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Chapter 81 Substitution Reactions of Alkyl Halides: Chapter 8.

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Presentation on theme: "Chapter 81 Substitution Reactions of Alkyl Halides: Chapter 8."— Presentation transcript:

1 Chapter 81 Substitution Reactions of Alkyl Halides: Chapter 8

2 Chapter 82 Contents of Chapter 8 Reactivity Considerations The S N 2 Reaction Reversibility of the S N 2 Reaction The S N 1 Reaction Stereochemistry of S N 2 and S N 1 Reactions Benzylic, Allylic, Vinylic & Aryl Halides Competition between S N 2 and S N 1 Reactions Role of the Solvent No Biological Methylating Reagents

3 Chapter 83 Substitution and Elimination A compound with an sp 3 hybridized carbon bonded to a halogen can undergo two types of reactions Two different mechanisms for substitution are S N 1 and S N 2 mechanisms These result in diff prods under diff conditions

4 Chapter 84 S N 2 Mechanism S N 2 mechanism: C–X bond weakens as nucleophile approaches all in one step

5 Chapter 85 S N 1 Mechanism S N 1 mechanism: C–X bond breaks first without any help from nucleophile This is a two-step process slow step fast step

6 Chapter 86 Substitution 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 out

7 Chapter 87 The S N 2 Reaction Bimolecular nucleophilic substitution rate = k [alkyl halide][nucleophile]

8 Chapter 88 The S N 2 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.

9 Chapter 89 Steric Accessibility in the S N 2 Reaction

10 Chapter 810 The S N 2 Reaction: Leaving Group Stability

11 Chapter 811 The S N 2 Reaction: Nucleophile Basicity stronger baseweaker base better nucleophilepoorer nucleophile HO – >H 2 O CH 3 O – >CH 3 OH – NH 2 >NH 3 CH 3 CH 2 NH – > CH 3 CH 2 NH 2

12 Chapter 812 The S N 2 Reaction: Nucleophile Basicity Comparing nucleophiles with attacking atoms of approximately the same size, the stronger base is also the stronger nucleophile

13 Chapter 813 The S N 2 Reaction: Nucleophile Size In nonpolar solvents nucleophilicity order same as basicity order- size doesn’t matter

14 Chapter 814 The S N 2 Reaction: Nucleophile Size Size is related to polarizability

15 Chapter 815 The S N 2 Reaction: Nucleophile Size and Type Nucleophilicity ~ both size and basicity

16 Chapter 816 The S N 2 Reaction: Nucleophile Bulkiness Nucleophilicity is affected by steric effects A bulky nucleophile has difficulty getting near the back side of a sp 3 carbon ethoxide ion tert-butoxide ion better nucleophile stronger base

17 Chapter 817 The S N 1 Reaction The more stable the C+ the lower the  G ‡, and the faster the rxn

18 Chapter 818 The S N 1 Reaction

19 Chapter 819 The S N 1 Reaction The S N 1 reaction leads to a mixture of stereoisomers

20 Chapter 820 The S N 1 Reaction: Factors Affecting the Rate increasing reactivity RI > RBr > RCl > RF Two factors affect the rate of formation of the carbocation ease with which the leaving group leaves stability of the carbocation increasing reactivity 3 º alkyl halide > 2 º alkyl halide > 1 º alkyl halide

21 Chapter 821 The S N 1 Reaction: Carbocation Rearrangements

22 Chapter 822 Stereochemistry of S N 2 and S N 1 Reactions inversion both enantiomers

23 Chapter 823 Competition Between S N 2 and S N 1 Reactions

24 Chapter 824 Competition Between S N 2 and S N 1 Reactions TABLE 9.6 Summary of the Reactivity of Alkyl Halides in Nucleophilic Substitution Reactions methyl & 1 o alkyl halides S N 2 only 2 o alkyl halides S N 2 & S N 1 3 o alkyl halidesS N 1 only benzylic & allylic halides S N 2 & S N 1 vinylic & aryl halides neither S N 2 nor S N 1 3 o benzylic & allylic halides S N 1 only

25 Chapter 825 Competition Between S N 2 and S N 1 Reactions What are the factors that determine which mechanism operates? concentration of the nucleophile concentration of the nucleophile reactivity of the nucleophile reactivity of the nucleophile solvent in which the reaction is carried out solvent in which the reaction is carried out For S N 2rate = k 2 [alkyl halide][nucleophile] For S N 1rate = k 1 [alkyl halide]

