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Organic Chemistry · Carboxylic Acids and Nitriles

Chemistry of Nitriles

7 min read
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Constants (pKₐ ≈ 25 for nitrile α-H, bond length ≈ 1.16 Å, acetonitrile dipole ≈ 3.9 D) are standard textbook values; safety notes are general principles only.
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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

A has the structure R–C≡N: a carbon triple-bonded to nitrogen. The nitrile carbon is and linear, and the triple bond is one σ plus two π bonds. Because nitrogen is more electronegative, the C≡N bond is polarized (carbon δ+), making the nitrile carbon a good electrophile — while the α-hydrogens are weakly acidic (pKₐ ≈ 25), enabling enolate-like chemistry.

This topic covers the structure and polarity of C≡N, the main preparations (S_N2 with cyanide, amide dehydration, HCN addition to carbonyls), and the major reactions (hydrolysis, reduction, Grignard addition, α-alkylation).

Why this matters

  • One-carbon extensions. Alkyl halide + NaCN lengthens the chain by one carbon; the nitrile then hydrolyzes to an acid or reduces to an amine — two of the most useful groups in synthesis.
  • Industry: Acrylonitrile (CH₂=CH–CN) is the monomer of acrylic fibers and nitrile rubber; adiponitrile is a nylon-66 intermediate.
  • Pharmaceuticals: Nitriles appear in drugs (citalopram, anastrozole, sitagliptin) because C≡N is stable, polar, and improves binding or metabolic stability.
  • Cyanohydrins: HCN adds to aldehydes/ketones; hydrolysis of the –CN gives α-hydroxy acids used in skin care and synthesis.
  • Safety: Nitriles can release toxic HCN under strong acid hydrolysis — fume hood, no skin contact, and never acidify cyanide waste untreated.

The college version

Core Concepts

Structure and polarity of the nitrile group

The nitrile carbon is sp-hybridized, so R–C≡N is linear (180°). The C≡N bond (~1.16 Å) is shorter and stronger than C=N or C–N. The group is strongly polarized (C δ+, N δ−), giving large dipole moments (acetonitrile ≈ 3.9 D). The carbon is electrophilic and attacked by nucleophiles; the nitrogen is a weak base that can coordinate metals. The α C–H bonds (pKₐ ≈ 25) allow strong bases like LDA to form nitrile anions, which alkylate at α.

Preparation 1: S_N2 displacement with cyanide

Alkyl halides react with sodium or potassium cyanide in a polar aprotic solvent (DMSO) by S_N2:

R–X + NaCN → R–C≡N + NaX

Primary halides work best; secondary halides react slowly with some elimination; tertiary halides give mainly E2 and are useless here. The reaction adds one carbon. Because CN⁻ is ambident (nucleophilic at both C and N), a small amount of isocyanide can form, but the nitrile dominates with alkyl halides.

Preparation 2: Dehydration of amides

Amides lose water when heated with P₂O₅ (or SOCl₂, or POCl₃) to give nitriles:

R–CONH2 P2O5, Δ⟶ R–C≡N + H2O

This removes water from the amide's –NH₂ and carbonyl oxygen. Since amides are easily made from acids (Chapter 21), this route converts an acid to a nitrile of the same carbon count.

Preparation 3: Cyanohydrin formation (addition of HCN to carbonyls)

HCN adds to aldehydes and most ketones to give cyanohydrins, R₂C(OH)–CN:

R2C=O + HCN ⇌ R2C(OH)–CN

The reaction is base-catalyzed and reversible; the equilibrium favors the for aldehydes and simple ketones. The –CN can be hydrolyzed to –COOH (α-hydroxy acids) or reduced to –CH₂NH₂ (β-amino alcohols).

Reaction 1: Hydrolysis to carboxylic acids

Nitriles hydrolyze to carboxylic acids (topic 5) under acidic or basic conditions, through the amide:

R–C≡N + 2 H2O + H+ → R–COOH + NH4+

Under basic conditions the carboxylate salt forms first. The hydrolysis is slower than ester hydrolysis but works with hot acid or base.

