Synthesis of Acetanilide

1
Synthesis of Acetanilide

• Synthesis of Acetanilide Nucleophilic Acyl
  Substitution (addition / elimination) reaction
  between Aniline and Acetic Anhydride
• References
• Pavia p. 65 68
• Schornick http//classweb.gmu.edu/jschorni/chem31
  8

2
Synthesis of Acetanilide

• Overview
• Synthesis of Acetanilide Nucleophilic Acyl
  Substitution (addition / elimination) reaction
  between Aniline and Acetic Anhydride
• Determine Mass, Moles, Molar Ratio, Limiting
  Reagent, Theoretical Yield
• Recrystallize Product (from water)
• Vacuum Filtration
• Dry Product
• Mass and Experimental Yield of Product
• Melting Point

3
Synthesis of Acetanilide

• Laboratory Report
• Synthesis Experiment
• Mass, Moles, Molar Ratio, Limiting Reagent,
  Theoretical Yield
• Procedures
• Title Concise Mass reagent, Vacuum Filtration,
  Recrystallization, Melting Point, etc.
• Materials Equipment - 2 Columns in list
  (bullet) form)Note include all reagents and
  principal equipment

4
Synthesis of Acetanilide

• Description of Procedure
• Use list (bullet) form
• Concise, but complete
• Use your own words - Dont copy book!!
• Neat, logically designed template to present
  results
• Summary
• Paragraph summarizing the experimental results
  and computed results
• Analysis Conclusions
• Limiting reagent
• Discuss the reaction in context with the results
  you obtained what evidence to you have to
  indicate you got the intended product?
• Yield How could the experimental process be
  improved?.

5
Synthesis of Acetanilide

• Background
• Acetanilide is an Amide (RCONRR)
• (MW 135.17, MP - 114.3oC)Note the Carbonyl
  Group!
• Aniline is an Amine (RNRR)
• (MW 92.13, BP - 184oC)
• Acetic Anhydride, an Acid Anhydride,is a source
  of Acyl groups
• (MW - 102.1, BP - 139.9oC, Den 1.08 g/mL)
• Synthesis
• Amines can be treated (Acylated, adding a
  Carbonyl and losing a proton) using Acetic
  Anhydride as a source of an Acyl group to form
  an Amide.

6
Synthesis of Acetanilide

• Amines
• Amines are similar to Amides (Amides have a
  Carbonyl group
• The non-bonding electron pair on the Nitrogen
  atom is readily available for donation or it can
  accept a proton.
• Thus, Amines are basic (weakly)
• Amines are more susceptible to oxidation (gain
  oxygen or lose protons) than Amides.
• The electron pair is available to an aromatic
  ring increasing electron density in the ring,
  especially at the ortho para positions.

• Amides
• Electron pair on the Nitrogen in an Amide is less
  likely to move to aromatic ring.
• An Amide is stabilized by the resonance involving
  the nonbonding pair of electrons on the Nitrogen
  atom and the strong electron-withdrawing effect
  of the Carbonyl group.
• The strong electron withdrawing Carbonyl oxygen
  takes on a partial negative charge.
• Protonation of an Amide occurs on the Oxygen
  rather than the Nitrogen.

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Synthesis of Acetanilide

• Amines
• Thus, Amines are strongly activating and are
  ortho - para directing.
• Amines are easily oxidized (lose electrons,
  protons, gain oxygen).
• Oxidation of a group substituted on the aromatic
  ring will also result in oxidation of the Amine
  group.
• The Amine can be protected by first acylating it
  to the Amide form.

• Amides
• The Carbonyl Carbon atom competes for the
  Nitrogen electron pair forming a NC double bond.
• Thus, Amides are less basic than Amines.
• Amides are also ortho- para directing, but are
  only moderately activating.
• Substitution groups on the ring of an aromatic
  Amide can be oxidized with little impact on the
  Amide group, thus protecting its use as an Amine.
• The Amide can then be hydrolyzed to return to the
  Amine form.

