Chapter Objectives Present reactions of alkenes and alkynes Reactions related to those found in biology Must know reactions Fall, 2007 1 Preparation of Alkenes Precursors Alcohols (especially in biological chemistry) Alkyl Halides (industrial chemistry) OH stro n g a cid H dehydration X strong base H dehydrohalogenation Fall, 2007 2 Biological Dehydration Rarely done on free alcohol Generally done on molecules containing carbonyl and hydroxyl groups H2O - CO - HO CO 2 2 - - - - O C CO O C CO 2 2 2 aconitase 2 Fall, 2007 3 1 Reaction with X 2 Halogenation Reaction with Cl 2 and Br 2 C l 2 C l C l B r 2 B r B r Fall, 2007 4 Stereochemistry Reaction provides the trans product Fall, 2007 5 Explanation Not a carbocation intermediate as shown Bromonium ion intermediate forms H H Br H Br + H Br Br - Fall, 2007 6 2 Biological Halogenation Marine organisms Haloperoxidase - - + H2O2 oxidizes Cl or Br to X B r C l C l B r Fall, 2007 7 Reaction with X 2 in H 2O Cl 2 in water yields HO -Cl (hypochlorous acid) Br 2 in water yields HO -Br ( hypobromous acid) Br /H O 2 2 OH Br Fall, 2007 8 Hydration of Alkenes Alkenes react with water to give alcohols Require high temperatures and pressures H2O CH 3CH 2OH Does not work well in the laboratory Fall, 2007 9 3 Biological Hydration of Alkenes O O OH O- -O -O fumarase O O fumarate maleate Relatively rare reaction Cellular constraints are not present. Fall, 2007 10 Cellular Constraints Solvent is water Narrow pH range Fixed temperature Limited elemental choice Fall, 2007 11 Laboratory Hydration of Alkenes Oxymercuration Mercuric Acetate in THF Markovnikov Product Fall, 2007 12 4 Laboratory Hydration of Alkenes Hydroboration Non -Markovnikov Product Fall, 2007 13 Mechanism of Hydroboration Borane is a Lewis acid Alkene is Lewis base Transition state involves anionic development on B The components of BH 3 add across C=C Fall, 2007 14 Reduction and Oxidation Carbon always has 4 bonds Oxidation changes are more difficult to see Reduction: Increase in H content Decrease in O content Oxidation: Decrease in H content Increase in O content Fall, 2007 15 5 Reduction of Alkenes: Hydrogenation Addition of H 2 Requires Pt or Pd catalyst (or NR) Heterogeneous Reaction Process is not in solution Fall, 2007 16 Mechanism of Catalytic Hydrogenation Heterogeneous – reaction between phases Addition of H -H is syn Fall, 2007 17 Biological Reductions Rare Reaction Uses NADPH as reducing agent N NH2 O O O O O O N N N P P O N H O O HO OH - - H -2 HO OPO2 O NH2 Nicotinamide Adenine Dinucleotide Phosphate Fall, 2007 18 6 Oxidation of Alkenes: Epoxides mcpba O CH 2Cl 2 H O OOH peroxide mcpba = Cl Reaction with a peracid Epoxide or oxirane Cyclic ether Fall, 2007 19 Epoxide Preparation From Halohydrin Br 2/H 2O OH base O Br bromohydrin Fall, 2007 20 Biological Epoxidation Present in variety of processes Does not involve peracids Peroxides formed by reaction with O 2 Very selective reaction (see Figure 7.8) Fall, 2007 21 7 Hydroxylation of Alkenes Diol formation + H3O OH O OH Laboratory and Biological Reaction Biological process useful for detoxification Fall, 2007 22 Laboratory Hydroxylation Reaction with osmium tetroxide Stereochemistry of addition is syn (product is cis ) Product is a 1,2 -dialcohol or diol (also called a glycol ) Fall, 2007 23 Reaction with Carbenes H2C: The carbene functional group Carbenes are electrically neutral with six electrons in the outer shell They add symmetrically to double bonds giving cyclopropanes Fall, 2007 24 8 Formation of Dichlorocarbene Base removes proton from chloroform Stabilized carbanion remains Unimolecular Elimination of Cl - gives electron deficient species, dichlorocarbene Fall, 2007 25 Reaction of Dichlorocarbene Addition of dichlorocarbene is stereospecific cis Fall, 2007 26 Simmons-Smith Reaction Equivalent of addition of CH 2: Reaction of diiodomethane with zinc -copper alloy produces a carbenoid species Forms cyclopropanes by cycloaddition Fall, 2007 27 9 Radical Reactions Mechanism of addition of HBr was hotly debated Non -Markovnikov product was observed Peroxides form readily in starting material HBr Br On occasion HBr Br + Br Fall, 2007 28 Radical Reactions - HBr If reaction is done with HBr /peroxides Get the non -Markovnikov product HBr/peroxides Br Fall, 2007 29 Radical Reactions: Polymer Formation Polymer – a very large molecule made of repeating units of smaller molecules (monomers) Biological Polymers Starch Cellulose Protein Nucleic Acid Fall, 2007 30 10 Polymers Alkene polymerization Initiator used generally is a radical n re p e a tin g u n it Fall, 2007 31 Mechanism Initiation Propagation Termination See page 241 in text for details High reactivity of