1. The Study of Chemical Reactions
Organic Chemistry, 8th Edition L. G. Wade, Jr.
Chapter 4 Lecture
The Study of Chemical Reactions

2. Lecture 8: Overview Kinetics & Thermodynamics
Free-Radical Chain Reaction (Free-Radical Halogenation)
Equilibrium Constant
Thermodynamics (Free Energy, Enthalpy, Entropy)

3. Introduction Reactants  Products (overall reaction)
Mechanism: step-by-step pathway
To learn more about a reaction:
Thermodyamics
Kinetics

4. Kinetics & Thermodynamics
Thermodynamics – energetics of the reaction at equilibrium
Kinetics – the variation of reaction rates with different conditions and concentrations of reagents.

5. Chlorination of Methane
Requires heat or light for initiation.
The most effective wavelength is blue, which is absorbed by chlorine gas.
Many molecules of product are formed from absorption of only one photon of light (chain reaction).
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6. Why?
Description of why a reaction behaves as it does has to do with the mechanism.
Step-by-step description of exactly which bonds break and which bonds form in what order to give the observed products.

7. The Free-Radical Chain Reaction
Initiation: Generates a radical intermediate.
Propagation: The intermediate reacts with a stable molecule to produce another reactive intermediate (and a product molecule).
Termination: Side reactions that destroy the reactive intermediate.
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8. Initiation Step: Formation of Chlorine Atom
A chlorine molecule splits homolytically into chlorine atoms (free radicals).
Notice that half-arrows show homolytic cleavage!
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9. Lewis Structures of Free Radicals
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Free radicals are reactive species with odd numbers of electrons.
Halogens have seven valence electrons, so one of them will be unpaired (radical). We refer to the halides as atoms, not radicals.
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10. Propagation Step: Carbon Radical
The chlorine atom collides with a methane molecule and abstracts (removes) a hydrogen (H), forming another free radical and one of the products (HCl).
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11. Propagation Step: Product Formation
The methyl free radical collides with another chlorine molecule, producing the organic product (methyl chloride) and regenerating the chlorine radical.
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12. Overall Reaction
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13. Termination Steps
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A reaction is classified as a termination step when any two free radicals join together, producing a nonradical compound.
Combination of a free radical with a contaminant or collision with wall are also termination steps.
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14. More Termination Steps
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15. Hint Initiation steps generally create new free radicals.
Propagation steps usually combine a free radical and a reactant to give a product and another free radical.
Termination steps generally decrease the number of free radicals.
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16. Equilibrium Constant Keq = [products] [reactants]
For CH4 + Cl2  CH3Cl + HCl
Keq = [CH3Cl][HCl] = 1.1 x [CH4][Cl2]
Large value indicates reaction “goes to completion.”
Chapter 4

17. Free Energy Change DG = (energy of products) - (energy of reactants)
DG is the amount of energy available to do work.
A reaction with a negative DG is favorable and spontaneous.
DGo = -RT(lnKeq) = RT(log10Keq)
where R = J/K-mol and T = temperature in Kelvin (K).
Chapter 4

18. Factors Determining G
Free energy change depends on:
Enthalpy
H = (enthalpy of products) - (enthalpy of reactants)
Entropy
S = (entropy of products) - (entropy of reactants)
G = H - TS
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19. Enthalpy
DHo = heat released or absorbed during a chemical reaction at standard conditions.
Exothermic (-DH): Heat is released.
Endothermic (+DH): Heat is absorbed.
Reactions favor products with the lowest enthalpy (strongest bonds).
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20. Entropy DSo = change in randomness, disorder, or freedom of movement.
Increasing heat, volume, or number of particles increases entropy.
Spontaneous reactions maximize disorder and minimize enthalpy.
In the equation DGo = DHo - TDSo, the entropy value is often small.
Chapter 4

21. Solved Problem 1 Solution
Calculate the value of DG° for the chlorination of methane.
Solution
DG° = –2.303RT(log Keq)
Keq for the chlorination is 1.1 x 1019, and log Keq = 19.04
At 25 °C (about 298 K), the value of RT is
RT = (8.314 J/kelvin-mol)(298 kelvins) = 2478 J/mol, or 2.48 kJ/mol
Copyright © 2006 Pearson Prentice Hall, Inc.
Substituting, we have
DG° = (–2.303)(2.478 kJ/mol)(19.04) = –108.7 kJ/mol (–25.9 kcal/mol)
This is a large negative value for DG°, showing that this chlorination has a large driving force that pushes it toward completion.
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22. Enthalpy Continued.
Enthalpy is the driving force in most organic reactions
The heat of reaction can be determined by adding and subtracting the energies of the breaking and forming of bonds.

