1. 6-1 Reactions of Alkenes Chapter 6

2. 6-2 6.1 Characteristic Reactions, Table 6-1  The reaction typical of alkenes is addition

3. 6-3 Characteristic Reactions, Table 6-1

4. 6-4 6.2 Reaction Mechanisms  A reaction mechanism describes how a reaction occurs: which bonds are broken and which new ones are formed the order and relative rates of the various bond- breaking 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

5. 6-5 Gibbs Free Energy  Gibbs free energy change,  G 0 (standard state):  Gibbs free energy change,  G 0 (standard state): a thermodynamic function relating enthalpy, entropy, and temperature exergonic reaction:exergonic reaction: a reaction in which the Gibbs free energy of the products is lower than that of the reactants; the position of equilibrium for an exergonic reaction favors products endergonic reaction:endergonic reaction: a reaction in which the Gibbs free energy of the products is higher than that of the reactants; the position of equilibrium for an endergonic reaction favors starting materials

6. 6-6 Gibbs Free Energy a change in Gibbs free energy is directly related to chemical equilibrium: summary of the relationships between  G 0,  H 0,  S 0, and the position of chemical equilibrium

7. 6-7 Energy Diagrams  Enthalpy change,   :  Enthalpy change,   : the difference in total bond energy between reactants and products a measure of bond making (exothermic) and bond breaking (endothermic)  Heat of reaction,   :  Heat of reaction,   : the difference in enthalpy between reactants and products exothermic reaction: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 reactionendothermic reaction: a reaction in which the enthalpy of the products is higher than that of the reactants; a reaction in which heat is absorbed

8. 6-8 A. Energy Diagrams  Energy diagram:  Energy diagram: a graph showing the changes in energy that occur during a chemical reaction  Reaction coordinate:  Reaction coordinate: a measure in the change in positions of atoms during a reaction

9. 6-9 Activation Energy  Transition state: an unstable species of maximum energy formed during the course of a reaction a maximum on an energy diagram  Activation Energy,  G ‡ :  Activation Energy,  G ‡ : the difference in Gibbs free energy between reactants and a transition state if  G ‡ is large, few collisions occur with sufficient energy to reach the transition state; reaction is slow if  G ‡ is small, many collisions occur with sufficient energy to reach the transition state; reaction is fast

10. 6-10 Energy Diagram, Fig. 6-1  A one-step reaction with no intermediate

11. 6-11 Energy Diagram, Fig. 6-2  A two-step reaction with one intermediate

12. 6-12 B. Developing a Reaction Mechanism  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

13. 6-13 Why Mechanisms? they are the framework within which to organize descriptive chemistry they provide an intellectual satisfaction derived from constructing models that accurately reflect the behavior of chemical systems they are tools with which to search for new information and new understanding they help us understand what events occur in the pathway from reactants to products

14. 6-14 6.3 Electrophilic Additions  An alkene reacts using electrons from the pi bond as a nucleophile, the other reactant is an electrophile. hydrohalogenation using HCl, HBr, HI hydration using H 2 O in the presence of H 2 SO 4 halogenation using Cl 2, Br 2 halohydrination using HOCl, HOBr oxymercuration using Hg(OAc) 2, H 2 O followed by reduction

15. 6-15 A. Addition of HX  Carried out with pure reagents or in a polar solvent such as acetic acid  Addition is regioselective regioselective reaction:regioselective reaction: an addition or substitution reaction in which one of two or more possible products is formed in preference to all others that might be formed Markovnikov’s rule: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 Hs.

