Chemistry (9620) | Carboxylic acids and derivatives

Welcome to the World of Carboxylic Acids and Derivatives!

Ready to dive into one of the most important families in organic chemistry? Carboxylic acids and their derivatives are everywhere—from the sour tang of vinegar (ethanoic acid) to the fats and oils that make up living things. These compounds are defined by the powerful carbonyl group ($\text{C=O}$) and are incredibly versatile in synthesis.

In these notes, we will break down their structures, understand their key reactions (especially how they make fragrant esters and other useful compounds), and explore the quick, high-yield reactions of acyl compounds. Don't worry if this seems tricky at first; we'll take it step by step!

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3.3.9.1 Carboxylic Acids and Esters

1. Carboxylic Acids ($\text{RCOOH}$)

A carboxylic acid contains the carboxyl functional group ($\text{-COOH}$). This group is a combination of a carbonyl ($\text{C=O}$) and a hydroxyl ($\text{-OH}$) group.

A. Acidity and Key Property

Carboxylic acids are generally weak acids. This means they only partially dissociate (ionise) in aqueous solution:

\( \text{RCOOH} (\text{aq}) \rightleftharpoons \text{RCOO}^- (\text{aq}) + \text{H}^+ (\text{aq}) \)

The resulting carboxylate ion ($\text{RCOO}^-$) is stabilised by delocalisation, which makes the $\text{H}^+$ easier to release compared to an alcohol.

Key Reaction: Carbonate Test

Although they are weak acids, carboxylic acids are strong enough to react with carbonates (like sodium carbonate, $\text{Na}_2\text{CO}_3$) or hydrogencarbonates (like $\text{NaHCO}_3$). This reaction produces carbon dioxide gas ($\text{CO}_2$).

This is a key test to distinguish carboxylic acids from less acidic compounds like alcohols or phenols.

Equation Example (Ethanoic acid):
\( 2\text{CH}_3\text{COOH} + \text{Na}_2\text{CO}_3 \rightarrow 2\text{CH}_3\text{COONa} + \text{H}_2\text{O} + \text{CO}_2 \)

Key Takeaway: Carboxylic acids are weak, but strong enough to fizz when mixed with baking soda!

2. Esters ($\text{RCOOR}'$)

Esters are derivatives of carboxylic acids where the hydrogen atom of the $\text{-COOH}$ group is replaced by an alkyl group ($\text{R}'$). They are often responsible for the sweet, fruity smells in nature.

Did you know? Esters are commonly used as solvents, plasticisers, perfumes, and food flavourings! Think of ethyl ethanoate (nail polish remover smell) or pentyl ethanoate (banana flavour).

A. Formation of Esters (Esterification)

Esters are formed when a carboxylic acid reacts with an alcohol in the presence of a strong acid catalyst (usually concentrated sulfuric acid, $\text{H}_2\text{SO}_4$).

Reaction Type: Condensation (since water is eliminated) and it is reversible.

\( \text{Carboxylic acid} + \text{Alcohol} \rightleftharpoons \text{Ester} + \text{Water} \)

To get a high yield of the ester, you often need to remove the water as it forms or use an excess of one reactant (often the alcohol) to shift the equilibrium to the right (Le Chatelier's principle).

B. Hydrolysis of Esters

Hydrolysis is the breakdown of an ester using water. Since the esterification reaction is reversible, hydrolysis is simply the reverse process.

1. Acid Hydrolysis (Reversible)
An ester is heated with dilute aqueous acid (e.g., $\text{H}_2\text{SO}_4$ or $\text{HCl}$) as a catalyst. This produces the original carboxylic acid and alcohol.

\( \text{Ester} + \text{Water} \rightleftharpoons \text{Carboxylic acid} + \text{Alcohol} \)

2. Alkaline Hydrolysis (Saponification - Irreversible)
An ester is heated with hot aqueous alkali (e.g., $\text{NaOH}$ or $\text{KOH}$). This reaction is irreversible and produces the alcohol and a salt of the carboxylic acid (a carboxylate salt).

Analogy: This is called Saponification because it is the reaction used to make soap! Vegetable oils and animal fats are large esters of propane-1,2,3-triol (glycerol). When these large esters are hydrolysed with alkali, they form soap (the sodium or potassium salt of a long-chain carboxylic acid) and glycerol.

C. Biodiesel Production

Biodiesel is a renewable fuel source, defined as a mixture of methyl esters of long-chain carboxylic acids.

It is produced by reacting vegetable oils (which are complex esters) with methanol ($\text{CH}_3\text{OH}$) in the presence of a catalyst (often an alkali).

\( \text{Vegetable Oil (Triglyceride)} + 3\text{Methanol} \rightarrow \text{Biodiesel (Methyl Esters)} + \text{Glycerol} \)

3.3.9.2 Acylation: Highly Reactive Derivatives

Acylation involves substituting an atom or group into a molecule using an acyl group ($\text{RCO}-$). The most common acylating agents are acyl chlorides and acid anhydrides.

