Alcohols and carboxylic acids

Alcohols

Alcohols contain a hydroxyl group ($–OH$) that fundamentally alters their chemical and physical properties compared to hydrocarbons. They often function as versatile intermediates in synthesis, serving as starting points for oxidation or substitution reactions.

Nomenclature

Commonly named with the suffix “-ol” (e.g., methanol, ethanol). In more complex molecules, “hydroxy” may be used as a prefix to denote the $–OH$ substituent. Numbering the longest carbon chain ensures the lowest possible number for the hydroxyl group.

Physical properties

Alcohols form hydrogen bonds, resulting in significantly higher boiling points than analogous hydrocarbons. They readily dissolve in water as long as the carbon chain remains relatively short. In IR spectroscopy, their $O–H$ stretch appears as a broad peak near 3300 $c{m}^{-1}$.

Important reactions

1. Substitution reactions: SN1 or SN2

• $R\text{-OH}+HX\leftrightarrow R\text{-X}+H_{2}O$
  • SN1 occurs via carbocation intermediates, favored by tertiary centers and protic solvents.
  • SN2 is a one-step mechanism typical of primary centers under aprotic, polar conditions.
  • Both require a good leaving group, so sometimes the $–OH$ is converted into a sulfonate ester or halide first.

2. Oxidation

   • Primary alcohols fully oxidize to carboxylic acids under strong oxidizers ($KMn{O}_4,Cr{O}_3$) or to aldehydes using milder reagents like PCC.
   • Secondary alcohols oxidize to ketones.
   • Tertiary alcohols generally do not oxidize due to lack of α-hydrogens.
   • Pinacol rearrangement can occur in polyhydroxyalcohols under acidic conditions, rearranging the skeleton.

3. Protection of alcohols

   • Trimethylsilyl (TMS) groups protect the $–OH$ from undesirable reactions.
   • To protect: $R–OH+Cl–SiM{e}_3$ → $R–O–SiM{e}_3$.
   • To deprotect: add $F^{-}$.

4. Preparation of mesylates and tosylates

   • Mesylates: React $R–OH$ with mesyl chloride ($MsCl$).
   • Tosylates: React $R–OH$ with tosyl chloride ($TsCl$).
   • Both convert $–OH$ into a better leaving group for substitution or elimination.

Additional transformations include reactions with $SOC{l}_2$ to form alkyl chlorides, $PB{r}_3$ for alkyl bromides, and esterification with carboxylic acids. Inorganic esters appear when the alcohol reacts with non-carbon acid derivatives, such as phosphate groups in DNA/RNA polymerization forming phosphodiester bonds.

Carboxylic acids

Carboxylic acids contain a carboxyl group ($–COOH$) that defines their chemical behavior. They are notable for their acidic nature, evidenced by the ease with which they donate the proton on the $–OH$.
Many naturally occurring substances, such as acetic acid in vinegar, exemplify this class of compounds.

Nomenclature

IUPAC names typically end in “-oic acid,” though “carboxylic acid” or “-dioic acid” may be used for certain structures (e.g., ethanedioic acid for oxalic acid). Common names (like formic or acetic acid) are also widely accepted.

Physical properties and solubility

They exhibit strong hydrogen bonding, resulting in higher boiling points than other compounds of similar molecular weight. Carboxylic acids are generally soluble in water when their alkyl chains are short; solubility diminishes with increasing chain length. In IR spectroscopy, they show a broad $–OH$ stretch near 3100 $c{m}^{-1}$ and a sharp $C=O$ peak around 1700 $c{m}^{-1}$.

Important reactions

They are susceptible to nucleophilic attack at the electrophilic carbonyl carbon, often involving the substitution of the $–OH$ with another nucleophile. Conversion to more reactive derivatives (e.g., acyl halides) frequently precedes further reactions such as halogenation at the $\alpha$ position.

Carboxyl group reactions

• Esterification: Under acidic conditions, a carboxylic acid reacts with an alcohol to form an ester.
• Nucleophilic attack: The carbon of the $C=O$ is electrophilic, so nucleophiles can attach, assisted by the acidic proton facilitating proton transfers.

• Amide formation: Reaction with ammonia or amines can yield amides, especially if an activated acid derivative (e.g., acyl chloride) is used.

• Anhydride formation: Two molecules of a carboxylic acid can link (losing water) to form an anhydride, which is more reactive toward nucleophiles.

• Reduction

  • Using strong reagents like $LiAl{H}_4$, a carboxylic acid is reduced to a primary alcohol. Milder reagents (e.g., $NaB{H}_4$) are generally insufficient to reduce carboxylic acids.

• Decarboxylation

  • $\beta$-Keto acids readily lose $C{O}_2$ upon heating, breaking the bond between the carbonyl group and the carboxylate. This process is facilitated by an internal cyclic transition state.

Reactions at 2 position, substitution

• The $\alpha$ carbon (2 position) can be halogenated when an acid derivative (acyl halide) temporarily enolizes. Electrophiles then attach at this enolized $\alpha$ position, and subsequent hydrolysis reforms the carboxylic acid but with the $\alpha$-substituent now in place.