6 Organic Chemistry William H Brown Christopher S

6 Organic Chemistry William H. Brown & Christopher S. Foote 6 -1

6 Alkenes II Chapter 6 6 -2

6 Characteristic Reactions 6 -3

6 Characteristic Reactions 6 -4

6 Reaction Mechanisms u. A reaction mechanism describes details of how a reaction occurs • which bonds are broken and which new ones are formed • the order and relative rates of the various bondbreaking and bond-forming steps • if in solution, the role of the solvent • if there is a catalyst, the role of a catalyst • the position of all atoms and energy of the entire system during the reaction 6 -5

6 Energy Diagrams u Energy diagram: a graph showing the changes in energy that occur during a chemical reaction u Reaction coordinate: a measure in the change in positions of atoms during a reaction 6 -6

6 Gibbs Free Energy u Gibbs free energy: a thermodynamic function relating enthalpy, entropy, and temperature • exergonic reaction: a reaction in which the Gibbs free energy of the products is lower than that of the reactants; an exergonic reaction is spontaneous • endergonic reaction: a reaction in which the Gibbs free energy of the products is higher than that of the reactants; an endergonic reaction is never spontaneous. 6 -7

6 Gibbs Free Energy 6 -8

6 Energy Diagrams u Heat of reaction: the difference in energy between reactants and products • exothermic reaction: a reaction in which the enthalpy of the products is lower than that of the reactants; a reaction in which heat is released • endothermic reaction: reaction a reaction in which the enthalpy of the products is higher than that of the reactants; a reaction in which heat is absorbed 6 -9

6 Activation Energy u Transition state: • an unstable species of maximum energy formed during the course of a reaction • a maximum on an energy diagram Energy, G‡: the difference in energy between reactants and a transition state u Activation • if large, only a few collisions occur with sufficient energy to reach the transition state; reaction is slow • if small, many collisions occur with sufficient energy to reach the transition state; reaction is fast 6 -10

6 Energy Diagram A one-step reaction with no intermediate 6 -11

6 Energy Diagram A two-step reaction with one intermediate 6 -12

6 Activation Energy & Rate u The relationship between a rate constant, k, and activation energy is given by the equation C = a constant (units s-1) that depends on the reaction R = gas constant, 8. 315 x 10 -3 k. J (1. 987 x 10 -3 kcal) • mol-1 • K -1 T = temperature in Kelvins 6 -13

6 Activation Energy & Rate Example: What is the activation energy for a reaction whose rate at 35°C is twice that at 25°C? Solution: the ratio of rate constants k 2 and k 1 for the reaction at temperatures T 2 and T 1 is taking the log of both sides and rearranging gives 6 -14

6 Activation Energy & Rate • substituting values and solving gives 6 -15

6 Developing a Mechanism u How it is done • design experiments to reveal details of a particular chemical reaction • propose a set or sets of steps that might account for the overall transformation • a mechanism becomes established when it is shown to be consistent with every test that can be devised • this does mean that the mechanism is correct, only that it is the best explanation we are able to devise 6 -16

6 Why Mechanisms? • framework within which to organize descriptive chemistry • intellectual satisfaction derived from constructing models that accurately reflect the behavior of chemical systems • a tool with which to search for new information and new understanding 6 -17

6 Electrophilic Additions • • • hydrohalogenation using HCl, HBr, HI hydration using H 2 O, H 2 SO 4 halogenation using Cl 2, Br 2 halohydrination using HOCl, HOBr oxymercuration using Hg(OAc)2, H 2 O 6 -18

6 Addition of HX u Carried out with pure reagents or in a polar solvent such as acetic acid u Addition is regioselective • regioselective reaction: a reaction in which one direction of bond forming or breaking occurs in preference to all other directions of bond forming or breaking • regiospecific reaction: a reaction in which one direction of bond forming or breaking occurs to the exclusion of all other directions of bond forming or breaking 6 -19

6 Addition of HX u. H adds to the less substituted carbon u Markovnikov’s rule: in the addition of HX, H 2 O, or ROH to an alkene, H adds to the carbon of the double bond having the greater number of hydrogens 6 -20

6 HCl + 2 -Butene u. A two-step mechanism Step 1: formation of sec-butyl cation, a 2° carbocation intermediate Step 2: reaction of the sec-butyl cation (a Lewis acid) with chloride ion (a Lewis base) completes the reaction 6 -21

