Experiment: preparation of acetanilide and p-nitroacetanilide

How are acetanilide and p-nitroacetanilide prepared?

The NCERT Class 12 textbook explains the chemistry: acylation of amines (NCERT Section 9.6, page 270) and why aniline is acetylated before nitration (page 273). It does not describe the method. The method below follows the NCERT Laboratory Manual (Chemistry, Class 12), Unit 10 (pages 104–109).

These practical descriptions explain the NCERT manual. Carry out laboratory work only under the institution’s approved supervised procedure, including reagent handling, cooling and waste collection.

In plain words: an –NH₂ group makes the ring so reactive that nitric acid oxidises aniline to tar. Turning –NH₂ into –NHCOCH₃ tames it, so that one nitro group goes on, mostly para.

Acetanilide by acetylation of aniline

• Theory. One hydrogen of the –NH₂ group of aniline is replaced by a CH₃CO– group: this is acylation, a nucleophilic substitution (NCERT page 270), with the amine as the nucleophile (reasoned). In the laboratory acetic anhydride is usual; acetyl chloride may be used instead, usually with pyridine (Lab Manual, page 104). Pyridine is a base stronger than the amine: it removes the HCl formed and shifts the equilibrium to the right (NCERT page 270). For aniline this holds: beyond the NCERT text, pyridine’s pK_b is about 8.8 (pK_a of its cation 5.23, HSDB via PubChem) against aniline’s 9.38 (NCERT Table 9.3), and by taking up the acid it keeps the aniline unprotonated (reasoned).

• Procedure (Experiment 10.1).

  1. Take 5 mL of aniline in a 100 mL round-bottom flask. Add 5 mL of acetic anhydride and 5 mL of glacial acetic acid, or 5 mL of acetyl chloride and 5 mL of dry pyridine.
  2. Add a few pumice stones, fit an air condenser and reflux gently for 10–15 minutes on a sand bath.
  3. Cool, and pour slowly into 150–200 mL of ice-cold water with stirring.
  4. Filter the solid and wash it with cold water.

  (Lab Manual, pages 104–105.)

• Alternative, without acetic anhydride or pyridine.

  1. Mix 1 mL of aniline with 1 mL of glacial acetic acid in a dry boiling tube.
  2. Add 1 mL of acetyl chloride, 0.3 mL at a time. The mixture warms; if the tube becomes unbearable to touch, the Lab Manual cools it under tap water (page 106). Our safety advice: control the warming with the approved cooling arrangement and a thermometer rather than judging it by touch.
  3. Heat for five minutes in a boiling water bath, cool, and add about 10 mL of ice-cold water with stirring.
  4. Filter the white powder of acetanilide and wash it with water until the filtrate is neutral to litmus.

  (Lab Manual, page 106.)

p-Nitroacetanilide by nitration of acetanilide

• Theory. Concentrated nitric and sulphuric acids together release the nitronium ion, NO₂⁺, the electrophile. It attacks the ring mainly para to the anilide group: an aromatic electrophilic substitution (Lab Manual, page 108).
• In acetanilide the lone pair on nitrogen is shared with the C=O oxygen by resonance, so –NHCOCH₃ activates the ring less than –NH₂ does (NCERT pages 272–273). Direct nitration of aniline gives tarry oxidation products, and in strong acid the anilinium ion, which is meta directing, gives much m-nitroaniline too (NCERT page 273).

The first equation is the Lab Manual’s (page 108); the second sums up its scheme, with the water added (reasoned). In short ionic form the first is HNO₃ + H⁺ → NO₂⁺ + H₂O, the H⁺ coming from the sulphuric acid (reasoned).

• Procedure (Experiment 10.3).

  1. Dissolve 2 g of acetanilide in 2 mL of glacial acetic acid in a 100 mL beaker.
  2. Add 4 mL of concentrated H₂SO₄ gradually, with stirring; the mixture becomes hot and clear. Cool it in an ice bath at 0–5 °C.
  3. Add a cold mixture of 1.0 mL of concentrated HNO₃ and 1.0 mL of concentrated H₂SO₄ drop by drop, stirring all the time, so that the temperature does not rise above 10 °C.
  4. Take the beaker out of the ice bath and let it stand at room temperature for about 30 minutes, then pour the mixture onto 100 g of crushed ice with stirring.
  5. Filter, wash with cold water and dry.

