CHEM 494 Special Topics in Chemistry University of Illinois at Chicago UIC CHEM 494 - Lecture 7 Prof. Duncan Wardrop October 22, 2012 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago UIC Preparation of Alkenes Elimination Chapter 19 Dehydration can be “Coupled” with Other Chemical Transformation Cl O N OH HF Cl Cl HF N N N N N Me Me Me Loratidine (Claritin Two-step, one-pot transformation involves a Friedel-Crafts reaction (see, Chapter 12) and dehydration of the resulting 3° alcohol University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 3 Lecture 8: November 5 Rate of Alcohol Dehydration Mirrors Ease of Carbocation Formation rate of dehydration = 3º > 2º > 1º alcohol primary alcohol (1º) University of Illinois at Chicago UIC OH Stability secondary alcohol (2º) tertiary cation (3º) Reactivity tertiary alcohol (3º) OH H secondary cation (2°) H OH H CHEM 494, Spring 2010 primary cation (1°) Slide 4 Lecture 8: November 5 Self Test Question Predict the product for the following reaction scheme. OH H2SO4 ? A. B. C. D. 140 ºC -H H O H H H H H University of Illinois at Chicago UIC -H2O H H H H CHEM 494, Fall 2012 E. no reaction Slide 5 Lecture 8: November 5 Self Test Question Predict the product for the following reaction scheme. OH H2SO4 ? A. B. C. D. 140 ºC -Hor -H H H H H H O -H2O H H H H E. no reaction University of Illinois at Chicago UIC CHEM 494, Fall 2012 Slide 6 Lecture 8: November 5 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago Regioselectivity & Stereoselectivity of Dehydration Chapter 19 UIC Self Test Question What is the product(s) of the following reaction? A. B. H2SO4 HO ? 80 ºC C. D. E. University of Illinois at Chicago UIC CHEM 494, Fall 2012 O2S Slide 8 Lecture 8: November 5 Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider . . . . Chemoselectivity: which functional group will react • Regioselectivity: where it will react • Stereoselectivity: how it will react with regards to stereochemical outcome . . . for each transformation, always question which of these are factors are at play. University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 9 Lecture 8: November 5 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009 H2SO4 HO + 80 ºC H H H3C HO + 10% (identical) 90% CH3 CH3 University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 10 Lecture 8: November 5 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009 OH CH3 CH3 H3PO4 CH3 + heat 84% OH H CH3 H University of Illinois at Chicago 16% H UIC 2 different leaving group/Hrelationships CHEM 494, Spring 2010 Slide 11 Lecture 8: November 5 Greek Lettering & Elimination Reactions Nomenclature The α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at αcarbon University of Illinois at Chicago UIC Cl H 2 C H3C C H2 CHEM 494, Spring 2010 H C H2 ' CH3 ' Slide 12 Lecture 8: November 5 Regioselectivity of Elimination Zaitsev Rule HO CH3 CH3 KHSO4 CH3 CH3 CH3 CH3 + CH3 + heat 87% O 13% 0% Na+ -O S OH O hydrosulfate 3 Hs on this β carbon HO H H CH3 H CH3 1 Hs on this β carbon 2 Hs on this β carbon University of Illinois at Chicago UIC Zaitsev Rule When elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens CHEM 494, Spring 2010 Slide 13 Lecture 8: November 5 Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) OH H2SO4 80 ºC major product trisubstituted University of Illinois at Chicago UIC trisubstituted disubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other CHEM 494, Spring 2010 Slide 14 Lecture 8: November 5 Self Test Question What is the major product expected for the reaction scheme below? A. B. H2SO4 HO ? C. 80 ºC D. E. University of Illinois at Chicago UIC CHEM 494, Fall 2012 Slide 15 Lecture 8: November 5 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago UIC E1 & E2 Mechanisms of Alcohol Dehydration Chapter 19 Organic Mechanisms (SN1) fast & reversible H O H Cl O H Cl H alkyloxonium ion slow Me Me fast Cl Cl Me carbocation (t-butyl cation) University of Illinois at