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Organic Chemistry · Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

Reactions of Carboxylic Acids

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6 key termsSourcesReport an error
pKa values (acetic 4.76, formic 3.75, chloroacetic 2.86, trifluoroacetic ≈ 0.5, phenol ≈ 10) and the Fischer esterification equilibrium constant (K ≈ 3–4) are standard reference values — verify against current sources before relying on them in assessments.
Want it in plain words first? Jump to Eli explains — the same idea, no jargon.
On this page 9 sections
  1. In 30 seconds
  2. Why this matters
  3. The college version
  4. Eli explains
  5. Worked example
  6. Key takeaway
  7. Check yourself
  8. Study tools
  9. Sources & references

In 30 seconds

Carboxylic acids (RCOOH) are the parent compounds of the acyl-derivative family: every acid chloride, anhydride, ester, amide, and thioester traces back to an acid. Their chemistry is dominated by two features. First, the –COOH group is acidic — it transfers a proton to bases, giving resonance-stabilized carboxylate salts. Second, the hydroxyl group is a poor leaving group, so the acid cannot undergo nucleophilic acyl substitution directly; the –OH must first be converted into something that can leave (a chloride, an anhydride, or an activated ester). The central reactions to master: deprotonation (salt formation), , conversion to acid chlorides and anhydrides, amide formation, and reduction to primary alcohols.

Why this matters

  • The pivot of the derivative family: Interconvert acids with their derivatives and you can navigate the whole chapter — drug synthesis, polymer chemistry, and biochemistry all depend on choosing the right derivative at the right step.
  • Acidity controls drug behavior: Whether a drug is ionized or neutral at body pH (7.4) determines solubility, membrane crossing, and receptor binding. With pKa ≈ 4–5, most carboxylic acids exist largely as carboxylate anions at physiological pH.
  • Fischer esterification is everywhere: Flavors, fragrances, aspirin, and polyester monomers are made by esterification; knowing it is an equilibrium tells you how to drive it (excess alcohol, remove water).
  • Exams: Acid–base reactions, esterification equilibria, pKa comparisons, and reagent-based conversions (SOCl₂, LiAlH₄) are frequent test items.

The college version

Core Concepts

Acidity and the resonance-stabilized carboxylate

A carboxylic acid is a weak acid:

RCOOH ⇌ RCOO- + H+

For acetic acid, pKa = 4.76, so Ka = 1.8 × 10-5. The conjugate base, the , is stabilized because the negative charge is delocalized over two equivalent oxygens by resonance. Electron-withdrawing substituents further stabilize the anion and raise acidity — chloroacetic acid has pKa = 2.86, trifluoroacetic acid pKa ≈ 0.5. Electron-donating alkyl groups lower acidity slightly (formic acid, pKa = 3.75, is stronger than acetic acid).

Salt formation: the acid–base reaction

RCOOH + NaOH ⟶ RCOO-Na+ + H2O

RCOOH + NaHCO3 ⟶ RCOO-Na+ + H2O + CO2

The reaction with bicarbonate is a useful diagnostic: carboxylic acids (pKa ≈ 4–5) are strong enough to protonate HCO3-, while phenols (pKa ≈ 10) are not. The ionic carboxylate salt dissolves in water — the basis of acid–base extraction.

Fischer esterification

Heating an acid with an alcohol in the presence of a strong acid catalyst (typically H2SO4) gives an ester and water:

RCOOH + R'OH H+⟶ RCOOR' + H2O

This is an equilibrium with K ≈ 3–4 for simple primary alcohols. To push it toward product, use a large excess of the alcohol (usually the cheaper reagent) or remove water as it forms. The acid catalyst protonates the carbonyl oxygen (making the acyl carbon more electrophilic) and later protonates the –OH of the tetrahedral intermediate so that water — a better leaving group than hydroxide — can depart.

Conversion to acid chlorides

The –OH cannot leave on its own, so to make an acid chloride you convert it. does this cleanly:

RCOOH + SOCl2 ⟶ RCOCl + SO2 + HCl

Both byproducts are gases that escape, leaving pure acid chloride. PCl3, PCl5, and oxalyl chloride accomplish the same conversion.