6 HCl + 2 -Butene 6 -22

6 Carbocations u u Carbocation: a species in which a carbon atom has only six electrons in its valence shell and bears positive charge Carbocations are • classified as 1°, 2°, or 3° depending on the number of carbons bonded to the carbon bearing the positive charge • electrophiles; that is, they are electron-loving • Lewis acids 6 -23

6 Carbocation Structure • bond angles about a positively charged carbon are approx. 120° • carbon uses sp 2 hybrid orbitals to form sigma bonds to the three attached groups • the unhybridized 2 p orbital lies perpendicular to the sigma bond framework and contains no electrons 6 -24

6 Carbocation Stability • a 3° carbocation is more stable than a 2° carbocation, and requires a lower activation energy for its formation • a 2° carbocation is, in turn, more stable than a 1° carbocation, and requires a lower activation energy for its formation • methyl and primary carbocations are so unstable that they are never observed in solution 6 -25

6 Carbocation Stability • relative stability • methyl and primary carbocations are so unstable that they are never observed in solution 6 -26

6 Carbocation Stability • we can account for the relative stability of carbocations if we assume that alkyl groups attached to the positively charged carbon are electron-releasing and thereby help delocalize the positive charge of the cation • we account for this electron-releasing ability of alkyl groups by (1) the inductive effect, and (2) hyperconjugation 6 -27

6 Carbocation Stability u The inductive effect • the electron-deficient carbon bearing the positive charge polarizes electrons of the adjacent sigma bonds toward it • the positive charge on the cation is not localized on the trivalent carbon, but delocalized over nearby atoms • the larger the volume over which the positive charge is delocalized, the greater the stability of the cation 6 -28

6 Carbocation Stability u Hyperconjugation • partial overlap of the bonding orbital of an adjacent C-H bond with the vacant 2 p orbital of the cationic carbon delocalizes the positive charge and also the electrons of the adjacent bond • replacing a C-H bond with a C-C bond increases the possibility for hyperconjugation 6 -29

6 Addition of H 2 O • addition of water is called hydration • acid-catalyzed hydration of an alkene is regioselective; hydrogen adds preferentially to the less substituted carbon of the double bond 6 -30

6 Addition of H 2 O • Step 1: proton transfer from solvent to the alkene • Step 2: a Lewis acid/base reaction • Step 3: proton transfer to solvent 6 -31

6 C+ Rearrangements u In electrophilic addition to alkenes, there is the possibility for rearrangement u Rearrangement: a change in connectivity of the atoms in a product compared with the connectivity of the same atoms in the starting material 6 -32

6 C+ Rearrangements • in addition of HCl to an alkene • in acid-catalyzed hydration of an alkene 6 -33

6 C+ Rearrangements • driving force is rearrangement of a less stable carbocation to a more stable one • the less stable 2° carbocation rearranges to a more stable 3° one by 1, 2 -shift of a hydride ion 6 -34

6 C+ Rearrangements • reaction of the more stable carbocation (a Lewis acid) with chloride ion (a Lewis base) completes the reaction 6 -35

6 Addition of Cl 2 and Br 2 • carried out with either the pure reagents or in an inert solvent such as CH 2 Cl 2 • addition is stereoselective u Stereoselective reaction: a reaction in which one stereoisomer is formed or destroyed in preference to all others u Stereospecific reaction: reaction a reaction in which one stereoisomer is formed or destroyed to the exclusion to all others 6 -36

6 Addition of Cl 2 and Br 2 6 -37

6 Addition of Cl 2 and Br 2 • Step 1: formation of a bridged bromonium ion intermediate • Step 2: attack of halide ion from the opposite side of the three-membered ring 6 -38

6 Addition of Cl 2 and Br 2 u For a cyclohexene, anti coplanar addition corresponds to trans diaxial addition 6 -39

6 Addition of HOCl and HOBr u Treatment of an alkene with Br 2 or Cl 2 in water forms a halohydrin u Halohydrin: a compound containing -OH and -X on adjacent carbons 6 -40

6 Addition of HOCl and HOBr • reaction is both regiospecific (anti addition) and stereoselective (OH to the more substituted carbon) 6 -41

6 Addition of HOCl and HOBr Step 1: formation of a bridged halonium ion intermediate Step 2: attack of H 2 O on the more substituted carbon opens the three-membered ring 6 -42

6 Oxymercuration/Reduction • oxymercuration followed by reduction results in hydration of a carbon-carbon double bond 6 -43

