11.3 Alcohols: Reactions & Properties

Nomenclature and Physical Properties

Alcohols are named with the suffix -ol and a locant for the hydroxyl (OH) group's position. They are classified as primary (1°), secondary (2°), or tertiary (3°) based on how many carbon substituents are attached to the carbinol carbon — the carbon bearing the OH.

Acidity

An alcohol's O–H is comparable to, but not identical to, water's acidity: simple alcohols have pKa values around 16–18 (methanol about 15.5, tert-butanol about 18), reflecting how alkyl groups' weak electron donation and added steric bulk around the developing alkoxide slightly destabilize the conjugate base as substitution increases. Electron-withdrawing groups near the OH dramatically increase acidity by stabilizing the alkoxide through induction: 2,2,2-trifluoroethanol (pKa about 12.5) is far more acidic than ethanol (pKa about 16) because the three fluorines pull electron density away from the developing negative charge on oxygen. This is the same inductive logic used throughout the MCAT for carboxylic acid and phenol acidity trends.

Hydrogen Bonding

Because alcohols have both a hydrogen-bond donor (the O–H) and a hydrogen-bond acceptor (the oxygen lone pairs), they hydrogen-bond extensively with each other and with water. This gives alcohols much higher boiling points than alkanes, ethers, or aldehydes/ketones of comparable molecular weight, which can only accept, not donate, hydrogen bonds, and gives small alcohols (methanol through butanol) high water solubility. As the nonpolar hydrocarbon chain lengthens, that solubility drops off as the hydrophobic alkyl chain begins to dominate over the hydrophilic OH.

Oxidation of Alcohols

How far an alcohol oxidizes depends on how many C–H bonds can be removed from the carbinol carbon, and the choice of oxidant controls how far the reaction is allowed to proceed:

Pyridinium chlorochromate (PCC) is an anhydrous, mild oxidant that stops cleanly at the aldehyde stage for primary alcohols because it does not supply the water needed to hydrate the aldehyde into the geminal diol that further oxidation requires. Aqueous chromium(VI) reagents such as Jones reagent do supply that water and carry a primary alcohol all the way to the carboxylic acid. Tertiary alcohols cannot be oxidized by these reagents at all, because oxidation requires removing a C–H bond from the carbinol carbon, and a tertiary carbinol carbon has none — a frequently tested fact whenever a passage describes an "unreactive" alcohol under chromium(VI) conditions.

Substitution Reactions: SN1 vs. SN2

Hydroxide is a poor leaving group, so alcohols do not undergo substitution directly at neutral pH. Under acidic conditions, however, protonation converts OH into water, an excellent leaving group, and the alcohol becomes susceptible to the same SN1/SN2 logic as an alkyl halide:

• Tertiary alcohols react through SN1: acid protonates the OH, water leaves to generate a stabilized tertiary carbocation, and a nucleophile, often the solvent itself, adds to either face — with possible rearrangement (hydride or alkyl shift) if a more stable carbocation is accessible, and racemization at the reacting carbon.
• Primary alcohols react through SN2, since a primary carbocation is too unstable to form: a good nucleophile attacks the backside of the protonated alcohol's carbon in a single concerted step, inverting configuration there as the leaving water departs from the front.
• Secondary alcohols can go either way, depending on the nucleophile's strength, the solvent, and the specific reagent used.

Protection of Alcohols

When a synthesis calls for a strong nucleophile, base, or reducing agent to react selectively at one site in a molecule that also contains a free OH elsewhere, that OH must first be "protected" — converted to a group that is unreactive under the planned conditions, then converted back afterward. A common strategy converts the alcohol to a silyl ether, for example using tert-butyldimethylsilyl chloride (TBSCl), or masks it as a cyclic acetal, for example forming a tetrahydropyranyl (THP) ether with dihydropyran. The protecting group is removed later, typically with mild aqueous acid or fluoride, to reveal the original alcohol once the sensitive step is complete. Protection is a strategic timing tool, not a permanent structural change.

