Substitution Reactions 1: The Sn 2 Reaction The Synthesis of 1-Bromobutane Organic Chemistry Lab II, Fall 2009 Dr. Milkevitch November 9 & 12, 2009.

Substitution Reactions 1: The SnSubstitution Reactions 1: The Sn22

ReactionReaction The Synthesis of 1-BromobutaneThe Synthesis of 1-Bromobutane

Organic Chemistry Lab II, Fall 2009Dr. Milkevitch

November 9 & 12, 2009

Substitution ReactionsSubstitution Reactions

TodayToday: Learn about an Sn: Learn about an Sn2 2 reactionreaction

Type of reaction:Type of reaction: Substitution SubstitutionOne thing substitutes for anotherOne thing substitutes for another

Primarily a reaction of alkyl halidesPrimarily a reaction of alkyl halides

The SnThe Sn22 Reaction Reaction

SnSn22 = = Substitution, nucleophilic, Substitution, nucleophilic,

bimolecularbimolecularSubstitution:Substitution: One things substitutes for One things substitutes for anotheranother

NucleophilicNucleophilic: Nucleophile does the substituting: Nucleophile does the substituting– Something must leave Something must leave

Called the leaving groupCalled the leaving group

Bimolecular:Bimolecular: The kinetics of the reaction The kinetics of the reaction involve the concentrations of 2 reactantsinvolve the concentrations of 2 reactants

Mechanism of the SnMechanism of the Sn2 2 Reaction Reaction

General mechanism:General mechanism:

Nu _

= nucleophile (“nucleus loving”), species that seeks a + charge

L = leaving group, the species that leaves

substrate

More DetailMore Detail

X

L

YZ

substrate

Nu_

X

L

YZ

X

YZ

Nu + L

X

L

Y Z

Nuδ− δ−δ+

Transition state Nucleophilesubstitutes for L group

Factors That Affect SnFactors That Affect Sn2 2

ReactionsReactions

Strength of nucleophileStrength of nucleophile

Structure of substrateStructure of substrate

Nature of solventNature of solvent

Concentration of reactantsConcentration of reactants

Nature of the leaving groupNature of the leaving group

Kinetics of the SnKinetics of the Sn2 2 ReactionReaction

Reaction kinetics: how fast a reaction goesReaction kinetics: how fast a reaction goesAppearance of product per unit timeAppearance of product per unit time

Rate Law:Rate Law:– Rate = kRate = k{A}{A}xx{B}{B}yy

Reaction rate dependent on concentrations Reaction rate dependent on concentrations of reactantsof reactants

First order reaction:First order reaction: rate dependent on the concentration rate dependent on the concentration of one reactantof one reactant

Second order reactionSecond order reaction: rate dependent on the : rate dependent on the concentration of both reactantsconcentration of both reactants

Kinetics of the SnKinetics of the Sn22 Reaction Reaction

““2” means the kinetics are second 2” means the kinetics are second orderorder

Rate of reaction dependent on Rate of reaction dependent on concentration of both reactantsconcentration of both reactants

Double concentration of either one, rate Double concentration of either one, rate doublesdoubles

Synthesis of 1-bromobutane from 1-Synthesis of 1-bromobutane from 1-butanolbutanol

Acid catalyzed Acid catalyzed reactionreaction

MechanismMechanism

Good leaving group

Br

+ H+ H2O

H2SO4 + NaBr HBr + NaHSO4

RefluxReflux

Reflux:Reflux: continual boilingcontinual boilingof a solution in a vial or flaskof a solution in a vial or flaskwhere solvent is continually where solvent is continually returned to the reaction vessel returned to the reaction vessel from a condenser atop the vial from a condenser atop the vial or flaskor flask

Water cooled condenser is usedWater cooled condenser is used

Possible to heat a reaction at the boiling Possible to heat a reaction at the boiling point of the solvent for extended periodspoint of the solvent for extended periods

ProcedureProcedureWeigh out 12.5 g of NaBr and add it to 12 ml of ddHWeigh out 12.5 g of NaBr and add it to 12 ml of ddH22O in a 100 ml RB flask (with O in a 100 ml RB flask (with stir bar)stir bar)Clamp to ring stand, stir until NaBr dissolvesClamp to ring stand, stir until NaBr dissolvesAdd 10 ml of 1-butanol to this flaskAdd 10 ml of 1-butanol to this flaskPlace in an ice bath and continue to stirPlace in an ice bath and continue to stirMeasure out 11 ml of concentrated HMeasure out 11 ml of concentrated H22SOSO44 into a clean 50 ml erlenmeyer flask into a clean 50 ml erlenmeyer flaskPut this in its own ice bathPut this in its own ice bathCarefully add the acid to the solution of NaBr and 1-butanol in small amounts Carefully add the acid to the solution of NaBr and 1-butanol in small amounts (maybe 0.5 ml) with stirring. (maybe 0.5 ml) with stirring. Both solutionsBoth solutions must must be in ice baths.be in ice baths.Once completed, remove the RB flask (with acid, 1-butanol in it) and fit a Once completed, remove the RB flask (with acid, 1-butanol in it) and fit a heating mantle with condenser.heating mantle with condenser.Reflux for 45 min with stirring.Reflux for 45 min with stirring.When done refluxing, remove the condenser and fit a still head for distillation. When done refluxing, remove the condenser and fit a still head for distillation. Using a 50 ml RB flask for collection, distill until 20-25 ml of distillate has been Using a 50 ml RB flask for collection, distill until 20-25 ml of distillate has been collected. collected. You should have 2 layers in the receiving flask.You should have 2 layers in the receiving flask.Parafilm the receiving flask and leave it until next week. We will complete the Parafilm the receiving flask and leave it until next week. We will complete the experiment then.experiment then.

