1. Consider the following general substitution reaction: How might this reaction proceed? Substitution reactions are reactions in which a nucleophile displaces an atom or group of atoms (the leaving group) from a tetrahedral carbon atom. Substitution Reactions 1

2. Consider the following general substitution reaction: How might this reaction proceed? Substitution reactions are reactions in which a nucleophile displaces an atom or group of atoms (the leaving group) from a tetrahedral carbon atom. Substitution Reactions 2

3. S stands for substitution N stands for nucleophilic The number refers to the number of reacting molecules in the rate determining step. In substitution reactions the RDS is the step where the leaving groups leaves. The two mechanisms that are operative in substitution reactions are the S N 1 and S N 2 reactions. Reactions in which the leaving group leaves before the attack of the nucleophile are referred to as S N 1 reactions. Reactions in which the nucleophile attacks at the same time as the leaving group leaves are referred to as S N 2 reaction. Consider the two different mechanisms for a substitution reaction. What factors would favour one pathway over the other? 3

4. All of these reactions: involve displacement of a heteroatom from carbon -- the "leaving group" the leaving group is always more EN than carbon making the carbon electrophilic the carbon is always tetrahedral there is always a nucleophile present, either -ve or  - Remember: Good leaving groups are weak bases! 4

5. The S N 2 reaction is favoured for 1° and methyl substrates. The S N 2 Reaction. Sketch a reaction profile diagram for the above reaction. 5

6. The S N 2 Reaction. Now sketch a reaction profile diagram for the following reaction. Only the first reaction proceeds via S N 2. How do your reaction profile diagrams account for this? 6

7. The S N 2 Reaction - Kinetics. Recall that the ‘2’ in S N 2 refers to the number of reacting molecules in the rate determining step. Because there are two reactant molecules in the RDS in an S N 2 reaction, we say that it is second order. The rate of a reaction is generally measured as the change in the concentration of one reactant over a given unit of time. Alternatively, the rate can also be measured as the change in concentration of product over a given unit of time. These are expressed mathematically as: or 7

8. The S N 2 Reaction - Kinetics. What happens to the rate of production of CH 3 I if the concentration of CH 3 Br is held constant and the concentration of I - is increased? Consider: What happens to the rate of production of CH 3 I if the concentration of I - is held constant and the concentration of CH 3 Br is increased? 8

9. The S N 2 Reaction - Kinetics. We can also write a rate law for this reaction. A rate law is a mathematical equation that relates the concentrations of each reactant (in the RDS) to the overall rate of reaction. The rate law for the above reaction is: k is the rate constant and must be determined experimentally. 9

10. The S N 2 Reaction - Kinetics. This type of graph is not that as useful since we cannot predict the rate of reaction at some future time. In order to do so we would need to convert the graph into a linear function which is outside the scope of this course. Considering what happens to the concentrations of reactants, what would a graph or reaction rate vs. time look? 10

11. The S N 2 Reaction For this reaction: draw a reasonable mechanism identify the rate determining step sketch a reaction profile diagram So far we have only considered an S N 2 reaction with one elementary step. Consider the following two-step S N 2: 11

12. The Stereochemistry of the S N 2 reaction The reaction geometry is such that the collision must occur with the nucleophile attacking the back side of the C—LG bond. When attack occurs at an asymmetric carbon, the reaction occurs exclusively with inversion of the absolute stereochemistry. 12

13. Why backside attack? Consider the MOs that are involved in this reaction. The Stereochemistry of the S N 2 reaction 13

14. S N 2 reactions - Reactivity Substrate dependance: 14

15. S N 2 reactions - Reactivity When evaluating S N 2 reactions, you have to consider everything involved in the reaction. This includes the substrate, the nucleophile, the leaving group and the solvent. For each set of reactions, draw the S N 2 products. Then indicate which reaction should proceed faster and why. A B 15

16. S N 2 reactions - Reactivity For each set of reactions, draw the S N 2 products. Then indicate which reaction should proceed faster and why. C 16