Chem 263 ct. 10, 2013 The strongest donating group determines where new substituents are introduced. N 2 N 3 2 S 4 + N 3 N 2 2 S 4 N 2 N 2 + 2 N N 2 N 3 2 S 4 N 2 2 N N 2 2,4,6-trinitrophenol picric acid This reactivity can be explained by the following resonance forms: N 2 N 3 2 S 4 N 2 + In this reaction, chlorobenzene has a chloro (-) group attached on the benzene ring. When we perform nitration, only ortho and para substitution occurs. Chloro group is an electron withdraw group inductively, however, the lone pairs of electrons are conjugated to the benzene ring through resonance as electron donating group. As result, resonance beats inductive effect, which gives ortho and para substitution products.
SC 3 S is under in the periodic table, and it also has two lone pairs. It is resonance donating, and thus ortho/para directing. Acetophenone is meta directing: N 3 2 S 4 N 2 + Al 3 When the electrophile attacks, it avoids the partial positive charges on the ortho and para positions:
Aromatic compounds with an alkyl chain are considered inductively donating and will direct substitution to the ortho or para positions. Alkyl groups are inductively (weak) ortho-para directing. R Br AlBr 3 Al 4 This cation is stabilized by resonance as well as the donation of electrons from the t-bu group via induction effects (shown by the red arrow) The reaction occurs at the para position instead of the ortho position due to sterics. S 3 2 S 4 S Sterics again explains the predominance of the para product.
Notice how the order that reactions are done affect the following two examples: N 3 Al 3 2 S 4 2 N N 3 2 S 4 2 N Al 3 2 N The products of the above two reactions are structural (or constitutional) isomers. Aromatic compounds that have an electron-withdrawing group attached but that do not fall into the above categories (eg. C 3 ) are inductively withdrawing and direct substitution to the meta position. N 3 N 2 If ortho: 2 S 4 N 2 disfavored (not observed) N 2 N 2 -C 3 is electron-withdrawing and does not want to withdraw electrons from a carbon that is already positively-charged.
Multiple Substitution If there is more than one group on an aromatic ring, electrophilic aromatic substitution is controlled by the strongest donating group. This is governed by the same resonance and inductive effects discussed before but it is necessary to consider the effects of the two groups. An example is the di-alkylation of methoxybenzene with methyl iodide by a riedel-crafts alkylation. Since the methoxy group is an electron-donating group (resonance donator), it will direct the first alkylation to the ortho and para positions. The second alkylation is also directed to the ortho and para positions relative to the methoxy group because it is a stronger director (resonance donator) than the methyl group (inductive donator). The second alkylation will go ortho to the methoxy rather than ortho to the methyl. As demonstrated, the strongest donating group always determines the site of substitution. C 3 I C 3 I Al 3 Al 3 Similarly, nitration occurs at the ortho position for the following example: C 3 C 3 N 3 N 2 2 S 4 C 3 C 3 An interesting example is the chlorination of chlorobenzene. In this case, the inductive effects of the chlorine could suggest the substitution should go meta, but chlorine also displays a resonance effect which directs substitution to the ortho and para positions. In general, a resonance effect always is a stronger director than an inductive effect. 2 e 3 chlorobenzene p-dichlorobenzene o-dichlorobenzene
In this case, the nitro group is an electron-withdrawing group, so the methyl group is the strongest donating group and takes precedent over where the acetyl group will go. Note that the position that is ortho to both the methyl and nitro groups (between meta substituents) is too sterically hindered for the acetyl to form a bond with that carbon. C 3 C 3 C 3 3 C N 2 N 2 N 2 B 3 In this last example, the position between the two meta substituents is too sterically hindered. Therefore, substitution in that position is not observed. ollow-up question: ow do you synthesize the starting material in the above reaction? Answer: N 3 C 3 C 3 2 S 4 N 2 Al 3 N2 If alkylation was done first, followed by nitration, the meta-substituted aromatic compound could not be obtained, since the methyl group is an ortho/para-directing group. ow to determine position and reactivity: 6 & 5 membered rings are favoured S 2 thionyl chloride + (this reaction will be covered later in the course) phthalic anhydride Al 3 anthraquinone
After the first two reactions, the substituent (a ketone) would normally direct the second acylation to the meta position as a resonance withdrawer. This does not occur, as this would produce a very strained structure. In this example, the second acylation goes to the ortho position to relieve the strain to produce anthraquinone. 6-rings are also favoured Synthesis the sequence of steps is critical ow to make versalide, shown below, from benzene? The answer is below. Be able to rationalize this sequence B 3 B 3 B 3 REACTINS SIDE CAINS: 1) Alkyl Side Chain xidation 2) emmensen Reduction 3) Nitro Reduction Amino Diazotization Diazo Replacement + Coupling
Alkyl Side Chain xidation Reaction If the carbon directly attached to the aromatic ring has > 1 hydrogen attached to it, it can be oxidized to the corresponding carboxylic acid with hot aqueous potassium permanganate (KMn 4 ) as shown below. Carbon dioxide (C 2 ) is one of the side products C R' R KMn 4 2, KMn 4 propyl benzene KMn 4 KMn 4 + C 2 no rxn (no adjacent 's to the aromatic ring) More examples for alkyl side chain oxidation: KMn 4 KMn 4 KMn 4 C 2 tetralin C 2 (phthalic acid)