16. 6-16 HBr + 2-Butene  A two-step mechanism Step 1: proton transfer from HBr to the alkene gives a carbocation intermediate Step 2: reaction of the sec-butyl cation (an electrophile) with bromide ion (a nucleophile) completes the reaction

17. 6-17 HBr + 2-Butene, Fig. 6-4  An energy diagram for the two-step addition of HBr to 2-butene the reaction is exergonic

18. 6-18 Carbocations  Carbocation:  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

19. 6-19 Carbocations, Fig. 6-3 bond angles about a positively charged carbon are approximately 120° carbon uses sp 2 hybrid orbitals to form sigma bonds to the three attached groups the unhybridized 2p orbital lies perpendicular to the sigma bond framework and contains no electrons

20. 6-20 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, methyl and 1° carbocations are so unstable that they are never observed in solution

21. 6-21 Carbocation Stability relative stability methyl and primary carbocations are so unstable that they are never observed in solution

22. 6-22 Carbocation Stability we can account for the relative stability of carbocations if we assume that alkyl groups bonded to the positively charged carbon are electron releasing and thereby 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

23. 6-23 The Inductive Effect, Fig. 6-5 the positively charged carbon polarizes electrons of adjacent sigma bonds toward it the positive charge on the cation is thus localized over nearby atoms the larger the volume over which the positive charge is delocalized, the greater the stability of the cation

24. 6-24 Hyperconjugation, Fig. 6-6 involves partial overlap of the  -bonding orbital of an adjacent C-H or C-C bond with the vacant 2p orbital of the cationic carbon the result is delocalization of the positive charge

25. 6-25 B. 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 HOH adds in accordance with Markovnikov’s rule

26. 6-26 Addition of H 2 O Step 1: proton transfer from H 3 O + to the alkene oxonium ionStep 2: reaction of the carbocation (an electrophile) with water (a nucleophile) gives an oxonium ion Step 3: proton transfer to water gives the alcohol + + + intermediate A 2 o carbocation + HO H HOH H CH 3 CH=CH 2 CH 3 CHCH 3 slow, rate determining : : : : : + + + An oxonium ion H O H H CH 3 CHCH 3 O-H CH 3 CHCH 3 fast :

27. 6-27 C. Carbocation Rearrangements  In electrophilic addition to alkenes, there is the possibility for rearrangement  Rearrangement:  Rearrangement: a change in connectivity of the atoms in a product compared with the connectivity of the same atoms in the starting material

28. 6-28 Carbocation Rearrangements in addition of HCl to an alkene in acid-catalyzed hydration of an alkene

29. 6-29 Carbocation Rearrangements the 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 + + A 3° carbocation CH 3 H CH 3 H CH 3 C-CHCH 3 CH 3 C-CHCH 3 fast

30. 6-30 Carbocation Rearrangements reaction of the more stable carbocation (an electrophile) with chloride ion (a nucleophile) completes the reaction - Cl : : : : 2-Chloro-2-methylbutane + + CH 3 CH 3 CH 3 C-CH 2 CH 3 CH 3 C-CH 2 CH 3 fast Cl : : :

31. 6-31 D. 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 of bromine or chlorine to a cycloalkene gives a trans-dihalocycloalkane anti stereoselectivityaddition occurs with anti stereoselectivity; halogen atoms add to opposite faces of the double bond this selectivity discussed in detail in Section 6.7

32. 6-32 Addition of Cl 2 and Br 2 Step 1: formation of a bridged bromonium ion intermediate

33. 6-33 Addition of Cl 2 and Br 2 Step 2: attack of halide ion (a nucleophile) from the opposite side of the bromonium ion (an electrophile) opens the three-membered ring to give the product

34. 6-34 Addition of Cl 2 and Br 2 for a cyclohexene, anti coplanar addition corresponds to trans diaxial addition the initial trans diaxial conformation is in equilibrium with the more stable trans diequatorial conformation because the bromonium ion can form on either face of the alkene with equal probability, both trans enantiomers are formed as a racemic mixture

35. 6-35 E. Addition of HOCl and HOBr  Treatment of an alkene with Br 2 or Cl 2 in water forms a halohydrin  Halohydrin:  Halohydrin: a compound containing -OH and -X on adjacent carbons

