How Substituents Steer Substitution: Activation and Directing Effects

25 min

Same reaction, different speed, different place

Benzene needs concentrated nitric and sulfuric acids at about 50 °C to be nitrated. Methylbenzene nitrates at about 30 °C. Phenol reacts with dilute nitric acid at room temperature. Nitrobenzene needs fuming nitric acid at about 100 °C to take a second nitro group. And the new group does not go just anywhere: methylbenzene gives 2- and 4-nitromethylbenzene, while nitrobenzene gives 1,3-dinitrobenzene. The group already on the ring controls both the rate and the position of substitution.

Definition

Activating group: a substituent that makes the ring react faster than benzene with electrophiles, by releasing electrons into the ring. Examples: –OH, –NH₂, –CH₃.

Deactivating group: a substituent that makes the ring react more slowly than benzene, by withdrawing electrons from the ring. Examples: –NO₂, –COOH, –CHO.

Directing effect: the tendency of a substituent to send an incoming electrophile to particular positions: 2,4-directing (ortho and para) or 3-directing (meta).

Figure 1.1: Substituents change the electron density round the ring. Electrophiles attack where it is highest.

Why the ring changes

Groups with a lone pair on the atom joined to the ring (–OH, –NH₂, –OCH₃) delocalise that lone pair into the π system. Electron density rises over the whole ring, most of all at carbons 2, 4 and 6 (Figure 1.1). These groups strongly activate and direct to 2 and 4.
Alkyl groups (–CH₃, –C₂H₅) push electrons weakly towards the ring through the σ bond (a positive inductive effect). They activate slightly and direct to 2 and 4.
Groups whose atom next to the ring carries a positive or partial positive charge, usually in a multiple bond (–NO₂, –COOH, –CHO, –COCH₃, –CN, –SO₃H), pull π electrons out of the ring. They deactivate it, most of all at 2, 4 and 6, so the electrophile attacks carbon 3 instead.
Halogens are the exception: they withdraw electrons through the σ bond (deactivating) but donate a lone pair into the ring (2,4-directing).

The same idea can be seen in the intermediate. When an electrophile attacks carbon 2 or 4 of methylbenzene, one arrangement of the arenium ion puts the positive charge on the carbon that carries the $\mathrm{CH_3}$ group, which stabilises it; attack at carbon 3 cannot do this. With $\mathrm{-NO_2}$ , attack at 2 or 4 would put the positive charge next to the already positive nitrogen, which is very unfavourable, so attack at 3 is preferred.

Table 1.1: Directing effects of common substituents

Substituent	Effect on the ring	Directs new group to	Example
–OH, –NH₂	strongly activating	2 and 4 (and 6)	phenol + bromine water → 2,4,6-tribromophenol
–OCH₃	activating	2 and 4	methoxybenzene nitrates easily
–CH₃ and other alkyl groups	weakly activating	2 and 4	methylbenzene → 2- and 4-nitromethylbenzene
–Cl, –Br	weakly deactivating	2 and 4	chlorobenzene → 1-chloro-2- and 1-chloro-4-nitrobenzene
–CHO, –COCH₃	deactivating	3	benzaldehyde → 3-nitrobenzaldehyde
–COOH	deactivating	3	benzoic acid → 3-nitrobenzoic acid
–CN, –SO₃H	deactivating	3	benzenesulfonic acid → 3-nitrobenzenesulfonic acid
–NO₂	strongly deactivating	3	nitrobenzene → 1,3-dinitrobenzene

Figure 1.2: An activating, 2,4-directing group (top) and a deactivating, 3-directing group (bottom).

Worked example

Problem. Predict the main organic product(s) of: (a) bromine with $\mathrm{FeBr_3}$ and nitrobenzene; (b) chlorine with $\mathrm{AlCl_3}$ and methylbenzene, in the dark.

Solution. (a) $\mathrm{-NO_2}$ is 3-directing: the product is 1-bromo-3-nitrobenzene. The reaction is slower than for benzene.

(b) $\mathrm{-CH_3}$ is 2,4-directing: a mixture of 1-chloro-2-methylbenzene and 1-chloro-4-methylbenzene. (In the dark with a catalyst the ring is substituted; the side chain is not touched. Lesson 2 shows what ultraviolet light does instead.)