23. Bond-Dissociation Enthalpies (BDEs)
Bond dissociation requires energy (+BDE).
Bond formation releases energy (-BDE).
BDE can be used to estimate H for a reaction.
BDE for homolytic cleavage of bonds in a gaseous molecule.
Homolytic cleavage: When the bond breaks, each atom gets one electron.
Heterolytic cleavage: When the bond breaks, the most electronegative atom gets both electrons.
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24. Homolytic and Heterolytic Cleavages
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25. Enthalpy Changes in Chlorination
CH3-H + Cl-Cl  CH3-Cl + H-Cl
Bonds Broken
DH° (per Mole)
Bonds Formed
Cl-Cl
+242 kJ
H-Cl
-431 kJ
CH3-H
+435 kJ
CH3-Cl
-351 kJ
TOTAL
+677 kJ
-782 kJ
DH° = +677 kJ + (-782 kJ) = -105 kJ/mol
Chapter 4

26. Kinetics Kinetics is the study of reaction rates.
Rate of the reaction is a measure of how the concentration of the products increases while the concentration of the starting materials decreases.
A rate equation (also called the rate law) is the relationship between the concentrations of the reactants and the observed reaction rate.
Rate law is determined experimentally.
Chapter 4

27. Rate Law For the reaction A + B  C + D, rate = kr[A]a[B]b
Where kr is the rate constant
a is the order with respect to A
b is the order with respect to B
a + b is the overall order (also called molecularity)
Order is the number of molecules of that reactant which is present in the rate-determining step of the mechanism.
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28. Activation Energy
The rate constant, kr, depends on the conditions of the reaction, especially the temperature:
where A = constant (frequency factor) Ea = activation energy R = gas constant, J/kelvin-mole T = absolute temperature in kelvin
Ea is the minimum kinetic energy needed to react.
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29. Temperature Dependence of Ea
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At higher temperatures, more molecules have the required energy to react.
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30. Energy Diagram of an Exothermic Reaction
The vertical axis in this graph represents the potential energy.
The transition state (‡) is the highest point on the graph, and the activation energy (Ea) is the energy difference between the reactants and the transition state.
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31. Rates of Multistep Reactions
The highest points in an energy diagram are transition states.
The lowest points in an energy diagram are intermediates.
The reaction step with the highest Ea will be the slowest step and will determine the rate at which the reaction proceeds (rate-limiting step).
Chapter 4

32. Energy Diagram for the Chlorination of Methane
Chapter 4

33. Rate, Ea, and TemperatureX
Ea(per Mole)
Rate at 27 °C
Rate at 227 °C F 5
140,000
300,000 Cl 17
1300
18,000 Br 75
9 x 10-8
0.015 I
140
2 x 10-19
2 x 10-9
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34. Halogenation Thermodynamics
Klein, Organic Chemistry 2e

35. Halogenation Thermodynamics
Consider chlorination and bromination in more detail
Chlorination is more product favored than bromination
Klein, Organic Chemistry 2e

36. Halogenation Thermodynamics
Which reaction is more exothermic?
What is the rate determining step for both reactions?
How many intermediates are present in each reaction?
Klein, Organic Chemistry 2e

37. Conclusions With increasing Ea, rate decreases.
With increasing temperature, rate increases.
Fluorine reacts explosively.
Chlorine reacts at a moderate rate.
Bromine must be heated to react.
Iodine does not react (detectably).
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38. Chlorination of Methane and Ethane
In molecules of methane and ethane, it does not matter which protons are replaced as all of them are equal.
All H’s on methyl carbon (methane) or on primary carbons (ethane)

39. Halogenation Regioselectivity
With substrates more complex than ethane, multiple monohalogenation products are possible
If the halogen were indiscriminant, predict the product ratio? .
Klein, Organic Chemistry 2e

40. Primary, Secondary, and Tertiary Hydrogens
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41. Halogenation Regioselectivity
For the CHLORINATION process, the actual product distribution favors 2-chloropropane over 1- chloropropane
Klein, Organic Chemistry 2e

42. Bond Dissociation Energies for the Formation of Free Radicals
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43. Stability of Free Radicals
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Highly substituted free radicals are more stable.
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44. Chlorination Energy Diagram
Lower Ea, faster rate, so more stable intermediate is formed faster.
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45. Halogenation Regioselectivity
For the BROMINATION process, the product distribution vastly favors 2-bromopropane over 1- bromopropane
Klein, Organic Chemistry 2e

46. Halogenation Regioselectivity
Focus on the H abstraction step, and consider the Hammond postulate: species on the energy diagram that are similar in energy are similar in structure
Klein, Organic Chemistry 2e

47. Halogenation Regioselectivity
Klein, Organic Chemistry 2e

48. Halogenation Regioselectivity
Which process is more regioselective? WHY?
Klein, Organic Chemistry 2e

49. Halogenation Regioselectivity
Bromination at the 3° position happens 1600 times more often than at the 1° position .
Klein, Organic Chemistry 2e

50. Halogenation Regioselectivity
Which process is least regioselective? WHY?
What is the general relationship between reactivity and selectivity? WHY? .
Klein, Organic Chemistry 2e

51. Radical Inhibitors
Often added to food to retard spoilage by radical chain reactions.
Without an inhibitor, each initiation step will cause a chain reaction so that many molecules will react.
An inhibitor combines with the free radical to form a stable molecule.
Vitamin E and vitamin C are thought to protect living cells from free radicals.
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52. Antioxidants
Foods with unsaturated fatty acids have a short shelf life unless preservatives are used.

