substitution

Examples of substitution in the following topics:

• Substitution Reactions of Benzene and Other Aromatic Compounds

  • The chemical reactivity of benzene contrasts with that of the alkenes in that substitution reactions occur in preference to addition reactions, as illustrated in the following diagram (some comparable reactions of cyclohexene are shown in the green box).
  • Many other substitution reactions of benzene have been observed, the five most useful are listed below (chlorination and bromination are the most common halogenation reactions).
  • Since the reagents and conditions employed in these reactions are electrophilic, these reactions are commonly referred to as Electrophilic Aromatic Substitution.
  • The catalysts and co-reagents serve to generate the strong electrophilic species needed to effect the initial step of the substitution.

• Substitution of the Hydroxyl Hydrogen

• Substitution

  • This apparent nucleophilic substitution reaction is surprising, since aryl halides are generally incapable of reacting by either an SN1 or SN2 pathway.
  • To explain this, a third mechanism for nucleophilic substitution has been proposed.
  • Three additional examples of aryl halide nucleophilic substitution are presented on the right.
  • Only the 2- and 4-chloropyridine isomers undergo rapid substitution, the 3-chloro isomer is relatively unreactive.
  • Some distinguishing features of the three common nucleophilic substitution mechanisms are summarized in the following table.

• Reactions of Aromatic Compounds

  • Aromatic compounds can participate in a range of reactions including substitution, coupling, and hydrogenation reactions.
  • An example of an aromatic substitution reaction is shown below.
  • A number of patterns have been observed regarding the reaction of substituted benzene rings.
  • Example of an aromatic substitution reaction.
  • As an exercise, draw out the stabilization of the positive charge when ortho substitution occurs.

• Electrophilic Substitution of the Phenol Aromatic Ring

  • The facility with which the aromatic ring of phenols and phenol ethers undergoes electrophilic substitution has been noted.
  • The sodium salt of salicylic acid is the major product, and the preference for ortho substitution may reflect the influence of the sodium cation.

• Reactions at the α-Carbon

  • Many aldehydes and ketones undergo substitution reactions at an alpha carbon, as shown in the following diagram (alpha-carbon atoms are colored blue).
  • First, these substitutions are limited to carbon atoms alpha to the carbonyl group.
  • Cyclohexanone (the first ketone) has two alpha-carbons and four potential substitutions (the alpha-hydrogens).
  • The second ketone confirms this fact, only the alpha-carbon undergoing substitution, despite the presence of many other sites.
  • Second, the substitutions are limited to hydrogen atoms.

• Substitution Reactions of Benzene Derivatives

  • When substituted benzene compounds undergo electrophilic substitution reactions of the kind discussed above, two related features must be considered:
  • The second factor that becomes important in reactions of substituted benzenes concerns the site at which electrophilic substitution occurs.
  • Since a mono-substituted benzene ring has two equivalent ortho-sites, two equivalent meta-sites and a unique para-site, three possible constitutional isomers may be formed in such a substitution.
  • The first thing to recognize is that the proportions of ortho, meta and para substitution in a given case reflect the relative rates of substitution at each of these sites.
  • Structures in which like-charges are close to each other are destabilized by charge repulsion, so these substituents inhibit ortho and para substitution more than meta substitution.

• Substitution of the Hydroxyl Hydrogen

  • The mechanism by which many substitution reactions of this kind take place is straightforward.
  • The resulting "onium" intermediate then loses a proton to a base, giving the substitution product.
  • These two variations of the substitution mechanism are illustrated in the following diagram.
  • Alkyl substitution of the hydroxyl group leads to ethers.
  • This reaction provides examples of both strong electrophilic substitution (first equation below), and weak electrophilic substitution (second equation).

• A Mechanism for Electrophilic Substitution Reactions of Benzene

  • A two-step mechanism has been proposed for these electrophilic substitution reactions.
  • In the second, fast step, a proton is removed from this intermediate, yielding a substituted benzene ring.
  • This mechanism for electrophilic aromatic substitution should be considered in context with other mechanisms involving carbocation intermediates.
  • The cation may bond to a nucleophile to give a substitution or addition product.
  • The carbocation intermediate in electrophilic aromatic substitution (the benzenonium ion) is stabilized by charge delocalization (resonance) so it is not subject to rearrangement.

• Substitution of the Hydroxyl Hydrogen

  • This reaction class could be termed electrophilic substitution at oxygen, and is defined as follows (E is an electrophile).
  • Some examples of this substitution are provided in equations (1) through (4).
  • If E is a weak electrophile, such as an alkyl halide, it is necessary to convert the carboxylic acid to the more nucleophilic carboxylate anion to facilitate the substitution.
  • Alkynes may also serve as electrophiles in substitution reactions of this kind, as illustrated by the synthesis of vinyl acetate from acetylene.