CHEM 494 Lecture 6

Home , Heterolysis (chemistry), Homolysis (chemistry)

CHEM 494 University of Illinois Special Topics in Chemistry at Chicago UIC

CHEM 494 - Lecture 6

Prof. Duncan Wardrop October 15, 2012 Midterm “Papers”

• Factors that Control Hydrocarbon Acidity

• Factors that Control Hydrocarbon Conformation

• Platonic Hydrocarbons (Cubane and Beyond)

• Hydrocarbon Chemistry of Gasoline

• Hydrocarbon Chemistry of Anesthesia

• Chemistry of the Perfect Pasta Sauce

University of Slide CHEM 494, Spring 2010 2 Illinois at Chicago UIC Lecture 6: October 15 CHEM 494 University of Illinois Special Topics in Chemistry at Chicago UIC

Nucleophilic Substitution at Saturated Carbon

Chapter 19 Structure of Carbocations

• carbocations are high energy intermediates; hard, but not impossible to isolate 2pZ • carbon is sp2-hybridized with a single, H unoccupied 2pZ orbital; 6 valence electrons H3C C • planar structure : three bonds to carbon are H at 120º angles from each other and 90º to empty p-orbital; VSEPR • nucleophiles add to either lobe of the empty carbocations can be stabilized by inductive effects and hyperconjugation p-orbital; since it is !at, there is no preference to which side nucleophile adds

University of Slide CHEM 494, Spring 2010 4 Illinois at Chicago UIC Lecture 6: October 15 Stability of Carbocations

1. Inductive Effects electron withdrawal or electron donation that is transmitted through σ- bonds; polarization of σ-bonds

• electron donation through 1º cation σ-bonds toward δ+ carbocation delocalizes δ+ H charge (spreads out) • C-C σ-bonds are more H3C C polarizable, therefore δ+ donate more electron H density through σ-bonds • more C-C σ-bonds = more stable carbocation

University of Slide CHEM 494, Spring 2010 5 Illinois at Chicago UIC Lecture 6: October 15 Stability of Carbocations

1. Inductive Effects Since C-C σ-bonds are more polarizable than C-H bonds, the additional of more alkyl groups leads to stabilization of the cation

2º cation 3º cation

δ+ δ+ δ+ CH3 H C C δ+ CH3 3 H3C C H δ+ CH3 δ+

University of Slide CHEM 494, Spring 2010 6 Illinois at Chicago UIC Lecture 6: October 15 Stability of Carbocations

2. Hyperconjugation stabilizing interaction that results from the interaction of the electrons in a σ-bond (C–H or C–C bond ) with an adjacent empty (or partially #lled) orbital. Leads to the formation of an extended molecular orbital that increases the stability of the system

filled σ orbital • stabilization results from σ-donation to empty p orbital of planar carbocation empty • electron donation through σ-bonds H p orbital toward carbocation delocalizes charge H (spreads out) C C H H • methyl cations cannot be stabilized by hyperconjugation since σ-bonds are H perpendicular to the empty p orbital 1º cation

University of Slide CHEM 494, Spring 2010 7 Illinois at Chicago UIC Lecture 6: October 15 Stability of Carbocations

2. Hyperconjugation

filled empty σ orbital 2pZ orbital

empty C-H 2pZ H p orbital bonding

y (filled) g

H r e C C n E H H Stabilization resulting from H σ hyperconjugation

University of Slide CHEM 494, Spring 2010 8 Illinois at Chicago UIC Lecture 6: October 15 Stability of Carbocations

H H CH3 H H H3C

CH2 CH2 CH2 C C C C C C H H H CH2 H CH2 H H H H CH3

2º carbocation 3º carbocation 3º carbocation

2 C-H bond 3 C-H bond 3 C-C or C-H bond hyperconjugative hyperconjugative hyperconjugative donors donors donors

University of Slide CHEM 494, Spring 2010 9 Illinois at Chicago UIC Lecture 6: October 15 i>Clicker Question

Rank the following carbocations in order of increasing stability?