Conversion to anhydrides and amides

  • Anhydrides: Direct dehydration of most acids needs harsh conditions (P2O5, heat); the practical route is acid chloride + carboxylate salt: RCOCl + R'COO- ⟶ RCO-O-COR' + Cl-.
  • Amides: Mixing an acid with an amine gives only the — an acid–base reaction, not a substitution. To make the amide you must activate the acid (acid chloride, anhydride, or a coupling reagent such as DCC) or heat the salt strongly to drive off water.

Reduction to primary alcohols

Lithium aluminum hydride (LiAlH4) reduces carboxylic acids all the way to primary alcohols:

RCOOH LiAlH4⟶ RCH2OH

The hydride adds twice: first to give an aldehyde, which is reduced further before it can escape. Sodium borohydride (NaBH4) is too mild to reduce carboxylic acids at a useful rate — a classic reagent-selection trap.

How It Works / Step-by-Step Process

Choosing a reaction for a carboxylic acid is a decision tree:

  1. Need a salt? Add NaOH or NaHCO3 — immediate, quantitative acid–base reaction.
  2. Need an ester? Fischer conditions: alcohol + catalytic H2SO4, heat, excess alcohol.
  3. Need an acid chloride? Add SOCl2 (or PCl3/PCl5/oxalyl chloride).
  4. Need an amide? Activate first (acid chloride + amine, or DCC + amine) — do not expect direct reaction.
  5. Need an alcohol? Reduce with LiAlH4 in anhydrous ether, then quench with water.

Common Confusions

Do Not ConfuseWithDifference
Carboxylic acidPhenolBoth are "acids," but pKa ≈ 4–5 vs. ≈ 10; only the acid reacts with NaHCO3 to give CO₂
Carboxylate salt formationEsterificationSalt formation is a fast acid–base reaction (no catalyst, no heat); esterification is a catalyzed equilibrium
Acid + amineAmide formationMixing gives the ammonium carboxylate salt; the amide needs activation (acid chloride/DCC) or strong heating
LiAlH4 reductionNaBH4 reductionLiAlH4 reduces carboxylic acids to primary alcohols; NaBH4 generally does not
Fischer esterification direction"Add acid, get ester"It is an equilibrium: water can hydrolyze the ester back. Manage with excess alcohol or water removal
Eli, the EliExplains learning guide

Eli explains

The same idea, in plain words

Explain it like I’m 10

A carboxylic acid is like a Lego brick with a loose stud on top that it can donate to anyone who asks politely — that's the acidic hydrogen. But the brick's bottom peg (the –OH) is stuck and cannot come off by itself, so you cannot swap parts on it directly. To change what's attached, you first click on a special adapter (like SOCl₂) that makes the peg removable, and then the new part can snap on. Same brick, new attachments.

Worked example

Example 1: Percent ionization of acetic acid in water

Calculate the pH and percent ionization of a 0.10 M solution of acetic acid (Ka = 1.8 × 10-5).

Write the equilibrium expression first:

Ka = [H+][CH3COO-][CH3COOH] = 1.8 × 10-5

Set up: let x = [H+] = [CH3COO-]; then [CH3COOH] = 0.10 - x. Because Ka is small, 0.10 - x ≈ 0.10.

1.8 × 10-5 = x20.10   ⇒  x = 1.8 × 10-6 = 1.3 × 10-3 M

pH = -log(1.3 × 10-3) = 2.87

% ionization = x0.10 × 100% = 1.3%

Answer: pH ≈ 2.9, with about 1.3% of the acid ionized — a typical weak-acid result.

Example 2: Stoichiometry of Fischer esterification

How many grams of ethyl acetate (CH3COOCH2CH3, 88.11 g/mol) could form from 10.0 g of acetic acid (CH3COOH, 60.05 g/mol) and excess ethanol?

