Lecture Summary 31 November 8, 2006 Chapter 11 - Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations Summary of Substitution and Elimination Reactions Sometimes it is difficult to tell what mechanism will be the predominant pathway in a reaction. Usually the most important factor is the substrate. For competing elimination reactions, the base strength (vs. nucleophile) is key. R-X SN1 X 1° SN2 E1 E2 favored with good nucleophile X favored with strong base can occur with good nucleophile can occur best if allylic favored with strong base favored if basic competes with SN1 favored with strong base doesn't matter antiperiplanar required 2° can occur best if allylic 3° favored competes with E1 X racemic 100% inversion Stereochem Nucleophiles vs Bases The competition between different reaction mechanisms depends first on the substrate as summarized above. However, the type of reagent (nucleophile or base) is critical in most cases. It is improtant to recognize the difference. Alkoxides (tightly held electrons) are good bases, but terrible nucleophiles. Good Nucleophiles I Br N3 Cl CN Strong Bases SH SR OH OR NH2 bulkier is less nucleophilic C CR Reaction Examples Below are several examples of competition between the various reaction pathways. ©2006 Gregory R. Cook North Dakota State University page 1 Chem 341 NaCN Br CN 1° subtrate Good nucleophile Aprotic polar solvent SN2 HMPA t-BuOK Br 1° subtrate Good Base Protic polar solvent E2 tBuOH O Br CH3CO2Na Br O 2° subtrate Good nucleophile very weak base SN2 O NaOEt E2 SN2 80% Br CH3CH2OH 20% OH SN1 80% Br 2° subtrate Good Base some subst competes E1 20% 3° subtrate Neutral Conditions Protic polar solvent NaOEt 3° subtrate Strong Base elim wins E2 EtOH 97% OH Cl HCl SN1 racemic O Tos OH CN Tos-Cl NaCN Et3N DMSO SN2 inversion OH Cl (or Br) PBr3 or SOCl2 NaCN Et3N DMSO SN2 inversion ©2006 Gregory R. Cook North Dakota State University CN page 2 SN2 inversion NOTE overall retention of configuration (2 inversions) Chem 341