radicals limits usefulness Not true in biological chemistry Fall, 2007 32 Biological Radical Reactions Enzyme permits a single substrate at a time at the active site Greater control over reactivity Radical reactions are common Example given on page 244 for biosynthesis of the PGAs Fall, 2007 33 11 Dienes Contain two double bonds Non -conjugated Conjugated Fall, 2007 34 Common Feature in Nature Fall, 2007 35 Conjugation Absorption of visible light produces color Conjugated hydrocarbon with many double bonds are polyenes Lycopene - red color in tomatoes Carrotene – orange color Extended conjugation in ketones (enones ) found in hormones such as progesterone Fall, 2007 36 12 Conjugated Dienes Chemistry is slightly different More stable than non -conjugated dienes Heat of hydrogenation Fall, 2007 37 Greater Stability Why? Orbital Picture of alkene bonding Fall, 2007 38 Fall, 2007 39 13 Orbital picture of conjugated diene Electrons are delocalized (spread -out) over the entire pi framework Impact upon the chemistry Fall, 2007 40 Fall, 2007 41 Reactions With HBr Br (71%) HBr H Br (29%) H Why? Fall, 2007 42 14 Mechanism Fall, 2007 43 Allylic Cation Fall, 2007 44 Some Data H H HX X X 1,4 product 1,2 product Nucleophile 1,2 Product 1,4 Product Bromide 71% 29% Chloride 30% 70% If HBr is added at 0 oC we see the above data. If the reaction is done at 40 oC, we see 30% of the 1,2 product and 70% of the 1,4 product. How do we explain these results? Fall, 2007 45 15 A B + C B forms faster than C Energy of activation is lower for B than C C is more stable than B Constructing reaction energy diagram energy B A C reaction progress Fall, 2007 46 Thermodynamic Control Transition state leading to more stable species is higher in energy, therefore, it is easier to get to the less stable product Reaction is reversable At high temperatures, sufficient E for both reactions to occur A B (fast) and A C (slower) or B A C We see more stable product dominate. Fall, 2007 47 Kinetic Control At low temperatures Reaction is not reversable Equilibrium is not reached Insufficient energy for A to C Sufficient energy for A to B Less stable product dominates. Fall, 2007 48 16 Reactions of Alkynes Alkynes are rare in biological chemistry Chemistry is similar to alkenes Generally less reactive than alkenes Reactions can be stopped at alkene stage using one equivalent of the reagent Fall, 2007 49 Reactions with HX Regiochemistry is Markovnikov Fall, 2007 50 Reactions with X 2 Initial addition gives trans intermediate Product with excess reagent is tetra -halide Fall, 2007 51 17 Reactions with H 2 Reduction using Pd or Pt does not stop Alkene is more reactive than alkyne Fall, 2007 52 Reactions with H 2 Lindler’s catalyst is poisoned Not as reactive Stops at cis -alkene Fall, 2007 53 Reduction using dissolving metals Anhydrous ammonia (NH 3) is a liquid below -33 ºC Alkali metals dissolve in liquid ammonia - Provide a solution of e in NH 3 Alkynes are reduced to trans alkenes with sodium or lithium in liquid ammonia Fall, 2007 54 18 Hydration of Alkynes Hydration (Hg +2 ) of terminal alkynes provides methyl ketones Hydration (BH 3) of terminal alkynes provides aldehydes Fall, 2007 55 Alkyne Acidity: Acetylide Anion Terminal alkynes are weak Br ønsted acids pK a is approximately 25 alkenes and alkanes are much less acidic Reaction of strong anhydrous bases with a terminal acetylene produces an acetylide ion Fall, 2007 56 Alkylation of Acetylide Anions Acetylide ions are nucleophiles Acetylide ions are bases React with a primary alkyl halides Fall, 2007 57 19 PROBLEMS ON ALKENE CHEMISTRY ©2004 OCHeM.com 1. Answer the following questions concerning the three alkenes shown below. Your answer should use words and illustrations. 1 2 3 4 5 6 CH3 O CH3 CF3 A B C a) Which alkene would be most reactive with H+ ? Why? b) Which alkene would be least reactive with H+ ? Why? c) Which alkene would be most reactive under conditions of catalytic hydrogenation? Why? d) Will all three alkenes undergo Markovnikov addition of HBr? If not, which alkene or alkenes won’t and why? 1 PROBLEMS ON ALKENE CHEMISTRY ©2004 OCHeM.com 2. Provide a mechanism for the following reaction. Then, predict the reaction energy diagram for the entire reaction in the space provided. In your diagram, you must indicate the ΔH of the reaction, label the activation energy (Ea) of the rate-determining step, and clearly identify all intermediates and products of the reaction. H Br Br y g r e n E Reaction Coordinate 2 PROBLEMS ON ALKENE CHEMISTRY ©2004 OCHeM.com 3. What starting materials & reagents are needed to produce the following compound? Br Br 4. Draw the major product of each of the following reactions.