Chicago UIC H2O CHEM 494, Spring 2010 t-butyl chloride Slide 17 Lecture 8: November 5 Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms O N H3C CH3 atoms electrons resonance: electrons in a covalent bond moving out to an atom H O H bond making: lone pair of electrons H3O+ forming a new bond to another atom H CH3 O H3C N CH3 CH3 University of Illinois at Chicago resonance: lone pair of electrons moving in between two atoms to form a new covalent bond UIC O H3C O O H H3C CHEM 494, Spring 2010 O bond breaking: electrons in a bond + H leaving to most electronegative atom Slide 18 Lecture 8: November 5 Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) O fast & reversible H H O S OH O H O pKa = -3.0 University of Illinois at Chicago O UIC O O S OH H O alkyloxonium ion CHEM 494, Spring 2010 Slide 19 Lecture 8: November 5 Mechanism of Dehydration (E1) Step Two Dissociation H slow Me Me O H2O H Me carbocation (t-butyl cation) University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 20 Lecture 8: November 5 Mechanism of Dehydration (E1) Step Three Carbocation Capture βDeprotonation! H O CH2 Me O S OH O Me carbocation (t-butyl cation) fast O H O S OH Me Me alkene (2-methylpropene) O O S OH O University of Illinois at Chicago UIC CHEM 494, Spring 2010 O sulfuric acid (regenerated) alkyl hydrogen sulfate (product of SN1) Slide 21 Lecture 8: November 5 Hughes-Ingold Nomenclature H slow Me Me O H2O H Me carbocation (t-butyl cation) E1 elimination unimolecular overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 22 Lecture 8: November 5 Each Step of E1 Mechanism is Reversible fast & reversible O H O S OH O H O O H slow & reversible CH2 Me O O S OH UIC O fast & reversible Me University of Illinois at Chicago O S OH H O H2O O H Me Me If all steps in E1 are reversible, what drives the reaction forward? CHEM 494, Spring 2010 Slide 23 Lecture 8: November 5 Alkenes Isolated from Dehydration Reactions by Distillation H2SO4 OH + + 4-methyl-2-pentanol bp = 132 ºC 2-methyl-1-pentene bp = 62 ºC 2-methyl-2-pentene bp = 67 ºC + trans-4-methyl2-pentene bp = 59 ºC + cis-4-methyl2-pentene bp = 58 ºC 4-methyl-1-pentene bp = 54 ºC • alkenes have much lower boiling points than alcohols • alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogenbonding • by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remain University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 24 Lecture 8: November 5 Why Can’t Hydrogen Halides Be Used for Elimination Reactions? fast & reversible H H Cl O H H H slow & reversible O H CH2 Me fast & reversible fast & irreversible Cl University of Illinois at Chicago UIC Me Me Me nucleophilic addition Nucleophilic addition of chloride (Cl–) to a carbocation is not reversible H Cl H Cl Cl O alkyl chloride (product of SN1) CHEM 494, Spring 2010 Slide Lecture 8: November 5 Reactivity Explained R2 R1 = C R2 = C R3 3 R2 R =H 2º Carbocation R2 R1 = C R2 = C 3 1 R R R3 = C 3º Carbocation R2 R1 • 3º carbocations are more stable than 2º = 3º lower in energy • smaller activation energy leading to 3º carbocation results in faster reaction R3 OH H3O+ R2 R3 R1 University of Illinois at Chicago UIC OH2 H2O CHEM 494, Spring 2010 Slide 26 Lecture 8: November 5 Bimolecular Substitution - SN2 Mechanism (from Lecture 8) H3C O H fast H H3C O H Br H3C H H H Br slow (rate-determining) Step 1 Protonation Step 2 Nucleophilic Attack CH3 - Br C H H H ‡ O + H H3C Br + H O H • C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond • RDS is nucleophilic attack; bimolecular, therefore Ingold notation = SN2 • fewer steps does not mean faster reaction University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 27 Lecture 8: November 5 Dehydration of Primary Alcohols Proceeds via E2 Mechanism H H3C C fast & reversible O H3C O Step 1 Protonation Step 2 -Deprotonation (elimination) H O O H O S OH H H 1° Cation H3C O O HO S O O S OH H O H slow H2C O H O H H H H H • C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond • RDS is nucleophilic attack; bimolecular, therefore Ingold notation = SN2 • fewer steps does not mean faster reaction University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 28 Lecture 8: November 5 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago Regioselectivity & Stereoselectivity of Dehydration UIC Self Test Question What is the product(s) of the following reaction? A. B. H2SO4 HO ? 