Radicals – Part 1 Summary

Mechanism:

Br Brhν or heat

Br2

H Br

CH3 CH3

+ H Br

Br

CH3CH3

Br Br + Br

Chain reaction: A reaction whosemechanism includes one or moresteps that are repeated indefinitely,until the chain is terminated.

Can Other Halogens Be Used?

Highly selective

CH3

Br

CH3

hν or heat

Br2

Less selective

CH3

Cl

CH3

hν or heat

Cl2+

CH3

Cl

+ others

CH3

hν or heat

I2No reaction

Nonselective

CH3F

CF3

hν or heat

F2

F

F

F F

F

F

F

F

FF

More on Addition of HBr to Alkenes and Alkynes

Recall:Markovnikov addition

But it's not quite that simple...

C

H3C

H3C

CH2H Br

C

H3C

CH2

BrH3C

H

Mixture

•Impurity = peroxide R-O-O-R

•Adding peroxide causes 100% anti-Markovnikov addition

Kharasch, Mayo (1933):

C

H3C

H3C

CH2H Br

C

H3C

CH2

BrH3C

H

+ C

H3C

CH2

HH3C

Br

C

H3C

H3C

CH2H Br

HO OHC

H3C

CH2

HH3C

BrAnti-Markovnikov is major product"Peroxide effect" observed for HBr only

More on Addition of HBr to Alkenes and Alkynes

Mechanism?

Conclusion: Which adds to pi bond first? Br. H

.

comes from

versus

When choosing between two potential products of a mechanism step, we generally

choose __________________________________.

C

H3C

H3C

CH2

Br

C

H3C

H3C

CH2

Br

C

H3C

CH2

HH3C

Br

•Kharasch and Mayo show it to be a radical chain reaction

•Radical addition to pi bond gives most stable radical

C

H3C

H3C

CH2 C

H3C

H3C

CH2

HH

More on Addition of HBr to Alkenes and Alkynes

Mechanism? Radical chain = initiate then propagate

Initiation:

Propagation: Generate Br

HO OH 2 HO

Weak bond

HO H Br HO H + Br

Add to make most stable radical C

H3C

H3C

CH2

Br

C

H3C

H3C

CH2

Br

Last step = termination

propagationC

H3C

H3C

CH2

Br

H Br

C

H3C

H3C

CH2

BrH

+ Br

.

Chain continues

H-X Addition Reactions Orientation SummaryMarkovnikov versus Anti-Markovnikov?

Markovnikov Anti-Markovnikov

C

H3C

H3C

CH2H Br

no peroxideC

H3C

CH2

BrH3C

H

C

H3C

H3C

CH2H Br

C

H3C

CH2

HH3C

Br

RO OR

Markovnikov Anti-Markovnikov

Markovnikov Anti-Markovnikov

Markovnikov Anti-Markovnikov

Only HBr experiences the peroxide effect

C

H3C

H3C

CH2H Cl

no peroxideC

H3C

CH2

ClH3C

H

C

H3C

H3C

CH2H Cl

C

H3C

CH2

ClH3C

H

RO OR

C

H3C

H3C

CH21. BH3

2. HOOH, HOC

H3C

CH2

HH3C

OH

Markovnikov Anti-Markovnikov

Dioxygen and Metabolites – Biological Oxidation

O O

Molecular Structure of Dioxygen (O2)

Dioxygen does not have a double bond.

Simple Lewis theory gets it wrong.Lewis theory predicts:

Quantum mechanics predicts:Dioxygen is a diradical.

Quantum mechanics gets it right.O O

Dioxygen and Metabolites – Biological OxidationOrganisms bathed in O2, a diradical. Is this a problem?

O2 is less reactive than most radicals

Electron "leaks" from normal mitochondrial metabolic pathways

Superoxide .

Hydrogen peroxide

Hydroxyl radical

O O

e-

O O

e-

2 "H+"

HO OH

2 HO

•A radical anion•More reactive than O2 but less reactive than HO•Defense against invading microorganisms

•Very aggressive radical•Can attack DNA, lipids, proteins, etc.

Dioxygen and Metabolites – Biological Oxidation

Potential for damage to biological structures...

Phospholipid bilayer

•Contains fatty acid alkenes

•Susceptible to attack by HO .

Resonancestabilization

Cross-linkedfatty acids

H

HH +

HOFatty acidalkenes

Radical chaincontinues

Dioxygen and Metabolites – Biological Oxidation

Phospholipid cross-linking can lead to...

•...membranes less flexible, distorted, and damaged

•...reduced solubility lipid → plaque in arteries → atherosclerosis

Biological defenses against radicals: Antioxidants

•Radical scavenger enzymes

Example: Superoxide dismutase (SOD)

•Nonenzymatic defenses

Lipids susceptible to attack by HO because ______________________________

O O2 "H+"

SODO2 + HOOH2

.Therefore an efficient antioxidant has ____________________________________

HO H antiox HO H + antiox Resonance contributors•Reduces reactivity•Slows chain propagation

Dioxygen and Metabolites – Biological OxidationLipophilic (Hydrophobic) Antioxidants

α-Tocopherol Main component of vitamin E Ubiquinone (coenzyme Q)

Carotenes β-Carotene is shown

CH3 CH3 CH3

CH3 CH3 CH3

O

HO

CH3

CH3

CH3CH3

CH3

CH3 CH3 CH3CH3O

CH3O

CH3

O

O CH3

H

6-10

Dioxygen and Metabolites – Biological OxidationLipophobic (Hydrophilic) Antioxidants

Ascorbate (vitamin C) Uric acid

O

HO O

O OH

OHH

N

NN

N O

H

O

O

H

H

H

Chlorofluorocarbons and Ozone Depletion

Chlorofluorocarbons (CFCs)

•Used as refrigerants, spray can propellants, etc.

•Low chemical reactivity → atmospheric half-life typically 50-100 years

•Released in atmosphere; not removed until stratosphere (8-50 km altitude)

•Crutzen, Rowland, and Molina implicate CFCs in ozone depletion

2 O3 3 O2

hν

•Hazardous at ground level (ozonolysis!)

•Protects against high-energy solar UV in ozone layer (few ppm O3 at 15-35 km altitude)

Ozone (O3)

Chlorofluorocarbons and Ozone Depletion•Reaction occurs on polar atmospheric ice crystals → polar "ozone hole"

Montreal Protocol (1987)

•Agreement to phase out manufacture and release of CFCs and related substances

•Atmosphere will fully recover by 2070

•Nobel Prize in Chemistry 1995 (www.nobelprize.org)

Chlorofluorocarbons and Ozone Depletion

Mechanism (simplified):

Chain reaction: On average one Cl radical destroys ~104 O3 before termination

C Cl

Cl

F

F

hνC

Cl

F

F

+ Cl

Freon 12

Cl + O O O Cl O + O O

2 Cl O Cl O O Cl Cl O O + Cl

Cl O O Cl O O+

Nitric Oxide -- NO!N O

Gaseous radical and air pollutant

•Presence in high altitude exhaust implicated in ozone destruction

Physiological effects

•Important for signaling between nerve cells in brain

•Endogenous antibacterial/antiparasitic

•Relaxes blood vessel wall smooth muscle (vasodilation)

Short lived: In vivo half-life ~10 seconds

Nobel Prize in Medicine 1998: Furchgott, Murad, and Ignarro (UCLA)

End Exam 2 Coverage