Aromatic compounds tend to undergo electrophilic aromatic substitutions rather than addition reactions. Substitution of a new group for a hydrogen atom takes place via a resonance-stabilized carbocation. As the benzene ring is quite electron-rich, it almost always behaves as a nucleophile in a reaction which means the substitution on benzene occurs by the addition of an electrophile. Substituted benzenes tend to react at predictable positions. Alkyl groups and other electron-donating substituents enhance substitution and direct it toward the ortho and para positions.
Electron-withdrawing substituents slow the substitution and direct it toward the meta positions. Aromatic compounds also undergo reactions in their side-chains, often at the benzylic position next to the aromatic ring. Reactions at benzylic positions are often promoted by resonance stabilization of the intermediate and/or transition state with the aromatic ring. Aromatic amides are formed via electrophilic substitution. The NH2 group is electron-donating and therefore the substituted ring is considered “activated” and will often react even without a catalyst. The nitrogen based activating group increases reactivity by a resonance effect:
The resonance stabilisation from an amide group in an aromatic compound is mainly due to the delocalisation of the nitrogen lone pair onto the amide oxygen (which makes the lone pair less available to the aromatic ring) and the increased steric bulk of the group, favouring substitution at the 4-position over the 2-positions which it shields. Aniline is the simplest aromatic amine and is synthesised by first nitrating benzene using a concentrated mixture of nitric acid and sulphuric acid to give nitrobenzene which is then hydrogenated in the presence of a nickel catalyst to give the final product.
Aniline undergoes very readily electrophilic substitution reactions as the aromatic ring of aniline is very electron rich due to the ability of the lone pair on the nitrogen to be delocalised into the ?-system. Aniline can be used as a precursor to more complex materials notably acetamide, sulphanilic acid and sulpha drugs. Currently the largest market for aniline is preparation of methylene diphenyl diisocyanate (MDI), with some 85% of aniline serving this market. It is also used in the reparation of diazonium compounds which are used in dye industry and to produce Anil’s (Schiff’s bases from aniline) for use as antioxidants in the rubber industry. In this experiment, aniline is first converted to N-phenylethanamide which is then brominated in the 4-position to produce N-(4-bromophenyl) ethanamide. After bromination, the amide group is hydrolysed back to the amine to produce the final product, 4-bromoaniline. Procedure Acetanilide is synthesised by reacting 10ml of aniline with 25ml of ethanoic acid in a flask followed by 12ml of ethanoic anyhydride.
After mixing and allowing the solution to stand for 5 minutes, it is with 100-200ml of water until crystallisation of the product occurred. The crystals of the N-phenylethanamide are filtered off and dried in air. To form the p-bromoacetanilide, the 5g of the acetanilide and 2. 1ml are dissolved in separate 25ml portions of ethanoic acid. The bromine solution is then added to the acetanilide solution slowly over 5 minutes, whilst stirring. The mixture was allowed to stad at room temperature for 15 minutes and then poured into 300ml of cold water. g of sodium metabisulfate was added to remove any remaining bromine. The product was then filtered off by suction.
The 4-bromoaniline was prepared by refluxing the p-bromoacetanilide with hydrochloric acid and then neutralising it with sodium hydroxide solution. The product separates as an oil which solidifies on complete crystallisation of the product. The colourless crystals are collected by centrifugation and then dried in air. Results ProductYield of crude product/ gMelting point of crude product/ ?CMelting point of pure product/ ?C N-phenylethanamide11. 78106 N-(4-bromophenyl) ethanamide5. 0082144 4-bromoaniline1. 6064- Experimental yield calculations For preparation of N-phenylethanamide: ProductRMMVolume used/ gVolume used/ mLMoles usedLimiting reagent? Aniline93. 1100. 107Yes Ethanoic anhydride102. 1120. 118No Glacial ethanoic acid60. 1250. 416No No. moles produced by aniline = 0. 107 moles Theoretical mass of N-phenylethanamide = n*MR = 0. 107 ? 135 = 14. 44g Percentage yield = actual yield (g)/theoretical yield (g) ? 100 = (11. 9/14. 44) ? 100 = 82% For preparation of N-(4-bromophenyl) ethanamide:
ProductRMMVolume used/ gVolume used/ mLMoles usedLimiting reagent? N-phenylethanamide135. 250. 0370No Bromine159. 82. 10. 0131Yes No. moles produced by bromine = 0. 0131 moles Theoretical mass of N-(4-bromophenyl) ethanamide = n*MR = 0. 0131 ? 159. 8 = 2. 10 g Percentage yield = actual yield (g)/theoretical yield (g) ? 100 = (5. 00/2. 10) ? 100 = 238% For preparation of 4-bromoaniline: ProductRMMVolume used/ gVolume used/ mLMoles usedLimiting reagent? N-(4-bromophenyl) ethanamide214. 150. 0234Yes Hydrochloric acid36505. 00No No. moles produced by N-(4-bromophenyl) ethanamide = 0. 234 moles Theoretical mass of 4-bromoaniline= n*MR = 0. 0234 ? 214. 1 = 5. 01 g Percentage yield = actual yield (g)/theoretical yield (g) ? 100 = (1. 60/5. 01) ? 100 = 32% Discussion The preparation of N-phenylethanamide from aniline was the first step of the experiment.
