1	Chapter 11: Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations
2	Goals After this chapter, you should be able to: Determine the stereochemistry of S_N2 reactions Determine Products of S_N2 vs S_N1 reactions Determine whether S_N2, S_N1, E1 or E2 will occur
3	Review http://www.chem.monash.edu.au/Docs/DGHewitt/Powerpnt/Lect5/sld001.htm
4	Walden Inversion
5	What is an S_N2 Reaction? S_N2 mechanism; S for substitution, N for nucleophilic and 2 because two molecules collide at the critical point in the reaction.
6	An S_N2 Reaction From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV From Zip Ch11files\11_03.MOV
7	Stereochemistry of Inversion If the nucleophile and the leaving group are both high in the R/S priority order, this means that an R alkyl halide gives an S product, and vice-versa
8	Energy of Inversion
9	Energy of Inversion
10	With S_N2, Size of Substituent Groups Matters
11	Kinetics of Nucleophilic Substitution Rate = k[RBr][Nu^-] Second order kinetics
12	Effect of Bond Strength of the Leaving Group on S_N2 Reactivity Since the carbon-halogen bond strength increases up the periodic table the relative S_N2 reactivity of the alkyl halide is: RF < RCl < RBr < RI TosO^- is a better leaving group than I^- OH^-, NH₂^-, and RO^- are worse than F^-
13	Nucleophilicity:
14	Nucleophilicity Parallels basicity H₂O < C₂H₃O₂^- < OH^- Increases down the periodic table I^- < Cl^- < F^- Anions are more nucleophilic than neutral compounds The solvent matters!
15	Solvent Effects Consider KBr as a nucleophile source Protic solvents with –OH, -NH slow S_N2 rxn These solvents cluster around the nucleophile lowering the effective nucleophilicity Polar aprotic solvents speed S_N2 These solvents cluster around the metal ion of the salt freeing the nucleophile to be nucleophilic.
16	Characteristics of S_N2 Reactions Single Step Mechanism Inversion of configuration S_N2 reactions are generally reliable only when the alkyl halide is primary Halogen is generally Cl or Br since C-F bond is too strong C-I bond is weak and compounds are unstable
17	An S_N2 Reaction From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_03.MOV From Zip Ch11files\11_03.MOV
18	Test Your Knowledge Quiz Type Questions: http://www.cem.msu.edu/~reusch/OrgPage/VirtualText/alhalrx2.htm
19	S_N1 Reactions S_N1 reactions proceed by a two step mechanism First: Leaving group leaves giving a carbocation Second: Nucleophile attacks carbocation
20	An S_N1 Reaction From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV From Zip Ch11files\11_09.MOV
21	S_N1 Reactions
22	Leaving Groups OH^-< NH₂^-<RO^- F ^- < Cl ^- < Br ^- < I < TosO^- Susceptibility to leaving
23	Evidence for S_N1 Kinetics The reaction rate is only dependent upon the concentration of the substance with the leaving group R-X à R⁺ + X^- is a slow = rate determining Racemic mixtures are usual Carbocation formation Rate = k[R-X] where X is leaving group
24	S_N1 Reaction Rates Depend on stability of the carbocation More stable carbocation=faster reaction -CH₃ < 1° < » 2° < 3° Relative Stability of Carbocation
25	The Nucleophile and S_N1 NO EFFECT!
26	Energy for S_N1
27	Solvent Effects on S_N1 Polar solvents stabilize the intermediate carbocation.
28	Summary S_N1 Fastest with Compounds that form stable carbocation Good leaving group Nucleophiles that are not basic to prevent competing elimination reactions Polar solvents
29	An S_N1 Reaction From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_09.MOV From Zip Ch11files\11_09.MOV
30	Elimination Reactions Zaitsev’s Rule: Base induced elimination reactions generally give the more highly substituted double bond alkene product
31	An E2 Reactions From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV From Zip Ch11files\11_17.MOV
32	E2 Reactions Single step attack of nucleophile on hydrogen on carbon adjacent to the carbon containing the leaving group.
33	E2 Kinetics The rate of the reaction is dependent upon the concentration of the compound containing the leaving group and the nucleophile base. Rate = k[RX][Base]
34	Geometry of E2 All atoms involved are in same plane The hydrogen and leaving group are anti
35	Cycloalkane E2: What do you expect?
36	E2 Reaction
37	An E2 Reactions From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_17.MOV From Zip Ch11files\11_17.MOV
38	The E1 Reaction From CD D:\OCOL_HTM\OCOL\MECH\MOVIE\11_21.MOV E:\OCOL_HTM\OCOL\MECH\MOVIE\11_21.MOV From Zip Ch11files\11_21.MOV
39	E1 Reactions First step is identical to S_N1 – Elimination of the leaving group giving a carbocation First step is slow and rate determining Second step is the attack of a hydrogen on a carbon adjacent to the carbocation Racemic mixtures are usual
40	E1 Kinetics Rate = k[R-X]
41	Substitutions in Synthesis See Text
42