Preparation of Mesylates and Tosylates

The direct fix for an alcohol's poor leaving-group ability is to convert the OH into a better one without ever breaking the C–O bond to the carbinol carbon. Treating an alcohol with methanesulfonyl chloride (MsCl) or p-toluenesulfonyl chloride (TsCl), in the presence of a mild base such as pyridine or triethylamine to mop up the HCl byproduct, replaces the alcohol's hydrogen with a sulfonate group, giving a mesylate (OMs) or tosylate (OTs). Because this substitution happens at the oxygen, not the carbinol carbon, the stereochemistry at that carbon is completely retained — no bond to the stereocenter is broken. The resulting sulfonate ester is an excellent leaving group, comparable to or better than a halide, setting up a subsequent, cleanly stereospecific SN2 reaction. This two-step sequence — alcohol to tosylate with retention, then SN2 displacement by a nucleophile with inversion — is the standard MCAT route for deliberately inverting configuration at a stereocenter that bears a hydroxyl group.

Preparation of Alcohols

Three high-yield routes to alcohols appear repeatedly in MCAT passages. Hydride reduction of carbonyls (NaBH4 for aldehydes and ketones; LiAlH4 for aldehydes, ketones, esters, and carboxylic acids) was covered with carbonyl chemistry and remains the cleanest laboratory path to primary and secondary alcohols. Grignard addition builds a new C–C bond: an organomagnesium halide (RMgX) attacks a carbonyl carbon, and aqueous workup protonates the resulting alkoxide. Formaldehyde gives a primary alcohol with one extra carbon from the Grignard reagent; other aldehydes give secondary alcohols; ketones give tertiary alcohols — so the product's substitution class immediately reports which carbonyl was the electrophile. Alkene hydration (acid-catalyzed or oxymercuration–demercuration for Markovnikov addition; hydroboration–oxidation for anti-Markovnikov) converts C=C bonds into alcohols regioselectively and is the bridge between alkene and alcohol functional-group interconversions.

Dehydration of Alcohols and Conversion to Alkyl Halides

Under strong acid and heat, alcohols undergo E1 or E2 dehydration to alkenes, losing water. Tertiary alcohols dehydrate most readily (stable carbocation, E1), primary alcohols require harsher conditions and often go E2, and the alkene product follows Zaitsev's rule (more substituted alkene preferred) unless a bulky base or special reagent steers otherwise. This is the reverse of acid-catalyzed hydration and is a classic way to remove the OH functional group entirely.

Alcohols can also be converted to alkyl halides without first making a sulfonate. PBr3 converts primary and secondary alcohols to alkyl bromides with inversion at the carbinol carbon (the mechanism is SN2 after the alcohol's oxygen attacks phosphorus, making a good leaving group). SOCl2 (often with pyridine) similarly converts primary and secondary alcohols to alkyl chlorides, typically with inversion under standard SN2 conditions. Tertiary alcohols usually form alkyl halides through SN1 pathways (HBr, HCl) via carbocations, with possible rearrangement. These reagents appear on the MCAT as the practical alternative to MsCl/TsCl when the goal is a halide rather than a sulfonate leaving group.

The Lucas Test (Qualitative Classification)

The Lucas test distinguishes alcohol substitution classes by reaction rate with ZnCl2 in concentrated HCl. Tertiary alcohols form cloudy alkyl chlorides almost immediately (fast SN1), secondary alcohols react within minutes, and primary alcohols are essentially unreactive at room temperature. The cloudiness is the insoluble alkyl chloride separating from the aqueous reagent — a qualitative observation, not a preparative method, but a frequent discrete-item hook.

Common MCAT Traps for Alcohols

• Tertiary alcohols do not oxidize with PCC or Jones reagent — no carbinol C–H to remove.
• PCC stops primary alcohols at the aldehyde; aqueous Cr(VI) continues to the carboxylic acid.
• Free OH is a terrible leaving group; protonation, conversion to a halide (PBr3/SOCl2), or mesylate/tosylate activation is required before substitution.
• Tosylation retains configuration at carbon; the subsequent SN2 inverts it — net inversion overall for the two-step sequence.
• Grignard reagents are destroyed by acidic protons (water, alcohols, carboxylic acids); the carbonyl electrophile must be dry and free of protic groups, or those groups must be protected first.