8
Synthesis of Acetanilide

• The Reaction
• The Mechanism

Acetic Anhydride Resonance
9
Synthesis of Acetanilide

• Todays Reaction
• The Synthesis of Acetanilide, an Amide, through a
  Nucleophilic Acyl Substitution (addition /
  elimination) reaction between Aniline, an Amine,
  acting as the Nucleophile, and an Acyl group from
  Acetic Anhydride acting as the Electrophile.
• Safety
• Acetic Anhydride causes irritation of tissue,
  especially the nasal passages.
• Aniline is toxic, can be absorbed through the
  skin
• Waste Disposal
• Put all Organics in marked jar in hood.
• Put all Inorganic (Aqueous) solutions down drain
  with lots of water.

10
Synthesis of Acetanilide

• General Steps
• Determine Mass Moles of Reactants
• Aniline Acetic Anhydride
• Determine Molar Ratio, Limiting Reagent,
  Theoretical Yield
• Mix Reactants in Erlenmeyer Flask
• Recrystallize Product
• Add Water Heat to Dissolve solids
• Add Norite Charcoal (only if directed by
  instructor)
• Filter Hot Solution through Fluted Gravity filter

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Synthesis of Acetanilide

• General Steps (Cont)
• Cool slowly to room temperature
• Place water/crystal mixture in Ice/Water bath
• Vacuum Filter Crystals
• Dry Crystals in oven at 75oC for 30 minutes
• Weigh Crystals
• Determine yield and percent yield
• Determine Melting Point

12
Synthesis of Acetanilide

• Procedure
• Obtain vial containing approximately 2 g Aniline
  from instructor. Determine mass to nearest
  0.001g.
• Empty content into 125 Erlenmeyer flask.
• Reweigh empty vial and compute mass of Aniline.
• Add 15 mL Distilled Water with swirling.
• Slowly, with swirling, add approximately 2.7 g
  (2.5 mL) Acetic Anhydride weighed to nearest
  0.001 g). Note any changes.
• In your report compute moles, determine molar
  ratio, limiting reagent, theoretical yield

13
Synthesis of Acetanilide

• Once the crude Acetanilide precipitates, add 40
  mL Distilled Water and a carborundum boiling chip
  to the flask.
• Heat on hot plate until all solid oily
  materials have dissolved.
• DO NOT remove the 1 mL aliquot as directed in the
  text.
• Note Do step 10 only if the instructor tells
  you to do so
• Otherwise, go directly to step 11 to
  Recrystallize product

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Synthesis of Acetanilide

• Procedure (Cont)
• Decolorize the Reaction Mixture
• Add a small amount of NORIT (fine-grained
  activated charcoal) to reaction flask
• Assemble Gravimetric filtration unit using fluted
  filter paper (a fluted filter paper exposes more
  filter area to liquid)
• Prepare additional 25 mL boiling Distilled Water
  to be used as washing solvent in filtration
• Warm short-stem funnel (in drawer beneath hood)
  with 10 mL of warmer water

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Synthesis of Acetanilide

• Procedure (Cont)
• Decolorize the Mixture (Cont)
• Prepare fluted filter paper and place in funnel.
• Bring the Acetanilide / Charcoal mixture to a
  boil,
• Keep the solution hot (not boiling) on hot plate
  until poured into funnel.
• Filter hot Acetanilide / Charcoal mixture as
  quickly as possible, but in small portions.
• Keep new collection flask warm also in order to
  prevent formation of crystals in the funnel.
• Add additional hot water to funnel to dissolve
  any crystals

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Synthesis of Acetanilide

• Procedure (Cont)
• Recrystallize the Product
• Cool solution SLOWLY to room temperature
• Place flask in ice bath for 10 minutes
• Setup Buchner funnel
• Vacuum filter crystals, washing crystals with a
  few mL of cold distilled water
• Continue vacuum for at least 5 minutes to
  maximize drying

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Synthesis of Acetanilide

• Spread crystals evenly on pre-weighed watch
  glass.
• Put crystals in oven at 75oC for 30 minutes.
• Cool for 5 minutes
• Determine mass of dried product.
• Compute percent yield.
• Determine melting point