Chapter 11: Radical Reactions 11.1 Radicals – species that contain unpaired electrons

double-headed arrow single-headed

arrow

The movement of a single electron is denoted by a curved single headed arrow (fishhook or hook) – radical reactions.

The movement of an electron pair is denoted by a curved double headed arrow – polar reactions.

Polar  reac)on                                                                                            Radical  Reac)ons  A B

heterolyticA:– + B+ A B A• + B•

homolytic

Structure and geometry of radicals

carbocation – sp2 carboanion – sp3

+

–

radical – sp2 229

R3C-H R3C• + H • BDE

ΔH° H

C

H

HH

H

C

H

HH3C

H3C

C

H

HH3C

H3C

C

H3C

HH3C

H

C

H

HCCH

H

H

H

C

H

H

ΔH° = 435 KJ/mol

410

397

381

ΔH° = 364 KJ/mol

356

The bond dissociation energies (BDEs) reflect the stabilities of the radical products.

Table 6.1, p. 238

230

115

The stability and structure of alkyl radicals parallels those of carbocations:

231

11.2 Common Patterns in Radical Mechanisms

Homolytic cleavage – Coupling (radical combination) Addition to a π-bond – Elimination (β-scission)

232

116

Hydrogen atom abstraction (transfer) Halogen atom abstraction (transfer) Mechanism of free radical reactions have three distinct steps:

1. Initiation (Homolytic cleavage)

2. Propagation (Addition to a π-bond, Elimination, Hydrogen atom abstraction, Halogen abstraction)

3. Termination (Coupling) 233

11.3 Chlorination of Methane Free-radical chain mechanism:

234

117

H

C

H

HHCl2

H

C

H

ClH

+ HCl

Cl2Cl

C

H

ClH

+ HCl

Cl2Cl

C

H

ClCl

+ HCl

Cl2Cl

C

Cl

ClCl

+ HCl

Free radical chlorination is not very useful for making alkyl chlorides due to polychlorination and non-specific chlorination

C-H BDEs (KJ/mol): 431 423 414 377

Radical initiators

Cl Cl RO OR

O

OR

O

RO

BDEs (KJ/mol): 243 159 121  

235

11.4 Thermodynamic Considerations for Halogenation Reactions.

X= F ΔH° (KJ/mol) 435 159 456 569 – 431 KJ/mol

X= Cl 435 243 351 431 – 104

X= Br 435 193 293 368 – 33

X= I 435 151 234 297 + 55

H

C

H

HH X X+

H

C

H

XH + H X

Free radical . . . fluorination is so exothermic that it cannot be controlled.

iodination is endothermic and does not precede.

chlorination and bromination are useful reactions

236

118

The propagation step for free radical bromination is endergonic, as opposed to chlorination which is exergonic.

Cl: ΔH = – 21 KJ/mol Br: = + 42 KJ/mol

R

C

R

HR X+

R

C

R

R + H X• •

According to the Hammond postulate the transition state for bromination should resemble the product radical, and therefore be more selective for the product going through the more stable radical intermediate  

237

11.5 Selectivity of Halogenation

Since the transition state for bromination resemble the product radical, the stability of the radical intermediate greatly influences the rate of the reaction. This results in higher selectivity for free radical bromination

CH3

C

CH3

HH3C

H

C

H

CH3H3CX2, hν

X

C

H

CH3H3C

H

C

H

CH2XH3C

X = Cl 60 : 40X = Br 97 : 3

+

X2, hν CH3

C

CH3

XH3C

CH3

C

CH2X

HH3C+

X = Cl 35 : 65X = Br 99 : 1

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119

Halogenation reactions that create new chiral centers and involving existing chiral centers.

