Organic Chemistry II  | Lecture | Laboratory

Organic Chemistry Laboratory II
Friedel-Crafts Alkylation of Dimethoxybenzene
Experiment Description and Background

Description
In this two-week experiment, students will work in pairs to prepare 1,4-di-tert-butyl-2,5-dimethoxybenzene from 1,4-dimethoxybenzene using tert-butyl alcohol in the presence of sulfuric acid as electrophile (Figure 1).  The reaction is an example of an electrophilic aromatic substitution (Friedel-Crafts Alkylation) that incorporates the effect of substitution of the aromatic ring into the experiment. Students will prepare the product the first week of the experiment. During the second week, students will analyze the products by TLC analysis and melting point determination. In addition, the product will be weighed and the percent yield of the reaction determined.
Mechanism of the Friedel Crafts Reaction
The Friedel-Crafts alkylation reaction is one of five types of electrophilic aromatic substitution (EAS) reactions.  All five specific types of EAS follow the same reaction mechanism. The general mechanism of the EAS reaction is shown in Figure 2, and a specific mechanism with a tertiary carbocation is shown in Figure 2a. The pi electrons of one of the pi bonds (C1-C2) of benzene is used to form a new bond between C2 and the carbon atom of the carbocation.  This results in the generation of a new carbocation intermediate, where the carbocation is localized on C1. The hydrogen at C2 gives up its electrons from the C2-H bond to regenerate the pi bond between C1 and C2, restoring the aromatic character to the benzene ring.   		     

Figure 1:  Reaction scheme depicting the Friedel Creafts reaction of 1,4-dimethoxybenzene with tert-butyl alcohol
.

Figure 2:  General Mechanism of the electrophilic aromatic substitution










Figure 2a:  Electrophilic aromatic substitution with a tertiary carbocation
Friedel-Crafts alkylation of benzene and substituted benzenes  involves substituting a hydrogen atom on a benzene ring with an alkyl group.  Alkylation refers to any reaction in which a new alkyl group is introduced to a molecule.  In the Friedel Crafts reaction, a new alkyl group becomes bonded to a carbon atom of the aromatic ring.  This reaction occurs by treatment of benzene or substituted benzene with a stable carbocation.  The carbocation serves as the electrophile and is derived from an alcohol, an alkyl halide or an alkene. The "new" alkyl group that substitutes the hydrogen on the benzene ring corresponds to the alcohol, alkyl halide or alkene used to generate the carbocation.The carbocation can be generated from various starting materials such as an alkene, alcohols or alkyl halides.  Carbocations may be generated from alcohols or alkenes through treatment with strong acid. Alternatively, the carbocation may be generated from an alkyl halide upon treatment with an aluminum halide (Figure 3).  In the reaction that is done in this experiment, the carbocation is generated from reaction of tert-butyl alcohol with strong acid.   Aryl or vinyl halides will not undergo this reaction since these compounds will not generate carbocations.



Figure 3:  Generation of carbocations from alcohols, alkyl halides and alkenes
Benzene rings substituted with strong electron-withdrawing groups, such as nitro groups, are not as reactive as benzene.  Conversely, benzene substituted with electron-donating groups, such as methoxy or alkyl groups are more reactive than benzene itself.  In this experiment, 1,4-dimethoxybenzene is a highly reactive starting material in the EAS reaction because it is substituted with two electron-donating groups, also referred to as "activating" groups.  When 1,4-dimethoxybenzene reacts with the carbocation generated from tert-butyl alcohol, a trisubstituted product, 1-tert-butyl-2,5-dimethoxybenzene is generated.  Since this trisubsituted product contains two activating methoxy groups and one activating tert-butyl group (alkyl groups such as the tert-butyl group are activating) it is more reactive in the EAS reaction than 1,4-dimethoxybenzene.  As a result, 1-tert-butyl-2,5-dimethoxybenzene continues to react with a second equivalent of the tertiary carbocation dervied from tert-butyl alcohol, to generate 1,4-di-tert-butyl-2,5-dimethoxybenzene (Figure 4).



Figure 4:  Mechanism of the reaction to form 1,4-di-tert-butyl-2,5-dimethoxybenzene

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