36. 6-36 Addition of HOCl and HOBr reaction is both regiospecific (OH adds to the more substituted carbon) and anti stereoselective both selectivities are illustrated by the addition of HOBr to 1-methylcyclopentene to account for the regioselectivity and the anti stereoselectivity, chemists propose the three-step mechanism in the next screen

37. 6-37 Addition of HOCl and HOBr Step 1: forms a bridged halonium ion intermediate Step 2: attack of H 2 O on the more substituted carbon opens the three-membered ring

38. 6-38 Addition of HOCl and HOBr Step 3: proton transfer to H 2 O completes the reaction  As the e-plot map on the next screen shows the C-X bond to the more substituted carbon is longer than the one to the less substituted carbon because of this difference in bond lengths, the transition state for ring opening can be reached more easily by attack of the nucleophile at the more substituted carbon

39. 6-39 Addition of HOCl and HOBr bridged bromonium ion from propene

40. 6-40 F. Oxymercuration/Reduction  Oxymercuration followed by reduction results in hydration of a carbon-carbon double bond oxymercuration reduction

41. 6-41 Oxymercuration/Reduction an important feature of oxymercuration/reduction is that it occurs without rearrangement oxymercuration occurs with anti stereoselectivity

42. 6-42 Oxymercuration/Reduction Step 1: dissociation of mercury(II) acetate Step 2: formation of a bridged mercurinium ion intermediate; a two-atom three-center bond

43. 6-43 Oxymercuration/Reduction Step 3: regioselective attack of H 2 O (a nucleophile) on the bridged intermediate opens the three- membered ring Step 4: reduction of the C-HgOAc bond

44. 6-44 Oxymercuration/Reduction  Anti stereoselective we account for the stereoselectivity by formation of the bridged bromonium ion and anti attack of the nucleophile which opens the 3-membered ring  Regioselective of the two carbons of the mercurinium ion intermediate, the more substituted carbon has the greater degree of partial positive character alternatively, computer modeling indicates that the C-Hg bond to the more substituted carbon of the bridged intermediate is longer than the one to the less substituted carbon therefore, the ring-opening transition state is reached more easily by attack at the more substituted carbon

45. 6-45 6.4 Hydroboration/Oxidation  Hydroboration:  Hydroboration: the addition of borane, BH 3, to an alkene to form a trialkylborane  Borane dimerizes to diborane, B 2 H 6 Borane HB H H 3CH 2 =CH 2 CH 3 CH 2 B CH 2 CH 3 CH 2 CH 3 Triethylborane (a trialkylborane) + BoraneDiborane 2BH 3 B 2 H 6

46. 6-46 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

47. 6-47 Hydroboration/Oxidation  Hydroboration is both regioselective (boron to the less hindered carbon) and syn stereoselective CH 3 H BH 3 BR 2 HH 3 C H + 1-Methylcyclopentene (Syn addition of BH 3 ) (R = 2-methylcyclopentyl)

48. 6-48 Hydroboration/Oxidation concerted regioselective and syn stereoselective addition of B and H to the carbon-carbon double bond trialkylboranes are rarely isolated oxidation with alkaline hydrogen peroxide gives an alcohol and sodium borate

49. 6-49 Hydroboration/Oxidation  Hydrogen peroxide oxidation of a trialkylborane step 1: hydroperoxide ion (a nucleophile) donates a pair of electrons to boron (an electrophile) step 2: rearrangement of an R group with its pair of bonding electrons to an adjacent oxygen atom

50. 6-50 Hydroboration/Oxidation step 3: reaction of the trialkylborane with aqueous NaOH gives the alcohol and sodium borate

51. 6-51 6.5 Oxidation/Reduction  Oxidation:  Oxidation: the loss of electrons alternatively, the loss of H, the gain of O, or both  Reduction:  Reduction: the gain of electrons alternatively, the gain of H, the loss of O, or both  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 -

