Radical Chain Reactions

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Radical Chain Reactions
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Radicals

• A radical is a reactive intermediate with a
  single unpaired electron, formed by homolysis of
  a covalent bond.
• A radical contains an atom that does not have an
  octet of electrons.
• Half-headed arrows are used to show the movement
  of electrons in radical processes.

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Halogenation of Alkanes

• In the presence of heat or light, alkanes react
  with halogens to form alkyl halides.
• Halogenation of alkanes is a radical substitution
  reaction.
• Halogenation of alkanes is only useful with Cl2
  or Br2. Reaction with F2 is too violent, and
  reaction with I2 is too slow to be useful.

Example Monochlorination of Methane
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Control of Chlorination

• When a single hydrogen atom on a carbon has been
  replaced by a halogen atom, monohalogenation has
  taken place.
• When excess halogen is used, it is possible to
  replace more than one hydrogen atom on a single
  carbon with halogen atoms.
• Monohalogenation can be achieved experimentally
  by adding halogen X2 to an excess of alkane.

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Mechanism

• Radical halogenation has three distinct parts.

• A mechanism such as radical halogenation that
  involves two or more repeating steps is called a
  chain mechanism.
• The most important steps of radical halogenation
  are those that lead to product formationthe
  propagation steps.

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Evidence for a Radical Mechanism

• Three facts about halogenation suggest that the
  mechanism involves radical, not ionic,
  intermediates

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Radical Inhibitors

• Compounds that prevent radical reactions from
  occurring are called radical inhibitors or
  radical scavengers. Besides O2, vitamin E and
  other related compounds are radical scavengers.

• Oxygen (O2)- is a diradical in its ground state
  electronic configuration.
• In halogenation reactions, O2 is believed to
  react with the methyl radical (CH3) to form the
  CH3OO radical which is far less reactive than
  CH3. One O2 molecule breaks the chain and
  prevents formation of chlorinated product , i. e.
  CH3Cl.

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Chlorination of Propane

• Note that CH3CH2CH3 has six 10 hydrogens and only
  two 20 hydrogens, so the expected product ratio
  of CH3CH2CH2Cl to (CH3)2CHCl (assuming all
  hydrogens are equally reactive) is 31.
• Product Distribution
• Chlorination of CH3CH2CH3 affords a 11 mixture
  of CH3CH2CH2Cl and (CH3)2CHCl.

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Formation of 2 1 Carbon Radicals from Propane

• Since the observed ratio between CH3CH2CH2Cl and
  (CH3)2CHCl is 11, the 20 CH bonds must be more
  reactive than the 10 CH bonds.

• Thus, when alkanes react with Cl2, a mixture of
  products results, with more product formed by
  cleavage of the weaker CH bond than you would
  expect on statistical grounds.

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Carbon Radicals
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Carbon Radicals

• A carbon radical is sp2 hybridized and trigonal
  planar, like sp2 hybridized carbocations.
• The unhybridized p orbital contains the unpaired
  electron and extends above and below the trigonal
  planar carbon.

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Relative Stability of Carbon Radicals
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Inductive Effects

• Also explained in the organic text (7.14A page
  248)
• Alkyl groups stabilize the electron deficient
  carbon radical by donation of electron density
  through the C-C s bonds.
• Alkyl groups are versatile and may donate
  electron density or withdrawal electron density
  thourgh the C-C s bonds.
• Thus, neighboring alkyl groups my stabilize
  carbon radicals, carbocations, and carbanions.

Example
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Hyperconjugation

• Explained in Text 7.14B page 249.
• An electron deficient carbon is believed to be
  stabilized through orbital overlap between the
  electron rich s bonding molecular orbitals from
  an adjacent alkyl group with the half filled p
  orbital of the carbon radical.
• Methyl radicals are not stabilized via
  hyperconjugation!
• Hyperconjugation can not happen in a methyl
  radical b/c the hydrogen s orbitals are not of
  the right symmetry to overlap with the half
  filled p orbital of the carbon radical.

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Halogenation Rxns
Practice Rxns
Cl2, hn
Cl2, hn
Cl2, hn
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Energy Diagrams
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Bond Dissociation Energy

• The energy absorbed or released in any reaction,
  symbolized by ?Ho, is called the enthalpy change
  or heat of reaction.

• Bond dissociation energy is the ?Ho for a
  specific kind of reactionthe homolysis of a
  covalent bond to form two radicals.