80 ºC C. D. E. University of Illinois at Chicago UIC CHEM 494, Fall 2012 O2S Slide 30 Lecture 8: November 5 Types of Selectivity in Organic Chemistry There are three forms of selectivity to consider . . . . Chemoselectivity: which functional group will react • Regioselectivity: where it will react • Stereoselectivity: how it will react with regards to stereochemical outcome . . . for each transformation, always question which of these are factors are at play. University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 31 Lecture 8: November 5 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009 H2SO4 HO + 80 ºC H H H3C HO + 10% (identical) 90% CH3 CH3 University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 32 Lecture 8: November 5 Regioselectivity of Elimination Regioselectivity: Where Will It React? Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2009 OH CH3 CH3 H3PO4 CH3 + heat 84% OH H CH3 H University of Illinois at Chicago 16% H UIC 2 different leaving group/Hrelationships CHEM 494, Spring 2010 Slide 33 Lecture 8: November 5 Greek Lettering & Elimination Reactions Nomenclature The α-carbon is the one to which the leaving group is initially bonded, and the carbon chain from this may be labelled β (beta), γ (gamma), δ (delta) etc, following Greek alphabet. Use primed letters for chains branching at αcarbon University of Illinois at Chicago UIC Cl H 2 C H3C C H2 CHEM 494, Spring 2010 H C H2 ' CH3 ' Slide 34 Lecture 8: November 5 Regioselectivity of Elimination Zaitsev Rule HO CH3 CH3 KHSO4 CH3 CH3 CH3 CH3 + CH3 + heat 87% O 13% 0% Na+ -O S OH O hydrosulfate 3 Hs on this β carbon HO H H CH3 H CH3 1 Hs on this β carbon 2 Hs on this β carbon University of Illinois at Chicago UIC Zaitsev Rule When elimination can occur in more than one direction, the major alkene is the one formed by loss of a H atom from the β carbon having the fewest hydrogens CHEM 494, Spring 2010 Slide 35 Lecture 8: November 5 Considering Stereo & Regioselectivity Combine Zaitsev’s Rule and observations about stereoselectivity to predict the major products of dehydration (elimination) OH H2SO4 80 ºC major product trisubstituted University of Illinois at Chicago UIC trisubstituted disubstituted disubstituted most stable alkenes have largest groups on each carbon trans to each other CHEM 494, Spring 2010 Slide 36 Lecture 8: November 5 Self Test Question What is the major product expected for the reaction scheme below? A. B. H2SO4 HO ? C. 80 ºC D. E. University of Illinois at Chicago UIC CHEM 494, Fall 2012 Slide 37 Lecture 8: November 5 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago UIC E1 & E2 Mechanisms of Alcohol Dehydration Section: 5.12 Organic Mechanisms (SN1) fast & reversible H O H Cl O H Cl H alkyloxonium ion slow Me Me fast Cl Cl Me carbocation (t-butyl cation) University of Illinois at Chicago UIC H2O CHEM 494, Spring 2010 t-butyl chloride Slide 39 Lecture 8: November 5 Remember Curved Arrow Notation? curved arrows show the movement of electrons; never atoms O N H3C CH3 atoms electrons resonance: electrons in a covalent bond moving out to an atom H O H bond making: lone pair of electrons H3O+ forming a new bond to another atom H CH3 O H3C N CH3 CH3 University of Illinois at Chicago resonance: lone pair of electrons moving in between two atoms to form a new covalent bond UIC O H3C O O H H3C CHEM 494, Spring 2010 O bond breaking: electrons in a bond + H leaving to most electronegative atom Slide 40 Lecture 8: November 5 Mechanism of Dehydration (E1) Step One Proton Transfer (Protonation) O fast & reversible H H O S OH O H O pKa = -3.0 University of Illinois at Chicago O UIC O O S OH H O alkyloxonium ion CHEM 494, Spring 2010 Slide 41 Lecture 8: November 5 Mechanism of Dehydration (E1) Step Two Dissociation H slow Me Me O H2O H Me carbocation (t-butyl cation) University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 42 Lecture 8: November 5 Mechanism of Dehydration (E1) Step Three Carbocation Capture βDeprotonation! H O CH2 Me O S OH O Me carbocation (t-butyl cation) fast O H O S OH Me Me alkene (2-methylpropene) O O S OH O University of Illinois at Chicago UIC CHEM 494, Spring 2010 O sulfuric acid (regenerated) alkyl hydrogen sulfate (product of SN1) Slide 43 Lecture 8: November 5 Hughes-Ingold Nomenclature H slow Me Me O H2O H Me carbocation (t-butyl cation) E1 elimination unimolecular overall reaction = β-Elimination rate determining step (RDS) involves on species = unimolecular rate = k[alkyl oxonium ion] = first order University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 44 Lecture 8: November 5 Each Step of E1 Mechanism is Reversible fast & reversible O H O S OH O H O O H slow & reversible CH2 Me O O S OH UIC O fast & reversible Me University of Illinois at Chicago O S OH H O H2O O H Me Me If all steps in E1 are reversible, what drives the reaction forward? CHEM 494, Spring 2010 Slide 45 Lecture 8: November 5 Alkenes Isolated from Dehydration Reactions by Distillation H2SO4 OH + + 4-methyl-2-pentanol bp = 132 ºC 2-methyl-1-pentene bp = 62 ºC 2-methyl-2-pentene bp = 67 ºC + trans-4-methyl2-pentene bp = 59 ºC + cis-4-methyl2-pentene bp = 58 ºC 4-methyl-1-pentene bp = 54 ºC • alkenes have much lower boiling points than alcohols • alcohols have higher boiling points (b.p.) because of larger van der Waals forces, including strong hydrogenbonding • by removing alkenes through distillation (boiling), equilibrium is shifted toward products (LeChatlier Principle) until no more reactants remain University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 46 Lecture 8: November 5 Why Can’t Hydrogen Halides Be Used for Elimination Reactions? fast & reversible H H Cl O H H H slow & reversible O H CH2 Me fast & reversible fast & irreversible Cl University of Illinois at Chicago UIC Me Me Me nucleophilic addition Nucleophilic addition of chloride (Cl–) to a carbocation is not reversible H Cl H Cl Cl O alkyl chloride (product of SN1) CHEM 494, Spring 2010 Slide Lecture 8: November 5 Reactivity Explained R2 R1 = C R2 = C R3 3 R2 R =H 2º Carbocation R2 R1 = C R2 = C 3 1 R R R3 = C 3º Carbocation R2 R1 • 3º carbocations are more stable than 2º = 3º lower in energy • smaller activation energy leading to 3º carbocation results in faster reaction R3 OH H3O+ R2 R3 R1 University of Illinois at Chicago UIC OH2 H2O CHEM 494, Spring 2010 Slide 48 Lecture 8: November 5 Bimolecular Substitution - SN2 Mechanism (from Lecture 8) H3C O H fast H H3C O H Br H3C H H H Br slow (rate-determining) Step 1 Protonation Step 2 Nucleophilic Attack CH3 - Br C H H H ‡ O + H H3C Br + H O H • C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond • RDS is nucleophilic attack; bimolecular, therefore Ingold notation = SN2 • fewer steps does not mean faster reaction University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 49 Lecture 8: November 5 Dehydration of Primary Alcohols Proceeds via E2 Mechanism H H3C C fast & reversible O H3C O Step 1 Protonation Step 2 -Deprotonation (elimination) H O O H O S OH H H 1° Cation H3C O O HO S O O S OH H O H slow H2C O H O H H H H H • C-O bond breaks at the same time the nucleophile (Br) forms the C-X bond • RDS is nucleophilic attack; bimolecular, therefore Ingold notation = SN2 • fewer steps does not mean faster reaction University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 50 Lecture 8: November 5 CHEM 494 Special Topics in Chemistry University of Illinois at Chicago Addition Reactions of Alkenes UIC Addition Reactions of Alkenes C