CHE2201, Chapter 8 Learn, 1 Chapter 8 Alkenes: Reactions and Synthesis Suggested Problems ,26-9,32-5,37-39

CHE2201, Chapter 8 Learn, 2 Alkenes undergo electrophilic addition reactions to give many useful products Diverse Reactions of Alkenes

CHE2201, Chapter 8 Learn, 3 Preparation of Alkenes: A Preview of Elimination Reactions Alkenes are commonly made by an elimination reaction 1.Dehydrohalogenation - Loss of HX from an alkyl halide Occurs by reaction of an alkyl halide with strong base

CHE2201, Chapter 8 Learn, 4 Preparation of Alkenes: A Preview of Elimination Reactions 2.Dehydration - Loss of water from an alcohol Carried out by treating an alcohol with a strong acid

CHE2201, Chapter 8 Learn, 5 Worked Example How many alkene products, including E,Z isomers, might be obtained by dehydration of 3- methyl-3-hexanol with aqueous sulfuric acid?

CHE2201, Chapter 8 Learn, 6 Worked Example Solution: –It is possible to obtain five alkene products by the dehydration of 3-methyl-3-hexanol

CHE2201, Chapter 8 Learn, 7 Electrophilic Addition Reactions

CHE2201, Chapter 8 Learn, 8 Halogenation of Alkenes: Addition of X 2 Halogenation - Bromine and chlorine add to alkenes to give 1,2-dihalides Example –1,2-dichloroethane is formed by addition of Cl 2 to ethylene Fluorine is too reactive and iodine does not react with majority of alkenes

CHE2201, Chapter 8 Learn, 9 Halogenation of Alkenes: Addition of X 2 Halogenation reaction of cycloalkane forms the trans stereoisomer of the dihalide addition product Reaction occurs with anti stereochemistry

CHE2201, Chapter 8 Learn, 10 Mechanism of Bromine Addition As suggested by George Kimball and Irving Roberts, for the observed stereochemistry the reaction intermediate is not a carbocation Bromonium ion, R 2 Br +, is formed by electrophilic addition of Br + to the alkene

CHE2201, Chapter 8 Learn, 11 Mechanism of Bromine Addition Bromonium ion is formed in a single step –Interaction of the alkene with Br 2 and simultaneous loss of Br - Reaction with Br - ion occurs only from the opposite, unshielded side to give trans product

CHE2201, Chapter 8 Learn, 12 Mechanism of Bromine Addition Bromonium ions were postulated more than 75 years ago to explain stereochemistry of halogen addition to alkenes George Olah showed that bromonium ions are stable in liquid SO 2

CHE2201, Chapter 8 Learn, 13 Addition of a Halogen is an Anti Addition

CHE2201, Chapter 8 Learn, 14 Anti Addition to a Cis Isomer Forms Only the Trans Stereoisomers

CHE2201, Chapter 8 Learn, 15 No Carbocation Rearrangements

CHE2201, Chapter 8 Learn, 16 Worked Example Addition of HCl to 1,2-dimethylcyclohexene yields a mixture of two products –Show the stereochemistry of each, and explain why a mixture is formed Solution: Addition of hydrogen halides involves formation of an open carbocation The carbocation, which is sp 2 -hybridized and planar, can be attacked by chloride from either top or bottom

CHE2201, Chapter 8 Learn, 17 Worked Example –This yields products in which the two methyl groups can be either cis or trans to each other

CHE2201, Chapter 8 Learn, 18 Halohydrins from Alkenes: Addition of HOX Reaction of alkenes with hypohalous acids HO–Cl or HO–Br yields 1,2-halo alcohol, called a halohydrin Addition takes place by reaction of the alkene with either Br 2 or Cl 2 in the presence of water

CHE2201, Chapter 8 Learn, 19 Formation of Halohydrins

CHE2201, Chapter 8 Learn, 20 Mechanism for Halohydrin Formation

CHE2201, Chapter 8 Learn, 21 How to Account for Regioselectivity The electrophile adds to the sp 2 carbon bonded to the most hydrogens.

