Phenols

A phenol is a compound with an OH bonded directly to a carbon of a benzene ring. The simplest one, C₆H₅OH, is itself called phenol. Its OH looks like an alcohol’s, yet phenol’s pKa is 10 while ethanol’s is 16, a millionfold difference in acidity. Everything else in this section follows from one cause: the oxygen sits on a ring carbon, so one of its lone pairs is conjugated with the ring’s π system.

The OH has to be on the ring itself. In benzyl alcohol, the OH sits on a CH₂ one carbon out from the ring, at the benzylic position (Benzylic reactivity). Benzyl alcohol behaves like an ordinary alcohol: its pKa is about 15, it oxidizes to an aldehyde, and in acid it ionizes easily to a benzylic cation. None of that is true of a phenol.

The acidity, and where it comes from

To compare two acids, compare their conjugate bases. When ethanol loses its O–H proton, the ethoxide ion keeps the whole negative charge on one oxygen. When phenol loses its proton, the anion left behind is called phenoxide. Its oxygen is conjugated with the ring, so the charge spreads into the ring, onto the two ortho carbons and the para carbon. Factors affecting acidity drew these contributors; the figure below adds the curved arrows that turn each one into the next.

Spreading a charge over more atoms stabilizes it. A more stable conjugate base means a stronger acid, so phenol is far more acidic than ethanol. The difference in acidity does not come from the O–H bond. It comes from how stable the anion is once the proton has gone.

That gap sets up a standard separation. NaOH deprotonates a phenol, but NaHCO₃ does not; a carboxylic acid is deprotonated by both. Carboxylic acids used bicarbonate to pull an acid away from a phenol. The worked example below adds a third compound and a second base.

Substituents move it, and predictably

Start with two isomers. 4-Nitrophenol has a pKa of 7.2, and 3-nitrophenol has a pKa of 8.4. Both carry the same nitro group on the same ring, yet the para isomer is more than ten times as acidic.

Anything that stabilizes the phenoxide makes the phenol more acidic, so electron-withdrawing groups increase acidity and electron-donating groups decrease it. For a group that withdraws by resonance, such as nitro, the effect is much larger from the ortho and para positions, because only there can it reach the charge.

Here is why position matters for nitro. At para, it sits on a carbon that carries the charge in one of the phenoxide contributors, so the charge can move on into the nitro group and onto its oxygens. At meta, it sits on a carbon that never carries the charge. It can only pull electron density through the σ bonds, by induction, and induction is the smaller effect.

Picric acid, the last row, carries three nitro groups at the two ortho positions and the para position. All three can take the charge by resonance, and together they turn an OH on a ring into an acid with pKa 0.4.

An ortho nitro group withdraws by resonance just as a para one does, and 2-nitrophenol’s pKa, 7.2, is close to that of 4-nitrophenol. Ortho brings one more effect, though. The OH hydrogen can form a hydrogen bond to a nitro oxygen inside the same molecule, closing a six-membered ring.

That internal hydrogen bond changes the physical properties. 4-Nitrophenol hydrogen-bonds to water and to its neighbors. In 2-nitrophenol the OH is already taken, so the molecules hold each other and water more weakly. As a result, 2-nitrophenol is much less soluble in water, and it distills over when boiled with water, a technique called steam distillation. So a group’s position changes physical properties as well as acidity.

The ring is strongly activated

The oxygen lone pair that spreads the phenoxide’s charge into the ring also donates into the ring of phenol itself, with no base present. Ortho/meta/para directing effects showed what that donation does: it makes OH a strong activator and an ortho/para director, among the strongest there are.

In practice, phenols are often too reactive. Benzene needs Br₂ with an FeBr₃ catalyst before it will brominate. Phenol needs no Lewis acid at all: add bromine water and 2,4,6-tribromophenol precipitates at once, with both ortho positions and the para position substituted.

Stopping at one bromine takes deliberately weaker conditions. Bromine in a nonpolar solvent such as CS₂, in the cold, gives mainly 4-bromophenol.

Reactions at the oxygen

Williamson ether synthesis. Sodium phenoxide and iodomethane give methoxybenzene (anisole). In general, a phenoxide and a primary alkyl halide give an aryl alkyl ether by S_N2, the Williamson synthesis of Ether chemistry. Because phenol’s pKa is only 10, aqueous NaOH is base enough to make the phenoxide.

The phenoxide must be the nucleophile. The reverse pairing, an alkoxide with an aryl halide, fails; SNAr and benzyne showed why a ring carbon does not undergo S_N2.

