Organic Chemistry Lab II, Fall 2009 Substitution Reactions 1: The Sn2 Reaction The Synthesis of 1-Bromobutane Organic Chemistry Lab II, Fall 2009 Dr. Milkevitch November 9 & 12, 2009

Substitution Reactions Today: Learn about an Sn2 reaction Type of reaction: Substitution One thing substitutes for another Primarily a reaction of alkyl halides

The Sn2 Reaction Sn2 = Substitution, nucleophilic, bimolecular Substitution: One things substitutes for another Nucleophilic: Nucleophile does the substituting Something must leave Called the leaving group Bimolecular: The kinetics of the reaction involve the concentrations of 2 reactants

Mechanism of the Sn2 Reaction General mechanism: substrate Nu _ = nucleophile (“nucleus loving”), species that seeks a + charge L = leaving group, the species that leaves

More Detail Transition state + L Nu _ Nucleophile substitutes for substrate Nu _ Nucleophile substitutes for L group

Factors That Affect Sn2 Reactions Strength of nucleophile Structure of substrate Nature of solvent Concentration of reactants Nature of the leaving group

Kinetics of the Sn2 Reaction Reaction kinetics: how fast a reaction goes Appearance of product per unit time Rate Law: Rate = k{A}x{B}y Reaction rate dependent on concentrations of reactants First order reaction: rate dependent on the concentration of one reactant Second order reaction: rate dependent on the concentration of both reactants

Kinetics of the Sn2 Reaction “2” means the kinetics are second order Rate of reaction dependent on concentration of both reactants Double concentration of either one, rate doubles

Synthesis of 1-bromobutane from 1-butanol Acid catalyzed reaction

Mechanism H2SO4 + NaBr HBr + NaHSO4 Good leaving group Br + H2O + H

Reflux Reflux: continual boiling Water cooled condenser is used of a solution in a vial or flask where solvent is continually returned to the reaction vessel from a condenser atop the vial or flask Water cooled condenser is used Possible to heat a reaction at the boiling point of the solvent for extended periods

Procedure Weigh out 12.5 g of NaBr and add it to 12 ml of ddH2O in a 100 ml RB flask (with stir bar) Clamp to ring stand, stir until NaBr dissolves Add 10 ml of 1-butanol to this flask Place in an ice bath and continue to stir Measure out 11 ml of concentrated H2SO4 into a clean 50 ml erlenmeyer flask Put this in its own ice bath Carefully add the acid to the solution of NaBr and 1-butanol in small amounts (maybe 0.5 ml) with stirring. Both solutions must be in ice baths. Once completed, remove the RB flask (with acid, 1-butanol in it) and fit a heating mantle with condenser. Reflux for 45 min with stirring. 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 collected. You should have 2 layers in the receiving flask. Parafilm the receiving flask and leave it until next week. We will complete the experiment then.

Acid Addition Set up your solution of NaBr/H2O/1-butanol for acid addition as follows: RB flask 50 ml erlenmeyer flask with acid, in an ice bath Crystalling Dish w/ ice Stir plate

Your Report This is a 2 week experiment This week: the synthesis Next week: purification & characterization

Organic Chemistry Lab II, Spring 2009 Substitution Reactions 1: The Sn2 Reaction The Synthesis of 1-Bromobutane Part II: Workup Organic Chemistry Lab II, Spring 2009 Dr. Milkevitch November 16 & 18, 2009

Procedure II Remove parafilm, pour your distillate (solution in RB flask) into a 125 ml separatory funnel Add 50 ml of ddH2O to the separatory funnel, stopper and shake like you did in the extraction lab Allow layers to separate, draw off bottom organic layer into a 125 ml erlenmeyer flask Pour off the upper (aqueous) layer and set aside (do NOT throw away yet) Transfer the organic layer back into the separatory funnel and add 25 ml of H2O Stopper and shake the separatory funnel again, let layers separate Draw 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 it away yet) Transfer the organic layer back into the separatory funnel, add 25 ml of saturated sodium bicarbonate solution (the bicarb solution is in the hood)

Procedure III Swirl the separatory funnel, notice CO2 escaping. Carefully shake the separatory funnel with frequent venting Allow the layers to separate Draw off the bottom organic layer into a 125 ml erlenmeyer flask Pour off the upper water layer and set aside (again, do NOT throw away yet) Filter the organic layer through a layer of anhydrous magnesium sulfate. Collect the dried organic layer Place the dried organic layer in a pre-weighed 50 ml RB flask with a spin bar Distill the organic layer until most of the liquid in the distilling flask has distilled over (about 105 deg C) Weigh the receiving flask, determine weight of product

Characterization Analyze a sample of your product by GC Analyze by TLC : Spot standards: 1-bromobutane, 1-butanol, dibutyl ether Spot your distilled product also Mobile phase: ethyl acetate Analyze under UV light in UV light box If you have enough product, acquire an IR spectrum: Consult with Dr. M. Complete reaction worksheet