Synthesis of Acetanilide Synthesis of Acetanilide Nucleophilic Acyl Substitution (addition / elimination) reaction between Aniline and Acetic Anhydride

ReferencesPaviap. 65 68Schornickhttp://classweb.gmu.edu/jschorni/chem318

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Synthesis of AcetanilideOverviewSynthesis of Acetanilide Nucleophilic Acyl Substitution (addition / elimination) reaction between Aniline and Acetic AnhydrideDetermine Mass, Moles, Molar Ratio, Limiting Reagent, Theoretical YieldRecrystallize Product (from water)Vacuum FiltrationDry ProductMass and Experimental Yield of ProductMelting Point**

Synthesis of AcetanilideLaboratory ReportSynthesis ExperimentMass, Moles, Molar Ratio, Limiting Reagent, Theoretical YieldProcedures: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**

Synthesis of AcetanilideDescription of Procedure:Use list (bullet) formConcise, but completeUse your own words - Dont copy book!!Neat, logically designed template to present resultsSummaryParagraph summarizing the experimental results and computed resultsAnalysis & ConclusionsLimiting reagentDiscuss 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?.**

Synthesis of AcetanilideBackgroundAcetanilide 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)SynthesisAmines 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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Synthesis of AcetanilideAminesAmines are similar to Amides (Amides have a Carbonyl groupThe 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.

**AmidesElectron 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.

Synthesis of AcetanilideAminesThus, 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.

**AmidesThe Carbonyl Carbon atom competes for the Nitrogen electron pair forming a N=C 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.

Acetic AnhydrideResonanceSynthesis of AcetanilideThe Reaction

The Mechanism

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Synthesis of AcetanilideTodays ReactionThe 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.SafetyAcetic Anhydride causes irritation of tissue, especially the nasal passages.Aniline is toxic, can be absorbed through the skinWaste DisposalPut all Organics in marked jar in hood.Put all Inorganic (Aqueous) solutions down drain with lots of water.

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Synthesis of AcetanilideGeneral StepsDetermine Mass & Moles of ReactantsAniline & Acetic AnhydrideDetermine Molar Ratio, Limiting Reagent, Theoretical YieldMix Reactants in Erlenmeyer FlaskRecrystallize ProductAdd Water & Heat to Dissolve solidsAdd Norite Charcoal (only if directed by instructor)Filter Hot Solution through Fluted Gravity filter**

Synthesis of AcetanilideGeneral Steps (Cont)Cool slowly to room temperaturePlace water/crystal mixture in Ice/Water bathVacuum Filter CrystalsDry Crystals in oven at 75oC for 30 minutesWeigh CrystalsDetermine yield and percent yieldDetermine Melting Point**

Synthesis of AcetanilideProcedureObtain 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**

Synthesis of AcetanilideOnce 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 soOtherwise, go directly to step 11 to Recrystallize product**

Synthesis of AcetanilideProcedure (Cont)Decolorize the Reaction MixtureAdd a small amount of NORIT (fine-grained activated charcoal) to reaction flaskAssemble 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 filtrationWarm short-stem funnel (in drawer beneath hood) with 10 mL of warmer water**

Synthesis of AcetanilideProcedure (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**

Synthesis of AcetanilideProcedure (Cont)Recrystallize the ProductCool solution SLOWLY to room temperaturePlace flask in ice bath for 10 minutesSetup Buchner funnelVacuum filter crystals, washing crystals with a few mL of cold distilled waterContinue vacuum for at least 5 minutes to maximize drying**

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