A. a,b,c,d a. b. c. d. CH3 H B. c,d,b,a H H C. d,c,a,b H3C C H H H D. b,c,a,d 2º 3º 1º methyl E. d,a,c,b

University of Slide CHEM 494, Spring 2010 10 Illinois at Chicago UIC Lecture 6: October 15 Stabilizing Eﬀects on Carbocations

• smallest inductive effect • largest inductive effect • no hyperconjugation • most hyperconjugation

University of Slide CHEM 494, Spring 2010 11 Illinois at Chicago UIC Lecture 6: October 15 How Carbocation Stability Eﬀects Rate of Reaction

• more stable (lower energy) carbocation = • more stable (lower energy) transition state (Hammond Post.) = • lower activation energy (Ea) = • faster reaction

University of Slide CHEM 494, Spring 2010 12 Illinois at Chicago UIC Lecture 6: October 15 Why are 1° & 2° Alcohols Less Reactive?

H-X EA too high H H O OH H H

simple 1° and 2° alcohols do not Ea undergo substitution by the SN1 OH + HCl Ea mechanism since methyl and

OH primary carbocations are too high in energy to be intermediates in nucleophilic substitution reactions = transition state RCl + H2O

an alternative mechanism is required......

University of Slide CHEM 494, Spring 2010 13 Illinois at Chicago UIC Lecture 6: October 15 Bimolecular Substitution - SN2 Mechanism

H fast H H3C O H H3C O Br H3C H H H Br slow (rate-determining)

Step 1 ‡ Protonation CH3 δ- H H3C Br + Step 2 Br C O δ+ H H H Nucleophilic Attack H H O

• 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 Slide CHEM 494, Spring 2010 14 Illinois at Chicago UIC Lecture 6: October 15 Self Test Question

Which rate equation below best describes the rate determining step (RDS) in an SN2 mechanism?

H H3C O Br H A. rate = k[oxonium ion] B. rate = k[carbocation] ‡ CH3 δ- H Br C O δ+ C. rate = k[oxonium ion][halide] H H H D. rate = k[carbocation][halide] E. rate = k[alcohol][HX] H3C Br

University of Slide CHEM 494, Spring 2010 15 Illinois at Chicago UIC Lecture 6: October 15 CHEM 494 University of Illinois Special Topics in Chemistry at Chicago UIC

Halogenation of Alkanes Methods and Mechanism

Chapter 39 Halogenation of Alkanes

Fluorination (F2): Highly Exothermic (Explosive !)

Chlorination (Cl2): Exothermic

Bromination (Br2): Slightly Exothermic Reactivity Increasing Iodination (I2): Endothermic

University of Slide CHEM 494, Spring 2010 17 Illinois at Chicago UIC Lecture 6: October 15 Radical Chain Mechanism

Step One Initiation via Homolysis

homolysis Cl Cl Cl + Cl light (hν)

free radical half-headed arrow homolysis heterolysis “"shhook” (homolytic cleavage) (heterolytic cleavage) unpaired electron; stabilized by same movement of a single cleavage of a covalent cleavage of a covalent factors that stabilized electron, not a pair bond so that each atom bond so that one atom carbocations in the bond retains one in the bond retains both electron electron Cl

University of Slide CHEM 494, Spring 2010 18 Illinois at Chicago UIC Lecture 6: October 15 Radical Chain Mechanism

Step Two Propagation vis H-Atom Abstraction alkyl hydrogen radical H abstraction H Cl H C CH3 C CH3 + HCl H H chlorine 7 valence radical electrons

• Cl radical abstracts H atom from most substituted C atom • alkyl radical is an intermediate in the mechanism ˛ • alkyl radicals are stabilized by same factors that stabilize carbocations • note that radical is generated - propagation!

University of Slide CHEM 494, Spring 2010 19 Illinois at Chicago UIC Lecture 6: October 15 Radical Chain Mechanism

Step Three Propagation vis Cl-Atom Abstraction halogen H abstraction H

Cl Cl C CH3 Cl C CH3 + Cl H H chlorine chlorine alkyl radical alkyl chloride molecule radical

• alkyl radical abstract a halogen from a 2nd X2 molecule • chlorine radical product continues on in chain; starts the cycle over again by abstracting hydrogen from another alkane • radical chain mechanisms are faster than a stepwise mechanism which would require initiation in each step

University of Slide CHEM 494, Spring 2010 20 Illinois at Chicago UIC Lecture 6: October 15 Complete Mechanism

homolysis n o i Cl Cl Cl + Cl t a

i light (hν) t

i 7 valence

n electrons I

hydrogen H abstraction H Cl H C CH3 C CH3 + HCl

n H H o i

t 7 valence

a electrons g a p o

r halogen

P H abstraction H Cl Cl C CH 3 Cl C CH3 + Cl H H

University of Slide CHEM 494, Spring 2010 21 Illinois at Chicago UIC Lecture 6: October 15 Structure of Alkyl Radical Intermediates