CHE2201, Chapter 8 Learn, 22 Halohydrins from Alkenes: Addition of HOX Bromohydrin formation is carried out in a solvent such as aqueous dimethyl sulfoxide, CH 3 SOCH 3 (DMSO), using the reagent N-bromosuccinimide (NBS) –Produces bromine in organic solvents and is a safer source

CHE2201, Chapter 8 Learn, 23 NBS Mechanism

CHE2201, Chapter 8 Learn, 24 More Reactions Different nucleophiles Each involves a chloronium or bromonium ion intermediate

CHE2201, Chapter 8 Learn, 25 Worked Example What product would you expect from the reaction of cyclopentene with NBS and water? –Show the stereochemistry Solution: ––Br and –OH are trans in the product

CHE2201, Chapter 8 Learn, 26 Hydration of Alkenes: Addition of H 2 O Hydration of an alkene is the addition of H 2 O to give an alcohol Reaction takes place on treatment of the alkene with water and a strong acid catalyst

CHE2201, Chapter 8 Learn, 27 Mechanism of Hydration

CHE2201, Chapter 8 Learn, 28 Hydration of Alkenes: Addition of H 2 O Acid-catalyzed hydration of isolated double bonds is uncommon in biological pathways Fumarate is hydrated to give malate as one step in the citric acid cycle of food metabolism In the laboratory, alkenes are often hydrated by the oxymercuration–demercuration procedure

CHE2201, Chapter 8 Learn, 29 Reaction is initiated by electrophilic addition of Hg 2+ ion to the alkene –Gives an intermediate mercurinium ion Regiochemistry of the reaction corresponds to Markovnikov addition of H 2 O Hydration of Alkenes: Addition of H 2 O by Oxymercuration

CHE2201, Chapter 8 Learn, 30 Acid-Catalyzed Addition of an Alcohol

CHE2201, Chapter 8 Learn, 31 Carbocation Rearrangement (a 1,2-hydride shift)

CHE2201, Chapter 8 Learn, 32 Carbocation Rearrangement (a 1,2-methyl shift)

CHE2201, Chapter 8 Learn, 33 The Carbocation Does Not Rearrange No Improvement in Carbocation Stability is afforded here

CHE2201, Chapter 8 Learn, 34 Worked Examples What products would you expect from oxymercuration–demercuration of the following alkenes? a) b)

CHE2201, Chapter 8 Learn, 35 Worked Examples Solution: –Oxymercuration is equivalent to Markovnikov addition of H 2 O to an alkene a) b)

CHE2201, Chapter 8 Learn, 36 Hydration of Alkenes: Addition of H 2 O by Hydroboration Hydroboration: Process involving addition of a B–H bond of borane, BH 3, to an alkene to yield an organoborane intermediate, RBH 2 Boron has six atoms in its valance shell making borane a very reactive Lewis acid

CHE2201, Chapter 8 Learn, 37 BH 3 Contains Three Hydrides – Dialkyl and Trialkylboranes Typically Form

CHE2201, Chapter 8 Learn, 38 Alkene reacts with BH 3 in THF solution, rapid addition to the double bond occurs three times and a trialkylborane is formed Net effect of the two-step hydroboration– oxidation sequence is hydration of the alkene double bond Hydration of Alkenes: Addition of H 2 O by Hydroboration

CHE2201, Chapter 8 Learn, 39 R 2 BH Allows Only Monoalkylation Because of its bulky R groups, it has a stronger preference for the less substituted sp 2 carbon.

CHE2201, Chapter 8 Learn, 40 Hydration of Alkenes: Addition of H 2 O by Hydroboration During hydroboration–oxidation of 1-methylcyclopentene, boron and hydrogen add to the alkene from the same face of the double bond with syn stereochemistry

CHE2201, Chapter 8 Learn, 41 Hydroboration Differs from other alkene addition reactions –Occurs in a single step without a carbocation intermediate

CHE2201, Chapter 8 Learn, 42 Addition of BH 3 and Addition of HBr Follow the Same Rule Regiochemistry that results when an unsymmetrical alkene is hydroborated makes the hydroboration reaction very useful Anti-Markovnikov

CHE2201, Chapter 8 Learn, 43 Mechanism for the Oxidation Reaction

CHE2201, Chapter 8 Learn, 44 Only Syn Addition

CHE2201, Chapter 8 Learn, 45 The H and OH Add to the Same Side of the Ring Hydroboration-oxidation is stereoselective – only two of the four possible stereoisomers are formed.