Ethanoic anhydride was reacted with aniline in the presence of glacial ethanoic acid, and the reaction occurred via an electrophilic substitution mechanism: In this reaction two products are formed, N-phenylethanamide and acetic acid. Here monosubstitution is easily achieved because the acetamino group HNC(=O)CH3] cannot activate the benzene ring towards electrophilic attack as well as the simple amino group does. The acetamido group is less effective in donating electron density to the benzene ring, because the electron pair on the nitrogen atom is delocalised by both the carbonyl group and the phenyl ring. The N-phenylethanamide was obtained in the form of crystals with a melting point of 78?C. After this product was purified by recrystallisation from aqueous ethanol it was found to have a melting point of 106?C which is much closer to the literature range of 113-114?C.
The percentage yield for the N-phenylethanamide was reasonably high at 82%. The second step in the formation of 4-bromoaniline, involved reacting the acetanilide with bromine in acidic conditions to produce N-(4-bromophenyl) ethanamide or p-bromoactetanilie. Acetanilide is a para-directing group and so an incoming electrophilic attack on the para position will yield p-bromoacetanilide. The reaction occurred via the following electrophilic substitution mechanism: An electron pair from the benzene ring attacks the Br2 forming a new C-Br bond and leaving a non-aromatic carbocation intermediate.
The carbocation intermediate loses H+, and the neutral substitution product forms as two electrons from the C-H bond move to regenerate the aromatic ring. Many aromatic compounds are readily brominated when treated with bromine in the presence of a Lewis acid (iron(III) bromide, aluminum chloride, metallic iron, etc. ). However, to prepare pure 4-bromoaniline, the activating effect of the amino group of aniline must be diminished by acetylation. The acetamido group of acetanilide is a much weaker activating group and ortho, para-director than the amino group, but it is still active enough that bromination does not require a catalyst.
This step in the procedure was necessary as direct bromination of aniline would yield 2,4,6,-tribromoaniline, as both ortho and the para position are substituted so readily by bromine that it is exceedingly difficult to prepare p-bromoaniline by direct bromination of aniline. Bromine was substituted onto the 4-position of the acetanilide molecule as the -NHCOR group is less powerfully activating than the -NH2 group in aniline as the carbonyl group competes effectively with the aromatic ring for the lone pair of electrons on the N atom, and the degree of steric hindrance is much greater in the ase of a -NHCOR group so the compound is much more para directing. Bromination in acetic acid results in monobromination, but can give a mixture of isomers. However, because the steric hindrance by the bulky acetamido group shields the ortho positions from attack to a large extent, only about 10% of the 2-bromo derivative is formed. This isomer remains in solution when the mixed product is recrystallised and pure 4-bromoacetanilide is isolated. The 4-bromoacetanilide was found to have a crude melting point of 82?C and the melting point of the pure product was found to be 144?C.
The literature value for melting point range is 166-170?C which was very far off from the obtained values especially that of the crude product. This could have been due to impurities in the sample tested, including the 10% of the 2-bromo derivative. The percentage yield for the N-(4-bromophenyl) ethanamide was also exceedingly high, an over 100%. This can be attributed to not enough sodium metabisulfite being added to the solution to remove excess bromine. The purpose of the sodium metabisulfite was to convert the excess orange bromine into colourless bromide ion.
Also the filtering by centrifugation may have not been effective enough so that a large amount of impurities were left in the sample. The 4-bromaniline was the desired product, so the acetyl group was removed from the p-bromoacetanilide molecule by hydrolysis to give pure 4-bromoaniline. This occurred via the following electrophilic substitution mechanism: The p-bromoacetanilide was refluxed with water using ethanol and HCl, then neutralised with the sodium hydroxide.
The hydrolysis of the amide function liberates the amino group and 4-bromoaniline results, with ethanoic acid as a by-product. The melting point of the isolated product was found to be 64?C which is in good accordance with the literature range of 60-64?C. The percentage yield was only 32% however, which can attributed to the fact that there was a large amount of impurities in the previous step to produce the p-bromoacetanilide. The possible products of bromination of toluene in the presence of ethanoic acid are: (2-bromotoluene) (4-bromotoluene)
The product of bromination of benzyl ethanoate in the presence of ethanoic acid is: (4-bromobenzyl ethanoate) The possible products of bromination of pyridine in the presence of a lewis acid are: (3-bromopyridine) (3,5-dibromopyridine) The product of bromination of naphthalene in the presence of a lewis acid catalyst is: (1,4-dibromonapthalene) The product of bromination of phenol in the presence of ethanoic acid is: (2,4,6-tribromophenol) The product of bromination of hydroxyphenyl nitrile in the presence of ethanoic acid is: (2,4-dibromo hydroxyl phenyl nitrile)
References
1.Harwood, L.M.; Moody, C.J.; Percy, J.M.; “Experimental organic chemistry: standard and microscale”, Blackwell Science 1999, Edition 2; p439-443.
2.http://www.chemicalbook.com/ChemicalProductProperty_EN_CB9760655.htm
3.http://www.chemexper.com/chemicals/supplier/cas/103-88-8.html
4.http://www.uni-r.de/Fakultaeten/nat_Fak_IV/Organische_Chemie/Didaktik/Keusch/chembox_brom_arom-e.htm
5.http://edivini.pbworks.com/f/bromination_acetanilide_JCE1996p0267.pdf
