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/chem318

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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

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Laboratory Report

Synthesis Experiment

Mass, Moles, Molar Ratio, Limiting Reagent, Theoretical Yield 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

Procedures:

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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?.

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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.

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Amines Amides Amines are similar to Amides (Amides haveElectron a Carbonyl group pair on the Nitrogen in an Amide isreadily less likely to move The non-bonding electron pair on the Nitrogen atom is available to aromatic ring. for donation or it can accept a proton. An Amide is stabilized by the resonance involving the Amines are more susceptible to oxidation (gain oxygen or lose nonbonding pair of electrons on protons) than Amides. the Nitrogen atom and the strong electron-withdrawing effect of The electron pair is available to an aromatic ring increasing electron Carbonyl group. density in the ring, especially at the ortho &the para positions. Thus, Amines are basic (weakly) 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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Amines Amides Thus, Amines are strongly activating and are ortho - para The Carbonyl Carbon atom directing. competes for the Nitrogen electron pair forming a N=C Amines are easily oxidized (lose electrons, protons, gain oxygen). double bond. Oxidation of a group substituted on the aromatic ring will also result in oxidation of the Amine group. Thus, Amides are less basic than Amines. The Amine can be protected by first acylating it to the Amide Amides are also ortho- para form. 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.
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Synthesis of Acetanilide

The Reaction

The Mechanism Acetic Anhydride Resonance

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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. Acetic Anhydride causes irritation of tissue, especially the nasal passages. Aniline is toxic, can be absorbed through the skin

Safety

Waste Disposal

Put all Organics in marked jar in hood. Put all Inorganic (Aqueous) solutions down drain with lots of water.

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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

10

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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

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Synthesis of Acetanilide

Procedure
1.

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.

2. 3. 4. 5.

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
12

6.

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7.

Once the crude Acetanilide precipitates, add 40 mL Distilled Water and a carborundum boiling chip to the flask.

8.

Heat on hot plate until all solid & oily materials have dissolved.
DO NOT remove the 1 mL aliquot as directed in the text.

9.

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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Procedure (Cont)
10.

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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Procedure (Cont)
10.

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)
11.

Recrystallize the Product

Cool solution SLOWLY to room temperature

Place flask in ice bath for 10 minutes

12. 13.

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

14.

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15. 16. 17. 18. 19. 20.

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

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