  (Lab Manual, pages 108–109.)

• NCERT slip (Laboratory Manual, page 108): the list of materials gives 1.5 mL of concentrated HNO₃, but the procedure uses 1.0 mL. The procedure’s sulphuric acid, 4 mL + 1.0 mL, matches the 5 mL in the list, so follow the procedure’s 1.0 mL of nitric acid, or your teacher’s figure (reasoned).

• The textbook’s scheme acetylates aniline with (CH₃CO)₂O and pyridine, nitrates acetanilide at 288 K and then hydrolyses p-nitroacetanilide with acid or base to p-nitroaniline (NCERT page 273). The Lab Manual keeps the mixture below 10 °C (283 K) while the nitrating acids are added.

Recrystallisation of the products

• Acetanilide: recrystallise a small amount from hot water with a few drops of methanol or ethanol (Lab Manual, page 105), or from hot water alone in the alternative method. White, shining, needle-shaped crystals form (page 106).
• p-Nitroacetanilide: recrystallise a small amount of the pale yellow solid from alcohol. Colourless crystals of p-nitroacetanilide separate, while the small amount of yellow o-nitroacetanilide stays dissolved in the mother liquor (Lab Manual, page 109).
• Recrystallisation works because the compound and its impurities dissolve to different extents in the chosen solvent; see crystallisation. The crude solid is dissolved in a solvent in which it is sparingly soluble at room temperature but appreciably soluble when hot; on cooling the pure compound crystallises out, and the mother liquor keeps the impurities. A mixture of two solvents works when the compound is very soluble in one and only slightly soluble in the other (NCERT Class 11 Chemistry, Unit 8, page 279), as with water and a few drops of methanol or ethanol for acetanilide (reasoned). Wash the acetanilide until the washings are neutral to litmus, and take the melting point only of a perfectly dry, recrystallised sample (Lab Manual, pages 105–106).
• Expected melting points (beyond the NCERT text): acetanilide 113–115 °C (Wikipedia, “Acetanilide”) and p-nitroacetanilide 215 °C (Wikipedia, “Nitroacetanilide”). Record the onset-to-clear range on a dry sample and compare it with these values; agreement supports, but does not by itself prove, identity and purity (reasoned).

Safety

• The Lab Manual marks aniline as toxic; beyond the NCERT text, it is also toxic in contact with skin (GHS hazard statement H311, ECHA notifications via PubChem), so wear gloves. Acetic anhydride, acetyl chloride and acetic acid are marked flammable and corrosive; acetic acid “causes serious burn”. Pyridine carries the flammable symbol and the St Andrew’s cross (pages 105 and 108). Our safety advice: use the approved supervised procedure, a fume hood, eye protection and compatible gloves, and follow each reagent’s current safety data sheet.
• Acetic anhydride and acetyl chloride irritate the eyes, and acetyl chloride fumes strongly in air. Dispense pyridine in an efficient fume cupboard. Do not breathe the vapours given off while acetyl chloride is added (Lab Manual, pages 105–106).
• The Lab Manual warns that acetanilide may cause cyanosis (page 108). Wikipedia records that it was used from 1886 as a fever-reducing medicine, Antifebrin, and later given up because it can cause methaemoglobinaemia, which shows as cyanosis.
• Add the nitrating mixture slowly and carefully, and never let the temperature pass 10 °C (Lab Manual, page 109).
• Experiment 10.3 prints no hazard symbol for the concentrated acids, but the same Laboratory Manual marks sulphuric acid (H₂SO₄) as corrosive (Unit 11, page 116) and nitric acid (HNO₃) as an oxidiser and corrosive (Unit 11, page 123). Pour concentrated sulphuric acid into the acetanilide solution slowly, with stirring: the mixture becomes hot (Lab Manual, page 108).