Esterification. Phenols react with an acyl chloride or an acid anhydride, usually with a base such as pyridine, giving aryl esters. Aspirin is one: acetic anhydride acetylates the phenol OH of salicylic acid, as Acid chlorides & anhydrides showed.

Reactions at the ring carbons

The phenoxide contributors put real negative charge on the ortho and para carbons, so those carbons are nucleophilic. Two classic reactions use this to attach a new carbon at an ortho position.

Kolbe–Schmitt carboxylation. Heat sodium phenoxide with CO₂ at about 125 °C under pressure, then add acid. The product is salicylic acid, 2-hydroxybenzoic acid. The new C–C bond joins an ortho ring carbon to the CO₂ carbon.

Ortho wins because of the sodium ion. It sits between the phenoxide oxygen and one oxygen of the incoming CO₂, which holds the CO₂ carbon right beside the ortho carbon. With potassium in place of sodium, and a higher temperature, the para acid, 4-hydroxybenzoic acid, becomes the main product.

Reimer–Tiemann formylation. Phenol with chloroform, CHCl₃, and aqueous NaOH gives mainly salicylaldehyde, 2-hydroxybenzaldehyde. The electrophile is dichlorocarbene, :CCl₂, the carbene from Carbenes & cyclopropanation. A carbene is a neutral carbon with only two bonds and two nonbonding electrons; in dichlorocarbene those two electrons form a lone pair. The carbon has six valence electrons instead of eight, so it is electron-poor and acts as an electrophile.

Hydroxide makes the carbene in two steps. It first removes chloroform’s proton, and the trichloromethyl anion, ⁻CCl₃, then loses a chloride ion.

An ortho carbon of the phenoxide then attacks the carbene carbon. Proton transfers restore the aromatic ring, which now carries a CHCl₂ group at ortho, and the hot aqueous base hydrolyzes that group to CHO.

Oxidation to a quinone

Start with hydroquinone, 1,4-dihydroxybenzene: a benzene ring with two OH groups para to each other. Mild oxidants remove two electrons and two protons from it and give p-benzoquinone, a six-membered ring with two C=O groups para to each other and two C=C bonds. Any ring of this kind, a cyclohexadienedione, is called a quinone.

The reaction also runs backward: mild reducing agents turn the quinone back into hydroquinone. That is why the pair is usually written as an interconversion rather than a one-way oxidation.

Phenol itself oxidizes to p-benzoquinone as well. Sodium dichromate in sulfuric acid does it, and Fremy’s salt (potassium nitrosodisulfonate) does it more cleanly. Hydroquinone, though, oxidizes far more easily than phenol.

The quinone ring is no longer aromatic. Each C=O is conjugated with the C=C bonds on either side of it, but the two C=C bonds are joined only through the carbonyl carbons. A conjugated system that branches like this is called cross-conjugated.

In this conjugated system the HOMO–LUMO gap is small enough that the molecule absorbs some visible light. (That gap sets the wavelength absorbed, as in UV-Vis spectroscopy.) That is why p-benzoquinone is yellow, while colorless hydroquinone, with its aromatic ring, absorbs only in the UV.

Quinones also carry electrons in living cells. Ubiquinone uses the same reversible two-electron, two-proton exchange in the respiratory chain, the series of reactions in mitochondria that passes electrons from food molecules to oxygen.

What a phenol’s C–O bond will not do

A phenol’s oxygen is bonded to an sp² ring carbon, and SNAr and benzyne showed why neither S_N2 nor S_N1 works at such a carbon. The side opposite the leaving group is inside the ring, and S_N1 would need an aryl cation, which is too unstable to form when only water or a halide is leaving. So nothing displaces a phenol’s OH by S_N1 or S_N2, and hydroxide does not displace chloride from chlorobenzene under normal conditions.

A phenol does not dehydrate either. Losing the OH would need the same aryl cation that blocks S_N1, and the ring already holds its carbons in C=C bonds. Nor does a phenol oxidize the way an alcohol does, because the carbon holding the OH carries no hydrogen to lose; its oxidation goes to a quinone instead, as the previous part showed.

What carries forward

One structural change, an OH on a ring instead of on a chain, has three consequences. The pKa drops from 16 to 10, because the phenoxide is delocalized. The ring is strongly activated, because the same lone pair donates into it. And the C–O bond will not undergo S_N1 or S_N2. Keep the bicarbonate test too: it pulls a carboxylic acid away from a phenol.