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Bond Dissociation Energy

• Because bond breaking requires energy, bond
  dissociation energies are always positive
  numbers, and homolysis is always endothermic.
• Conversely, bond formation always releases
  energy, and thus is always exothermic. For
  example, the HH bond requires 104 kcal/mol to
  cleave and releases 104 kcal/mol when formed.

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Bond Dissociation Energy

• Comparing bond dissociation energies is
  equivalent to comparing bond strength.
• The stronger the bond, the higher its bond
  dissociation energy.
• Bond dissociation energies decrease down a column
  of the periodic table.
• Generally, shorter bonds are stronger bonds.

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Enthalpy Change (DH) in a Rxn.

• Bond dissociation energies are used to calculate
  the enthalpy change (?H0) in a reaction in which
  several bonds are broken and formed.

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Bond dissociation energies have two important
limitations.

• Bond dissociation energies present overall energy
  changes only. They reveal nothing about the
  reaction mechanism or how fast a reaction
  proceeds.
• Bond dissociation energies are determined for
  reactions in the gas phase, whereas most organic
  reactions occur in a liquid solvent where
  solvation energy contributes to the overall
  enthalpy of a reaction.
• Bond dissociation energies are imperfect
  indicators of energy changes in a reaction.
  However, using bond dissociation energies to
  calculate ?H0 gives a useful approximation of the
  energy changes that occur when bonds are broken
  and formed in a reaction.

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Enthalpy (DH) of Halogenation Reactions
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Energy Diagrams

• An energy diagram is a schematic representation
  of the energy changes that take place as
  reactants are converted to products.
• An energy diagram plots the energy on the y axis
  versus the progress of reaction, often labeled as
  the reaction coordinate, on the x axis.
• The energy difference between reactants and
  products is ?H0. If the products are lower in
  energy than the reactants, the reaction is
  exothermic and energy is released. If the
  products are higher in energy than the reactants,
  the reaction is endothermic and energy is
  consumed.
• The unstable energy maximum as a chemical
  reaction proceeds from reactants to products is
  called the transition state. The transition state
  species can never be isolated.
• The energy difference between the transition
  state and the starting material is called the
  energy of activation, Ea.

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Exothermic Reaction

• For the general reaction

• The energy diagram would be shown as

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Quiz 2

• Thursday, October 12th

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Transition State

• The energy of activation is the minimum amount of
  energy needed to break the bonds in the
  reactants.
• The larger the Ea, the greater the amount of
  energy that is needed to break bonds, and the
  slower the reaction rate.
• The structure of the transition state is
  somewhere between the structures of the starting
  material and product. Any bond that is partially
  formed or broken is drawn with a dashed line. Any
  atom that gains or loses a charge contains a
  partial charge in the transition state.
• Transition states are drawn in brackets, with a
  superscript double dagger ().

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Two Different Exothermic Reactions
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Comparing Reactions
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Energy Diagram for a Chlorination Reaction
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Kinetics

• Kinetics is the study of reaction rates.
• Recall that Ea is the energy barrier that must be
  exceeded for reactants to be converted to
  products.

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Catalysts

• Some reactions do not proceed at a reasonable
  rate unless a catalyst is added.
• A catalyst is a substance that speeds up the rate
  of a reaction. It is recovered unchanged in a
  reaction, and it does not appear in the product.

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Chlorination vs. Bromination
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Chlorination versus Bromination

• Although alkanes undergo radical substitutions
  with both Cl2 and Br2, chlorination and
  bromination exhibit two important differences.
• Chlorination is faster than bromination.
• Chlorination is unselective, yielding a mixture
  of products, but bromination is often selective,
  yielding one major product.

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Energetics of the Bromination Rxn.

• The differences in chlorination and bromination
  can be explained by considering the energetics of
  each type of reaction.
• Calculating the ?H0 using bond dissociation
  energies reveals that abstraction of a 10 or 20
  hydrogen by Br is endothermic, but it takes less
  energy to form the more stable 20 radical.

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Transition State in the Bromination of Propane
Conclusion Because the rate-determining step is
endothermic, the more stable radical is formed
faster, and often a single radical halogenation
product predominates.
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Energetics of the Chlorination Rxn.

• Calculating the ?H0 using bond dissociation
  energies for chlorination reveals that
  abstraction of a 10 or 20 hydrogen by Cl is
  exothermic.

• Since chlorination has an exothermic
  rate-determining step, the transition state to
  form both radicals resembles the same starting
  material, CH3CH2CH3. Thus, the relative stability
  of the two radicals is much less important, and
  both radicals are formed.