CHE2201, Chapter 8 Learn, 46 No Carbocation Rearrangements

CHE2201, Chapter 8 Learn, 47 Worked Example What alkene might be used to prepare the following alcohol by hydroboration–oxidation? Solution: –The products result from hydroboration/oxidation of a double bond –The –OH group is bonded to the less substituted carbon of the double bond in the starting material

CHE2201, Chapter 8 Learn, 48 Retrosynthesis How would you make this molecule?

CHE2201, Chapter 8 Learn, 49 Reduction of Alkenes: Hydrogenation Hydrogenation: Addition of hydrogen to a double or triple bond to yield a saturated product Reduction: Reaction that results in gain of electron density for carbon caused either by: –Bond formation between carbon and a less electronegative atom (usually H) –Bond-breaking between carbon and a more electronegative atom (usually O,N,X)

CHE2201, Chapter 8 Learn, 50 Reduction of Alkenes: Hydrogenation Usually occurs with syn stereochemistry H 2 is adsorbed onto a catalyst surface

CHE2201, Chapter 8 Learn, 51 Mechanism for Hydrogen Addition catalytic hydrogenation

CHE2201, Chapter 8 Learn, 52 Reduction of Alkenes: Hydrogenation Catalytic hydrogenation is extremely sensitive to the steric environment around the double bond In α-pinene reduction occurs exclusively from the bottom face

CHE2201, Chapter 8 Learn, 53 Selectivity in Hydrogenation

CHE2201, Chapter 8 Learn, 54 Reduction of Alkenes: Hydrogenation Catalytic hydrogenation is important in the food industry Incomplete hydrogenation results in partial cis– trans isomerization of a remaining double bond In biological hydrations, biological reductions occur in two steps: –Reducing agent, NADPH, adds a hydride ion to the double bond to give an anion –Anion is protonated by acid HA, leading to overall addition of H 2

CHE2201, Chapter 8 Learn, 55 Trans Fatty Acids Raise LDL

CHE2201, Chapter 8 Learn, 56 Reduction of the Carbon–Carbon Double Bond in Trans-crotonyl ACP

CHE2201, Chapter 8 Learn, 57 Worked Example What products are obtained from catalytic hydrogenation of the following alkenes? a) b)

CHE2201, Chapter 8 Learn, 58 Worked Example Solution: a) b)

CHE2201, Chapter 8 Learn, 59 Oxidation of Alkenes: Epoxidation and Hydroxylation Oxidation: Reaction that results in a loss of electron density for carbon by: –Bond formation between carbon and a more electronegative atom (usually O,N,X) –Bond-breaking between carbon and a less electronegative atom (usually H)

CHE2201, Chapter 8 Learn, 60 Oxidation of Alkenes: Epoxidation Alkenes oxidize to give epoxides on treatment with a peroxyacid, RCO 3 H Epoxide: Cyclic ether with an oxygen atom in a three-membered ring

CHE2201, Chapter 8 Learn, 61 Only Syn Addition is Observed

CHE2201, Chapter 8 Learn, 62 Mechanism for Epoxidation The mechanism is similar to that for the addition of Br 2

CHE2201, Chapter 8 Learn, 63 Syn Addition to a Cis Isomer Forms Only the Cis Stereoisomers

CHE2201, Chapter 8 Learn, 64 Syn Addition to a Trans Isomer Forms Only the Trans Stereoisomers

CHE2201, Chapter 8 Learn, 65 Oxidation of Alkenes: Epoxidation Treating a base with halohydrin leads to elimination of HX and production of an epoxide

CHE2201, Chapter 8 Learn, 66 Oxidation of Alkenes: Hydroxylation Epoxides undergo an acid-catalyzed ring- opening reaction with water –Gives corresponding 1,2-dialcohol, or diol, also called a glycol

