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15 April 2012 Organic II Multistep synthesis of 2-chloro-4-bromoaniline Introduction: The purpose of the completed experiments where to perform a multi-step synthesis of the molecule 2-Chloro-4-bromoanalin from the starting building block of nitrobenzene. A total of five separate conversions from the original starting material were needed to result in the desired product. A final solid sample Infrared spectroscopy was performed and analysis on the final synthesized product to give further indication that the conversions were performed successfully. The topic that was emphasized in this synthesis lab was to understand how the order and addition of substituents around a carbon ring affect the region in which other substituents can be added. The first two steps converted nitrobenzene to acetanilide which is a primary para director. From here it was possible to direct the bromine addition to the para position. From the bromine in the para position it then became possible to affix a chlorine group in the ortho position due to the back the bromine was blacking the para position. The final step in the synthesis was the conversion of the acetilide group into an aniline group though the use of HCL and ethanol. Procedure The first process in the multi-step synthesis involved the preparation of Aniline from nitrobenzene. In a 100mL boiling flask, 6.0g Tin, 2.5mL nitrobenzene and 13mL concentrated HCL were

Crider 2 combined then swirled to mix. The mixture was then submerged in an ice bath for 15 minutes keeping temperature consistent between 55-60C with the aid of a thermometer. The flask was then fit with a condenser and heated on a steam bath until the unreached remaining nitrobenzene was no longer visible as oil drops. The flask was then cooled on an ice bath for 5 minutes back to 55-60C at which time 12mL 50% sodium hydroxide and 20mL distilled water were slowly added. Aniline was then distilled from the mixture by fitting the flask with a claisen adapter, by affixing a seperatory funnel to the boiling flask with DI water to slowly add and keep volume constant during the distillation process, the attachment of the collection flask and through heating at a controlled boil with a heating mantel. Distillate was collected until the collected solution began to turn clear upon condensing, 10 additional mL of distillate were collected from this point. Collection of the distillate was the final step in the first synthesis conversion. The conversion of Aniline to Acetanilide was made possible by first dissolving 2.3g aniline into 65mL Di water and slowly adding 2.1mL concentrated HCL. The solution was then combined in 2.8mL acetic anhydride and brought to a boil. Then a sodium acetate solution of 2.5g anhydrous sodium acetate in 15mL of water was added. The mixture was then cooled on an ice bath for 10 minutes before collection the production by suction filtration. The product was then dried and a melting point obtained. Acetanilide was then synthesized into p-bromoacetanilide in the next process of the multi-step synthesis. 1.647g acetanilide was dissolved into 6.1mL acetic acid in a 125mL Erlenmeyer flask. While being stirred a solution of .643mL bromine in 2mL of glacial acetic acid was also added to the acetanilide solution. While continuing to stir 48.8mL of water were added. Then enough sodium bisulfate in order to discharge the yellow color was added before collecting the product by suction filtration, and washing with water. The product was then recystalized using ethanol at a ratio of 3.3mL per gram.

Crider 3 Synthesis of 2chloro-4-bromoacetanilide from p-bromoacetanilide was made possible by suspending 5.35g of p-bromoacetanilide in a mixture of 12mL of concentrated HCL and 14mL of glacial acetic acid in a 125mL boiling flask. The solution was then heated on a steam bather until the solid went completely into solution. The solution was then cooled to 0C on an ice bath at which time 1.39g of sodium chloride dissolved in 3.5mL of water. After the addition was complete it was allowed to stand at room temperature for 1 hour, and collected by suction filtration. A melting point was then obtained to allude that the conversion has been successful up until this point. The final step in the multi-step synthesis was the conversion of 2-chloro-4-bromoaniline from 2chloro-4-bromoacetilide. 5.047g of 2-chloro-4-bromoanilide were placed in a 100mL boiling flask and combined with a solution of 8.14mL 95% ethanol and 5.29mL concentrated HCL. A condenser was then fitted to the boiling flask and the solution was then heated on steam bath for 30 minutes. A white precipitate could then been seen falling out of solution. At the end of the heating period 32.56mL of hot water was added to dissolve the solid. The solution was then poured over 61.05g ice and 4.88ml 50% sodium hydroxide was added. The crude product was collected by suction filtration, rinsing with water as much as possible. The final product was then recrystalized for a final time using hexane in a ration of 2mL per gram. A melting point using a MelTemp Pro was then collected for the obtained product, and a solid infrared spectrosocopy has been performed and analyzed to gain information in determining if the conversion from nitrobenzene to 2-chloro-4-bromoaniline.