6 Oxymercuration/Reduction • addition of Hg(II) and oxygen is anti coplanar stereoselective 6 -44

6 Oxymercuration/Reduction • Step 1: dissociation of mercury (II) acetate gives Ac. OHg+, a Lewis acid • Step 2: attack of Ac. OHg+ on the double bond gives a bridged mercurinium ion intermediate in which the two electrons of the pi bond form a two-atom three-center bond 6 -45

6 Oxymercuration/Reduction 6 -46

6 Oxymercuration/Reduction • Step 3: stereospecific and regioselective attack of H 2 O on the bridged intermediate opens the mercurinium ion ring • Step 4: reduction of the C-Hg. OAc bond 6 -47

6 Oxymercuration/Reduction • the fact that oxymercuration occurs without rearrangement indicates that the intermediate is not a true carbocation, but rather a resonance hybrid closely resembling a bridged mercurinium ion intermediate • regioselectivity is accounted for by at least some carbocation character in the bridged intermediate • stereospecificity is accounted for by anti attack on the bridged intermediate 6 -48

6 Hydroboration/Oxidation u Hydroboration: the addition of borane, BH 3, to an alkene to form a trialkylborane u Borane dimerizes to diborane, B 2 H 6 6 -49

6 Hydroboration/Oxidation • borane forms a stable complex with ethers such as THF • the reagent is used most often as a commercially available solution of BH 3 in THF 6 -50

6 Hydroboration/Oxidation u Hydroboration is both regioselective (boron to the less hindered carbon) and stereospecific (syn addition) 6 -51

6 Hydroboration/Oxidation • mechanism involves concerted regioselective and stereospecific addition of B and H to the carbon double bond 6 -52

6 Hydroboration/Oxidation • trialkylboranes are rarely isolated • oxidation with alkaline hydrogen peroxide gives an alcohol and sodium borate u The result of hydroboration/oxidation is regioselective and stereospecific hydration of a carbon-carbon double bond 6 -53

6 Hydroboration/Oxidation 6 -54

6 Oxidation/Reduction u Oxidation: the loss of electrons • or the loss of H, the gain of O, or both u Reduction: the gain of electrons • or the gain of H, the loss of O, or both u Recognize using a balanced half-reaction 1. write a half-reaction showing one reactant and its product(s) 2. complete a material balance. Use H 2 O and H+ in acid solution; use H 2 O and OH- in basic solution 3. complete a charge balance using electrons, e- 6 -55

6 Oxidation/Reduction • three balanced half-reactions 6 -56

6 Oxidation with Os. O 4 u Oxidation by Os. O 4 converts an alkene to a glycol, a compound with -OH groups on adjacent carbons • oxidation is syn stereospecific 6 -57

6 Oxidation with Os. O 4 • Os. O 4 is both expensive and highly toxic • it is used in catalytic amounts with another oxidizing agent to reoxidize its reduced forms and, thus, recycle Os. O 4 6 -58

6 Oxidation with O 3 u Treatment of an alkene with ozone followed by a weak reducing agent cleaves the C=C and forms two carbonyl groups in its place 6 -59

6 Oxidation with O 3 • the initial product is a molozinide which rearranges to an isomeric ozonide 6 -60

6 Reduction of Alkenes u Most alkenes react with H 2 in the presence of a transition metal catalyst to give alkanes • commonly used catalysts are Pt, Pd, Ru, and Ni u The process is called catalytic reduction or, alternatively, catalytic hydrogenation 6 -61

6 Reduction of Alkenes u Most common pattern is syn stereoselectivity 6 -62

6 Reduction of Alkenes u Mechanism of catalytic hydrogenation • H 2 is absorbed on the metal surface with formation of metal-hydrogen bonds • the alkene is also absorbed with formation of metalcarbon bonds • a hydrogen atom is transferred to the alkene forming one new C-H bond • a second hydrogen atom is transferred forming the second C-H bond 6 -63

6 H° of Hydrogenation u Reduction of an alkene to an alkane is exothermic • there is net conversion of one pi bond to one sigma bond u H° depends on the degree of substitution • the greater the substitution, the lower the value of H° u H° for a trans alkene is lower than that of an isomeric cis alkene 6 -64

6 H° of Hydrogenation 6 -65

6 H° of Hydrogenation u The greater the degree of substitution of a double bond, the lower its heat of hydrogenation • the greater the degree of substitution, the more stable the double bond u The heat of hydrogenation of a trans alkene is lower than that of the isomeric cis alkene • a trans alkene is more stable than its isomeric cis alkene • the difference is due to nonbonded interaction strain in the cis alkene 6 -66