53. Natural Antioxidants
Vitamin E

54. Radical Inhibitors (Continued)
A radical chain reaction is fast and has many exothermic steps that create more reactive radicals.
When an inhibitor reacts with the radical, it creates a stable intermediate, and any further reactions will be endothermic and slow.
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55. Reactive Intermediates
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Reactive intermediates are short-lived species.
Never present in high concentrations because they
react as quickly as they are formed.
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56. Carbocation Structure
A carbocation (also called a carbonium ion or a carbenium ion) is a positively charged carbon.
Carbon is sp2 hybridized with vacant p orbital.
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57. Carbocation Stability
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More highly substituted carbocations
are more stable.
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58. Carbocation Stability (Continued)
Stabilized by alkyl substituents in two ways:
1. Inductive effect: Donation of electron density along the sigma bonds.
2. Hyperconjugation: Overlap of sigma bonding orbitals with empty p orbital.
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59. Unsaturated Carbocations
Unsaturated carbocations are also stabilized by resonance stabilization.
If a pi bond is adjacent to a carbocation, the filled p orbitals of the bond will overlap with the empty p orbital of the carbocation.
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60. Free Radicals
Carbon is sp2 hybridized with one electron in the p orbital.
Stabilized by alkyl substituents.
Order of stability: 3 > 2 > 1 > methyl
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61. Stability of Carbon Radicals
More highly substituted radicals
are more stable.
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62. Unsaturated Radicals
Like carbocations, radicals can be stabilized by resonance.
Overlap with the p orbitals of a p bond allows the odd electron to be delocalized over two carbon atoms.
Resonance delocalization is particularly effective in stabilizing a radical.
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63. Carbanions Eight electrons on carbon: six bonding plus one lone pair.
Carbon has a negative charge.
Carbanions are nucleophilic and basic.
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64. Stability of Carbanions
Alkyl groups and other electron-donating groups slightly destabilize a carbanion.
The order of stability is usually the opposite of that for carbocations and free radicals.
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65. Basicity of Carbanions
A carbanion has a negative charge on its carbon atom, making it a more powerful base and a stronger nucleophile than an amine.
A carbanion is sufficiently basic to remove a proton from ammonia.
Figure: 04_16-02UN.jpg
Title:
Reactivity of a Carbanion
Caption:
Like amines, carbanions are nucleophilic and basic. A carbanion has a negative charge on its carbon atom, however, making it a more powerful base and a stronger nucleophile than an amine. For example, a carbanion is sufficiently basic to remove a proton from ammonia.
Notes:
Carbanions are a stronger base than amines, so they can deprotonate amines easily.
Chapter 4

66. Carbenes Carbon in carbenes is neutral.
It has a vacant p orbital so can react as an electrophile.
It has a lone pair of electrons in the sp2 orbital so can react as a nucleophile.
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67. Carbenes as Reaction Intermediates
A strong base can abstract a proton from tribromomethane (CHBr3) to give an inductively stabilized carbanion.
This carbanion expels bromide ion to give dibromocarbene. The carbon atom is sp2 hybridized with trigonal geometry.
A carbene has both a lone pair of electrons and an empty p orbital, so it can react as a nucleophile or as an electrophile.
Figure: 04_16-06UN.jpg
Title:
Carbenes as Reaction Intermediates
Caption:
Carbenes are uncharged reactive intermediates containing a divalent carbon atom. The simplest carbene has the formula CH2 and is called methylene, just as a –CH2- group in a molecule is called a methylene group. One way of generating carbenes is to form a carbanion that can expel a halide ion. For example, a strong base can abstract a proton from tribromomethane (CHBr3) to give an inductively stabilized carbanion. This carbanion expels bromide ion to give dibromocarbene. The carbon atom is sp2 hybridized, with trigonal geometry. An unshared pair of electrons occupies one of the sp2 hybrid orbitals, and there is an empty p orbital extending above and below the plane of the atoms. A carbene has both a lone pair of electrons and an empty p orbital, so it can react as a nucleophile or as an electrophile.
Notes:
The reactivity of carbenes lies in its orbitals. The carbon of carbenes have sp2 hybrid orbitals. Two of the hybrid orbitals are bonded to other atoms, one of the sp2 orbitals contains the lone pair of electrons so they can act as a nucleophile. Perpendicular to the plane of the sp2 orbitals is an unoccupied p orbital which allows them to act as an electrophile.
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68. Summary of Reactive Species
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