Chapters 7 & 8: Alcohols, Phenols, Ethers - Synthesis & Reactions

Alcohols, Phenols, Ethers, and Thiols

• Alcohols: Contain an $OH$ group connected to a saturated carbon (sp3). They are important solvents and synthesis intermediates.
  • Methanol ($CH3OH$), or methyl alcohol, is a common solvent and fuel additive produced in large quantities.
  • Ethanol ($CH3CH2OH$), or ethyl alcohol, is a solvent, fuel, and beverage.
• Phenols: Contain an $OH$ group connected to a carbon in a benzene ring.
  • Phenol ($C6H5OH$), or phenyl alcohol, has diverse uses and gives its name to the general class of compounds.

Phenols

• Phenols are ingredients found in cloves, vanilla, nutmeg, and mint.
• Examples include: Vanillin, Eugenol, Thymol, Isoeugenol.

Ethers and Thiols

• Ethers: Have two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom ($R–O–R'$).
  • Diethyl ether is used industrially as a solvent.
  • Tetrahydrofuran (THF) is a cyclic ether used as a solvent.
• Thiols ($R–S–H$) and sulfides ($R–S–R'$) are sulfur analogs of alcohols and ethers.

Thiols

• Methanethiol is found in oysters and cheese.
• Ethanethiol.
• 2-Propanethiol.
• 2-Propene-1-thiol is found in garlic.
• 1-Propanethiol is found in onions.

Classification of Alcohols

• Classification depends on the number of organic groups ($R$) bonded to the hydroxyl-bearing carbon.
  • Primary (1°) alcohol: The $–OH$ group is on a carbon atom bonded to one $R$ group.
  • Secondary (2°) alcohol: The $–OH$ group is on a carbon atom bonded to two $R$ groups.
  • Tertiary (3°) alcohol: The $–OH$ group is on a carbon atom bonded to three $R$ groups.

Properties

• The structure around the oxygen atom in alcohols, ethers, and phenols is similar to that in water ($sp^3$ hybridized).
• Alcohols and phenols have much higher boiling points than similar alkanes and alkyl halides.
• The oxygen atom gives ethers a slight dipole moment.
• Alcohols and phenols have higher boiling points than expected due to hydrogen bonding.
• Thiols do not typically form hydrogen bonds because sulfur is not sufficiently electronegative.

Relative Acidity of Alcohols and Phenols

• Acidity constants ($pK_a$) vary for different alcohols and phenols.
• Examples (with $pK_a$ values):
  • $(CH<em>3)</em>3COH$: 18.00 (Weaker acid)
  • $CH<em>2CH</em>2OH$: 16.00
  • $HOH$ (water): 15.74
  • $CH_3OH$: 15.54
  • $CF<em>3CH</em>2OH$: 12.43
  • p-Aminophenol: 10.46
  • p-Methoxyphenol: 10.21
  • p-Methylphenol: 10.17
  • Phenol: 9.89
  • p-Chlorophenol: 9.38
  • p-Bromophenol: 9.35
  • p-Nitrophenol: 7.15
  • 2,4,6-Trinitrophenol: 0.60 (Stronger acid)

Alcohol Acidity: Inductive Effect

• Electron-withdrawing groups make an alcohol a stronger acid by stabilizing the conjugate base (alkoxide).
• Example: $CF<em>3$ groups stabilize alkoxide and lower the $pK</em>a$.

Generating Alkoxides from Alcohols

• Alcohols are weak acids, requiring a strong base to form an alkoxide (e.g., $NaH$, $NaNH_2$, Grignard reagents ($RMgX$)).
• Alkoxides are bases used as reagents in organic chemistry.

Phenol Acidity

• Phenols ($pK<em>a ≈ 10$) are much more acidic than alcohols ($pK</em>a ≈ 16$) due to resonance stabilization of the phenoxide ion.
• Phenols react with $NaOH$ solutions (but alcohols do not), forming soluble salts.
• Electron-withdrawing substituents make a phenol more acidic by delocalizing the negative charge.
• Electron-donating substituents make a phenol less acidic because they concentrate the charge.

Synthesis/Reactions of Alcohols

• Alcohols can be synthesized from alkenes, carboxylic acids, ketones, esters, alkyl halides, aldehydes, and ethers.

Preparation of Alcohols: Hydration of Alkenes

• Hydration of alkenes produces alcohols using an acid catalyst (e.g., $H<em>3PO</em>4$).
• Epoxidation of alkenes followed by treatment with $H_3O^+$ yields 1,2-diols.

Preparation of Alcohols: Reduction of Carbonyl

• Reduction of a carbonyl compound generally gives an alcohol.
• Organic reduction reactions add the equivalent of $H_2$ to a molecule.

Mechanism of Reduction

• The reagent adds the equivalent of hydride to the carbon of $C=O$ and polarizes the group.

Reduction of Aldehydes and Ketones

• Aldehydes give primary alcohols upon reduction.
• Ketones give secondary alcohols upon reduction.

Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents

• Grignard formation: $R–X + Mg → R–MgX$ (Grignard reagent)

Mechanism of Grignard Reagents

• Grignard reagents react with carbonyl compounds to form alkoxide ions, which are then protonated to form alcohols ($RMgX$).

Preparation from Alkyl Halides

• Alkyl halides react with hydroxide ions to form alcohols.
  • $CH<em>3-Br + HO^- → HO-CH</em>3 + Br^-$

Reactions of Alcohols

• Two general classes of reactions:
  • At the carbon of the $C–O$ bond.
  • At the proton of the $O–H$ bond.

Dehydration of Alcohols to Yield Alkenes

• The general reaction forms an alkene from an alcohol through the loss of $O–H$ and $H$ from the neighboring $C–H$ to give a $\pi$ bond.
• Specific reagents are needed.

Acid-Catalyzed Dehydration

• Tertiary alcohols are readily dehydrated with acid.
• Secondary alcohols require more severe conditions (75% $H<em>2SO</em>4$, 100°C).
• Primary alcohols require very harsh conditions, which is often impractical.
• In the elimination, the more highly substituted alkene product predominates (Zaitsev’s Rule).

Conversion of Alcohols into Alkyl Halides

• 3° alcohols are converted by $HCl$ or $HBr$ at low temperature.
• 1° and 2° alcohols are resistant to acid; use $SOCl<em>2$ or $PBr</em>3$.

Oxidation of Alcohols

• Can be accomplished by inorganic reagents such as $KMnO<em>4$, $CrO</em>3$, and $Na<em>2Cr</em>2O_7$, or by more selective reagents.

Oxidation of Primary Alcohols

• To aldehyde: pyridinium chlorochromate (PCC, $C<em>5H</em>6NCrO_3Cl$) in dichloromethane.
• Other reagents produce carboxylic acids.

Oxidation of Secondary Alcohols

• Effective with inexpensive reagents such as $Na<em>2Cr</em>2O_7$ in acetic acid.
• PCC is used for sensitive alcohols at lower temperatures.

The Williamson Ether Synthesis

• Reaction of metal alkoxides and primary alkyl halides and tosylates.
• Alkoxides are prepared by the reaction of an alcohol with a strong base such as sodium hydride, $NaH$.

Acidic Cleavage of Ethers

• Ethers are generally unreactive.
• Strong acid will cleave an ether at elevated temperature.