Selectivity (relative reactivity) for free radical . . . chlorination bromination

H

C

H

HR

H

C

R

HR

R

C

R

HR< <

primary (1°)hydrogens

secondary (2°)hydrogens

tertiary (3°)hydrogens

1.0 2.3 4.9

H

C

H

HR

H

C

R

HR

R

C

R

HR< <

primary (1°)hydrogens

secondary (2°)hydrogens

tertiary (3°)hydrogens

1.0 82 890

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11.7 Allylic Bromination – allylic position is the next to a double bond

C CC H

allylic carbon

allylic hydrogen

NBS, hν

CCl4

Br

Allylic and benzylic bromination of an alkene takes place through a free radical mechanism.

240

120

C CR

H H

H

H–Br C CR

Br

H

HH

H+ C CR

H

H

HH

Br

C CR"

R H

H

H–Br C CR

Br

H

HR"

H+ C CR

H

H

HR"

Br

C CR"

R R'

H

H–Br C CR

Br

R'

HR"

H+ C CR

H

R'

HR"

Br

C CR

H R'

H

H–Br C CR

Br

R'

HH

H+ C CR

H

R'

HH

Br

Polar mechanism

11.10 Radical Addition to HBr: Anti-Markovnikov Addition

none of this

none of this

none of this

Both products observed

C CR

H H

H

H–Br

C CR"

R H

H

H–Br

C CR"

R R'

H

H–Br

C CR

H R'

H

H–Br

RO–OR(peroxides)

RO–OR(peroxides)

RO–OR(peroxides)

RO–OR(peroxides)

Radical mechanism

none of this

none of this

none of this

241

Polar mechanism (Markovnikov addition)

Radical mechanism (Anti-Markovnikov addition)

H3CH2C CC HH

H

H-BrC CBr

HH3CH2C

H

HH C C

H

HH3CH2C

Br

HH+

none of this

H3CH2C CC HH

H

H-BrC CBr

HH3CH2C

H

HH C C

H

HH3CH2C

Br

HH

+

peroxides(RO-OR)

none of this

The regiochemistry of HBr addition is reversed in the presence of peroxides. Peroxides are radical initiators - change in mechanism

242

121

243

11.13 Halogenation as a Synthetic Technique

244

Radical inhibitors (scavengers) – compounds that terminate radical chain reactions.

Phenols and hydroquinones OH OH

OH

phenol hydroquinone

O

O

- 2 H•

quinone

OH

BHT

11.8 Atmospheric Chemistry and the Ozone Layer (please read) 11.12 Radical Processes in the Petrochemical Industry

(please read) 11.11 Radical Polymerization (please read) 11.9 Autooxidation and Antioxidants (please read)

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245

Oxidative Stress- a free radical chain process

Cellular respiration

O2•_ + Fe (III)

HO• + HO _ + Fe(III)

Fe (II) + O2

Fe (II) + H2O2

O2•_ + •NO ONO2

_

nitricoxide peroxynitrate

H+

ONO2H

peroxynitrousacid

NO2• + HO•

Reactive Oxygen Species (ROS)

O2

4 e ,4H+

2 H2O

•_

O2•_

Superoxide:one-electron reduction of O2

HO•

hydroxylradical

H2O2

hydrogen peroxide

The Oxygen Paradox: oxygen is necessary for cellular metabolism; however, oxygen is transformed into highly reactive species that can damage biomolecules.

246

OH

O

Linoleic Acid (unsaturated fatty acid)H-atom abstractionala the free radicalchlorination of methane

HO•

OH

O

•

OH

OO O • linoleic acid

Propagation OH

OO OH

+  linoleate  radical  

anti-oxidants(vitamin e)

Termination

Degrada)on  (lipid  peroxida)on)  

Linked to DNA damage, protein damage, diabetes, neurodegenerative disease, cardiovascular disease

O

HO

Vitamin Eα-tocopherol

OO

OHHO

OH

OH

H

Vitamin C

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247

Chapter 12: Synthesis

12.1 One-Step Syntheses

12.1 Identify the reagents necessary to accomplish each pf the transformations shown below. (Chapter 9)

248

12.2 Identify the reagents necessary to accomplish each pf the transformations shown below. (Chapter 10)

124