Balanced reaction first (1:1 mole ratio):

CH3COOH + CH3CH2OH ⇌ CH3COOCH2CH3 + H2O

Dimensional analysis:

10.0 g CH3COOH × 1 mol60.05 g × 1 mol ester1 mol acid × 88.11 g1 mol = 14.7 g

Answer: 14.7 g theoretical. The actual yield is lower because the reaction is an equilibrium (K ≈ 3–4); excess ethanol or water removal raises the real yield toward this ceiling.

Example 3: Predicting the product of reduction

What is the product when butanoic acid, CH3CH2CH2COOH, is treated with excess LiAlH4 in dry ether, followed by aqueous workup?

Reason: Hydride adds to the carbonyl; the first addition gives butanal, which is reduced again before workup. The carboxyl carbon ends up with two new C–H bonds and one C–OH bond.

Answer: 1-butanol, CH3CH2CH2CH2OH — a primary alcohol with the same carbon count as the starting acid.

Key takeaways

  • Carboxylic acids: pKa ≈ 4–5; conjugate base stabilized by resonance over two oxygens.
  • RCOOH + NaOH → carboxylate salt + water; RCOOH + NaHCO3 → salt + water + CO₂.
  • Only acids (not phenols) fizz with bicarbonate — a practical test.
  • Fischer esterification: acid + alcohol ⇌ ester + water, H+ catalyst, K ≈ 3–4; drive with excess alcohol or water removal.
  • –OH is a poor leaving group; acids must be activated (SOCl₂, PCl₃/PCl₅, oxalyl chloride, DCC) before acyl substitution.
  • Acid + amine → ammonium carboxylate salt, not an amide; amides need activation or strong heat.
  • LiAlH4 reduces acids to primary alcohols; NaBH4 does not.

Check yourself

6 review questions from the chapter. Try each one, then open the answer.

  1. Write the acid–base reaction between acetic acid and sodium bicarbonate. What gas is evolved?

    Show answer

    CH3COOH + NaHCO3 → CH3COO-Na+ + H2O + CO2. Carbon dioxide gas is evolved (the "fizz").

  2. Why is the carboxylate ion more stable than an alkoxide ion of similar structure?

    Show answer

    In the carboxylate, the negative charge is delocalized over two equivalent oxygen atoms by resonance; in an alkoxide it is localized on one oxygen.

  3. Which is the stronger acid, acetic acid or chloroacetic acid? Explain.

    Show answer

    Chloroacetic acid (pKa = 2.86). The electron-withdrawing chlorine stabilizes the conjugate base by induction, lowering the energy of the negative charge; acetic acid has no such substituent.

  4. What are the two standard ways to drive Fischer esterification toward the ester?

    Show answer

    Use a large excess of the alcohol, and/or remove water from the equilibrium (e.g., with a Dean–Stark trap or drying agent).

  5. Why can't you prepare an amide simply by mixing a carboxylic acid with an amine at room temperature?

    Show answer

    The acid and amine react instantly as acid and base, giving the ammonium carboxylate salt RCOO-+NH3R'. Converting this salt to the amide requires heat (loss of water) or prior activation of the acid.

  6. What reagent converts a carboxylic acid to an acid chloride, and why are the byproducts convenient?

    Show answer

    Thionyl chloride (SOCl2); also PCl3, PCl5, or oxalyl chloride. The byproducts (SO2 and HCl) are gases that leave the mixture, so purification is easy.

Keep learning

Ready to build on this? Continue to the next lesson.

Study tools & related lessonsKey vocabulary · Related

Key vocabulary

Carboxylate ion
RCOO-, the conjugate base of the acid
Fischer esterification
Acid + alcohol ⇌ ester + water, acid-catalyzed
pKₐ
-logKa; lower value = stronger acid
Activation
Converting –OH into a better leaving group
Thionyl chloride
SOCl2, converts RCOOH to RCOCl
Ammonium carboxylate salt
RCOO-+NH3R', from acid + amine

Sources & references

  1. openstax.org — Organic Chemistry

This lesson was adapted from the open educational references above; their licenses and attributions are preserved. See Copyright & Licensing.

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