52. 6-52 Oxidation/Reduction three balanced half-reactions

53. 6-53 Oxidation to glycols  Alkene is converted to a cis-1,2-diol  Two reagents: Osmium tetroxide (expensive!), followed by hydrogen peroxide or Cold (25 o ), dilute aqueous potassium permanganate, followed by hydrolysis with base

54. 6-54 A. Oxidation with OsO 4 glycol  OsO 4 oxidizes an alkene to a glycol, a compound with OH groups on adjacent carbons. oxidation is syn stereoselective OsO 4 O Os O O O HOOH H 2 O cis -1,2-Cyclopentanediol (a cis glycol) A cyclic osmate OH OH

55. 6-55 Oxidation with OsO 4 OsO 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 OsO 4

56. 6-56 B. Oxidation with dilute KMnO 4 glycol  KMnO 4 (dilute) oxidizes an alkene to a glycol, as did OsO 4, here the cyclic ester is hydrolyzed with base. oxidation is syn stereoselective O Mn O O O - OH H 2 O cis -1,2-Cyclopentanediol (a cis glycol) A cyclic osmate OH OH KMnO 4

57. 6-57 Cleavage of both bonds of an alkene  Both the pi and sigma bonds of the alkene are broken (cleavage of the double bond)  Two reagent systems: Ozone followed by reduction or Hot, concentrated potassium permanganate in base, followed by acidification

58. 6-58 C. Oxidation with O 3  Treatment of an alkene with ozone followed by a weak reducing agent cleaves the C=C and forms two carbonyl groups in its place Propanal (an aldehyde) Propanone (a ketone) 2-Methyl-2-pentene CH 3 O O CH 3 C=CHCH 2 CH 3 1. O 3 2. (CH 3 ) 2 S CH 3 CCH 3 + HCCH 2 CH 3

59. 6-59 Oxidation with O 3 the initial product is a molozonide which rearranges to an isomeric ozonide Acetaldehyde 2-Butene O CH 3 CH=CHCH 3 O 3 (CH 3 ) 2 S CH 3 CH CH 3 CH-CHCH 3 OO O OO C O C H CH 3 H H 3 C A molozonide An ozonide

60. 6-60 D. Oxidation with conc. KMnO 4  Treatment of an alkene with permanganate cleaves the C=C and and continues to oxidize the two alkene carbon atoms if they contain hydrogen atoms Propanoic acid (a carboxyic acid) Propanone (a ketone) 2-Methyl-2-pentene CH 3 O O CH 3 C=CHCH 2 CH 3 2. H + CH 3 CCH 3 + HOCCH 2 CH 3 1. Conc. KMnO 4, OH -

61. 6-61 Determining cleavage products  Predicting products from cleavage of an alkene, C=C, depends upon the number of H’s on each C of the double bond  # hydrogens Products on carbon:From O 3 From conc KMnO 4 None ketone ketone One aldehyde carboxylic acid Two formaldehyde CO 2 + HOH

62. 6-62 6.6 Reduction of Alkenes  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 catalytic reduction catalytic hydrogenationthe process is called catalytic reduction or, alternatively, catalytic hydrogenation addition occurs with syn stereoselectivity + H 2 Pd CyclohexeneCyclohexane 25°C, 3 atm

63. 6-63 A. Reduction of Alkenes  Mechanism of catalytic hydrogenation

64. 6-64 Reduction of Alkenes even though addition syn stereoselectivity, some product may appear to result from trans addition reversal of the reaction after the addition of the first hydrogen gives an isomeric alkene, etc.