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Transition State in the Chlorination of Propane
Conclusion Because the rate-determining step in
chlorination is exothermic, the transition state
resembles the starting material, both radicals
are formed, and a mixture of products results.
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Radical Inhibitors
41
Radical Inhibitors

• Compounds that prevent radical reactions from
  occurring are called radical inhibitors or
  radical scavengers. Besides O2, vitamin E and
  other related compounds are radical scavengers.

• The reaction of a radical with oxygen (a
  diradical in its ground state electronic
  configuration) is an example of two radicals
  reacting with each other.

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Antioxidants

• An antioxidant is a compound that stops an
  oxidation from occurring.
• Naturally occurring antioxidants such as vitamin
  E prevent radical reactions that can cause cell
  damage.
• Synthetic antioxidants such as BHTbutylated
  hydroxy tolueneare added to packaged and
  prepared foods to prevent oxidation and spoilage.
• Vitamin E and BHT are radical inhibitors, so they
  terminate radical chain mechanisms by reacting
  with the radical.

43
Resonance-Stabilized Radical

• To trap free radicals, both vitamin E and BHT use
  a hydroxy group bonded to a benzene ringa
  general structure called a phenol.
• Radicals (R) abstract a hydrogen atom from the
  OH group of an antioxidant, forming a new
  resonance-stabilized radical. This new radical
  does not participate in chain propagation, but
  rather terminates the chain and halts the
  oxidation process.
• Because oxidative damage to lipids in cells is
  thought to play a role in the aging process, many
  anti-aging formulations contain antioxidants.

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SN2 SN1 Reacitons
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Rate Equation

• A rate law or rate equation shows the
  relationship between the reaction rate and the
  concentration of the reactants. It is
  experimentally determined.

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Rate Constants

• Fast reactions have large rate constants.
• Slow reactions have small rate constants.
• The rate constant k and the energy of activation
  Ea are inversely related. A high Ea corresponds
  to a small k.
• A rate equation contains concentration terms for
  all reactants in a one-step mechanism.
• A rate equation contains concentration terms for
  only the reactants involved in the
  rate-determining step in a multi-step reaction.
• The order of a rate equation equals the sum of
  the exponents of the concentration terms in the
  rate equation.

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Reaction Kinetics

• The larger the Ea the slower the reaction.
• The higher the concentration, the faster the
  rate. (increasing concentration increases number
  of collisions between reacting molecules)
• The higher the temperature, the faster the rate.
  (increasing temp. increases the average kinetic
  energy of the reacting molecules-kinetic energy
  of molecules is used for bond cleavage) As a
  general rule, increasing the reaction temp. by
  10C doubles the reaction rate.
• ?G0, ?H0, and Keq do not determine the rate of
  a reaction. These quantities indicate the
  direction of the equilibrium and the relative
  energy of reactants and products.

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Rate Determining Step

• A two-step reaction has a slow rate-determining
  step, and a fast step.
• In a multi-step mechanism, the reaction can occur
  no faster than its rate-determining step.
• Only the concentration of the reactants in the
  rate-determining step appear in the rate equation.

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Stereochemistry of Halogenation
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Radical Reactions
Stereochemistry of Halogenation
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Radical Reactions
Stereochemistry of Halogenation

• Halogenation of an achiral starting material such
  as CH3CH2CH2CH3 forms two constitutional isomers
  by replacement of either a 10 or 20 hydrogen.

• 1-Chlorobutane has no stereogenic centers and is
  thus achiral.
• 2-Chlorobutane has a new stereogenic center, and
  so an equal amount of two enantiomers must forma
  racemic mixture.

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Radical Reactions
Stereochemistry of Halogenation

• A racemic mixture results because the first
  propagation step generates a planar sp2
  hybridized radical. Cl2 then reacts with it from
  either side to form an equal amount of two
  enantiomers.

54
Radical Reactions
Stereochemistry of Halogenation

• Suppose we were to chlorinate the chiral starting
  material (R)-2-bromobutane at C2 and C3.

• Chlorination at C2 occurs at the stereogenic
  center.

• Radical halogenation reactions at a stereogenic
  center occur with racemization.

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Radical Reactions
Stereochemistry of Halogenation

• Chlorination at C3 does not occur at the
  stereogenic center, but forms a new stereogenic
  center.
• Since no bond is broken to the stereogenic center
  at C2, its configuration is retained during the
  reaction.
• The trigonal planar sp2 hybridized radical is
  attacked from either side by Cl2, forming a new
  stereogenic center.
• A pair of diastereomers is formed.