Reaction 2: Reduction to primary amines

Lithium aluminum hydride reduces nitriles to primary amines:

R–C≡N LiAlH4, then H2O⟶ R–CH2NH2

Catalytic hydrogenation (H₂/Ni, H₂/Pd) also works. Because the imine intermediate (R–CH=NH) is reduced before workup, the product is the — reliably making R–CH₂NH₂ from R–X.

Reaction 3: Grignard addition to nitriles → ketones

Grignard reagents add to the nitrile carbon; hydrolysis of the resulting imine salt gives a ketone:

R–C≡N + R′MgX → R–C(=NMgX)–R′ H3O+⟶ R–CO–R′

This is one of the best ways to make unsymmetrical ketones R–CO–R′ with two different alkyl or aryl groups, because the nitrile and the Grignard reagent can each be chosen independently.

Common Confusions

Do Not ConfuseWithDifference
Nitrile hydrolysisNitrile reductionHydrolysis (H⁺/OH⁻, H₂O) gives R–COOH; reduction (LiAlH₄) gives R–CH₂NH₂
Nitrile carbon countProduct chain carbon countThe nitrile carbon is the extra one: R–X → R–CN adds one C; reduction keeps it as CH₂
S_N2 with CN⁻E2 with CN⁻Primary halides: S_N2 (nitrile); tertiary halides: elimination dominates
Cyanohydrin formationNitrile hydrolysisHCN adds to C=O (no C–N cleavage); hydrolysis converts C≡N to COOH (C–N broken)
Grignard + nitrileGrignard + esterNitrile gives a ketone (one addition); ester gives a tertiary alcohol (two additions)
Nitrile (R–C≡N)Isocyanide (R–N⁺≡C⁻)In the nitrile, carbon is bonded to the alkyl group; in the isocyanide, nitrogen is
Eli, the EliExplains learning guide

Eli explains

The same idea, in plain words

Explain it like I’m 10

A nitrile is like a strong, straight arrow: carbon and nitrogen held together by a very tight triple bond, with the carbon end as the tip that gets attacked. Dip an alkyl halide in cyanide "ink" to make the arrow (it lengthens by one segment), then fire it at different targets — water turns it into a carboxylic acid, hydrogen into an amine, a Grignard reagent into a ketone. One arrow, three destinations.

Worked example

Example 1: Chain extension by S_N2 + hydrolysis (with stoichiometry)

Convert 1-bromopropane to butanoic acid via the nitrile, and calculate the theoretical mass of butanoic acid from 12.3 g of 1-bromopropane.

Step 1 — Write the two reactions.

CH3CH2CH2Br + NaCN → CH3CH2CH2CN + NaBr

CH3CH2CH2CN + 2 H2O + H+ → CH3CH2CH2COOH + NH4+

Step 2 — Moles of starting halide. Molar mass of 1-bromopropane (C₃H₇Br) = 123.0 g/mol:

n = mM = 12.3 g123.0 g mol-1 = 0.100 mol

Step 3 — 1:1 stoichiometry to the acid. Molar mass of butanoic acid (C₄H₈O₂) = 88.11 g/mol:

m = 0.100 mol × 88.11 g mol-1 = 8.81 g

Dimensional check: g ÷ (g mol⁻¹) = mol; mol × (g mol⁻¹) = g. Theoretical yield: 8.81 g.

Example 2: Nitrile reduction to a primary amine

Show how to prepare butan-1-amine from 1-chlorobutane, and identify the intermediate's functional group.

Step 1 — S_N2 with cyanide: 1-chlorobutane + NaCN gives butanenitrile, CH₃CH₂CH₂CH₂CN (the chain keeps four carbons; the new one is the nitrile carbon).

