Table of Contents
Aromatic compounds refer to any compounds that produce a fragrant smell, such as the benzaldehydes that produce the scent of cherries, peaches, and almonds. Later on, some aromatic compounds were discovered but did not exhibit this property. Instead, aromatic compounds are classified through their chemical behavior.
Biologically relevant examples of aromatic compounds
Classification of aromatic compounds
Compounds are classified as aromatic if they are able to exhibit the following properties.
- The molecule should be cyclic and contain conjugated high or low electron density areas.
- The molecule should be very stable, compared to their aliphatic counterparts.
- The molecule should be planar to allow easier delocalization of the π electrons.
- All atoms in the cycle should contain a p-orbital for overlap.
- The molecule should follow the Huckel 4n + 2 π electron rule where n should be an integer.
If the compound is able to exhibit all of the properties included in the list, the compound is conserved to be aromatic. Otherwise, the compound can be classified as either a non-aromatic or anti-aromatic compound.
An aromatic compound is considered a big family of compounds as it comprises of compounds with a six-membered ring, to more complex structures. Aromatic compounds are also not limited to hydrocarbons as there are also aromatic compounds like thiophene and pyridine that are considered aromatic, even if they have S and N in their structure. Ions can also be considered as aromatic, as long as it will exhibit the properties included above.
Some important aromatic compounds to biological organisms are the steroids that include the hormones responsible for growth and the development of physical features. In the pharmaceutical industry, some compounds such as atorvastatin, a cholesterol-lowering drug, are also aromatic. Pyridine, C5H5N, is a common molecule present in vitamins and some other pharmaceuticals. Most of the essential vitamins that we need are aromatic. Benzene, the most common aromatic compound, is used in the manufacture of polystyrene plastics. It is also used, in small amounts, in pesticides and some pharmaceutical drugs.
Benzene is a hydrocarbon with the molecular formula of C6H6. It has a cyclic structure with alternating or conjugated double bonds. Although the compound is unsaturated, it does not exhibit the relative reactivity of its acyclic and other alkene counterparts. For example, a cyclohexene molecule readily reacts with Br2 to produce a 1,2-dibromocyclohexane. On the other hand, a benzene molecule reacts very slowly with Br2 to form a bromobenzene but still retaining the presence of three double bonds. This tells us about the relative stability of benzene.
Another important observation for the benzene molecule is the bond lengths in a benzene molecule. In ordinary compounds, it is expected that a single bond should be longer than a double bond. However, bond length analysis of benzene shows that the C to C bond lengths, regardless if it is a single bond or a double bond, are all equal. The electrostatic potential map also shows that the electron density in all six carbon-carbon bonds is all identical. The bond angle also of C-C-C is all at 120°. Each carbon also has a p-orbital that lies perpendicular to the plane of the six-membered ring.
Because of the peculiar properties of benzene, we cannot consider each multiple bond to be localized and is overlapping to only one other p-orbital. These properties are only possible if the compound has all p-orbitals, equally overlapping adjacent p-orbitals. This overlap of orbitals enables delocalization of the 6 π electrons around the ring. Because of this, there is a difficulty in isolating the two possible isomers of benzene. Instead, a circle is included inside the 6 sides of the molecule to indicate delocalization of the π electrons.
Electrophilic Aromatic Substitution Reaction
Electrophilic aromatic substitution (EAS) occurs when an electrophile reacts with an aromatic ring, substituting in the process one of the H atoms in the ring. A number of different electrophiles may be used in EAS. Possible electrophiles include halogens (-Cl, -Br, -I), sulfonic acid group (-SO3H), a hydroxyl group (-OH), a nitro group (-NO2), an acyl group (-COR), and alkyl groups (-R). Even with benzene alone, one can come up with some compounds because of the number of possible electrophiles for the reaction.
Aromatic compounds, unlike ordinary alkenes, are less reactive to their acyclic counterparts because of the relative stability of aromatic compounds due to the delocalization of the pi electrons. For the halogenation reaction, Br2 can readily react with ethene to produce di-bromoethane. This is not true for benzene. For the bromination reaction to proceed in benzene, a catalyst such as FeBr3 is needed. The catalyst provides a different mechanism for the reaction to proceed.
The 1st step in the reaction is the polarization of the Br2 molecule by FeBr3. In the process, a more electrophilic molecule is produced in the form of FeBr4– Br+. The presence of Br+ is more electrophilic than an ordinary Br2 molecule. The FeBr4– Br+ will then attack the benzene molecule, and a base will remove the H+ in the process. Below is the mechanism of the reaction:
Nitration of aromatic rings can be achieved using a mixture of concentrated nitric and sulfuric acids. The electrophile in the reaction is the nitronium ion, NO2+, which is produced by the protonation and loss of water of HNO3. Just like in halogenation, when the nitronium ion interacts with the benzene ring, a carbocation intermediate is produced, and upon loss of proton, the neutral substitution product, the nitrobenzene, is produced. Below is the basic mechanism for the nitration of benzene:
Sulfonation of Benzene
A sulfonation reaction of aromatic rings is achieved by reacting benzenes with fuming sulfuric acid (a mixture of H2SO4 and SO3). The electrophile for the reaction is either HSO3+ or neutral SO3, depending on the reaction conditions. The reaction mechanism for this reaction is just similar to that of the bromination and nitration reactions previously discussed. A sulfonation reaction is favored in the presence of strong acids, while desulfonation is favored in hot, dilute aqueous acid. The mechanism for sulfonation is as follow:
A hydroxylation reaction of aromatic rings is very difficult to achieve in ordinary reaction conditions. Hydroxylation is achieved in the presence of biological enzymes. An example of a hydroxylation reaction through a biological pathway is the hydroxylation of p-hydroxyphenyl acetate to produce 3, 4-dihydroxyphenyl acetate using the p-hydroxyphenylacetate-3-hydroxylase. The process requires molecular oxygen plus the coenzyme reduced Flavin adenine dinucleotide, FADH2.
An alkylation reaction proceeds in the presence of an alkylchloride in the presence of AlCl3. The aluminum chloride enables the dissociation of R-X to produce the carbocation that will serve as the electrophile. The electrophile then attacks the benzene ring and the reaction is completed by proton loss. The mechanism of the reaction is shown below:
The mechanism for the acylation reaction is similar to that of the alkylation reaction. The alkyl halide is just replaced by an acyl halide. For example, for the acylation reaction of benzene, the 1st step is the generation of a strong electrophile by the interaction between the acyl chloride and the AlCl3 molecule. The acyl cation is then stabilized by the re-arrangement in the acyl cation with the + charge present in the C atom. The +C then interacts with the double bond in the benzene molecule forming a carbocation that can be stabilized by abstracting one of the protons using the AlCl4– ion produced in the 1st step. The mechanism for acylation is shown in the figure below:
The correct answers can be found below the references.
- Conjugated double bond
- All atoms in the cycle contain a p-orbital.
- Huckel rule (4n + 2 π electrons)