26 Chapter 826 Competition Between S N 2 and S N 1 Reactions An increase in the concentration of the nucleophile increases the rate of the S N 2 reaction but has no effect on rate of S N 1 reaction An increase in the reactivity of nucleophile also speeds up an S N 2 rxn but not an S N 1 rxn

27 Chapter 827 Role of the Solvent The solvent in which a nucleophilic substitution reaction is carried out has an influence on whether the reaction proceeds via an S N 2 or an S N 1 mechanism Two important solvent aspects include solvent polarity whether it is protic or aprotic

28 Chapter 828 Solvent Polarity The dielectric constant is a measure of how well the solvent can insulate opposite charges from each other

29 Chapter 829 Role 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 solvents

30 Chapter 830 Role 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 rxn

31 Chapter 831 S N 1 Reaction: Effect of Solvent Most S N 1 reactions involve a neutral alkyl halide which needs to produce a C+ Consequently a polar solvent stabilizes the transition state more than the reactant Increasing the polarity of the solvent speeds up such an S N 1 reaction Protic solvents stabilize the leaving group by H-bonding and thus stabilize the transition state

32 Chapter 832 S N 2 Reaction: Effect of Solvent Most S N 2 reactions involve a neutral alkyl halide and a charged nucleophile Consequently a polar solvent stabilizes the nucleophile more than the transition state and slows rxn The nucleophiles used in S N 2 reactions however are generally insoluble in nonpolar solvents - some solvent polarity is needed, but it’s best to use an aprotic solvent to avoid overstabilizing nucleophile reactant

33 Chapter 833 Competition Between S N 2 and S N 1 Reactions S N 2 and S N 1 : When a halide can undergo both an S N 2 and S N 1 reaction: S N 2 will be favored by a high concentration of a good (negatively charged) nucleophile S N 2 will be favored by a high concentration of a good (negatively charged) nucleophile S N 2 will be favored in a polar aprotic solvent S N 2 will be favored in a polar aprotic solvent S N 1 will be favored by a poor (neutral) nucleophile in a polar protic solvent S N 1 will be favored by a poor (neutral) nucleophile in a polar protic solvent

34 Chapter 834 Problem-solving Info Nucleophile strength Protic solvent Size most important Look at basicity if same row of periodic table Aprotic solvent- look at basicity only Strength in aprotic solvent > protic solvent First two points not strictly true but will work in this course

35 Chapter 835 Problem-solving Info Electrophile strength S N 2 reactions Steric accessibility Electron withdrawing group (EWG) attached to C reaction site Good leaving group S N 1 reactions Carbocation stability EWG not attached to reaction site Good leaving group

36 Chapter 836 Problem-solving Info Solvent polarity Reduces rate with charged reactants Charge on both nucleophile and electrophile important in S N 2 Only electrophile important in S N 1 Increases rate with uncharged reactants Reduces nucleophilicity Stabilizes leaving group for S N 1

37 Chapter 837 Problem-solving Info Reaction speed comparisons Increasing speed in S N 1 reaction Polar solv/uncharged electrophile, vice-versa Relief of steric strain making C+ More stable carbocation formed Anything which destabilizes electrophile Increased leaving group stability (less basic) Increasing speed in S N 2 reaction Charge on electrophile & nuc vs. solv polarity

38 Chapter 838 Problem-solving Info Increased leaving group stability Less steric hindrance (both nuc & electrophile) Switch from protic to aprotic solvent Higher concentration of nucleophile More basic nucleophile Larger size of nucleophile’s attacking atom Anything which destabilizes nuc or electrophile Stereochemistry S N 1 reactions give both isomers at chiral C S N 2 reactions give only inversion at chiral C

39 Chapter 839 Problem-solving Info Carbocation rearrangements Will occur if posible with S N 1 Will not occur with S N 2 S N 1 vs S N 2 chemistry Conditions which give S N 1 Tertiary C reaction center C+ stability  2 & weak nuc (H-nuc pKa <7) Carboxylates and sulfonates Neutral O nucleophiles Halides Neutral large-atom (row >2) nucleophiles

40 Chapter 840 Problem-solving Info Conditions which give S N 2 C+ stability index = 1 and unhindered rxn site C+ stability  2, not 3°, strong nucleophile Any nuc with conj acid pKa  7 (Table 10.3 pg 373) Alkoxides and hydroxide Ammonia and amines Carbanions Sulfides Hydride Nitrogen anions In this text “high conc” of nuc is code for S N 2 Other conditions give S N 1/S N 2 mixture


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