1. Mechanisms One of the most practical aspects of organic chemistry is the study and application of chemical reactions. Due to the large number of reactants that can be used, it is virtually impossible to memorize all possible reactions. Organic reactions are often organized into groups based on their mechanisms and the intermediates that are involved.

2. Mechanisms Mechanism: a step-by-step pathway from reactants to products that shows which bonds break, which bonds form and the order in which they happen includes structures of all reactants, intermediates and products and curved arrows showing the movement of electrons

3. Mechanisms Your success in this class depends in large part on learning the mechanisms of key reactions and applying these mechanisms to predict the products formed from starting materials you have not used before.

4. Mechanisms Halogenation of alkanes: alkane + halogen alkyl halide(s) + HX CH 4 (g) + Cl 2 (g) CH 3 Cl + CH 2 Cl 2 + CHCl 3 + CCl 4 + HCl  or h 

5. Mechanisms The halogenation of alkanes is a substitution reaction that occurs via a chain reaction mechanism. Substitution reaction: a reaction in which one atom substitutes for or replaces another atom In the chlorination of methane, a chlorine atom replaces a hydrogen atom.

6. Mechanisms Three types of steps occur in all chain reactions: Initiation: generates a reactive intermediate Reactive intermediate: a short-lived species that reacts as quickly as it is formed never present in high concentration

7. Mechanisms Three types of steps occur in all chain reactions: propagation reactive intermediate reacts with a stable molecule to form a new reactive intermediate and a new stable molecule continues until reactants are exhausted or reactive intermediate is destroyed termination side reaction that destroy the reactive intermediate slows or stops reaction

8. Mechanisms Chlorination of Methane (Mechanism) Initiation: Chlorine absorbs h  generating two free radicals. Use half arrows to show movement of one electron.

9. Mechanisms Free radical a reactive intermediate with one or more unpaired electrons also called a radical electron deficient (doesn’t have octet)

10. Mechanisms Chlorination of Methane (Mechanism) cont. Propagation: First propagation step: Chlorine radical collides with a methane molecule and abstracts a hydrogen atom

11. Mechanisms Chlorination of Methane (Mechanism) cont. Second Propagation step: methyl radical reacts with chlorine molecule, generating product and another reactive species The new chlorine radical continues the chain by abstracting another hydrogen atom from methane, etc.

12. Mechanisms Chlorination of Methane (Mechanism) con’t. Termination: Any reaction that produces fewer reactive intermediates than it uses will slow or stop the reaction:

13. Mechanisms More possible termination reactions:

14. Thermodynamics Information about chemical reactions is obtained using thermodynamics and kinetics. Thermodynamics: used to study the stability of reactants and products predicts which compounds are favored by the equilibrium

15. Thermodynamics For an equilibrium reaction: a A + b B c C + d D  G o = -RTlnK c Spontaneous reaction (favors products): K c > 1  G = neg Nonspontaneous reaction (favors reactants): K c < 1  G = pos

16. Thermodynamics Two thermodynamic quantities contribute to  G:  G =  H - T  S  H = enthalpy change (amount of heat gained or lost)  H = positive (endothermic: heat gained)  H = negative (exothermic: heat lost)  S = entropy change change in the randomness or disorder

17. Thermodynamics For many organic reactions, T  S is small relative to  H  G ~  H Therefore, most exothermic organic reactions tend to favor the formation of products. The  H rxn can be estimated using the bond dissociation energies of the bonds broken and formed during the reaction.

18. Thermodynamics Bond dissociation energy: the amount of energy required to break a bond homolytically equally each atom in the bond being broken gets one electron forms free radicals As BDE increases, more energy is needed to break the bond: stronger bond

19. Thermodynamics Example: Which of the following bonds is the strongest? The weakest? F - F, Cl - Cl, CH 3 - F, CH 3 - Cl, H - F, or H - Cl F - F Cl - Cl CH 3 - F CH 3 - Cl H - F H - Cl 38 kcal/mol 58 109 84 136 103

20. Thermodynamics Example: Rank the following C-H bonds in order from the easiest to the hardest to break homolytically. Methyl H 104 kcal/mol 1 o H 98 kcal/mol 2 o H 95 kcal/mol 3 o H 91 kcal/mol

21. Thermodynamics As BDE increases, it is harder to break the bond: Ease of homolytic cleavage: 3 o > 2 o > 1 o > methyl The stability of methyl, 1 o, 2 o, and 3 o free radicals follows the same trend: 3 o > 2 o > 1 o > methyl i.e. 3 o free radicals are the most stable and methyl radicals are the least stable (easiest)(hardest)

22. Kinetics Many reactions that have favorable energy changes (  G = neg or  H = neg) occur so slowly that the reaction is imperceptible. Very slow reaction rate For the general reaction: a A + b B c C + d D Rate = k [A] m [B] n where k = rate constant m = reaction order with respect to A n = reaction order with respect to B

23. Kinetics The reaction rate depends on: collision frequency a probability or orientation factor activation energy (E a ) The reaction rate increases as the number of collisions between reacting species increase. Concentration temperature

24. Cl. Kinetics Collisions must occur in a particular orientation for reactions to occur. For the reaction: Cl. + H - Br H - Cl + Br. Br H No HCl formed Cl. Br H HCl can form Cl. Br H No HCl formed

25. Kinetics Collisions must occur with a specific minimum amount of energy in order for a reaction to take place. Activation energy (E a ) the minimum energy the reactants must have for a reaction to occur the energy difference between the reactants and the transition state

26. Kinetics Transition state: a particular arrangement of atoms of the reacting species in which bonds are partially broken and partially formed the state of highest energy between reactants and products a relative maximum on the reaction-energy diagram

27. Reaction Energy Diagram Reaction energy diagram: a plot of potential energy changes that occur as reactants are converted to products

28. Hammond Postulate What does the transition state look like? The appearance of the transition state depends on whether the reaction is endothermic or exothermic. governed by the Hammond Postulate Hammond Postulate: Related species that are closer in energy are also closer in structure. The structure of the transition state resembles the structure of the closest stable species.

29. Hammond Postulate For an endothermic reaction, the transition state more closely resembles the products. For an exothermic reaction, the transition state more closely resembles the reactants. endothermic exothermic

30. Rate Determining Step Chlorination of methane has two propagation steps. The first propagation step controls the rate of the overall reaction and is called the rate- determining step. Rate-determining step (rate-limiting step): the slowest step in a multi-step process the step with the highest energy transition state

31. Rate Determining Step intermediate