65. 6-65 B.  H 0 of Hydrogenation  Reduction of an alkene to an alkane is exothermic there is net conversion of one pi bond to one sigma bond   H 0 depends on the degree of substitution the greater the substitution, the lower the value of  H°   H 0 for a trans alkene is lower than that of an isomeric cis alkene a trans alkene is more stable than a cis alkene

66. 6-66  H 0 of Hydrogenation, Table 6-2

67. 6-67 6.7 Reaction Stereochemistry  In several of the reactions presented in this chapter, chiral centers are created  Where one or more chiral centers are created, is the product one enantiomer and, if so, which one? a pair of enantiomers as a racemic mixture? a meso compound? a mixture of stereoisomers? stereospecific  As we will see, the stereochemistry of the product for some reactions depends on the stereochemistry of the starting material; that is, some reactions are stereospecific

68. 6-68 A. Reaction Stereochemistry  We saw in Section 6.3D that bromine adds to 2- butene to give 2,3-dibromobutane two stereoisomers are possible for 2-butene; a pair of cis,trans isomers three stereoisomers are possible for the product; a pair of enantiomers and a meso compound if we start with the cis isomer, what is the stereochemistry of the product? if we start with the trans isomer, what is the stereochemistry of the product?

69. 6-69 Bromination of cis-2-Butene reaction of cis-2-butene with bromine forms bridged bromonium ions which are meso and identical

70. 6-70 Bromination of cis-2-Butene attack of bromide ion at carbons 2 and 3 occurs with equal probability to give enantiomeric products as a racemic mixture

71. 6-71 Bromination of trans-2-Butene reaction with bromine forms bridged bromonium ion intermediates which are enantiomers

72. 6-72 Bromination of trans-2-Butene attack of bromide ion in either carbon of either enantiomer gives meso-2,3-dibromobutane

73. 6-73 Bromination of 2-Butene  Given these results, we say that addition of Br 2 or Cl 2 to an alkene is stereospecific bromination of cis-2-butene gives the enantiomers of 2,3-dibromobutane as a racemic mixture bromination of trans-2-butene gives meso-2,3- dibromobutane  Stereospecific reaction:  Stereospecific reaction: a reaction in which the stereochemistry of the product depends on the stereochemistry of the starting material

74. 6-74 Oxidation of 2-Butene OsO 4 oxidation of cis-2-butene gives meso-2,3- butanediol

75. 6-75 Oxidation of 2-Butene  OsO 4 oxidation of an alkene is stereospecific oxidation of trans-2-butene gives the enantiomers of 2,3-butanediol as a racemic mixture (optically inactive) and oxidation of cis-2-butene gives meso 2,3- butanediol (also optically inactive)

76. 6-76 Reaction Stereochemistry  We have seen two examples in which reaction of achiral starting materials gives chiral products in each case, the product is formed as a racemic mixture (which is optically inactive) or as a meso compound (which is also optically inactive)  Th ese examples illustrate a very important point about the creation of chiral molecules optically active (enantiomerically pure) products can never be produced from achiral starting materials and achiral reagents under achiral conditions although the molecules of product may be chiral, the product is always optically inactive (either meso or a pair of enantiomers)

77. 6-77 B. Reaction Stereochemistry  Next let us consider the reaction of a chiral starting material in an achiral environment the bromination of (R)-4-tert-butylcyclohexene only a single diastereomer is formed the presence of the bulky tert-butyl group controls the orientation of the two bromine atoms added to the ring

78. 6-78 C. Reaction Stereochemistry  Finally, consider the reaction of an achiral starting material in an chiral environment BINAP can be resolved into its R and S enantiomers

79. 6-79 Reaction Stereochemistry treating (R)-BINAP with ruthenium(III) chloride forms a complex in which ruthenium is bound in the chiral environment of the larger BINAP molecule this complex is soluble in CH 2 Cl 2 and can be used as a homogeneous hydrogenation catalyst using (R)-BINAP-Ru as a hydrogenation catalyst, (S)-naproxen is formed in greater than 98% ee

80. 6-80 Reaction Stereochemistry BINAP-Ru complexes are somewhat specific for the types of C=C they reduce to be reduced, the double bond must have some kind of a neighboring group that serves a directing group

81. 6-81 Reactions of Alkenes End Chapter 6