Crider 4 Results: Table 1. Compounds Believed to Have Been Synthesized In the Multi-step synthesis, Their Percent Yields, yields and Melting Points Obtained. Compounds Yield (g) Percent Yields Melting Points Obtained Anilin Acetanilide p-bromoacetanilide 2-chlorobromoacetanilide 2-chloro-4bromoaniline 2.370g 57.25% 69.5-70.3C 2.3g 1.647g 1.365 5.047g 100% 53.56% 38.20% 81.01% NA 112-115C NA 157.2-158.8C

Table 2. Infrared Signals and Their Interpretations for the Crude Final Product Obtained in the Multi-step Synthesis Lab. Wavelength cm-1 649.15cm-1 862.18cm-1 1290.38cm-1 1550.00cm-1/1653cm-1 3000.00cm-1 Interpretation C-Cl stretching vibrations Aromatic H Atom C-N stretching vibrations C=C aromatic stretching vibrations C-H stretching Vibrations

3300.00cm-1

N-H Stretching Vibrations

Calculations % yield Acetanilide: 0.025 mol nitrobenzene -> 0.025 mol Acetanilide x 123g/mol = 3.075g theoretical. 1.647g obtained/3.075g theoretical = .5356 x 100 = 53.56%. % yield .025mol Acetanilide -> .020 mol p-bromoacetanilide x 214g/mol = 4.28g theoretical. 1.635g obtained/4.28g theoretical = .3820 x 100 = 38.20% % yield 2-chloro-4-bromoacetanilide: 5.35g (.025 mol) p-bromoacetanilide -> 0.025 mol 2-chloro-4bromoacetanilide x 249 g/mol = 6.225g theoretical. 5.047g obtained/6.225g theoretical = .8107 x 100 = 81.07%. % yield 2-chloro-4-bromoaniline : .020 mol 2-chloro-4-bromoacetanilide -> 0.020 mol 2-chloro-4bromoacetaniline x 207g/mol = 4.14g theoretical. 2.370g actual/ 4.14g theoretical = .5725 x 100 = 57.25%. Overall Total % yield = .5356 x .3820 x .8101 x .5725 = .0950 x 100 = 9.50%.

Discussion The first indication that our first process of converting from nitrobenzene to acetanilide had been a success came when the first melting point range was obtained. Using a MelTemp pro and slowly increasing the temperature, the melting point for the crude acetanilide was found to be in the range of 112-115C. According to Dr. Moon See-Lee of the National Environmental Research representing the Republic of Korea, the expected melting point for Acetanilide is found at 113.7C. Our range was found

Crider 6 to encompass this expected value, thus indicating that our synthesized product has some similar physical properties and possible some similar intermolecular forces causing the melting points to be similar. T he next check point was completed at the end of the conversion from p-Bromoacetanilide into 2-chloro-4-bromoacetanilide. Using a MelTemp pro a melting point range of 157.2-158.8C was found for the crude product isolated. The literature value for the melting point of 2-chloro-4-bromoacetanilide is expected to be 154-156C (Ault, A). Our obtained values were slightly higher than the expected value. This could be attributed to the fact that it is possible for the MelTemp device to display a temperature value that is slightly higher than the actual sample itself. As the temperature rises in the device, sometimes the sample takes longer to heat than it take for this analog temperature display to increase. This is what I believe is the reason for our slightly higher melting point. The final melting point obtained occurred at the final conversion of our multistep synthesis experiment. After 2-Chloro-4-bromoacetanilide had been converted into what is believed to be 2chloro-4-bromoaniline a melting point range was found to fall between 69.5-70.3C. The textbook Ault indicated the expected values should be between 70-71C. The value for melting pint obtained was well in the range of the expected value. This indicates that our crude product is again showing similar physical properties to that of the desired product. To further describe the physical properties of our crude product and to aid in identification; an infrared spectroscopic analysis was completed. The first of the signals found to be most similar to literature infrared spec obtained from SigmaAldrich were the C-Cl stretching and the single H aromatic bending vibration at 649.15cm-1 and 862.18cm-1, respectively. These sharp signals are directly visible in the same fingerprint regions for the crude and literature infrared spec. Another major similarity seen involves the Carbon-Carbon double

