The π electrons of benzene attack the fluorine of F-TEDA-BF₄, and the nonaromatic intermediate loses –H to give the fluorinated product.

Benzene can be protonated by strong acids. The resulting intermediate can lose either deuterium or hydrogen. If –H is lost, deuterated benzene is produced. Attack by deuterium can occur at all positions of the ring and leads to eventual replacement of all hydrogens by deuterium. Only the first step is shown.

In summary:

No rearrangement: (a) CH₃CH₂Cl, (b) CH₃CH₂CH(Cl)CH₃, (e) chlorocyclohexane

Rearrangement: (c) CH₃CH₂CH₂Cl, (d) (CH₃)₃CCH₂Cl

The isobutyl carbocation, initially formed when 1-chloro-2-methylpropane and AlCl₃ react, rearranges via a hydride shift to give the more stable tert–butyl carbocation, which can then alkylate benzene to form tert–butylbenzene.

Most Reactive ———————> Least Reactive

For acetanilide, resonance delocalization of the nitrogen lone pair electrons to the aromatic ring is less favored because the positive charge on nitrogen is next to the positively polarized carbonyl group. Resonance delocalization to the carbonyl oxygen is favored because of the electronegativity of oxygen. Since the nitrogen lone pair electrons are less available to the ring than in aniline, the reactivity of the ring toward electrophilic substitution is decreased, and acetanilide is less reactive than aniline toward electrophilic substitution.

The circled resonance forms are unfavorable, because they place two positive charges adjacent to each other. The intermediate from meta attack is thus favored.

Step 1: Addition of the nucleophile.

Step 2: Elimination of fluoride ion.

The nitro group makes the ring electron-poor and vulnerable to attack by the nucleophilic RO^– group. It also stabilizes the negatively charged Meisenheimer complex.

Treatment of m-bromotoluene with NaOH leads to two possible benzyne intermediates, which react with water to yield three methylphenol products.

Treatment with KMnO₄ oxidizes the methyl group but leaves the tert-butyl group untouched.

Bond dissociation energies measure the amount of energy that must be supplied to cleave a bond into two radical fragments. A radical is thus higher in energy and less stable than the compound from which it came. Since the C–H bond dissociation energy is 421 kJ/mol for ethane and 375 kJ/mol for a methyl group C–H bond of toluene, less energy is required to form a benzyl radical than to form an ethyl radical. A benzyl radical is thus more stable than a primary alkyl radical by 46 kJ/mol. The bond dissociation energy of an allyl C–H bond is 369 kJ/mol, indicating that a benzyl radical is nearly as stable as an allyl radical.

Thus, it isn’t possible to synthesize m-nitrotoluene by any route that we have studied in this chapter.

ICl can be represented as I^δ+ — Cl^δ− because chlorine is a more electronegative element than iodine. Iodine can act as an electrophile in electrophilic aromatic substitution reactions.

This mechanism is the reverse of the sulfonation mechanism illustrated in the text. H⁺ is the electrophile in this reaction.

Phosphoric acid protonates 2-methylpropene, forming a tert-butyl carbocation. This carbocation acts as an electrophile in a Friedel–Crafts reaction to yield tert-butylbenzene.

The N,N,N-trimethylammonium group has no electron-withdrawing resonance effect because it has no vacant p orbitals to overlap with the π orbital system of the aromatic ring. The (CH₃)₃N⁺– group is inductively deactivating, however, because it is positively charged. It is meta-directing because the cationic intermediate resulting from meta attack is somewhat more stable than those resulting from ortho or para attack.

Resonance structures show that bromination occurs in the ortho and para positions of the rings. The positively charged intermediate formed from ortho or para attack can be stabilized by resonance contributions from the second ring of biphenyl, but this stabilization is not possible for meta attack.

The reactive electrophile (protonated H₂O₂) is equivalent to ⁺OH.

Protonation of the double bond at carbon 2 of 1-phenylpropene leads to an intermediate that can be stabilized by resonance involving the benzene ring.

This cation is attacked by a second molecule of 2,4,5-trichlorophenol to produce hexachlorophene.

Step 1: Attack of the nucleophile diethylamine.

Step 2: Loss of proton.

Step 3: Loss of Cl^–.

This reaction is an example of nucleophilic aromatic substitution. Dimethylamine is a nucleophile, and the pyridine nitrogen acts as an electron-withdrawing group that can stabilize the negatively-charged intermediate.

Step 1: Formation of primary carbocation.

Step 2: Rearrangement to a secondary carbocation.

Step 3: Attack of ring π electrons on the carbocation.

Step 4: Loss of H⁺.

This reaction takes place despite the fact that an electron-withdrawing group is attached to the ring. Apparently, the cyclization reaction is strongly favored.

Step 1: S_N2 displacement takes place when the negatively charged oxygen of dimethyl sulfoxide attacks the benzylic carbon of benzyl bromide, displacing Br^–.Step 2: Base removes a benzylic proton, and dimethyl sulfide is eliminated in an E2 reaction.

Only methoxybenzene reacts faster than benzene (See Figure 16.12).

Phenol > Toluene > p-Bromotoluene > Bromobenzene

Aniline and nitrobenzene don’t undergo Friedel–Crafts alkylations.

In 3-phenylpropenenitrile, the –CN group interacts with the ring through the π electrons of the side chain. Resonance forms show that –CN deactivates the ring toward electrophilic substitution, and substitution occurs at the meta position.

The trivalent boron atom in phenylboronic acid has only six outer-shell electrons and is a Lewis acid. It is possible to write resonance forms for phenylboronic acid in which an electron pair from the phenyl ring is delocalized onto boron. In these resonance forms, the ortho and para positions of phenylboronic acid are the most electron-deficient, and substitutions occur primarily at the meta position.

Step 1: Addition of the nucleophile –OCH₃.

Step 2: Elimination of –Cl^–.

The carbonyl oxygens make the chlorine-containing ring electron-poor and open to attack by the nucleophile –OCH₃. They also stabilize the negatively charged Meisenheimer complex.

Step 1: Abstraction of proton and elimination of Br^–.

Step 2: Addition of NH₃ to the benzyne intermediate to form two aniline products. The reaction of an aryl halide with potassium amide proceeds through a benzyne intermediate. Ammonia can then add to either end of the triple bond to produce the two methylanilines observed.

Thus, the intermediate resulting from addition of HBr to the methoxyl-substituted styrene is more stable, and reaction of p-methoxystyrene is faster.

(a) CH₃CH₂COCl, AlCl₃;

(b) H₂, Pd/C;

(c) Br₂, FeBr₃;

(d) NBS, (PhCO₂)₂;

(e) KOH, ethanol

An electron-withdrawing substituent destabilizes a positively charged intermediate (as in electrophilic aromatic substitution) but stabilizes a negatively charged intermediate. For the dissociation of a phenol, an –NO₂ group stabilizes the phenoxide anion by resonance, thus lowering ΔG° and pK_a. In the starred resonance form for p-nitrophenol, the negative charge has been delocalized onto the oxygens of the nitro group.