13 Free Radicals

Date Started @February 8, 2021

Status

Unit/Module Chapter 13

Week 2

13 FREE RADICALS
Radicals
- reactive intermediate with single unpaired electron ← homolysis of a covalent bond
- uses half-headed reaction in radical reaction
- do not have an octet of electrons → unstable & reactive
Classification

primary, secondary or tertiary

by the number of R groups bonded to the carbon with unpaired electron

stability of radical increases as number of alkyl groups bonded to radical carbon increases → more alkyl group are more
polarizable than H-atoms, which can easily donate electron density to electron deficient radical, thus increasing stability

- a sp² hybridized and trigonal planar, same with carbocations

→ unhybridized p orbital contains the unpaired electron, extends above and below the trigonal planar carbon
Bond Dissociation Energies (BDE)
- energy required to cleave a C—H bond
- used to measure radical stability
→ Higher energy (𝚫Hº)—more energy required to cleave— stronger bond & less stable
→ lower energy (𝚫Hº)—less energy required to cleave— weaker bond & more stable
- lower BDE for C—H bond, more stable carbon radical

Features of Radical Reactions

- formed from covalent bonds by adding energy through heat (𝚫) or light (hv)
- carried out in presence of radical initiator— contains weak bond that serves as a source of radicals.

peroxides (RO—OR)
- heating, readily causes homolysis of weak O—O bond → RO· radical

Features of Radical Reactions: Two Common Reaction of Radicals

Main types reactions, achieving an octet of electrons:

Reaction of a Radical X· with a C—H bond: reaction with σ bonds

- radical X· abstracts H-atom from C—H bond → forming H—X and carbon radical
- result: radical X· is surrounded by an octet of electron & new radical
- typically seen with nonpolar C—H bonds of alkanes, whhich cannot react with polar/ionic electrophiles or ionic electrophiles and
nucleophiles

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 Reaction of a radical X· with a C=C bond: reaction with 𝜋 nonds
- using an electron from double bond → new C—X bond & other unpaired electron remains on the other carbon where the original
double bond is
- electron-rich alkene reacts with electrophiles by ionic addition mechanisms & with radicals because reactive intermedieate are
also electron deficient
- result: C—X bond & new radical

Features of Radical Reactions: Two Radicals Reacting with Each Other

- radicals rapidly reacts with whatever is available— stable σ or 𝜋 bond.
- when two radicals are in contact with each other, they react forming a σ bond.

reaction of a radical with oxygen → diradical in its ground state

Radical Inhibitors or Radical Scavengers

- compounds that prevents radical reactions from occuring
- eg. diradical O₂ with X· forms new radical

Halogenation of Alkanes
alkanes + halogens -hv or 𝚫→ alkyl halides

Halogenation
- radical substitution reaction: halogen (X) atom replaces a hydrogen via mechanism involving radical intermediates
- useful only with Cl₂ and Br₂— reaction with F₂ is too violent & with I₂ is too slow

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 Monohalogenation
- substitution of a single H by X— through experimentally adding halogen X₂ to an excess of alkane

Mechanism of Halogenation
- all halogenation reaction of alkanes—reagardless of the halogen & alkane used— process by the same mechanism

Facts Explanation
[1] light, heat or added peroxide is light or heat provides energy required for homolytic bond cleavage to from radicals
necessary
breaking weak O—O bond initiates radicals reactions

diradical removes radicals from a reaction mixture

[2] O₂ inhibits reactions
radicals do no rearrange
[3] no rearrangements are observed

Mechanism of Halogenation: Steps of Radical Halogenation

Three distinct parts of radical halogenation:

Initiation:
- homolysis of σ bond to form two radicals

¹ bond cleavage froms two radicals

Propagation:
- radical reacts with another reactant to form a new σ bond & another radical

² Cl· radical abstracts a hydrogen from cyclopentane → HCl & C·

³ C· abstracts a Cl-atom from a Cl—Cl → chlorocyclopentane & Cl·
* since, Cl· is a reactant step 2 & 3 with occur repeatedly without additional initiation— chain mechanism

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 Termination:
- two radicals combine to for a stable bond
- removal of radicals from reaction mixture without forming any new radicals to completely stop the reaction

combination of two radicals to form a bond, stoping the chain reaction of propagation

Energy Changes During Chlorination of Ethane

𝚫Hº = bond broken + (-) bond formed
𝚫Hº overall = 𝚫Hº₁ + 𝚫Hº₂

rate determining step

- higher energy of Transition Step

(+) endothermic, (-) exothermic

Chlorination of Other Alkanes

- weaker C—H bond, more readily the hydrogen atom is removed in radical halogenation
- when alkanes react with Cl₂ results to a mixture of products with more product by cleavage of weaker C—H bonds than you would
expect.