Crider 7 bonding vibrations indicative of aromatic ring are seen at 1550 and 1653cm-1 in the crude infrared spec. The same type of double peak is directly observable just above and below 1600cm-1. This observation infers that our synthesized compounds contain an aromatic ring involving C=C bonding. C-N stretching and N-H stretching absorption peaks were visible for our crude product at 1290.38cm-1 and 3300cm-1, respectively. Again these same peaks are visible in the literate spec obtained, further indicating that the addition and conversion to an Aniline group was a success. The final infrared signal observed for the crude product occurred at just below 2900cm-1. Through interpretation it has been concluded that this signal represents the C-H stretching vibrations involved in the aromatic ring. This same signal can be directly observed as a small sharp double signal just below 2900cm-1 on the literature spec obtained. When combining the physical property data collected in the form of melting points at various checkpoints during the multistep syntheses, through interpretation of an infrared spec on the final product, and a comparison to known standardized literature values, it is possible to conclude that our final product displays many similar physical qualities to that of 2-chloro-4-bromoaniline. The signals observed in the infrared spec indicate that each of the steps involving the conversion of nitrobenzene to 2-chloro-4-bromoaniline have been carried out correctly, with a final total percent yield of 9.50%. Several factors may be at play causing the percent yields at each of the steps, and thus the entire percent yield to be rather low at only 9.50%. According to an article obtained from Yahoo answers discussing problems with distillation recovery indicated that some liquid sample will be retained in the vapor distillation column, this is called vapor carryover. This will always prevent 100% separation. Despite the fact a reflux column had been used, the idea that hexane is such a volatile solvent, allows for the possibility that some of our sample could have been carried away in a vapor despite our low controlled boiling. If too much solvent had been used at either of the separation steps it is possible for

Crider 8 the product to remain in solution even after being cooled down (Matt, M). This can have an influence on our overall recovery, as it may have. Another issue involving solvents can occur after suction filtration. If an ice cold solvent is not used to rinse containers and product it is possible for product to go back into solution and pass right through the suction filter pad. It is also possible that some product remained dissolved in the solvents upon each of the recrystillization steps (Matt, M). Another fault in the techniques performed could come in as inaccurate measuring or standards of error in the measuring devices used throughout this lab. Although minimal degree or error exist, combined with other factors could lead to a small influence in yields. The final factor that could have influenced our total yield could be due to minor products being formed in some of the conversion steps between nitrobenzene and 2chloro-4-bromoaniline. A few minor modifications in future experiments could be observed to increase the possibility of a higher percent yield. The first of those steps could be to use a solvent for separation that has a boiling point much lower than the expected product in solution. This can allow for the easier separation of solvent from product. Second, after performing a first recrystillization, evaporate the left over solution down halfway and reperform a recrystillization. This will reduce the amount of product lost to the solution of impurities. Third, always wash chemicals and equipment with ice cold solvent to prevent to product from reentering solution and passing right through the collection filter pad. When all of these modification are followed it could greatly increase the possibility for higher future overall and intermediate percent yield.

Crider 9 References

"4-bromo-2-chloroaniline IR Spec." Sigma-Aldrich. N.p., 2012. Web. 14 Apr 2012. <http://www.sigmaaldrich.com/catalog/product/aldrich/154245?lang=enion=US>. Ault, A. techniques and experiments for organic chemistry. sith. sausalito, Ca: university science books, 1998. Print. Matt, M. "Preparation/Recystallization of Acetanilide." Mendel Set Beta . Mendel Set, 2012. Web. 15 Apr 2012. <http://www.mendelset.com/articles/680/preparationrecrystallization-acetanilide>. See-Lee, Dr. Moon. "SIDS Initial Assesment Report." Acetanilide . Republic of Korea , 06 11 2011. Web. 15 Apr 2012.<http://www.chem.unep.ch/irptc/sids/oecdsids/acetanilide.pdf>. Yahoo, Answers. "Steam Distillation and Low Percent Yields." Yahoo. Yahoo, 2011. Web. 15 Apr 2012. <http://answers.yahoo.com/question/index?qid=20111004023914AAMwotc>.