• radicals are high energy intermediates; 7 valence electrons; cannot be isolated • sp2-hybridized; contain one empty p- orbital; unpaired electron in the p- C H orbital; H C 3 H • approximately planar: three bonds to carbon are at ~120º angles from each other and ~90º to half-#lled p-orbital alkyl radicals can be stabilized by inductive effects and hyperconjugation; • stabilized by inductive eﬀects and similar to carbocations hyperconjugation

• Stability: 3º > 2º >> 1º > CH3

University of Slide CHEM 494, Spring 2010 22 Illinois at Chicago UIC Lecture 6: October 15 Stabilizing Eﬀects on Alkyl Radicals

• smallest inductive effect • largest inductive effect • no hyperconjugation • most hyperconjugation

University of Slide CHEM 494, Spring 2010 23 Illinois at Chicago UIC Lecture 6: October 15 Bromination is More Selective Than Chlorination

H H † Cl † ∆Ea (chlorination) Hammond Postulate H3C CH3

‡ • chlorine radicals are higher in energy than bromine radicals = ∆Ea (bromination) H H ‡ • transition states in chlorination are earlier= Br H3C CH3 • look more like reactants = H H • less diﬀerence in TS energy = less selective = H3C CH2 • H • greater mixture † = early transition state structures

‡ = late transition state structures H3C CH3 • bromine radicals are lower in energy than ∆Ea (bromination) > ∆Ea (chlorination) chlorine radicals = Bromination is more selective. • transition states in bromination are later=

Relative Rates (krel) of Halogenation • look more like products (radical interm.) = R3CH R2CH2 RCH3 • greater diﬀerence in TS energy = (tertiary, 3º) (secondary, 2º) (primary, 1º) more selective = chlorination 5.2 3.9 1.0 • bromination 1640 82 1.0 • less of a mixture

University of Slide CHEM 494, Spring 2010 24 Illinois at Chicago UIC Lecture 6: October 15 Quantifying Selectivity

Relative Rates (krel) of Halogenation R3CH R2CH2 RCH3 (krel) x (statistical factor) (tertiary, 3º) (secondary, 2º) (primary, 1º) % = chlorination 5.2 3.9 1.0 total bromination 1640 82 1.0

Predicted Product Ratios

Product Relative Yield Absolute Yield

H A (2 2º H’s) 2 x 3.9 = 7.8 7.8/13.8 = 57% H H Cl2 H Cl H + H3C CH3 H3C CH3 H3C CH2 B (6 1º H’s) 6 x 1 = 6.0 6.0/13.8 = 43% Cl A: 57% B: 43% Sum 13.8 100% chlorination

A (2 2º H’s) 2 x 82 = 164 164/170 = 96% H H Br2 H Br H H + B (6 1º H’s) 6 x 1 = 6.0 6.0/170 = 4% H3C CH3 H3C CH3 H3C CH2 Br Sum 170 100% A: 96% B: 4% bromination

University of Slide CHEM 494, Spring 2010 25 Illinois at Chicago UIC Lecture 6: October 15 Self Test Question

Determine the predicted product distribution for A in the following chlorination.

Br2 A. 99% + Br Br B. 97% C. 95% A B D. 93%

Relative Rates (krel) of Halogenation R3CH R2CH2 RCH3 E. 91% (tertiary, 3º) (secondary, 2º)(primary, 1º) chlorination 5.2 3.9 1.0 bromination 1640 82 1.0

University of Slide CHEM 494, Spring 2010 26 Illinois at Chicago UIC Lecture 6: October 15 De"ning Regioselectivity

Regioselectivity (regioselective) A regioselective reaction is one in which one direction of bond making or breaking occurs preferentially over all other possible directions. Reactions are termed completely (100%) regioselective if the discrimination is complete, or partially (<100%), if the product of reaction at one site predominates over the product of reaction at other sites. The discrimination may also semi-quantitatively be referred to as high or low regioselectivity.

IUPAC Compendium of Chemical Terminology 2nd Edition (1997)

O N O

CCl , hν 4 Cl Cl Cl

Regioselective Chlorination...... not stereoselective!

University of Slide CHEM 494, Spring 2010 27 Illinois at Chicago UIC Lecture 6: October 15 Mechanism of Alkane Chlorination