Acid AdditionAcid Addition

Set up your solution of NaBr/HSet up your solution of NaBr/H22O/1-butanol O/1-butanol

for acid addition as follows:for acid addition as follows:

Stir plate

RB flask

Crystalling Dish w/ ice

50 ml erlenmeyer flask with acid, in an ice bath

Your ReportYour Report

This is a 2 week experimentThis is a 2 week experiment– This week: the synthesisThis week: the synthesis– Next week: purification & characterizationNext week: purification & characterization

Substitution Reactions 1: The SnSubstitution Reactions 1: The Sn22

ReactionReaction The Synthesis of 1-BromobutaneThe Synthesis of 1-Bromobutane

Part II: WorkupPart II: Workup

Organic Chemistry Lab II, Spring 2009Dr. Milkevitch

November 16 & 18, 2009

Procedure IIProcedure II Remove parafilm, pour your distillate (solution in RB flask) into a 125 Remove parafilm, pour your distillate (solution in RB flask) into a 125

ml separatory funnelml separatory funnel Add 50 ml of ddHAdd 50 ml of ddH22O to the separatory funnel, stopper and shake like O to the separatory funnel, stopper and shake like

you did in the extraction labyou did in the extraction lab Allow layers to separate, draw off bottom organic layer into a 125 ml Allow layers to separate, draw off bottom organic layer into a 125 ml

erlenmeyer flaskerlenmeyer flask Pour off the upper (aqueous) layer and set aside (do NOT throw away Pour off the upper (aqueous) layer and set aside (do NOT throw away

yet)yet) Transfer the organic layer back into the separatory funnel and add 25 Transfer the organic layer back into the separatory funnel and add 25

ml of Hml of H22OO Stopper and shake the separatory funnel again, let layers separateStopper and shake the separatory funnel again, let layers separate Draw off the lower organic layer again, into a 125 ml erlenmeyer flaskDraw off the lower organic layer again, into a 125 ml erlenmeyer flask Pour off the upper (aqueous) layer and set aside (again do NOT throw Pour off the upper (aqueous) layer and set aside (again do NOT throw

it away yet)it away yet) Transfer the organic layer back into the separatory funnel, add 25 ml Transfer the organic layer back into the separatory funnel, add 25 ml

of saturated sodium bicarbonate solution (the bicarb solution is in the of saturated sodium bicarbonate solution (the bicarb solution is in the hood)hood)

Procedure IIIProcedure III Swirl the separatory funnel, notice COSwirl the separatory funnel, notice CO22 escaping. Carefully escaping. Carefully

shake the separatory funnel with frequent ventingshake the separatory funnel with frequent venting Allow the layers to separateAllow the layers to separate Draw off the bottom organic layer into a 125 ml erlenmeyer Draw off the bottom organic layer into a 125 ml erlenmeyer

flaskflask Pour off the upper water layer and set aside (again, do NOT Pour off the upper water layer and set aside (again, do NOT

throw away yet)throw away yet) Filter the organic layer through a layer of anhydrous Filter the organic layer through a layer of anhydrous

magnesium sulfate.magnesium sulfate. Collect the dried organic layerCollect the dried organic layer Place the dried organic layer in a pre-weighed 50 ml RB flask Place the dried organic layer in a pre-weighed 50 ml RB flask

with a spin barwith a spin bar Distill the organic layer until most of the liquid in the distilling Distill the organic layer until most of the liquid in the distilling

flask has distilled over (about 105 deg C)flask has distilled over (about 105 deg C) Weigh the receiving flask, determine weight of productWeigh the receiving flask, determine weight of product

CharacterizationCharacterization

Analyze a sample of your product by GCAnalyze a sample of your product by GCAnalyze by TLC :Analyze by TLC :– Spot standards: 1-bromobutane,Spot standards: 1-bromobutane, 1-butanol, dibutyl ether1-butanol, dibutyl ether– Spot your distilled product alsoSpot your distilled product also– Mobile phase: ethyl acetateMobile phase: ethyl acetate– Analyze under UV light in UV light boxAnalyze under UV light in UV light box

If you have enough product, acquire an IR If you have enough product, acquire an IR spectrum:spectrum:– Consult with Dr. M.Consult with Dr. M.

Complete reaction worksheetComplete reaction worksheet