When obtaining various types of alkylbenzenes and acylbenzenes in industry, the Friedel-Crafts reaction has become widespread. It is one of two known methods for the synthesis of these compounds, and its parameters are regulated to achieve a higher yield of the product.
More about arene alkylation processes
The most famous example of the Friedel-Crafts reaction is the interaction of methyl chloride (CH3Cl) with benzene (C6H 6) in the presence of aluminum chloride (AlCl3), where the output is toluene (C7H 9). This reaction was obtained in 1877 by two scientists - Charles Friedel and James Crafts. It subsequently became one of the important components for the industrial production of alkylarenes.
The main synthesis is the interaction of benzene and its homologues with any alkyl halides in the presence of the so-called Lewis acids. The essence of the change of reagents does not change: the reaction always proceeds according to the same principle. Derivatives of thismethod was the production of alkylbenzenes in organic chemistry by the interaction of alcohol and an inorganic acid, a carbonium ion and an aromatic ring.
The second method is the method of converting the side chain of various aromatic ketones in the presence of zinc amalgam (ZnHg) with hydrochloric acid (HCl) or hydrazine (N2H2) with a strong base. Both reactions are of a reducing nature: the first is called the Clemmens reaction, the second is called the Kizhner–Wolf reaction.
Also, if there are unsaturated bonds in the side chain, they can be reduced by reaction on a nickel catalyst (Ni) in the presence of hydrogen gas (H2).
Reaction mechanisms
The literature describes two possible ways of the reaction, and both of them follow the principle of electrophilic substitution. The difference lies only in the nature of the electrophile: in the first case, this is an alkyl carbonium ion (another name is carbocation), which is formed as a result of the addition of a halogen ion to a Lewis acid according to the donor-acceptor principle, and in the second case, it is a one-stage creation of an internal complex between all participating reagents according to the same way. Each option is detailed below.
Reaction to form a carbonium ion
This mechanism involves the passage of synthesis in 3 stages, where Lewis acids, for example AlCl3, TiCl4, SnCl 4, FeCl3, BF3, HF act as a process catalyst.
Forconsidering a typical Friedel-Crafts reaction, the interaction between benzene and 1-fluoropropane (C3H6F) in the presence of boron trifluoride BF was chosen 3 as a catalyst.
In the first step of the process, C3H6‒F reacts with BF3, adding halogen ion according to the donor-acceptor principle. At the external energy level, boron has a free cell (acceptor), which is occupied by fluorine with an unshared pair of electrons (donor). Due to this addition, the carbon atom C, standing next to the halogen F in 1-fluoropropane, acquires a positive charge and becomes a very reactive propyl carbonium ion. This property of these ions increases in the series primary → secondary → tertiary, therefore, depending on the conditions in the alkylation reaction products, the side chain may rearrange to a more advantageous position.
Further, the resulting carbocation reacts with benzene and adds at the bond site of carbon and hydrogen atoms, transferring electron density to C of the aromatic ring.
In the third stage, the resulting particle reacts with an ionized Lewis acid, where the H atom is split off from the arene and joins the detached F with the formation of hydrogen fluoride HF, and the reaction products become n-propylbenzene, isopropylbenzene and reduced BF3.
Synthesis to form an internal complex
The reaction mechanism involves the formation of an intermediate general complex, where in one stage the alkyl groupmoves from the halogen to the aromatic ring, and the halogen to the Lewis acid, creating an ion pair that decomposes into an alkylbenzene, a mineral compound, and a reduced catalyst.
Types of derivative reactions
The Friedel-Crafts reaction for benzene and its homologues with alcohols in the presence of mineral acids follows the same mechanisms. In this case, the hydrogen atom attaches to the hydroxide ion and, breaking off, forms a water molecule. The resulting carbonium ion is attached to the carbon in the aromatic ring at the site of its bond with H. This atom is split off, adding to the acid residue, and as a result, alkylbenzene is synthesized.
In unsaturated hydrocarbons, detached hydrogen rises at the place of the double bond, forming the same carbocation associated with the acid residue. Hydrogenation of an alkene takes place near the carbon atom that forms the most favorable structure. Then the reaction proceeds as in the previous case.
One of the derivatives of the syntheses is also the Friedel-Crafts acylation reaction, where acid chlorides (RCOCl) are used instead of alkyl halides to form aromatic ketones.
Addition of two or more alkyl residues
Benzene in the Friedel-Crafts reaction can add from 2 to 6 substituents. It should be noted that each time the interaction takes place faster, since the bond in the aromatic ring is weakened already at the firstsynthesis. The process of formation of polyalkylbenzenes can be carried out in the course of one reaction, therefore, an excess of an aromatic compound is used to control the production of the desired product. Using this method, you can gradually introduce one group at a time into the structure of benzene and its homologues.
In the Friedel-Crafts reaction, toluene easily adds the next alkyl group, since the arene has already been activated with respect to the electrophilic substitution. In the reaction products at 0 °C there will be an equilibrium mixture of ortho- and para-xylene, and when the temperature rises to 80 °C, mainly only the meta-compound will be synthesized. This is explained, as will be described below, by the energy benefit of the formation of certain positions depending on the heating of the mixture.
An extension of this synthesis is the possible ability of polyhaloalkanes to attach more than one aromatic ring via the main mechanism.
Synthesis features
In organic chemistry, the formation of a mixture of alkylbenzene isomers is explained by two reasons. First, as mentioned above, the formation of a carbocation sometimes involves a more favorable rearrangement, due to which various product structures are formed. Secondly, their quantitative composition is regulated by the temperature regime (from 0 °C to 80 °C), that is, with an increase in temperature in order to compensate for the energy consumption of the formation of a specific structure, one can achievehigher yield of one of the isomers. The same principle applies to the formation of dialkylbenzenes, where the ortho- and para-positions give way to the meta-orientations with increasing temperature.
Limitations in applying synthesis
There are 3 nuances due to which the Friedel‒Crafts reaction can go with side effects or not go at all.
Introduction of electrodedeficient substituents into the aromatic ring is accompanied by arene deactivation with respect to further substitution reactions. So, for example, when a nitronium ion is added to alkylbenzenes, the synthesis is more difficult, since it pulls the electron density towards itself due to the tendency of nitrogen to fill an empty cell at the external energy level. For the same reasons, polynitration or, for example, polysulfonation takes place under very harsh conditions, since with each subsequent synthesis the aromatic ring loses its reactivity.
Therefore, the Friedel-Crafts synthesis does not proceed if the aromatic ring contains electrodedeficient substituents, especially those with strongly basic properties that bind Lewis acids (for example -NH2, –NHR, -NR2). But reactions, for example, with halobenzenes or aromatic carboxylic acids follow a typical mechanism, although they are less reactive.
An important point is also the rearrangement of the carbonium ion in the process or the product at the end, since it is greatly influenced by the synthesis conditions, in particular, the temperature and the excess of the alkylated substance.
Instead ofalkyl halides R‒X (R=alkyl group, X=halogen) Ar‒X halogenides (Ar=aromatic compound) cannot be used, as they are very difficult to remove a substituent even under the influence of Lewis acids.