C + X Y C C + H H C C C C + + H X H Br O C C + H O S OH addition hydrogenation hydrogen halide addition free radical bromine addition sulfuric acid addition X C C Y H C C H H C C X H C C Br H C C OSO3H O C C University of Illinois at Chicago UIC + H OH hydration CHEM 494, Spring 2010 H C C OH Slide 52 Lecture 8: November 5 Hydrogenation Pd/C, CH3CH2OH University of Illinois at Chicago • exothermic reaction (-∆Hº), but high Eact - catalyst required • catalysts are heterogeneous transition metals (Pd, Rsolvent is typically an alcohol (e.g. ethanol, CH3CH2OH)metals are insoluble (heterogeneous mixture)heat of hydrogenation = -∆Hº UIC CHEM 494, Spring 2010 Slide 53 Lecture 8: November 5 Heat of Hydrogenation (-∆Hº) University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 54 Lecture 8: November 5 Heat of Hydrogenation (-∆Hº) Since only the double bond is undergoing the reaction, heat of hydrogenation is independent of the number of carbon atoms in the molecule Alkene -∆Hº (kJ/mol) ethylene 136 monosubstituted 126 cis-disubstituted 119 terminally disubstituted 117 trisubstituted 112 tetrasubstituted 110 UIC CHEM 494, Spring 2010 University of Illinois at Chicago example Slide 55 Lecture 8: November 5 General Mechanism for Heterogenious Hydrogenation H H H H d catalyst surface M0 oxidative addition reductive elimination H H H catalyst surface MII catalyst surface MII insertion H H H reaction takes places at the surface of the catalyst (many metal atoms combined) coordination catalyst surface MII University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 56 Lecture 8: November 5 Step 1: Oxidative Addition H H d catalyst surface M0 oxidative addition • • hydrogen (H2) is added to metal metal is oxidized from M0 to MII H H catalyst surface MII H H Pd0 University of Illinois at Chicago UIC H PdII H CHEM 494, Spring 2010 Slide 57 Lecture 8: November 5 Step 2: Coordination • metal is a Lewis acid (electron acceptor) • π-bond is a lewis base (electron donor) • coordination = Lewis acid/base complex H PdII H PdII H H H H catalyst surface MII H H coordination catalyst surface MII University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 58 Lecture 8: November 5 Step 3: Insertion • two carbon atoms inserted between Pd-H • formation of a weak metal-carbon σ-bond • formation of a strong C-H σ-bond • break a weak metal-H σ-bond H H H H PdII H H PdII catalyst surface MII insertion H H catalyst surface MII University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 59 Lecture 8: November 5 Step 4: Reductive Elimination H H H d H catalyst surface M0 reductive elimination H H catalyst surface MII • metal is reduced from MII to M0 • last σ C-H -bond is formed from the same • face of alkene as previous metal is a catalyst; it is regenerated H H University of Illinois at Chicago UIC PdII CHEM 494, Spring 2010 H H Slide 60 Lecture 8: November 5 Complete Mechanism H H H H oxidative addition Pd0 reductive elimination H H H PdII PdII H insertion coordination H University of Illinois at Chicago UIC PdII H CHEM 494, Spring 2010 Slide 61 Lecture 8: November 5 Syn Addition of Hydrogen • University of Illinois at Chicago as a consequence of mechanism, both hydrogens are added to the same face of the π-bond: syn additionno anti-addition products are formed (addition of hydrogen to opposite faces) UIC CHEM 494, Spring 2010 Slide 62 Lecture 8: November 5 Hydrogenation is Stereoselective This methyl group sterically hinders hydrogen from approaching the π-bond from the top face • both products are arise from syn additions of hydrogen to alkenestereoselecti preference for one stereoisomer when two or more are possible University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 63 Lecture 8: November 5 Example of Syn Addition CH3 CH3 C8H12 HO CH3 CH3 H CH3 C8H12 HO C8H12 HO H H H H 1. Diatomic hydrogen and alkene are present in solution phase. No reaction occurs. CH3 CH3 CH3 C H 8 12 H H 4. One hydrogen atom is transferred to alkene, forming C-catalyst bond. University of Illinois at Chicago UIC H 3. System of alkene coordinates catalyst surface. 