John E. McMurry Richard Morrison University of Georgia, Athens Chapter 8 Reactions of Alkenes and Alkynes

Alkene addition reactions Alkene Addition Reactions

Preparation of alkenes: elimination reactions Precursors to alkenes Biological systems – usually alcohols Laboratory – either alcohols or alkyl halides Alkenes and alcohols are chemically related through addition and elimination reactions Alkenes add H 2 O to form alcohols Alcohols eliminate water to form alkenes Preparing Alkenes: A Preview of Elimination Reactions

Dehydrohalogenation Loss of HX from alkyl halide Usually occurs by reaction of an alkyl halide with a strong base Preparing Alkenes: A Preview of Elimination Reactions

Dehydration Loss of water from an alcohol Usually occurs by treatment of an alcohol with a strong acid Preparing Alkenes: A Preview of Elimination Reactions

In biological pathways dehydrations normally take place on substrates in which –OH is positioned two carbons away from a carbonyl group Preparing Alkenes: A Preview of Elimination Reactions

Halogenation Addition reaction of alkenes Addition of Br 2 and Cl 2 to alkenes to yield 1,2-dihalides Halogenation of Alkenes

Halogenation of cycloalkenes Only trans-stereoisomer of dihalide product is formed Reaction occurs with anti stereochemistry – the two halogen atoms come from opposite faces of double- bond, one from top face and one form bottom face Halogenation of Alkenes

Reaction occurs through an intermediate bromonium ion (R 2 Br + ), formed by interaction of the alkene with Br 2 and simultaneous loss of Br - Halogenation of Alkenes

Bromonium ion shields one side of molecule so that reaction with Br - ion occurs only from opposite side Halogenation of Alkenes

Halohydrin Formation (electrophilic addition) Reaction of alkenes with hypohalous acids HO-Cl or HO-Br to yield 1,2-halo alcohols called halohydrins Halohydrins from Alkenes

X 2 reacts with alkene to give cyclic halonium ion intermediate Intermediate halonium ion is intercepted by water nucleophile Oxygen loses proton to give the neutral halohydrin product Halohydrins from Alkenes

Alkenes undergo an acid catalyzed addition reaction with water to yield alcohols Hydration of ethylene is not of much use in the laboratory because of the high temperatures often required Uncommon in biological pathways 8.4Hydration of Alkenes

Laboratory hydrations of alkenes Oxymercuration Electrophilic addition of Hg 2+ to alkene on treatment with mercury(II) acetate [(CH 3 CO 2 ) 2 Hg, or Hg(OAc) 2 ] in aqueous tetrahydrofuran (THF) solvent Reaction yields an alcohol Product corresponds to Markovnikov regiochemistry (more highly substituted alcohol formed) Hydration of Alkenes

Hydroboration/oxidation Addition of a B-H bond of borane, BH 3, to an alkene Occurs in single step No carbocation intermediate Reaction yields an alcohol Syn stereochemistry Both C-H and C-B bonds form at the same time and from the same face of the double-bond Product has “anti”-Markovnikov regiochemistry Hydration of Alkenes

Alkene Hydroboration Hydration of Alkenes

Solution Example Predicting the Products of a Hydration Reaction

How might you prepare the following alcohol? Example Synthesizing an Alcohol

Strategy To synthesize a specific target molecule work backwards Look at target molecule Identify functional group(s) Devise a method for preparing functional group Worked Example 8.2 Synthesizing an Alcohol

Solution Worked Example 8.2 Synthesizing an Alcohol

Oxidation A reaction that results in a loss of electron density by carbon Oxidation Decreases electron density on carbon by Breaking C-H bond Forming C-O, C-N, or C-X bond Note: oxidation often adds oxygen; reduction often adds hydrogen Oxidation of Alkenes: Epoxidation