6 H° of Hydrogenation 6 -67

6 Reaction Stereochemistry u In several of the reactions presented in this chapter, stereocenters are created u Where one or more stereocenters are created, is the product • • • one enantiomer and, if so, which one? a pair of enantiomers? a meso compound? a mixture of stereoisomers? or what? 6 -68

6 Reaction Stereochemistry u Which of the three possible stereoisomers of 2, 3 dibromobutane are formed in the addition of bromine to trans-2 -butene? • the three possible stereoisomers for this product are a pair of enantiomers and a meso compound 6 -69

6 Reaction Stereochemistry u Reaction of bromine with the alkene forms a cyclic bromonium ion intermediate • which is then opened by attack of bromide ion from the side opposite the bromine bridge 6 -70

6 Reaction Stereochemistry 6 -71

6 Reaction Stereochemistry u How many and what kind of stereoisomers are formed in the oxidation of cis-2 -butene by Os. O 4? 6 -72

6 Reaction Stereochemistry 6 -73

6 Reaction Stereochemistry u How many and what kind of stereoisomers are formed in the oxidation of trans-2 -butene by Os. O 4? 6 -74

6 Reaction Stereochemistry u Enantiomerically pure products can never be formed from achiral starting materials and reagents u An enantiomerically pure product can be generated in a reaction if at least one of the reactants is enantiomerically pure, or if the reaction is carried out in an achiral environment 6 -75

6 Prob 6. 15 Draw the isomeric carbocations formed on treatment of each alkene with HCl. Which is the more stable? 6 -76

6 Prob 6. 16 Arrange the alkenes in each set in order of increasing rate of reaction with HI. 6 -77

6 Prob 6. 17 Write the major product formed on treatment of 2 -butene with each reagent. 6 -78

6 Prob 6. 18 What alkene undergoes acid-catalyzed hydration to give each alcohol as the major product? 6 -79

6 Prob 6. 19 Reaction of 2 -methyl-2 -pentene with each reagent is regiospecific. What is the regiospecificity and how it is accounted for? 6 -80

6 Prob 6. 21 Draw the alkene of indicated molecular formula that gives the compound shown as the major product. 6 -81

6 Prob 6. 22 Account for the fact that addition of HCl to 1 bromopropene gives 1 -bromo-1 -chloropropane. 6 -82

6 Prob 6. 23 Propenoic acid reacts with HCl to give 3 -chloropropanoic acid. Account for this result. 6 -83

6 Prob 6. 24 Draw a structural formula for the alkene of molecular formula C 5 H 10 that reacts with Br 2 to give each product. 6 -84

6 Prob 6. 26 Draw a structural formula of the cycloalkene of molecular formula C 6 H 10 that reacts with Cl 2 to give each compound. 6 -85

6 Prob 6. 27 Treatment of this bicycloalkene with Br 2 gives a trans dibromide. Of the two possible trans dibromides, only one is formed. Which is formed? Account for its formation to the exclusion of its isomer. 6 -86

6 Prob 6. 28 Propose a structural formula for terpin. How many cis, trans isomers are possible for the structural formula you have proposed? 6 -87

6 Prob 6. 29 Propose a mechanism for this reaction. 6 -88

6 Prob 6. 30 Propose a mechanism for this reaction. 6 -89

6 Prob 6. 31 Propose a mechanism for the formation of each product. 6 -90

6 Prob 6. 32 Propose a mechanism for the formation of each product. 6 -91

6 Prob 6. 33 Propose a mechanism for this reaction. 6 -92

6 Prob 6. 34 Propose a mechanism for this reaction. 6 -93

6 Prob 6. 35 Propose a mechanism for each reaction. 6 -94

6 Prob 6. 36 Propose a mechanism for this reaction. 6 -95

6 Prob 6. 37 Draw a structural formula for the alcohol formed by treatment of each alkene with B 2 H 6 in THF followed by treatment with alkaline H 2 O 2. 6 -96

6 Prob 6. 38 Of the four possible cis, trans isomers possible for this compound, one is formed in 85% yield. Propose a structure for this isomer. 6 -97

6 Prob 6. 41 Draw a structural formula of the alkene that gives each set of products. 6 -98

6 Prob 6. 47 State the number and kind of stereoisomers formed when (R)-3 -methyl-1 -pentene is treated with each reagent. 6 -99

6 Prob 6. 49 For each reaction determine (1) how many stereoisomers are possible for the product, (2) which of the possible ones are formed, and (3) whether the product is optically active or inactive. 6 -100

6 Prob 6. 49 (cont’d) 6 -101

6 Alkenes II End Chapter 6 6 -102