Chlorinatiom Versus Bromination

chlorination is faster than bromination

chlorination is unselective that yields a mixture of products, bromination is often selective that yields a major product

in bromination, major product results from cleavage of weakest (most stable, more substituted) C—H bond

Hammond Postulate

- comparing of rate-determining step in halogenation—the abstraction of a hydrogen atom by halogen radical

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 📌 transition states in endothermic reactions resemble products → faster formation of more stable product

📌 transition states in exothermi reactions resemble reactants → relative stability of the product does not greatly affect the
relative energy of the transition state, resulting a mixture of products

Bromination: CH₃CH₂CH₃ + Br₂

- bromine radical can abstract either 1º or 2º hydrogen from propane → borming either 1º or 2º radical, and both reactions are
endothermic
- because the rate-determining step in bromination is endothermic, more stable radical is formed faster, and often sigle radical
halogen

more stable 2º radical is formed faster, hence the major product of bromination

Chlorination: CH₃CH₂CH₃ + Br₂

- chlorine radical can abstract either 1º or 2º hydrogen from propane → forming either 1º or 2º radical, and both reactions are
exothermic
- because the rate-determining step in chlorination is exothermic, both radicals are formed, hence, the mixture of products

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 Halogenation as a Tool in Organic Synthesis
- it is a useful tool because it adds fuctional group to a previously functionalized molecule → alkyl halide.
- alkyl halide can be converted to alkene by elimination, and to alcohols and ethers by nucleophilic substitution

conversion of alkane to alkene

→ two step method:

[1] radical halogenation (through Cl₂ + hv or 𝚫) → alkyl halide

[2] elimination of HCl with strong base (K⁺ ⁻OC(CH₃)₃) → alkene

Stereochemistry of Halogenation Reactions

- depends on whether the reaction occurs at a stereogenic center or at another atom, and whether a new stereogenic center is formed
Rules for Predicting the Stereochemistry of Reaction Products

Reactants Product

achiral gives either achiral or racemic product

chiral if: reaction is not at stereogenic center → configuration is retained in product

if: reaction is at stereoegenic center → know the mechanism to predict strereochemistry of product

Stereochemistry: Halogenation of Achiral Reactants

Halogenation: Achiral CH₃CH₂CH₂CH₃
→ 2 constitutional isomers by replacement of either 1º or 2º hydrogen

1-chlorobutane: no stereogenic center = achiral compound

2-chlrobutane: has a new stereogenic center = two enantiomers → racemic mixture: [(R)- and (S)-2-chlorobuatNe

Racemic Mixture
- formed because first propagation step generates a planar, sp² hybridized radical— halogens can attach from either from or back side
hence, the equal amount of two enantiomers (R & S)

Stereochemistry: Halogenation of Chiral Reactants

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 Chlorination: Chiral (R)-2-bromobutane at C2 & C3

Chlorination at C2
- occurs at the strereogenic center
- abstraction of hydrogen atom C2 → forming trigonal planar sp² hybridized radical → reacts with Cl₂ from either side → new
stereogenic center = two enantiomer → racemic mixture

Chlorination at C3
- occure not at the steogenic center, but forms new stereogenic center
- C2 stereogenic center is retains
- abstraction of a H-atom at C3 → forming trigonal planar sp² hybridized radical → reaction new stereogenic center → product has
twi stereogenic centers: same configuration @ C2 but different for C3 → diastereomers

Application: Ozone Layer and CFCs

Ozone (O₃)
- formed in upper atmosphere by reaction of oxygen molecules with oxygen atoms
- decomposes with sunlight back to the same two species.
→ overall result of these reaction is conersion of high-energy UV light into heat.

Chlorofluorocarbons (CFCs)
- suggested to be responsible for destroying ozone in upper atmosphere
- simple halogen containing organic compounds
- inert ordorless, and nontoxic, and have been used as refrigerants, solvents & aerosol propelllants
- volatile and water insoluble → readily escapes into upper atmosphere, where they decomposed by high-energy UV light → forming
radicals destroying ozone through radical chain mechanism

inititation: homolysis of C—Cl bon in CFCl₃

propagation: reaction of Cl· with O₃ → chloringmonoxide (ClO·) → recats with O-atoms → O₂ and Cl

- overall result: ozone (O₃) is consumed and O₂ is formed, wherein small amount of CFC can destroy large amount of O₃ ☹
Radical Halogenation at an Allylic Carbon
Allylic Carbon