Alkenes on treatment with a peroxyacid, RCO 3 H, are oxidized to give epoxides Epoxide (oxiranes) Cyclic ethers with an oxygen atom in a three-membered ring Oxidation of Alkenes: Epoxidation

Synthesis of epoxides from alkenes Peroxyacid transfers oxygen to alkene Syn stereochemistry Both C-O bonds form on the same face of the double One step mechanism No intermediates Oxidation of Alkenes: Epoxidation

Synthesis of epoxides from halohydrins Preparation of halohydrin through electrophilic addition of HO-X to alkene Treatment of halohydrin with base deprotonates OH O - nucleophile reacts with C-Cl electrophile substituting C- O bond for C-Cl bond Cl - eliminated yielding the epoxide Oxidation of Alkenes: Epoxidation

Hydroxylation The addition of an –OH group to each of the two double-bond carbons Two step process: 1. Epoxidation 2. Hydration Epoxides undergo an acid-catalyzed reaction with water to give corresponding 1,2-dialcohol, or diol 8.7Oxidation of Alkenes: Hydroxylation

Acid catalyzed epoxide-opening takes place by: 1. Protonation of the epoxide increasing the electrophilicity of carbon 2. Nucleophilic addition of water followed by deprotonation Trans-1,2-diol formed Oxidation of Alkenes: Hydroxylation

Hydroxylation in the Laboratory Carried out directly by oxidation of an alkene with osmium tetroxide, OsO 4 Catalytic amount of OsO 4 used in the presence of stoichiometric amount of N-methylmorpholine N-oxide (NMO) Syn stereochemistry No carbocation intermediate Occurs through cyclic osmate intermediate Oxidation of Alkenes: Hydroxylation

Ozone (O 3 ) is useful double-bond cleavage reagent Ozone is generated by passing a stream of oxygen through a high- voltage electrical discharge Ozone adds rapidly to C=C bond at low temperature to give molozonide which spontaneously rearranges to ozonide Ozonide is treated with reducing agent to convert it to carbonyl compounds 8.8 Oxidation of Alkenes: Cleavage to Carbonyl Compounds

If tetrasubstituted double bond is ozonized, two ketone fragments result If a carbon of the alkene is bonded to hydrogen, ozonolysis will cleave the double bond to yield an aldehyde Oxidation of Alkenes: Cleavage to Carbonyl Compounds

Potassium permanganate (KMnO 4 ) in neutral or acidic solution cleaves alkenes to give carbonyl-containing products If a carbon of the alkene is bonded to hydrogen a carboxylic acid is produced If a carbon of the alkene is bonded to two hydrogens, CO 2 is formed Oxidation of Alkenes: Cleavage to Carbonyl Compounds

Alkenes are also cleaved by hydroxylation to a 1,2-diol followed by treatment with periodic acid, HIO 4. If the two –OH groups of the diol are in an open chain, two carbonyl compounds result If the two –OH groups of the diol are on a ring, a single, open-chain dicarbonyl compound is formed Oxidation of Alkenes: Cleavage to Carbonyl Compounds

What alkene would yield a mixture of cyclopentanone and propanal on treatment with ozone followed by reduction with zinc? Example Predicting the Reactant in an Ozonolysis Reaction

Strategy Reaction alkene with ozone, followed by reduction with zinc, cleaves the carbon-carbon double bond and gives two carbonyl-containing fragments Working backward, the alkene precursor can be found by removing the oxygen from each product and joining the two carbon atoms to form a double bond Worked Example 8.3 Predicting the Reactant in an Ozonolysis Reaction

Solution Worked Example 8.3 Predicting the Reactant in an Ozonolysis Reaction

A carbene, R 2 C:, is a neutral molecule containing a divalent carbon with only six electrons in its valence shell One simple method for generating dichlorocarbene is by treatment of CHCl 3 with KOH Carbenes behave as electrophiles, adding to alkenes to yield cyclopropanes 8.9 Addition of Carbenes to Alkenes: Cyclopropane Synthesis