Step 2 — Reduce: LiAlH₄ converts butanenitrile to pentan-1-amine:

CH3CH2CH2CH2CN LiAlH4, then H2O⟶ CH3CH2CH2CH2CH2NH2

The product has five carbons: the original four plus the nitrile carbon, now part of –CH₂NH₂. The intermediate is an imine (R–CH=NH), reduced before workup, so the amine is the only product.

Example 3: Unsymmetrical ketone by Grignard + nitrile

Propose a synthesis of propiophenone, C₆H₅–CO–CH₂CH₃, from benzonitrile and an ethyl Grignard reagent.

Benzonitrile is treated with ethylmagnesium bromide. The Grignard carbon (a carbanion) attacks the electrophilic nitrile carbon; acidic workup hydrolyzes the imine salt to propiophenone:

C6H5–C≡N + CH3CH2MgBr then H3O+⟶ C6H5–CO–CH2CH3

The ethyl anion adds to the nitrile carbon, the intermediate is protonated and hydrolyzed, and C≡N becomes C=O with the ethyl group still attached — an aryl group on one side, ethyl on the other.

Key takeaways

  • Structure: sp carbon, linear R–C≡N, polarized (C δ+), dipole ≈ 3.9 D.
  • α-H acidity: pKₐ ≈ 25; LDA forms nitrile anions that alkylate at α.
  • Preparation: R–X + NaCN (S_N2, +1 C); R–CONH₂ + P₂O₅ (dehydration); R₂C=O + HCN (cyanohydrin).
  • Hydrolysis: R–CN + 2 H₂O + H⁺ → R–COOH + NH₄⁺ (via the amide).
  • Reduction: LiAlH₄ → R–CH₂NH₂ (primary amine, cleanly).
  • Grignard: R–CN + R′MgX → R–CO–R′ (unsymmetrical ketones).
  • S_N2 limits: primary halides good, tertiary useless (elimination).

Check yourself

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

  1. Why is the nitrile carbon electrophilic, and what geometry does C–C≡N adopt?

    Show answer

    Nitrogen pulls electron density, leaving the carbon δ+; the sp-hybridized carbon gives a linear 180° C–C≡N arrangement.

  2. Write the S_N2 preparation of butanenitrile from 1-bromopropane and state how many carbons are added.

    Show answer

    CH₃CH₂CH₂Br + NaCN → CH₃CH₂CH₂CN + NaBr; one carbon is added (the nitrile carbon).

  3. What reagents convert an amide to a nitrile, and what is the byproduct?

    Show answer

    P₂O₅ (or SOCl₂/POCl₃) with heat; the byproduct is water (R–CONH₂ → R–CN + H₂O).

  4. Products of (a) acid hydrolysis and (b) LiAlH₄ reduction of butanenitrile?

    Show answer

    (a) Butanoic acid + NH₄⁺; (b) butan-1-amine (CH₃CH₂CH₂CH₂CH₂NH₂, five carbons).

  5. How does the Grignard + nitrile route differ from Grignard + ester in product class?

    Show answer

    Grignard + nitrile gives a ketone (one addition); Grignard + ester gives a tertiary alcohol (two additions).

  6. 12.3 g of 1-bromopropane → butanoic acid via the nitrile: theoretical mass?

    Show answer

    0.100 mol × 88.11 g/mol = 8.81 g.

Keep learning

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

Study tools & related lessonsKey vocabulary · Related

Key vocabulary

Nitrile
R–C≡N: carbon triple-bonded to nitrogen
sp-Hybridized
Linear geometry: one s + two p orbitals
Ambident nucleophile
Nucleophile with two attacking atoms (C and N of CN⁻)
Cyanohydrin
R₂C(OH)–CN: carbonyl + HCN adduct
Dehydration of amides
R–CONH₂ → R–C≡N + H₂O with P₂O₅
Primary amine
R–CH₂NH₂: –NH₂ on a terminal carbon
Unsymmetrical ketone
R–CO–R′ with two different groups

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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