Electrophilic Aromatic Substitution to yield 4-Bromoacetanilide
Introduction
Halogenation is a common process in organic synthesis. It is used in industrial and research synthesis as halogenated compounds are used for numerous widely used goods, including plastics. The lab aimed to perform monohalogenation of acetanilide. The reaction is specific since it is performed without catalyst. The typical halogenation is realized in presence of Lewis acid. Halogens molecules are electrophilic, and do not actively react. In presence of Lewis acid, the interaction is rather active.2
The lab used catalyst-free halogenation. The acetanilide molecule contains the acylated amine. As a result, the electronic density is shifted towards the amine group, and the molecule gains inductive and resonance effects. The partial positive charge appears, and the reaction with bromine molecule is enabled. The method is selective since it allows obtaining the monohalogenated compound since the ortho- and para- positions are disabled by acyl group in the amine molecule.3 The experiment allows practicing numerous laboratory techniques: reaction conduction, evaporation, filtration, purification, and melting point measurement. The applied aspects of organic synthesis are also practiced.
Experimental Methods
100 mg of Acetanilide was placed in a conical vial (3 mL) with a cap. Then, 16 drops of glacial acetic acid were added. The mixture was stirred to intensify dissolution. As the solution became clear, 12 drops of bromine-acetic acid (1:2) solution was added in the hood, and the vial was immediately capped. The solution was reddish brown. It was left at room temperature for 10 minutes at shaking. The yellow-orange crystals precipitated from the solution. 2 mL of water was added to the mixture, and then 20 drops of 33% of aqueous sodium bisulphate (to destroy the residual bromine); as a result, white crystals were formed. The reaction mixture was cooled in an ice bath for 10 minutes to improve yield. The crystals were separated by vacuum filtration with a Hirsh funnel. The filter cake was washed three times with 1 mL of cold water, and then dried by drawing air though the crystals under reduced pressure. The product, 4-bromoacetanilide was purified from 95% ethanol. 5 mL of hot ethanol was added to crude product. The mixture was stirred, and hot ethanol was added until the product dissolved. The solution was filtered to the sample vial with the boiling chip that was pre-weighed. The solvent was evaporated on a sand bath in a fume hood. As no more solvent was evaporating, the vial was removed from bath. The product was cooled to crystallize, and dried. The dry product was weighted and its melting point determined (Electrophilic).
Results
Melting points and yield of 4-bromoacetanilide
Discussion
The reaction performed during the lab was electrophilic aromatic substitution3:
It is also known as electrophilic halogenation. Halogenated organic substances are commonly used in laboratory and industrial practice, so the reaction is significant for practical purposes.
The aromatic compounds are weak nucleophilic agents, and thus the electrophilic substitutions (as halogenation) require specific conditions. The bromine molecule is symmetrical, which means that the partial charges are not stable.
The common method of halogen introduction into the organic molecule is performed with catalyst, a Lewis acid. The typical catalyst used is a ferric chloride; it is used for polarization of the bromine, which enables electrophilic substitution.
However, this lab performed halogenation without the catalyst. Introduction of amine into phenyl groups forms acetanilide, which was a nucleophilic agent rich with electrons. The amine group contained an electronegative nitrogen atom, capable of electrons withdrawing, which causeed a moderate inductive effect. In addition, the amine group added the resonance effect to the molecule, and the molecule containing amine group became more nucleophilic. Thus, the electrically symmetrical phenyl molecule gained positive charge, because more electronegative nitrogen withdrew electronic density. The acetanilide molecule had the inductive and resonance effects, which significantly improved its nucleophilic characteristics. The phenyl with amine substation was a strong nucleophile, and it could react with electrophile without catalyst.
The amine group was acetylated to prevent activation of ortho- and para- positions, which would result in formation of tribromide acetanilide. When amine was acetylated, only monosubstituted halogenation was performed. The acetylation was performed by carbonyl group.3
When nucleophilic acetanilide reacted with electrophile molecule of bromine, the partial charge in bromine molecule caused bond breaking. In the reaction, the carbocation, an intermediate compound, was formed, which then caused re-forming of the double bond in the benzene ring. Thus, the bromine was introduced into acetanilide molecule, and the more stable molecule was formed.
The important part of the experiment was the interaction with ethanol. Ethanol was used for purification of crude product from ortho-substituted compound. Ethanol was a volatile compound, and it boiled at 78 oC. After treatment, the remaining crystals were pure 4-bromoacetanilide.
The residual amounts of bromine were deactivated by sodium bisulphate. As a result of the reaction, the light brown color of the solution disappeared, and the formed crystals were white. The reaction was exothermic, and therefore the reaction vial had to be kept on ice bath.
The melting point of the obtained product is 147.2-148.6oC. The weight is 0.0418 g, whereas the theoretical weight is 0.1650 g. Thus, the yield is 25.3%. The low yield is caused by product losses during the experiment. The possible stages where the product could be lost: primary crystals formation (less reagent halogenated due to inappropriate mixing), evaporation (crystals destroyed by hot temperature). The difference between the experimental and theoretical melting point indicates that there are impurities in the crude product. The slightly brown color of the crystal points that purification was not complete.
Therefore, the reasons of low yield are imperfect experiment conduction. The synthesis conditions and all procedures are to be performed perfectly in terms of time, reagent quantities and temperature conditions to maximize yield.
Conclusions
The lab assignment aimed to obtain the brominated compound, 4-bromoacetanilide. The reagent was acetanilide, a compound with an aromatic ring with amine substitution, which is reach for electrons. The use of an electron-rich reagent allowed performing the process without catalyst. The melting point of the received product was 147.2-148.6oC; the yield of the experiment was 25.3%. The low yield is explained by the insufficient purification of 4-bromoacetanilide crystals. Therefore, the experiment can be improved if more convenient experimental technique is applied.
Works Cited
Electrophilic Bromination of Acetanilide. Riverside Community College. n.d. Web. 6 July 2015. http://websites.rcc.edu/grey/files/2012/02/Bromination-of-Acetanilide.pdf
Hunt, Ian. "Reactions of Arenes. Electrophilic Aromatic Substitution". University of Calgary. n.d. Web. 20 June 2016.
http://www.chem.ucalgary.ca/courses/350/Carey5th/Ch12/ch12-0.html
Reusch, William. "Substitution Reactions of Benzene and Other Aromatic Compounds". Michigan State University. 5 May 2013. Web. 6 July 2015.
https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/benzrx1.htm