Mechanism of the formation of dichlorocarbene Addition of Carbenes to Alkenes: Cyclopropane Synthesis

Dichlorocarbene carbon atom is sp 2 -hybridized with a vacant p orbital extending above and below the plane of the three atoms with an unshared pair of electrons occupying the third sp 2 lobe Addition of Carbenes to Alkenes: Cyclopropane Synthesis

Reaction of dichlorocarbene with an alkene results in a dichlorocyclopropane Addition is stereospecific, meaning that only a single stereoisomer is formed as product Addition of Carbenes to Alkenes: Cyclopropane Synthesis

Simplest polymerization Result when an alkene is treated with a small amount of a radical as an initiator Radical Addition to Alkenes: Alkene Polymers

Initiation 1. Small amount of benzoyl peroxide catalyst is heated breaking weak O-O bonds and yielding radicals 2. Benzoyloxy radical adds to C=C bond of ethylene forming a carbon radical 3. a) One electron from C=C bond pairs up with electron of benzoyloxy radical to form C-O bond b) Other electron remains on carbon (a carbon-centered radical) Radical Addition to Alkenes: Alkene Polymers

Propagation Polymerization occurs when the carbon radical adds to another ethylene molecule to yield another radical Termination Chain process ends by a reaction that consumes a radical Combination of two growing chains 2-R–CH 2 CH 2 → R–CH 2 CH 2 CH 2 CH 2 –R Radical Addition to Alkenes: Alkene Polymers

Vinyl monomers Substituted ethylene Undergo polymerization to yield polymer with substituted groups regularly spaced in alternating carbon atom long chain Polypropylene Styrene Radical Addition to Alkenes: Alkene Polymers

Polymerization of unsymmetrically substituted vinyl monomers Propylene or Styrene Radical addition steps can take place at either end of the double bond to yield: A primary radical intermediate (RCH 2. ) A secondary radical (R 2 CH. ) Similar to electrophilic addition reaction More highly substituted, secondary radical is formed Radical Addition to Alkenes: Alkene Polymers

Show the structure of poly(vinyl chloride), a polymer made from H 2 C=CHCl, by drawing several repeating units Worked Example 8.4 Predicting the Structure of a Polymer

Strategy Mentally break the carbon-carbon double bond in the monomer unit, and form single bonds by connecting numerous units together Worked Example 8.4 Predicting the Structure of a Polymer

Solution The general structure of poly(vinyl chloride) is Worked Example 8.4 Predicting the Structure of a Polymer

Electrophilic addition Reaction occurs once Intermediate is then quenched and reaction stops. Radical vs. Electrophilic Addition Reactions Additions to Alkenes Polar

Radical addition Difficult to control Limited use in the laboratory Reaction intermediate is not quenched so reaction continues Radical vs. Electrophilic Addition Reactions Additions to Alkenes, Radicals

Sites of unsaturation Many compounds have numerous sites of unsaturation If sites are well separated in molecule they react independently If sites are close together they may interact with one another Conjugated double bonds Double bonds that alternate with single bonds Conjugated Dienes

Heats of Hydrogenation Conjugated dienes are more stable than nonconjugated dienes Conjugated Dienes

Buta-1,3-diene is approximately 16 kJ/mol (3.8 kcal/mol) more stable than expected Conjugated Dienes

Explanations for conjugated diene stability 1) Valence Bond Theory Stability due to orbital hybridization Alkanes C-C single bonds σ overlap of sp 3 orbitals on both carbons Conjugated dienes σ overlap of sp 2 orbitals (shorter and stronger) Conjugated Dienes

Conjugated dienes Undergo electrophilic addition reactions readily Mixture of products obtained Addition of HBr to buta-1,3-diene yields mixture of two addition products 8.13 Reactions of Conjugated Dienes

