Alcohols and ethers

Alcohols contain the functional group –OH. They form a homologous series with general formula \mathrm{C_nH_{2n+1}OH}: methanol CH_3OH, ethanol C_2H_5OH, propanol C_3H_7OH, butanol C_4H_9OH.

Properties and reactions

• Dissolve in water: the small alcohols mix completely, giving neutral solutions.
• Burn in air: \mathrm{C_2H_5OH + 3O_2 \rightarrow 2CO_2 + 3H_2O}. Ethanol is used as a fuel, often mixed with petrol.
• React with sodium, fizzing more gently than water does and releasing hydrogen gas.
• Oxidise to carboxylic acids, using an oxidising agent such as acidified potassium dichromate, or slowly in air by microbes. This is how wine turns into vinegar (ethanoic acid).

Making ethanol

1. Fermentation: yeast converts sugar to ethanol and carbon dioxide at about 30 °C without oxygen: \mathrm{C_6H_{12}O_6 \rightarrow 2C_2H_5OH + 2CO_2}. Renewable but slow, and it gives a dilute solution. 2. Hydration of ethene with steam at about 300 °C and 60–70 atm with a phosphoric acid catalyst. Fast, continuous and pure, but uses crude oil, which is non-renewable.

Uses

Ethanol: drinks, solvents and fuel. Methanol: making other chemicals and as a fuel (it is toxic). Alcohols also react with carboxylic acids to make esters, used in flavourings and perfumes.

Classification and naming

The carbon bearing OH determines the class: primary (attached to one other carbon, e.g. propan-1-ol), secondary (two, propan-2-ol), tertiary (three, 2-methylpropan-2-ol).

Physical properties

O–H bonds are polar, so alcohols form hydrogen bonds to each other and to water. Ethanol (Mr 46) boils at 78 °C, whereas propane (Mr 44) boils at about –42 °C. Solubility in water falls as the non-polar chain grows.

Oxidation with acidified dichromate

The orange \mathrm{Cr_2O_7^{2-}} is reduced to green \mathrm{Cr^{3+}}; write the oxidant as [O].

• Primary → aldehyde → carboxylic acid. Distil the aldehyde off as it forms to stop at the aldehyde; heat under reflux with excess oxidant for the acid. \mathrm{CH_3CH_2OH + [O] \rightarrow CH_3CHO + H_2O}.
• Secondary → ketone only.
• Tertiary: no reaction (no H on the carbon bearing OH), so the solution stays orange.

Distinguish aldehydes from ketones with Tollens' reagent (silver mirror) or Fehling's solution (brick-red Cu_2O): only aldehydes are oxidised.

Dehydration

Heating with concentrated H_3PO_4 or H_2SO_4 (or passing vapour over hot Al_2O_3) eliminates water to give alkenes. Mechanism: protonation of OH, loss of water to form a carbocation, then loss of H^+. Butan-2-ol gives but-1-ene plus E and Z but-2-ene. This offers a route to polymers from bio-ethanol.

Substitution

Alcohols react with HBr (from NaBr + H_2SO_4) or PCl_5 to give halogenoalkanes. With carboxylic acids and an acid catalyst they give esters (reversible).

Ethers

\mathrm{R{-}O{-}R'}, named as alkoxyalkanes (methoxyethane). No O–H, so no hydrogen bonding between molecules: ethers boil far lower than isomeric alcohols, but can accept hydrogen bonds from water. They are unreactive, which makes them good solvents.

Acidity and nucleophilicity

Alcohols are weak acids (pKa 15–18; tBuOH less acidic than MeOH in water because its bulky alkoxide is poorly solvated). Alkoxides, formed with Na or NaH, are strong bases and good nucleophiles; tBuOK is hindered and favours elimination.

Making OH a leaving group

Hydroxide is a poor leaving group, so OH must be activated:

• Protonation in strong acid (HBr, HI): 3° alcohols react by S_\mathrm{N}1, 1° by S_\mathrm{N}2. Carbocation rearrangements occur in S_\mathrm{N}1/E1 cases.
• Sulfonate esters: TsCl or MsCl with pyridine form tosylates/mesylates with retention at carbon; subsequent S_\mathrm{N}2 gives clean inversion.
• SOCl_2 and PBr_3 convert alcohols to chlorides and bromides; PBr_3 on secondary alcohols proceeds with inversion.
• Mitsunobu reaction (PPh_3, DEAD or DIAD, acidic nucleophile) activates OH as an oxyphosphonium and substitutes with inversion, useful for epimerising secondary alcohols.

Oxidation

Reagent choice controls the oxidation level of primary alcohols:

• To aldehydes: PCC in CH_2Cl_2, Swern (DMSO, oxalyl chloride, Et_3N at –78 °C), Dess–Martin periodinane, TEMPO/NaOCl.
• To acids: Jones reagent (CrO_3/H_2SO_4/acetone) or KMnO_4; water hydrates the aldehyde, and the hydrate is oxidised again.

In the Swern, the alcohol attacks an activated sulfonium species; base deprotonates to a sulfur ylide that removes the α-H intramolecularly, giving the carbonyl and dimethyl sulfide.

Dehydration

Acid-catalysed E1 for 2° and 3° alcohols gives the more substituted (Zaitsev) alkene and may rearrange. To avoid rearrangement, convert to a sulfonate and use E2 with a hindered base, or use POCl_3/pyridine.

Ethers

• Williamson synthesis: alkoxide + primary halide or sulfonate by S_\mathrm{N}2. Choose disconnection so the halide is primary: for tBu–O–Me, use tBuO^- + MeI, not MeO^- + tBuBr (which eliminates).
• Acid-catalysed dehydration of primary alcohols (symmetrical ethers only).
• Alkoxymercuration of alkenes for Markovnikov ethers.

Ethers are cleaved by HI or HBr (S_\mathrm{N}2 at the less hindered carbon, or S_\mathrm{N}1 for tertiary) and by BBr_3, used to demethylate aryl methyl ethers. Epoxides are strained three-membered cyclic ethers that open readily: under basic conditions nucleophiles attack the less hindered carbon (S_\mathrm{N}2); under acidic conditions attack occurs at the more substituted carbon, which carries more positive charge. Crown ethers bind alkali metal cations selectively by size (18-crown-6 with K^+), solubilising salts in organic solvents. Silyl ethers (TBS, TIPS) are the standard protecting groups for alcohols, removed with fluoride.