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 - carbon adjacent to a double bond
- through the homolysis of its C—H bond, it generates the allylic radical—unpaired electron on carbon adjacent to the double bond
Allylic Radical
- weaker C—H bond (more substituted), more stable the radical
- more stable thant 3º rdaical, because of it has more electron density to donate to stabilize the radical → hybrids
Resonance
- true structure if allylic radical isa hybrid of two resonance structures— 𝜋 bond and unpaired electron are delocalized
- delocalizing electron density lowers the energy of the hybrid, thus stabilizing the radical

Allylic Carbon: Selective Bromination at Allylic C—H Bonds

Allylic C—H bonds
- weaker tha other sp³ hybridixed C-H bonds
- halogenated by N-bromosuccinimide (NBS) in the presence of light or peroxides
NBS
- has a weak N—Br, which is homolytically cleaved with light → bromine radical—initiates allylic halogenation reaction
Allylic Bromination with NBS

inititation: homolysis of N—Br with light energy → forms Br·, initiating radical halogentaion

propagation: bromine radical abstracts an allylic H to afford allylic radical; allylic radical reacts with Br₂ to form allylic halide, bromine
radical formed as weel and repeatedly accour withough additional initiation
→ second chain propagation: needs low concentration of Br₂, which NBS generates

- favors allylic substitution (over addition)

Alkene with Allylic C—H bonds

- undergo two different reactions depending on reaction conditions:

with Br₂ -Addition via ionic intermediates→ vicinal (adjacent) dibromide

with NBS through hv or ROOR -Substitution via rdaical intermediates→allylic bromide

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 Allylic Carbon: Product Mixtures in Allylic Halogenation
Halogenation at Allylic Carbon
- results a mixture of product, because the reaction proceeds by way of resonance stabilized radical
- abstraction of allylic hydrogen from alkene with Br· (from NBS) forms ally;ic radical which two different lewis structure can be drawns
- when two different resonance structures can be drawn for an allylic radical, two different allylic halides are formed by radical
substitution

Application: Oxidation of Unsaturated Lipids

Oils—tricylglycerols
- have one or more sites if unsaturation in long carbon chains
- succeptible to oxidation— at their allylic carbon atoms— by way of radical chain mechanism
[1] oxogen (O₂) in air abstracts allylic hydrogen atom → allylic radical
[2] allylic radical reacts with other molecule of O₂ → peroxy radical
[3] peroxy radical abstracts an allylic hydrogrn from another lipid → hydroperoxide and another allylic radical (repeats until other
radical terminates the chain)
Hydroperoxides
- formed from previous process
- unstable and decompose to other oxidation products → oil rancid

Application: Antioxidants
Antioxidants
- compound that stops oxidation from occuring (radical inhibitor)

Vitamin E, prevents radical reatcions that causes cell damage

butyl hydroxy toluene (BHT_, added to packaged & prepped food to preven oxidation & spoilage
(radical inhibitors hence, terminates radical chain mechanism by reacting with radicals using hydroxy group bonded to a benzez
ring— phenol)

- radicals (R·) abstracts hydrogen atom from OH group of antioxidants → new resonance stabilized radical → new radical do not
partcipate in chain propagation but terminates the chain & halts oxidation processS

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 Radical Addition Reactions to Double Bond
Addition to Double Bonds
- second common radical reactions
- electron-deficient radical reacts to alkene, an electron-rich
- radicals react with alkenes via radical chain mechanism:

initiation, propagatioon and termination

Radical to Double Bond: Addition of HBr

HBr adds to alkenes → alkyl bromides in presence of light, heat or peroxides

without added light, heat or peroxides

- Br radical to more substituted carbon
- H to less substituted
- via carbocation intermediate

with added light, heat or peroxides

- Br radical to less substituted carbon
- H to more substited
- via radical intermediate

Radical Addition of Hbr to an Alkene

initiation: homolysis of weak O—O bond & abstraction of H from H—Br → Br·

propagation: addition to terminal carbon, abstraction of H from HBr → new C—H bond Br· (repeats)

radical addition: (HBr without added light, heat or peroxides) Br· to less substituted carbon forming more stable radical

ionic addition: (HBr with added light, heat or peroxides) Br· to more substituted carbon forming a more stable carbocation

termination: when any two radicals form a bond

Polymers

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 Radical Polymerization
preparation of polymers are by polymerization of alkene monomers by adding a radical to 𝜋 bond— resembles radical addition of HBr
to alkene except that a carbon radical rather than bromine atom is added to the double bond

inititaion: homolysis of weak O—O bond and addition of RO· to alkene → carbon radical

propagation: chain propagation— carbon radical adds to another alkene → C—C bond and another carbon radical. Addition formes
a radical with unpaired electron on the atom with Z substituent

termination: occurs when two radicals form a bond

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