CHE2201, Chapter 8 Learn, 67 Oxidation of Alkenes: Hydroxylation The net result of the two-step alkene epoxidation/hydrolysis is hydroxylation

CHE2201, Chapter 8 Learn, 68 Oxidation of Alkenes: Hydroxylation Hydroxylation can be carried out directly by treating an alkene with osmium tetroxide –Reaction occurs with syn stereochemistry –Does not involve a carbocation intermediate

CHE2201, Chapter 8 Learn, 69 Oxidation of Alkenes: Hydroxylation The use of NMO as a cooxidant permits a catalytic cycle

CHE2201, Chapter 8 Learn, 70 Worked Example What product is expected from reaction of cis-2- butene with meta-chloroperoxybenzoic acid (m- CPBA)? –Show the stereochemistry

CHE2201, Chapter 8 Learn, 71 Worked Example Solution: –Epoxidation using m-chloroperoxybenzoic acid (m- CPBA) is a syn addition –Original double bond stereochemistry is retained –The methyl groups are cis

CHE2201, Chapter 8 Learn, 72 Oxidation of Alkenes: Cleavage to Carbonyl Compounds Ozone (O 3 ) adds to C═C bond, at low temperature, to form molozonide Molozonide rearranges to form ozonide

CHE2201, Chapter 8 Learn, 73 Oxidation of Alkenes: Cleavage to Carbonyl Compounds Ozonide is treated with a reducing agent to produce carbonyl compounds (Zn/AcOH or dimethyl sulfide)

CHE2201, Chapter 8 Learn, 74 Ozonolysis

CHE2201, Chapter 8 Learn, 75 What Alkene Gave these Ozonolysis Products?

CHE2201, Chapter 8 Learn, 76 Oxidation of Alkenes: Cleavage to Carbonyl Compounds Oxidizing reagents other than ozone cause double-bond cleavage Potassium permanganate (KMnO 4 ) can produce carboxylic acids and carbon dioxide if hydrogens are present on C═C With no hydrogens, ketones are produced

CHE2201, Chapter 8 Learn, 77 Oxidation of Alkenes: Cleavage to Carbonyl Compounds Alkenes can be cleaved by hydroxylation to form a 1,2-diol followed by reaction of the diol with periodic acid, HIO 4, to afford carbonyl compounds

CHE2201, Chapter 8 Learn, 78 Worked Example What products would be expected from reaction of 1-methylcyclohexene with aqueous acidic KMnO 4 ? Solution: –Aqueous KMnO 4 produces: A carboxylic acid from a C═C A ketone from a double bond carbon that is disubstituted

CHE2201, Chapter 8 Learn, 79 Addition of Carbenes to Alkenes: Cyclopropane Synthesis Carbene, R 2 C: A neutral molecule containing a divalent carbon with only six electrons in its valence shell –Electrophilic addition of a carbene to an alkene yields a cyclopropane Adds symmetrically across the double bond

CHE2201, Chapter 8 Learn, 80 Dichlorocarbene Generation - Mechanism

CHE2201, Chapter 8 Learn, 81 The Structure of Dichlorocarbene A carbene is planar being sp 2 hybridized with a vacant p-orbital. Note its similarity in structure to that of a carbocation

CHE2201, Chapter 8 Learn, 82 Addition of Carbenes to Alkenes: Cyclopropane Synthesis Addition of dichlorocarbene with cis-2-pentene is stereospecific –Stereospecific: Only a single stereoisomer is formed as product

CHE2201, Chapter 8 Learn, 83 Simmons-Smith Reaction Method for preparing nonhalogenated cyclopropanes Does not involve a free carbene Utilizes a carbenoid Reaction of diiodomethane with zinc-copper alloy produces (iodomethyl)zinc iodide

CHE2201, Chapter 8 Learn, 84 Simmons-Smith Reaction (Iodomethyl)zinc iodide yields the corresponding cyclopropane in the presence of an alkene

CHE2201, Chapter 8 Learn, 85 Worked Example What product is expected from the following reaction

CHE2201, Chapter 8 Learn, 86 Worked Example Solution: –Reaction of a double bond with CH 2 I 2 yields a product with a cyclopropane ring that has a – CH2– group –Two different isomers can be formed, depending on stereochemistry of the double bond

