Structure and S N 2 Reactivity: The Leaving Group 6-7 The rates of S N 2 reactions depend upon: Nature of the leaving group. Reactivity of the nucleophile Structure of the alkyl portion of the substrate. Leaving-group ability is a measure of the ease of displacement. The leaving group ability of a leaving group can be correlated to its ability to accommodate a negative charge. For halogens, iodide is a good leaving group, while fluoride is a poor leaving group in S N 2 reactions. S N 2 reactions of fluoroalkanes are rarely observed. Leaving-Group Ability (best) I - > Br - > Cl - > F - (worst)

Weak bases are good leaving groups. Leaving group ability is inversely related to base strength. Weak bases are best able to accommodate negative charge and are the best leaving groups. (Weak bases are the conjugate bases of strong acids.) Note the sequence: I - > Br - > Cl - > F -

Structure and S N 2 Reactivity: The Nucleophile 6-8 Nucleophilicity of the nucleophile depends upon: Charge Basicity Solvent Polarizability Nature of substituents

Increasing negative charge increases nucleophilicity. Consider these experiments: Conclusion: Comparing nucleophiles having the same reactive atom, the species with the negative charge is the more powerful nucleophile. A base is always more nucleophilic than its conjugate acid.

Nucleophilicity decreases to the right in the periodic table. Consider these experiments: Conclusion: Nucleophilicity correlates with basicity. As we proceed from left to right across the periodic table, nucleophilicity decreases. (best) H 2 N - > HO - > NH 3 > F - > H 2 O (worst nucleophile)

Should basicity and nucleophilicity be correlated? Basicity is a thermodynamic property: Nucleophilicity is a kinetic phenomenon: Despite this difference in definition, there is a good correlation between nucleophilicy and basicity in the cases of charged versus neutral nucleophiles along a row in the periodic table.

Solvation impedes nucleophilicity. Consider these experiments: Conclusion: Nucleophilicity increases in the progression down a column of the periodic table which is opposite the trend predicted by the basicity of the nucleophiles tested.

When a solid dissolves in a polar solvent the molecules or ions are surrounded by solvent molecules and are said to be solvated. Generally solvation weakens a nucleophile by forming a shell of solvent molecules around the nucleophile which impedes its ability to attack an electrophile. Smaller ions are more tightly solvated in a polar solvent than larger ones, thus F - is much more heavily solvated than in I -.

Aprotic solvents lack positively polarized hydrogen atoms and are also often used in S N 2 reactions: Protic and aprotic solvents: the effect of hydrogen bonding. Protic solvents are those containing a hydrogen atom attached to an electronegative atom and are capable of hydrogen bonding.

Because aprotic solvents do not form hydrogen bonds, they solvate anionic nucleophiles relatively weakly. This results in an increase in the nucleophiles reactivity. Bromomethane reacts with KI 500 times faster in propanone than in methanol. Consider the reaction of iodomethane with chloride: The rate of the reaction is more than 10 6 times greater in the aprotic solvent DMF than in methanol.