Allylic carbocation is an intermediate Allylic means next to a double bond When buta-1,3-diene reacts with H + electrophile two carbocation intermediates are possible: 1. A primary carbocation 2. A secondary allylic carbocation (stabilized by resonance between two forms) Secondary allylic carbocation is more stable and forms faster than the nonallylic carbocation Reactions of Conjugated Dienes

Allylic carbocation reacts with Br - to complete the electrophilic addition Reaction can occur at C1 or C3 Both carbons share positive charge Mixture of 1,2- and 1,4-addition products results Reactions of Conjugated Dienes

Example Predicting the Products of Electrophilic Addition to a Conjugated Diene

Conjugated dienes undergo reactions with alkenes to yield substituted cyclohexene products The Diels-Alder Cycloaddition Reaction

Diels-Alder cycloaddition reaction is a Pericyclic reaction Pericyclic reactions take place in a single step by a cyclic redistribution of bonding electrons The Diels-Alder Cycloaddition Reaction

In the Diels-Alder transition state, the two alkene carbons and carbons 1 and 4 of the diene rehybridize from sp 2 to sp 3 to form two new single bonds, while carbons 2 and 3 of the diene remain sp 2 hybridized to from the new double bond in the cyclohexene product Diels-Alder cycloaddition reaction occurs most rapidly if the alkene component, or dienophile (“diene lover”), has an electron-withdrawing substituent group The Diels-Alder Cycloaddition Reaction

Diels-Alder reaction is stereospecific Reactant stereochemistry is also maintained The Diels-Alder Cycloaddition Reaction

Diene must adopt an s-cis conformation, meaning “cis-like” about the single bond The Diels-Alder Cycloaddition Reaction

Some dienes cannot adopt the s-cis conformation and cannot undergo Diels-Alder cycloaddition reactions The Diels-Alder Cycloaddition Reaction

Some dienes are fixed in the s-cis conformation and are highly reactive in Diels-Alder cycloaddition reactions The Diels-Alder Cycloaddition Reaction

A few biological Diels-Alder reactions are known Biosynthesis of lovastatin involves an intramolecular Diels- Alder reaction in the key step The Diels-Alder Cycloaddition Reaction

Predict the product of the following Diels-Alder reaction Worked Example 8.6 Predicting the Product of a Diels-Alder Reaction

Strategy Draw the diene so that the ends of the two double bonds are near the dienophile double bond. Then form two single bonds between the partners, convert the three double bonds into single bonds, and convert the former single bond of the diene into a double bond. Because the dienophile double bond is cis to begin with, the two attached hydrogens must remain cis in the product Worked Example 8.6 Predicting the Product of a Diels-Alder Reaction

Solution Worked Example 8.6 Predicting the Product of a Diels-Alder Reaction

Alkyne Addition Reactions Alkynes behave similarly to alkenes Alkynes are more reactive than alkenes Various reactions can often be stopped at the monoaddition stage if one molar equivalent of reagent is used 8.15 Reactions of Alkynes

Reactions of Alkynes

Alkyne acidity Terminal alkynes (RC≡CH) are relatively acidic RC≡CH treated with a strong base NaNH 2 Terminal hydrogen is removed forming and acetylide anion Reactions of Alkynes

Alkyne acidity Br Ø nsted-Lowry Acid A substance that donates H + Acidity order: Established by measuring acid dissociation constants and expressing the results as pKa values Low pK a = strong acid High pK a = weak acid Amide ion (NH 2 - ), the conjugated base of ammonia (pK a = 35), is often used to deprotonate terminal alkynes Reactions of Alkynes

Terminal alkynes more acidic than alkenes or alkanes Acetylide ions are more stable than vinylic (alkenyl) or alkyl ions Difference in acidities due to hybridization of negatively charged carbon atom Acetylide anion has sp-hybridized carbon Reactions of Alkynes

Presence of negative charge and an unshared electron pair on carbon makes acetylide anions strongly nucleophilic Nucleophilic substitutions not limited to acetylene Reactions of Alkynes