Solved examples

Common mistakes to avoid

Quick revision summary

• Acetanilide: 5 mL aniline + 5 mL acetic anhydride + 5 mL glacial acetic acid (or acetyl chloride and pyridine); reflux 10–15 min; pour into ice-cold water; recrystallise from hot water.
• p-Nitroacetanilide: 2 g acetanilide in 2 mL glacial acetic acid + 4 mL conc. H₂SO₄; ice bath; 1.0 mL conc. HNO₃ + 1.0 mL conc. H₂SO₄, drop by drop, below 10 °C; 30 min; onto ice; recrystallise from alcohol.
• Acetylation protects –NH₂, so that nitration gives mainly the para product.

Questions students ask

Why is p-nitroacetanilide the major product when acetanilide is nitrated?

p-Nitroacetanilide is the major product because –NHCOCH₃, like –NH₂, sends an incoming group ortho and para, the lone pair on its nitrogen still releasing some electron density into the ring though less than in aniline (NCERT pages 272–273), and of those positions the para carbon is the easiest for the nitronium ion to reach (reasoned). The acetyl part makes the group bulky, so it crowds the two carbons beside it, and the far para carbon wins even though there are two ortho positions to one para (reasoned; Lab Manual, page 108).

What is the IUPAC name of acetanilide?

The IUPAC name of acetanilide, C₆H₅NHCOCH₃, is N-phenylethanamide, the name NCERT prints under it in the acylation scheme (“N-Phenylethanamide or Acetanilide”, page 270); beyond the NCERT text, IUPAC’s preferred name is N-phenylacetamide (Wikipedia, “Acetanilide”; PubChem). The locant N shows that the phenyl group is on the nitrogen of the amide, as in NCERT’s N-methylbenzamide (page 270), so acetanilide is an amide, the product of acylating aniline, not an amine (reasoned).

What is acetanilide used for, and how is it related to paracetamol?

Acetanilide and paracetamol share an acetanilide framework; paracetamol has an additional para hydroxyl group. Acetanilide is a synthesis intermediate and was historically used as an antipyretic, but it can cause methaemoglobinaemia. These chemical relationships do not make laboratory acetanilide suitable for medicinal use.

Why is acetanilide recrystallised from hot water rather than from alcohol?

Acetanilide is recrystallised from hot water because it is about nine times more soluble in boiling water than in unheated water: beyond the NCERT text, 1 g dissolves in 20 mL of boiling water but needs about 185 mL of unheated water (PubChem, from the Hazardous Substances Data Bank). So a crude sample dissolved in just enough boiling water can give back up to 1 − 20/185 ≈ 89% of its acetanilide as crystals on cooling (reasoned). In alcohol it is far too soluble, 1 g in 3.4 mL even unheated (PubChem), so the Lab Manual adds only a few drops of methanol or ethanol to the water (page 105; reasoned).

What is the theoretical yield of acetanilide from 5 mL of aniline?

Specify the limiting reagent. Taking densities of 1.02 g mL^⁻¹ for aniline and 1.08 g mL^⁻¹ for acetic anhydride (NIOSH), 5 mL gives 5.10/93 = 0.05484 mol aniline and 5.40/102 = 0.05294 mol anhydride. In the stated 1:1 anhydride acetylation, the anhydride limits the theoretical acetanilide yield to 0.05294 × 135 = 7.15 g. The aniline-only ceiling is 7.40 g if the acetylating reagent is in excess. Do not assume the acetic-acid solvent quantitatively acetylates the remainder under this short procedure.

Practice questions

Try each question first, then open the answer to check your working.

1. Q1. What is the role of pyridine when aniline is acetylated with acetyl chloride? (Compare Lab Manual Unit 10, Discussion Question (v), page 113.)

   Show answerHide answer

   Pyridine is a base stronger than aniline (pK_b about 8.8 against 9.38): it removes the HCl formed, which shifts the equilibrium to the right (NCERT page 270), and so keeps the aniline unprotonated (reasoned).

2. Q2. Which minor product forms in the preparation of p-nitroacetanilide, and how is it removed? (Compare Lab Manual Unit 10, Discussion Question (ii), page 113.)

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   The manual identifies yellow o-nitroacetanilide as an impurity that remains in the mother liquor during recrystallisation from alcohol, describing the isolated para product as colourless (Lab Manual, page 109). Colour alone cannot establish identity or purity (reasoned).