Radicals – Part 1 - Chemistry2011.org · Radical desires one electron to fill octet. ... Radical...

Radicals – Part 1

CH3

Br Br+ +Br

CH3

+ H Br

Explain This Observation...

CH3Br Br Predict: No pi bonds, therefore no reaction

Observation:

CH3

Br

CH3

+ H BrBr Br

hν or heat

Consider: A mixture of Br2 and an alkane...

•Mechanism?

•Why reaction occurs at 3o carbon?

Questions:

Add energy via photons

Lecture Supplement - Radicals --

Mechanism

Colorless Red

So mechanism begins with Br2 absorbs hν

•Causes electronic excitation of lone pair electron to σ* orbital

•Weakens σ bond

CH3

Br

CH3

+ H Br+ Br Brhν or heat

= 2 electrons = 1 electron

Colorless – Does not absorb visible light

Red – Absorbs visible light

Br BrBr BrBr Brhν or heat

Br Brhν or heat

Br2Unpaired electron = free radical

Homolytic cleavage = even distribution of bond electrons

Photolysis (photo = light; lysis = destruction) = reaction via light

Radical Fates

Now that I have a radical, what do I do with it?

•How do radicals react?

•What is a radical's motivation?

Radicals react in ways to ...reduce or resolve their electron deficiency. ...become more stable.

Three common ways in which radicals react: The Radical Fates.

Br


Radical FatesRadicals desire to become more stable.

Radical Fate #1: Add to a pi bond

•Trade pi bond (weaker) for sigma bond (stronger)

Radical desires one electron to fill octet.

Electron can be provided by ________________________________.

Why not?H2C CH3

Br

H2C CH3

Br

Alternate possibility:

H2C CH3Br

Br

CH3


Radical Fate #2: Atom transfer

•Usually trades weaker sigma bond for stronger sigma bond



Br

CH3

H Br

Br

CH3

H

+ Br


Br Br Br Br


Radical Fate #3: Radical combination•Driven by completing two open octets, and by gaining a sigma bond



Fact: Radical mechanism steps generally have low ΔG‡

•Therefore one formed, radicals react quickly•[radicals] never becomes very high•Metaphor: Finding a friend (common) versus finding your soul mate (one-of-a-kind)

Conclusion: Radical combination is common uncommon event

Br Br

Back to the Radical Halogenation Mechanism...Our mechanism so far... Br Br

hν or heatBr2

What happens next? Three radical fates...

•Add to a pi bond – no pi bond present

•Atom transfer – possible

•Radical combination – possible but unlikely

What atom does Br steal? Bond change inventory....

Overall reaction is... Therefore next mechanism step is...

Br

CH3

H

CH3Br2 H Br

CH3 CH3

+ H Br

Br Next step?


Radical Halogenation Mechanism

Our mechanism so far... Br Brhν or heat

Br2

H Br

CH3 CH3

+ H Br

Why not... H Br

HHCH2

+ HBr

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

choose __________________________________.

Radical Structure and Stability

Structure: versus

Pyramidal Trigonal planar

CR RR

C RR

R

Stability

•Central electron-deficient carbon, like a carbocation

Which repels more strongly? One nonbonded electron Two bonded electrons

• So do radicals have same stability trends as carbocations?

R C

R

R

R C

R

R

sp3 carbon sp2 carbon


Radical Stability: Degree of Substitution

Carbocations: C

H

H

H

Methyl 1o 2o 3o

C

H

H

H3C C

H

CH3

H3C

Increasing number of electron-donating groupsIncreasing stability

C

CH3

CH3

H3C

Radicals:

Methyl 1o 2o 3o

Increasing number of electron-donating groupsIncreasing stability

H C

H

H

H3C C

H

H

H3C C

H

CH3

H3C C

CH3

CH3

CC

H H

C

H

H H CC

H H

C

H

H H

Radical Stability: Pi Bond Resonance

Carbocations:

Radicals:

Resonance hybrids

C C CH2H

CH2

Conclusion

•A radical does does not gain resonance stabilization from adjacent pi bond.

CC

H H

C

H

H HCC

H H

C

H

H HCC

H H

C

H

H H CC

H H

C

H

H H CC

H H

C

H

H Hδ+ δ+

CC

H H

C

H

H Hδ δ


H2C OH H2C OH

H2C OH H2C OH

Radical Stability: Lone Pair Resonance

Carbocations:

Radicals:

Resonance hybrid

Conclusion

•A radical does does not gain resonance stabilization from adjacent lone pair.

H2C OH H2C OH H2C OHδ+ δ+

H2C OHH2C OHH2C OH

FAQ: Radical Rearrangement?

Question: Do radicals rearrange?

Fact: Carbocations may rearrange.

Answer: Radical rearrangement is likely possible never occurs.

2o 3o

2o 3o

H3CCH3

CH3H3C

H3C

CH3

CH3

CH3

H3CCH3

CH3H3C

H3C

CH3

CH3

CH3

?



Our mechanism so far... Br Brhν or heat

Br2

H Br

CH3 CH3

+ H Br

Last step: Br

CH3CH3Three ways

Radical Halogenation MechanismWhat is final step of mechanism? Think of radical fates.

Addition to a pi bond – no pi bond present.

Atom transfer – steal Br from another molecule.

Br

CH3CH3

Br Br + Br

Br

CH3CH3

Br H + H

Radical combination –

Br

CH3CH3

BrRadical combination unlikely dueto low concentration of radicals.

Br-Br bond weaker than Br-H bond.



Complete 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.

One photon yields (in principle) many molecules of product.

Chain Reaction Mechanism Steps

Br Brhν or heat

Br2

H Br

CH3 CH3

+ H Br

Br

CH3CH3

Br Br + Br

Initiation (I) – starts chain

no radicals → radicals

Propagation (P) – continues chain

radicals → radicals

Termination (T) – ends chain

radicals → no radicals


Radicals – Part 2

F C

Cl

F

Cl + O3

N O

Radicals – Part 1 Summary

Mechanism:Radical: Has unpaired electron

Radical fates:

Free radical halogenation:

CH3

Br

CH3

+ H BrBr Br

hν or heat

Br Brhν or heat

Br2

H Br

CH3 CH3

+ H Br

•Add to pi bond

•Atom transfer

•Radical combination

Radical stability: •Methyl < 1o < 2o < 3o

•Pi bond resonance

•Lone pair resonance


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


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



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




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



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.



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


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


Radicals – Part 1 - Chemistry2011.org · Radical desires one electron to fill octet. ... Radical...

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