CHE2201, Chapter 8 Learn, 87 Radical Additions to Alkenes: Chain-Growth Polymers Polymer: Large molecule consisting of repeating units of simpler molecules, called monomers – Formed by polymerization Alkenes react with radical catalysts to undergo radical polymerization Simple alkene polymers are called chaingrowth polymers

CHE2201, Chapter 8 Learn, 88 Radical Additions to Alkenes: Chain-Growth Polymers

CHE2201, Chapter 8 Learn, 89 Radical Additions to Alkenes: Chain-Growth Polymers Initiation –A few radicals are generated on heating a small amount of benzoyl peroxide catalyst –Benzoyloxy radical loses CO 2 and gives a phenyl radical

CHE2201, Chapter 8 Learn, 90 Radical Additions to Alkenes: Chain-Growth Polymers Propagation –Radical from initiation adds to alkene to generate alkene derived radical –Process repeats to form the polymer chain Termination –Chain propagation ends when two radical chains combine

CHE2201, Chapter 8 Learn, 91 Radical Additions to Alkenes: Chain-Growth Polymers Other alkenes give other common polymers

CHE2201, Chapter 8 Learn, 92 Some Alkene Polymers and Their Uses

CHE2201, Chapter 8 Learn, 93 Worked Example Show the monomer units required to prepare the following polymer: Solution: –The smallest repeating unit in each polymer is identified and double bond is added –Monomer H 2 C═CHOCH 3

CHE2201, Chapter 8 Learn, 94 Biological Additions of Radicals to Alkenes More controlled and more common than laboratory or industrial radical reactions Radical addition reactions have severe limitations in a laboratory environment

CHE2201, Chapter 8 Learn, 95 Pathway of Biosynthesis of Prostaglandins from Arachidonic Acid

CHE2201, Chapter 8 Learn, 96 Reaction Stereochemistry: Addition of H 2 O to an Achiral Alkene The laboratory hydration of 1-butene yields an intermediate secondary carbocation by protonation It reacts with H 2 O from either the top or the bottom face to afford the two enantiomers Formation of a new chirality center by achiral reactants leads to a racemic mixture of enantiomeric products

CHE2201, Chapter 8 Learn, 97 Reaction of H 2 O with the Carbocation Resulting from Protonation of 1-Butene The two transition states are mirror images

CHE2201, Chapter 8 Learn, 98 Reaction Stereochemistry: Addition of H 2 O to an Achiral Alkene Optically active product can only result by starting with an optically active reactant or a chiral environment Cis-aconitate is achiral –Only the enantiomer of the product is formed in a biological reaction

CHE2201, Chapter 8 Learn, 99 Reaction Stereochemistry: Addition of H 2 O to a Chiral Alkene The stereochemistry in acid-catalyzed addition of H 2 O is established by reaction of H 2 O with a carbocation intermediate –Does not contain a plane of symmetry –Chiral because of existing chirality center Formation of a new chirality center by a chiral reactant leads to unequal amounts of diastereomeric products Products are also optically active, if the chiral reactant is optically active because only one enantiomer is used

CHE2201, Chapter 8 Learn, 100 Stereochemistry of the Acid-Catalyzed Addition of H 2 O to the Chiral Alkene

CHE2201, Chapter 8 Learn, 101 Worked Example 1 Which reaction would one predict to be faster, addition of HBr to cyclohexene or to 1- methylcyclohexene?

CHE2201, Chapter 8 Learn, 102 Worked Example 1 First, draw out both reactants with HBr. What we should realize at this point is that the formation of the intermediate that is more stabilized via carbocation formation is the one that will form product faster. At this point, we should see that the intermediate formed via the 3˚ intermediate from 1- methylcyclohexene (as opposed to the 2˚ carbocation intermediate in the case of cyclohexene) will proceed faster.

CHE2201, Chapter 8 Learn, 103 Worked Example 2 What products are formed from hydration of 4- methylcyclopentene? –Consider all stereoisomers formed

CHE2201, Chapter 8 Learn, 104 Worked Example 2 Solution: