Substitution Reactions 1: The Sn 2 Reaction The Synthesis of 1-Bromobutane

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

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

3. 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

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

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

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

7. 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

8. 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

9. Synthesis of 1-bromobutane from 1-butanol • Acid catalyzed reaction

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

11. Reflux • Reflux:continual boiling 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

12. 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.

13. 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

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

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

16. 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)

17. 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

18. 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