Worked example

Problem. Starting from methylbenzene, plan the synthesis of (a) 4-nitrobenzoic acid and (b) 3-nitrobenzoic acid. The side chain $\mathrm{-CH_3}$ can be oxidised to $\mathrm{-COOH}$ with hot alkaline potassium manganate(VII) (Lesson 2).

Solution. The order of the two steps decides the position.

(a) Nitrate first: $\mathrm{-CH_3}$ directs to 2 and 4; separate 4-nitromethylbenzene; then oxidise $\mathrm{-CH_3}$ to $\mathrm{-COOH}$ : 4-nitrobenzoic acid.

(b) Oxidise first: methylbenzene → benzoic acid; then nitrate: $\mathrm{-COOH}$ directs to 3, giving 3-nitrobenzoic acid.

Warning

Activating does not mean 2,4 by magic, and deactivating does not mean "no reaction". Always name both effects: "–NO₂ deactivates the ring (slower reaction, harsher conditions) and directs to position 3." Remember that halogens are deactivating but 2,4-directing.

Tip

Look at the atom joined to the ring. Lone pair, or an alkyl group → 2,4-directing. A multiple bond to a more electronegative atom (N=O, C=O, C≡N, S=O) → 3-directing and deactivating.

Professor Dave Explains: Ortho/Meta/Para Directors (16 min). Watch how drawing the intermediate for attack at each position shows which groups direct to 2 and 4 and which to 3. The video uses the older names ortho, meta and para.

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Practice

Define an activating group and a deactivating group, giving two examples of each.
State the position(s) at which nitration occurs for: phenol, benzoic acid, chlorobenzene, benzaldehyde.
Explain why phenol reacts with dilute nitric acid at room temperature, while benzene needs a concentrated acid mixture at about 50 °C.
Name the main product(s) when bromine with $\mathrm{FeBr_3}$ reacts with (a) methylbenzene, (b) benzoic acid.
Explain, using the arenium ion, why the methyl group directs an electrophile to carbons 2 and 4.
Plan a two-step synthesis of 3-bromonitrobenzene (1-bromo-3-nitrobenzene) from benzene. Explain why the order of the steps matters.
Methylbenzene is nitrated at 30 °C, but nitrobenzene needs about 100 °C and fuming nitric acid. Explain the difference.

Show answersHide answers

Activating: releases electrons into the ring, making it react faster than benzene (–OH, –NH₂, –CH₃). Deactivating: withdraws electrons, making it react more slowly (–NO₂, –COOH, –CHO).
Phenol: 2 and 4; benzoic acid: 3; chlorobenzene: 2 and 4; benzaldehyde: 3.
The –OH group donates a lone pair into the ring, greatly increasing its electron density, especially at 2, 4 and 6, so even the small concentration of electrophile in dilute nitric acid reacts.
(a) 1-bromo-2-methylbenzene and 1-bromo-4-methylbenzene; (b) 3-bromobenzoic acid.
For attack at 2 or 4, one arrangement of the positive arenium ion places the positive charge on the ring carbon bonded to $\mathrm{CH_3}$ ; the electron-releasing methyl group stabilises it, lowering the activation energy. Attack at 3 cannot put the charge there.
Nitrate benzene first (conc. $\mathrm{HNO_3}$ + $\mathrm{H_2SO_4}$ , below 55 °C) to give nitrobenzene; then brominate ( $\mathrm{Br_2}$ + $\mathrm{FeBr_3}$ ): $\mathrm{-NO_2}$ directs Br to 3. If bromination came first, –Br would direct the nitro group to 2 and 4, giving the wrong isomers.
$\mathrm{-CH_3}$ releases electrons and activates the ring, so it reacts under mild conditions. $\mathrm{-NO_2}$ strongly withdraws electrons and deactivates the ring, so a higher concentration of $\mathrm{NO_2^+}$ and a higher temperature are needed.

Sources and credits

Written by Ganzaa.
Video: Ortho/Meta/Para Directors, Professor Dave Explains, embedded from YouTube.
The diagrams, table, worked examples and Practice items were written and drawn by Ganzaa.

1Same reaction, different speed, different place

2Why the ring changes

Same reaction, different speed, different place

Why the ring changes