2. Hydrogen absorbed on to catalyst surface. H-H bond cleaved. CH3 CH3 C H 8 12 CH3 C8H12 HO HO H HO CH3 H 5. Second hydrogen atom is transferred, breaking substrate-catalyst bond. Alkane diffuses away from catalyst. CHEM 494, Spring 2010 H H 6. Steps 1-5 are repeated. Slide 64 Lecture 8: November 5 Self Test Question What is the major product of the following hydrogenation reaction? D A. H2, Pd/C H H D H H CH3CH2OH B. H H C. UIC CHEM 494, Fall 2012 H H H D D. University of Illinois at Chicago D catalyst surface D catalyst surface MII D H H MII H H H H D H Slide 65 Lecture 8: November 5 Addition of Electrophiles to Alkene C C C C C C + + + H H H X H Br O C C + H O S OH hydrogenation hydrogen halide addition free radical bromine addition sulfuric acid addition H C C H H C C X H C C Br H C C OSO3H O C C University of Illinois at Chicago UIC + H OH hydration CHEM 494, Spring 2010 H C C OH Slide 66 Lecture 8: November 5 Electrophilic Addition of HX C C + nucleophile University of Illinois at Chicago UIC δ+ δ– H X hydrogen halide addition H C C X electrophile CHEM 494, Spring 2010 Slide 67 Lecture 8: November 5 Reaction Conditions H H • University of Illinois at Chicago UIC HBr H CHCl3, -30 ºC H H Br hydrogen halide: HXcommon solvents: chloroform (CHCl3) ,dichloromethane (CH2Cl2), pentane, acetic acidgenerally performed at low temperature (below 0 °C)generally a fast reaction CHEM 494, Spring 2010 Slide 68 Lecture 8: November 5 Electrophilic Addition (AdE) Mechanism H Br Br Protonation (slow) H H H H • University of Illinois at Chicago H UIC H Cation Capture (fast) Br H H electrophilic addition: AdERDS = protonation of carbonrate = k[alkene][hydrogen halide]unlike oxygen and nitrogen, protonation of carbon is slowproceeds through carbocation intermediate CHEM 494, Spring 2010 Slide 69 Lecture 8: November 5 HX Addition is Regioselective Regioselectivity Preferential reaction at one site of a single functional group over other sites that could undergo the same reaction CHEM 232 Definition, 2010 R H H R H R H R H R University of Illinois at Chicago H UIC R H X R H H X R R H X X X R R X R H H H rather than H rather than H R H R H R H R H H H rather than CHEM 494, Spring 2010 R H H X H H X H H X R Slide 70 Lecture 8: November 5 Markovnikov’s Rule 3º 2º CH3 H3C Br H HBr H H CH2Cl2 -40 ºC addition of HX to an unsymmetrically substituted alkene proceeds so that hydrogen (H) adds to the least substituted carbon and the halide (X) adds to the most substituted carbon atom University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 71 Lecture 8: November 5 Self Test Question Predict the product when 2,4-dimethyl-2-pentene is treated with HCl? A. 3-chloro-2,4-dimethylpentane B. 2-chloroohexane HCl Cl C. 2,3-dichloro-2,4dimethylpentane D. 2-chloro-2,4-dimethylpentane E. 1-chloro-2,4-dimethylpentane University of Illinois at Chicago UIC CHEM 494, Fall 2012 Slide 72 Lecture 8: November 5 Mechanistic Basis for Markovnikov’s Rule X X H X H H 3º alkyl halide 3º carbocation X H X H + H X 2º carbocation curved arrows do not indicate which carbon is protonated University of Illinois at Chicago UIC fastest protonation leads to more stable (more substituted) carbocation CHEM 494, Spring 2010 2º alkyl halide more substituted carbocation = more substituted alkyl halide Slide 73 Lecture 8: November 5 Mechanistic Basis for Markovnikov’s Rule Hammond Postulate: transition state structure resembles closest energy intermediate •transition state resembles carbocation for endothermic RDS (late transition state) •what stabilizes carbocation also stabilizes transition state •lowest energy transition state leads to more substituted carbocation •more substituted carbocation provides more substituted alkyl halide University of Illinois at Chicago UIC CHEM 494, Spring 2010 Slide 74 Lecture 8: November 5