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Allylic Halogenation Reaction
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Allyl Carbon Radical

• An allylic carbon is a carbon adjacent to a
  double bond.
• Homolysis of the allylic CH bond in propene
  generates an allylic radical which has an
  unpaired electron on the carbon adjacent to the
  double bond.

• The bond dissociation energy for this process is
  even less than that for 30 CH bond (91
  kcal/mol).
• This means that an allyl radical is more stable
  than a 30 radical.

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Allylic Carbon Radical

• The allyl radical is more stable than other
  radicals because two resonance forms can be drawn
  for it.

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Autoxidation at the Allylic Carbon

• Oils are susceptible to allylic free radical
  oxidation.

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Radical Initiators

• Radicals are formed from covalent bonds by adding
  energy in the form of heat (?) or light (h?).
• Some radical reactions are carried out in the
  presence of a radical initiator, which contain an
  especially weak bond that serves as a source of
  radicals.
• Peroxides, compounds having the general structure
  ROOR, are the most commonly used radical
  initiators.
• Heating a peroxide readily causes homolysis of
  the weak OO bond, forming two RO radicals.

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Allylic Bromination w/ NBS

• Because allylic CH bonds are weaker than other
  sp3 hybridized CH bonds, the allylic carbon can
  be selectively halogenated using NBS in the
  presence of light or peroxides.

• NBS contains a weak NBr bond that is
  homolytically cleaved with light to generate a
  bromine radical, initiating an allylic
  halogenation reaction.
• Propagation then consists of the usual two steps
  of radical halogenation.

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NBS Promoted Allylic Bromination Reaction
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Dual Roles for NBS

• NBS also generates a low concentration of Br2
  needed in the second chain propagation step (Step
  3 of the mechanism).
• The HBr formed in Step 2 reacts with NBS to
  form Br2, which is then used for halogenation in
  Step 3 of the mechanism.

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Bromine Addition vs Allylic Brominations
Thus, an alkene with allylic CH bonds undergoes
two different reactions depending on the reaction
conditions.
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Understanding Product Outcome
Question Why does a low concentration of Br2
(from NBS) favor allylic substitution (over ionic
addition to form the dibromide)?

• Answer
• The key to getting substitution is to have a low
  concentration of bromine (Br2).
• The Br2 produced from NBS is present in very low
  concentrations.
• A low concentration of Br2 would first react with
  the double bond to form a low concentration of
  the bridged bromonium ion.
• The bridged bromonium ion must then react with
  more bromine (in the form of Br) in a second
  step to form the dibromide.
• If concentrations of both intermediatesthe
  bromonium ion and Br are low (as is the case
  here), the overall rate of addition is very slow,
  and the products of the very fast and facile
  radical chain reaction predominate.

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Addition of Br for Allyl Radical

• Halogenation at an allylic carbon often results
  in a mixture of products. Consider the following
  example

• A mixture results because the reaction proceeds
  by way of a resonance stabilized radical.

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Addition of Radicals to Double bonds
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Radical Additions to Double Bonds

• HBr adds to alkenes to form alkyl bromides in the
  presence of heat, light, or peroxides.
• The regioselectivity of the addition to
  unsymmetrical alkenes is different from that in
  addition of HBr in the absence of heat, light or
  peroxides.

• The addition of HBr to alkenes in the presence of
  heat, light or peroxides proceeds via a radical
  mechanism.

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Radical Additions to Double Bonds
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Radical Additions to Double Bonds

• Note that in the first propagation step, the
  addition of Br to the double bond, there are two
  possible paths
• Path A forms the less stable 10 radical
• Path B forms the more stable 20 radical

• The more stable 20 radical forms faster, so Path
  B is preferred.

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Radical Additions to Double Bonds

• The radical mechanism illustrates why the
  regioselectivity of HBr addition is different
  depending on the reaction conditions.

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Radical Additions to Double Bonds

• HBr adds to alkenes under radical conditions, but
  HCl and HI do not. This can be explained by
  considering the energetics of the reactions using
  bond dissociation energies.
• Both propagation steps for HBr addition are
  exothermic, so propagation is exothermic
  (energetically favorable) overall.
• For addition of HCl or HI, one of the chain
  propagating steps is quite endothermic, and thus
  too difficult to be part of a repeating chain
  mechanism.