Nucleophilic Substitution Reactions: SN1 Mechanism 12

Two Step Mechanism Which step is rate determining? A) Step #1 B) Step #2

Solvolysis Reactions Tertiary alkyl halides are very unreactive in substitutions that proceed by the SN2 mechanism. But they are highly reactive in solvolysis reactions where the solvent is generally one of the reactants. 2

Hydrolysis of tert-butyl bromide. + H Br .. : O C CH3 OH C + O : H Br .. – CH3 13

Hydrolysis of tert-butyl bromide. CH3 O : H CH3 H .. + C Br : + C O : .. + Br .. : – This is the nucleophilic substitution stage of the reaction; the one with which we are concerned. 13

Hydrolysis of tert-butyl bromide. CH3 O : H CH3 H .. + C Br : + C O : .. + Br .. : – The reaction rate is independent of the concentration of the nucleophile and follows a first-order rate law. rate = k[(CH3)3CBr] 13

Hydrolysis of tert-butyl bromide. C CH3 Br .. : C + O : H CH3 O : H + + Br .. : – The mechanism of this step is not SN2. It is called SN1 and begins with ionization of (CH3)3CBr. 13

Kinetics and Mechanism rate = k[alkyl halide] First-order kinetics implies a unimolecular rate-determining step. Proposed mechanism is called SN1, which stands for substitution nucleophilic unimolecular 2

C CH3 Br .. : Mechanism unimolecular slow C H3C CH3 + Br – .. : + 16

Mechanism C H3C CH3 + O : H bimolecular fast C + O : H CH3 17

carbocation formation carbocation capture proton transfer ROH RX ROH2 + 21

Characteristics of the SN1 mechanism first order kinetics: rate = k[RX] unimolecular rate-determining step carbocation intermediate rate follows carbocation stability rearrangements sometimes observed reaction is not stereospecific racemization occurs in reactions of optically active alkyl halides 19

Question What is the rate-determining step in the reaction of cyclobutanol with HCl? A) protonation of the OH group B) attack of the bromide on the carbocation C) simultaneous formation of the C-Br bond and the breaking of the C-OH bond D) carbocation formation

Question The species shown below represents _____ of the reaction between isopropyl alcohol and hydrogen bromide. A) the alkyloxonium ion intermediate B) the transition step of the bimolecular proton transfer C) the transition state of the attack of the nucleophile on the carbocation D) the transition state of the unimolecular dissociation

Carbocation Stability and SN1 Reaction Rates 20

Electronic Effects Govern SN1 Rates The rate of nucleophilic substitution by the SN1 mechanism is governed by electronic effects. Carbocation formation is rate-determining. The more stable the carbocation, the faster its rate of formation, and the greater the rate of unimolecular nucleophilic substitution. 33

Reactivity toward substitution by the SN1 mechanism RBr solvolysis in aqueous formic acid Alkyl bromide Class Relative rate CH3Br Methyl 1 CH3CH2Br Primary 2 (CH3)2CHBr Secondary 43 (CH3)3CBr Tertiary 100,000,000 33

Decreasing SN1 Reactivity (CH3)3CBr (CH3)2CHBr CH3CH2Br CH3Br 34

Question Select the most stable carbocation. A) B) C) D)

Question Which one of the following reacts with HBr at the fastest rate? A) B) C) D)

Stereochemistry of SN1 Reactions 23

Generalization Nucleophilic substitutions that exhibit first-order kinetic behavior are not stereospecific. 24

Stereochemistry of an SN1 Reaction Br CH3(CH2)5 R-(–)-2-Bromooctane (R)-(–)-2-Octanol (17%) H C CH3 OH CH3(CH2)5 HO (CH2)5CH3 (S)-(+)-2-Octanol (83%) H2O 24

Figure Ionization step gives carbocation; three bonds to chirality center become coplanar + Leaving group shields one face of carbocation; nucleophile attacks faster at opposite face. 25

Structure of tert-Butyl Cation CH3 H3C + Positively charged carbon is sp2 hybridized. All four carbons lie in same plane. Unhybridized p orbital is perpendicular to plane of four carbons. 10

+ More than 50% Less than 50% 25

Carbocation Capture + C CH3 H3C + C H3C CH3 Cl Cl – Lewis acid Lewis base Electrophile Nucleophile 9

Carbocation Rearrangements in SN1 Reactions 26

Because... carbocations are intermediates in SN1 reactions, rearrangements are possible. 24

Example CH3 C H CHCH3 Br H2O OH CH2CH3 (93%) CH3 C H CHCH3 + H2O CH3 C 27

Effect of Solvent on the Rate of Nucleophilic Substitution 28

SN1 Reaction Rates Increase in Polar Solvents In general... SN1 Reaction Rates Increase in Polar Solvents 24

SN1 Reactivity versus Solvent Polarity Solvent Dielectric Relative constant rate acetic acid methanol formic acid water Most polar Fastest rate 29

R transition state stabilized by polar solvent X  R+ energy of RX not much affected by polarity of solvent RX 6

activation energy decreases; transition state stabilized by polar solvent activation energy decreases; rate increases R X  R+ energy of RX not much affected by polarity of solvent RX 6

SN2 Reaction Rates Increase in Polar Aprotic Solvents In general... SN2 Reaction Rates Increase in Polar Aprotic Solvents An aprotic solvent is one that does not have an —OH group. 24

SN2 Reactivity versus Type of Solvent CH3CH2CH2CH2Br + N3– Solvent Type Relative Rate CH3OH polar protic 1 H2O polar protic 7 DMSO polar aprotic 1300 DMF polar aprotic 2800 Acetonitrile polar aprotic 5000 30

Mechanism Summary SN1 and SN2 24

When... primary alkyl halides undergo nucleophilic substitution, they always react by the SN2 mechanism tertiary alkyl halides undergo nucleophilic substitution, they always react by the SN1 mechanism secondary alkyl halides undergo nucleophilic substitution, they react by the SN1 mechanism in the presence of a weak nucleophile (solvolysis) SN2 mechanism in the presence of a good nucleophile 1

SN1 vs. SN2 – The Leaving Group The most commonly used leaving groups are halides and sulfonate ions. CONCEPTUAL CHECKPOINT 7.28.

SN2 vs. SN1 – Solvent SN2 reaction, use a polar, aprotic solvent To promote an SN1 reaction, use a polar, protic solvent: The protic solvent will hydrogen bond with the nucleophile, stabilizing it, while the leaving group leaves first.

Various Functions from Substitution Reactions

Calibrated Peer Review / Lab Experimentation http://chemconnections.org/organic/chem226/calendar-f-12