Substitution Reactions of Alkyl Halides: Chapter 8Contents of Chapter 8Substitution and EliminationSN2 MechanismSN1 MechanismSubstitution ReactionsThe SN2 ReactionSlide 8Steric Accessibility in the SN2 ReactionThe SN2 Reaction: Leaving Group StabilityThe SN2 Reaction: Nucleophile BasicitySlide 12The SN2 Reaction: Nucleophile SizeSlide 14The SN2 Reaction: Nucleophile Size and TypeThe SN2 Reaction: Nucleophile BulkinessThe SN1 ReactionSlide 18Slide 19The SN1 Reaction: Factors Affecting the RateThe SN1 Reaction: Carbocation RearrangementsStereochemistry of SN2 and SN1 ReactionsCompetition Between SN2 and SN1 ReactionsSlide 24Slide 25Slide 26Role of the SolventSolvent PolaritySlide 29Slide 30SN1 Reaction: Effect of SolventSN2 Reaction: Effect of SolventSlide 33Problem-solving InfoSlide 35Slide 36Slide 37Slide 38Slide 39Slide 40Chapter 8 1Substitution Reactions of Alkyl Substitution Reactions of Alkyl Halides:Halides:Chapter 8Chapter 8Chapter 8 2Contents of Chapter 8Reactivity ConsiderationsThe SN2 ReactionReversibility of the SN2 ReactionThe SN1 ReactionStereochemistry of SN2 and SN1 ReactionsBenzylic, Allylic, Vinylic & Aryl HalidesCompetition between SN2 and SN1 ReactionsRole of the SolventNo Biological Methylating ReagentsChapter 8 3Substitution and EliminationA compound with an sp3 hybridized carbon bonded to a halogen can undergo two types of reactionsTwo different mechanisms for substitution are SN1 and SN2 mechanismsThese result in diff prods under diff conditionsChapter 8 4SN2 MechanismSN2 mechanism: C–X bond weakens as nucleophile approaches all in one stepChapter 8 5SN1 MechanismSN1 mechanism: C–X bond breaks first without any help from nucleophile This is a two-step processslow stepfast stepChapter 8 6Substitution ReactionsBoth mechanisms are called nucleophilic substitutionsWhich one takes place depends onthe structure of the alkyl halidethe reactivity and structure of the nucleophilethe concentration of the nucleophile, andthe solvent in which reaction is carried outChapter 8 7The SN2 ReactionBimolecular nucleophilic substitution rate = k [alkyl halide][nucleophile]Chapter 8 8The SN2 ReactionThe inversion of configuration resembles the way an umbrella turns inside out in the windIf a single chiral enantiomer reacts a single chiral product (inverted) results.Chapter 8 9Steric Accessibility in the SN2 ReactionChapter 8 10The SN2 Reaction: Leaving Group StabilityChapter 8 11The SN2 Reaction: Nucleophile Basicitystronger base weaker base better nucleophile poorer nucleophileHO–> H2OCH3O–> CH3OH–NH2> NH3CH3CH2NH–> CH3CH2NH2Chapter 8 12The SN2 Reaction: Nucleophile BasicityComparing nucleophiles with attacking atoms of approximately the same size, the stronger base is also the stronger nucleophileChapter 8 13The SN2 Reaction: Nucleophile SizeIn nonpolar solvents nucleophilicity order same as basicity order- size doesn’t matterChapter 8 14The SN2 Reaction: Nucleophile SizeSize is related to polarizabilityChapter 8 15The SN2 Reaction: Nucleophile Size and TypeNucleophilicity ~ both size and basicityChapter 8 16The SN2 Reaction: Nucleophile BulkinessNucleophilicity is affected by steric effectsA bulky nucleophile has difficulty getting near the back side of a sp3 carbonCH3CH2O CH3COCH3CH3ethoxide ion tert-butoxide ion better nucleophile stronger baseChapter 8 17The SN1 ReactionThe more stable the C+ the lower the G‡, and the faster the rxnChapter 8 18The SN1 ReactionChapter 8 19The SN1 ReactionThe SN1 reaction leads to a mixture of stereoisomersChapter 8 20The SN1 Reaction: Factors Affecting the Rateincreasing reactivityRI > RBr > RCl > RFTwo factors affect the rate of formation of the carbocationease with which the leaving group leaves stability of the carbocationincreasing reactivity3º alkyl halide > 2º alkyl halide > 1º alkyl halideChapter 8 21The SN1 Reaction: Carbocation RearrangementsChapter 8 22Stereochemistry of SN2 and SN1 Reactionsinversionboth enantiomersChapter 8 23Competition Between SN2 and SN1 ReactionsChapter 8 24Competition Between SN2 and SN1 ReactionsTABLE 9.6 Summary of the Reactivity of Alkyl Halides in Nucleophilic Substitution Reactionsmethyl & 1o alkyl halides SN2 only2o alkyl halides SN2 & SN13o alkyl halides SN1 onlybenzylic & allylic halides SN2 & SN1 vinylic & aryl halides neither SN2 nor SN13o benzylic & allylic halides SN1 onlyChapter 8 25Competition Between SN2 and SN1 ReactionsWhat are the factors that determine which What are the factors that determine which mechanism operates?mechanism operates?concentration of the nucleophileconcentration of the nucleophilereactivity of the nucleophilereactivity of the nucleophilesolvent in which the reaction is carried outsolvent in which the reaction is carried outFor SN2 rate = k2 [alkyl halide][nucleophile]For SN1 rate = k1 [alkyl halide]Chapter 8 26Competition Between SN2 and SN1 ReactionsAn increase in the concentration of the nucleophile increases the rate of the SN2 reaction but has no effect on rate of SN1 reactionAn increase in the reactivity of nucleophile also speeds up an SN2 rxn but not an SN1 rxnChapter 8 27Role of the SolventThe solvent in which a nucleophilic substitution reaction is carried out has an influence on whether the reaction proceeds via an SN2 or an SN1 mechanismTwo important solvent aspects includesolvent polaritywhether it is protic or aproticChapter 8 28Solvent PolarityThe dielectric constant is a measure of how well the solvent can insulate opposite charges from each otherChapter 8 29Role of the SolventPolar solvents have a high dielectric constantWaterAlcoholsDimethylsulfoxide (DMSO)Solvents having O–H or N–H bonds are called protic solventsPolar solvents without O-H or N-H bonds called polar aprotic solventsChapter 8 30Role of the SolventIf charge on reactants(s) in slow step is greater than the charge on the transition state, a polar solvent will slow down rxn (by stabilizing reactants)If all reactant(s) involved in slow step are neutral polar solvent will speed up rxnIf reactant(s) involved in slow step are charged polar solvent slows down rxnChapter 8 31SN1 Reaction: Effect of SolventMost SN1 reactions involve a neutral alkyl halide which needs to produce a C+Consequently a polar solvent stabilizes the transition state more than the