-77. Print.

(2) "Material Safety Data Sheet Acetanilide MSDS." Sciencelab.com. N.p., 09 June 2005. Web. 18 Mar. 2013.

(3) Schorni, J. "Synthesis of Acetanilide." (n.d.): 8+. 13 Aug. 09. Web. 20 Mar. 2013.