Ethers: preparation, physical properties and chemical reactions

Dehydration of alcohols, and its mechanism

1. 1★
   2CH₃CH₂OH → CH₃CH₂OCH₂CH₃ + H₂O

   Conc H₂SO₄ at 413 K. Works only for 1° alcohols with unhindered alkyl groups; gives simple ethers
2. 2
   Step 1, protonation: CH₃CH₂OH + H⁺ → CH₃CH₂O⁺H₂
3. 3
   Step 2, SN2 attack: CH₃CH₂OH + CH₃CH₂O⁺H₂ → CH₃CH₂-O⁺(H)-CH₂CH₃ + H₂O

   A second alcohol molecule attacks the protonated alcohol; water leaves
4. 4
   Step 3, deprotonation: CH₃CH₂-O⁺(H)-CH₂CH₃ → CH₃CH₂OCH₂CH₃ + H⁺
5. 5
   2° and 3° alcohols give alkenes instead, because elimination wins over substitution.

★ key step

Williamson synthesis

An alkyl halide reacts with a sodium alkoxide.

1. 1★
   (CH₃)₃C-O⁻Na⁺ + CH₃Br → (CH₃)₃C-O-CH₃ + NaBr

   The alkoxide ion attacks a primary alkyl halide by SN2. Gives symmetrical or unsymmetrical ethers
2. 2
   C₆H₅OH + NaOH → C₆H₅ONa + H₂O; then C₆H₅ONa + CH₃CH₂Br → C₆H₅OCH₂CH₃ + NaBr

   For aryl alkyl ethers, use the phenoxide and an alkyl halide (never an aryl halide)
3. 3★
   (CH₃)₃C-Br + CH₃O⁻Na⁺ → (CH₃)₂C=CH₂ + CH₃OH + NaBr

   Limitation: with a 3° halide, the alkoxide acts as a strong base, and elimination gives only the alkene

★ key step

Physical properties: ethers vs alcohols

Cleavage of the C-O bond by hydrogen halides

1. 1
   R-O-R' + HX → R-X + R'-OH; with excess HX, R'-OH also → R'-X

   Drastic conditions: conc HI or HBr, high temperature. Reactivity HI > HBr > HCl
2. 2
   Step 1, protonation: CH₃-O-CH₂CH₃ + HI ⇌ CH₃-O⁺(H)-CH₂CH₃ + I⁻
3. 3★
   Step 2: I⁻ attacks the less substituted carbon (CH₃) by SN2: I⁻ + CH₃-O⁺(H)-CH₂CH₃ → CH₃I + CH₃CH₂OH

   With 1° and 2° groups, the smaller alkyl group becomes the alkyl iodide
4. 4
   (CH₃)₃C-O-CH₃ + HI → (CH₃)₃C-I + CH₃OH

   When one group is tertiary, the stable 3° carbocation forms (SN1), so the 3° halide is formed
5. 5★
   C₆H₅-O-CH₃ + HI → C₆H₅OH + CH₃I

   Anisole: the O-C₆H₅ bond has partial double bond character and the sp² carbon cannot undergo substitution, so the O-CH₃ bond breaks. Phenol does not react further

★ key step

Electrophilic substitution in anisole

The -OCH₃ group **activates** the ring and is **ortho-para directing**, just like -OH in phenol.

1. 1
   C₆H₅OCH₃ + Br₂ → 4-bromoanisole (major, about 90%) or 2-bromoanisole (minor), + HBr

   Bromine in ethanoic acid, with no FeBr₃ needed
2. 2
   C₆H₅OCH₃ + CH₃Cl → 2-methoxytoluene (minor) or 4-methoxytoluene (major), + HCl

   Friedel-Crafts alkylation, anhydrous AlCl₃
3. 3
   C₆H₅OCH₃ + CH₃COCl → 2-methoxyacetophenone (minor) or 4-methoxyacetophenone (major), + HCl

   Friedel-Crafts acylation, anhydrous AlCl₃
4. 4★
   C₆H₅OCH₃ + HNO₃ → 2-nitroanisole (minor) or 4-nitroanisole (major), + H₂O

   Conc H₂SO₄ + conc HNO₃

★ key step