1. Structures of Acylating Agents and Products

• Acyl Chloride: $\text{RCOCl}$ (e.g., Ethanoyl chloride, $\text{CH}_3\text{COCl}$)
• Acid Anhydride: $(\text{RCO})_2\text{O}$ (e.g., Ethanoic anhydride, $(\text{CH}_3\text{CO})_2\text{O}$)
• Amide: $\text{RCONH}_2$ (If R' = H) or $\text{RCONHR}'$ (If R' = alkyl group)

These derivatives are far more reactive than carboxylic acids or esters because they have a good leaving group attached to the carbonyl carbon ($\text{Cl}^-$ in acyl chlorides, or $\text{RCOO}^-$ in acid anhydrides).

2. Nucleophilic Addition-Elimination Reactions

Acyl chlorides and acid anhydrides react with various nucleophiles ($\text{Nu}$) to replace the chlorine atom or the carboxylate group, respectively. This reaction is always a nucleophilic addition-elimination.

Reagents and Products (General Overview)

Reactant ($\text{Nu}$)	Reagent Type	Product Class	Side Product (from Acyl Chloride)
$\text{H}_2\text{O}$ (Water)	Nucleophile	Carboxylic Acid	$\text{HCl}$
$\text{R}'\text{OH}$ (Alcohol)	Nucleophile	Ester	$\text{HCl}$
$\text{NH}_3$ (Ammonia)	Nucleophile	Primary Amide	$\text{HCl}$
$\text{R}'\text{NH}_2$ (Primary Amine)	Nucleophile	Secondary Amide	$\text{HCl}$

Important Distinction: Unlike esterification with carboxylic acids, these acylation reactions are fast, non-reversible, and often require no catalyst or heat.

3. Industrial Advantage: Acid Anhydrides vs. Acyl Chlorides

When making drugs like Aspirin, chemists must decide between using an acyl chloride (like ethanoyl chloride) or an acid anhydride (like ethanoic anhydride) to acetylate the starting material.

• Acyl Chlorides ($\text{RCOCl}$): Highly reactive, but produce toxic/corrosive $\text{HCl}$ gas as a byproduct.
• Acid Anhydrides ($(\text{RCO})_2\text{O}$): Less reactive than acyl chlorides, but the byproduct is a non-toxic carboxylic acid (e.g., ethanoic acid).

Conclusion for Aspirin Manufacture:

The industrial process prefers ethanoic anhydride because the production of the corrosive and hazardous $\text{HCl}$ gas is avoided, making the process safer and cleaner for large-scale industrial use.

4. The Acylation Mechanism (Nucleophilic Addition-Elimination)

The mechanism for reactions involving acyl chlorides (and acid anhydrides) with nucleophiles is critical.

Step-by-Step Mechanism Outline (Using Acyl Chloride)

Let's use an acyl chloride ($\text{RCOCl}$) reacting with a generic nucleophile ($\text{Nu}$) which has a lone pair of electrons (e.g., $\text{H}_2\text{O}$, $\text{R}'\text{OH}$, $\text{NH}_3$, $\text{R}'\text{NH}_2$).

The Driving Force: The carbonyl carbon ($\text{C}$) is highly electron deficient (electrophilic) due to being bonded to both an oxygen and a highly electronegative chlorine atom.

Step 1: Nucleophilic Addition

The nucleophile ($\text{Nu}$) attacks the electrophilic carbonyl carbon.
The curly arrow starts from the lone pair on the $\text{Nu}$ and points to the $\text{C}$ atom.
Simultaneously, the $\pi$ bond in the $\text{C=O}$ double bond breaks, and the electron pair moves onto the $\text{O}$ atom, forming a negatively charged tetrahedral intermediate (called a tetrahedral intermediate).

Step 2: Elimination (Reformation of $\text{C=O}$)

The $\text{O}^-$ reforms the $\text{C=O}$ double bond.
The curly arrow starts from the lone pair on the $\text{O}^-$ and points to reform the $\text{C=O}$ bond.
Simultaneously, the best leaving group is expelled. In an acyl chloride, this is the chloride ion ($\text{Cl}^-$).
The curly arrow starts from the $\text{C-Cl}$ bond and points onto the $\text{Cl}$.

Step 3: Deprotonation (if required)

If the nucleophile was neutral (like water, alcohol, or ammonia), the product formed after Step 2 will be positively charged. A second molecule of the nucleophile acts as a base to remove the extra proton ($\text{H}^+$), leaving the final neutral product (ester, amide, or carboxylic acid).

If the nucleophile is an amine or ammonia, the $\text{HCl}$ byproduct immediately reacts with the excess amine or ammonia present to form an ammonium salt. This means two moles of nucleophile are typically consumed per mole of acyl chloride.

Key Takeaway: Acylation reactions are fast and proceed via a nucleophilic addition followed by an elimination step, leading to product formation and the removal of the good leaving group ($\text{Cl}^-$ or $\text{RCOO}^-$).