19.6 Aldehydes, Ketones, Carboxylic Acids, Acid Derivatives & Amino Acids

Aldehydes, Ketones, Carboxylic Acids, Acid Derivatives & Amino Acids

The carbonyl group, $\text{C}=\text{O}$, is the reactive centre of aldehydes ($\text{RCHO}$), ketones ($\text{RCOR}'$) and carboxylic acids ($\text{RCOOH}$). Section 19.4 explained why the carbonyl carbon is attacked by nucleophiles and covered the classic identification tests and the aldol and Cannizzaro reactions. This section adds the preparation methods, the remaining addition reactions, the chemistry of carboxylic acids and their derivatives, and amino acids.

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1. Preparation of Aldehydes and Ketones

Methanal (formaldehyde) is sold as formalin, a 40% aqueous solution used to preserve biological specimens.

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2. Nucleophilic Addition Reactions

In each reaction a nucleophile attacks the electrophilic carbonyl carbon. Aldehydes react faster than ketones for steric and electronic reasons (Section 19.4).

Addition of Hydrogen Cyanide

$\text{CH}_3\text{CHO} + \text{HCN} \xrightarrow{\text{base}} \text{CH}_3\text{CH(OH)CN} \quad (\text{2-hydroxypropanenitrile, a cyanohydrin})$

The reaction is base-catalysed because the real nucleophile is $\text{CN}^-$, which attacks the carbonyl carbon; the alkoxide formed then takes a proton from HCN. The new chiral carbon means the product from ethanal is a racemic mixture. Hydrolysis of the cyanohydrin gives a 2-hydroxy acid (lactic acid from ethanal), so this reaction adds one carbon to the chain.

Addition of Sodium Bisulphite

Aldehydes and methyl ketones add saturated $\text{NaHSO}_3$ to form crystalline bisulphite adducts, which regenerate the carbonyl compound with dilute acid or alkali. The reaction is used to separate and purify these compounds.

Reduction

Addition–Elimination with 2,4-Dinitrophenylhydrazine (2,4-DNPH)

The $-\text{NH}_2$ group of 2,4-DNPH adds to the carbonyl group and a molecule of water is then eliminated (a condensation), giving a yellow, orange or red crystalline 2,4-dinitrophenylhydrazone. All aldehydes and ketones give this precipitate, so it identifies the carbonyl group; the sharp melting point of the derivative identifies the particular compound. Tollens' or Fehling's reagent then tells an aldehyde from a ketone.

Oxidation

Aldehydes are oxidized easily (by Tollens', Fehling's or acidified dichromate) to carboxylic acids. Ketones resist mild oxidizing agents; strong oxidizing agents break their carbon chain.

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3. Carboxylic Acids: Preparation

1. Oxidation of primary alcohols or aldehydes with acidified $\text{K}_2\text{Cr}_2\text{O}_7$ or $\text{KMnO}_4$ (heated under reflux so the aldehyde is not lost): $\text{CH}_3\text{CH}_2\text{OH} \xrightarrow{2[\text{O}]} \text{CH}_3\text{COOH} + \text{H}_2\text{O}$.
2. Hydrolysis of nitriles with acid: $\text{CH}_3\text{CN} + 2\text{H}_2\text{O} + \text{H}^+ \rightarrow \text{CH}_3\text{COOH} + \text{NH}_4^+$. Since a nitrile can be made from an alkyl halide and KCN, this route also adds one carbon.
3. Carbonation of Grignard reagents: $\text{RMgX} + \text{CO}_2$, then acid, gives $\text{RCOOH}$ (Section 19.4).
4. Side-chain oxidation of alkylbenzenes with hot alkaline $\text{KMnO}_4$ gives benzoic acid (Section 19.3).

Vinegar is a dilute (about 4–8%) solution of acetic acid made by bacterial oxidation of ethanol.

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4. Reactions of Carboxylic Acids

Acid Strength

A carboxylic acid is stronger than phenol and much stronger than an alcohol because its anion is stabilized by resonance over two equivalent oxygen atoms. Substituents change the strength further:

• Electron-withdrawing groups (Cl, $\text{NO}_2$, CN) near the COOH group stabilize the anion and increase acidity: $\text{CCl}_3\text{COOH} > \text{CHCl}_2\text{COOH} > \text{CH}_2\text{ClCOOH} > \text{CH}_3\text{COOH}$
• The closer the substituent, the bigger the effect: 2-chlorobutanoic acid is stronger than 3-chlorobutanoic acid.
• Electron-donating alkyl groups decrease acidity: $\text{HCOOH} > \text{CH}_3\text{COOH} > \text{CH}_3\text{CH}_2\text{COOH}$. Formic acid ($pK_a \approx 3.75$) is about ten times stronger than acetic acid ($pK_a \approx 4.76$).

Reactivity of Acid Derivatives

Towards nucleophiles such as water:

$\text{acid chloride} > \text{acid anhydride} > \text{ester} > \text{amide}$

Acid chlorides fume in moist air and hydrolyse rapidly; amides need prolonged heating with acid or alkali. The order reflects how good a leaving group is attached to the carbonyl carbon ($\text{Cl}^-$ is the best).

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5. Amino Acids

An $\alpha$-amino acid has an amino group and a carboxyl group on the same carbon:

$\text{H}_2\text{N}-\text{CH(R)}-\text{COOH}$

About 20 different amino acids are used to build proteins.

The Peptide Bond

The carboxyl group of one amino acid condenses with the amino group of another, eliminating water and forming an amide (peptide) linkage:

$\text{H}_2\text{N}-\text{CH}_2-\text{COOH} + \text{H}_2\text{N}-\text{CH(CH}_3)-\text{COOH} \rightarrow \text{H}_2\text{N}-\text{CH}_2-\text{CO}-\text{NH}-\text{CH(CH}_3)-\text{COOH} + \text{H}_2\text{O}$

Two amino acids give a dipeptide, many give a polypeptide, and proteins are large polypeptides (Section 20.1). Two different amino acids can form two different dipeptides, depending on which one supplies the carboxyl group.