Nucleophilic Substitution Reactions SN 1 Mechanism Two Step

Nucleophilic Substitution Reactions: SN 1 Mechanism

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 SN 2 mechanism. But they are highly reactive in solvolysis reactions where the solvent is generally one of the reactants.

Hydrolysis of tert-butyl bromide. CH 3 C . . : Br. . H + CH 3 : O: H CH 3 + O: C H CH 3 + CH 3 C CH 3 . . O H. . + H . . Br : . . H . . – : Br : . .

Hydrolysis of tert-butyl bromide. CH 3 C CH 3 . . : Br. . H + : O: H CH 3 + O: C H CH 3 + This is the nucleophilic substitution stage of the reaction; the one with which we are concerned. H . . – : Br : . .

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

Hydrolysis of tert-butyl bromide. CH 3 C CH 3 . . : Br. . H + : O: CH 3 H CH 3 + O: C H CH 3 + The mechanism of this step is not SN 2. It is called SN 1 and begins with ionization of (CH 3)3 CBr. H . . – : Br : . .

Kinetics and Mechanism rate = k[alkyl halide] First-order kinetics implies a unimolecular rate-determining step. Proposed mechanism is called SN 1, which stands for substitution nucleophilic unimolecular

CH 3 Mechanism . . : Br. . C CH 3 unimolecular slow H 3 C + C CH 3 + . . – : Br : . .

Mechanism H 3 C CH 3 + C H : O: CH 3 H bimolecular fast CH 3 C CH 3 + H O: H

carbocation formation R+ carbocation capture proton transfer RX + ROH 2 ROH

Characteristics of the SN 1 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

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) B) the alkyloxonium ion intermediate 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 SN 1 Reaction Rates

Electronic Effects Govern SN 1 Rates The rate of nucleophilic substitution by the SN 1 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.

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

Decreasing SN 1 Reactivity (CH 3)3 CBr (CH 3)2 CHBr CH 3 CH 2 Br CH 3 Br

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

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

Stereochemistry of SN 1 Reactions

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

Stereochemistry of an SN 1 Reaction CH 3 H C R-(–)-2 -Bromooctane Br CH 3(CH 2)5 H HO CH 3 C (CH 2)5 CH 3 (S)-(+)-2 -Octanol (83%) CH 3 H 2 O H C OH CH 3(CH 2)5 (R)-(–)-2 -Octanol (17%)

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.

Structure of tert-Butyl Cation CH 3 H 3 C + C CH 3 Positively charged carbon is sp 2 hybridized. All four carbons lie in same plane. Unhybridized p orbital is perpendicular to plane of four carbons.

+ More than 50% Less than 50%

Carbocation Capture + H 3 C CH 3 C+ Cl – CH 3 Lewis acid Lewis base Electrophile Nucleophile H 3 C CH 3 C Cl H 3 C

Carbocation Rearrangements in SN 1 Reactions

Because. . . carbocations are intermediates in SN 1 reactions, rearrangements are possible.

Example CH 3 C CHCH 3 H Br H 2 O CH 3 C CH 2 CH 3 OH (93%) H 2 O CH 3 C H CH 3 CHCH 3 + CH 3 C + CHCH 3 H

Effect of Solvent on the Rate of Nucleophilic Substitution

In general. . . SN 1 Reaction Rates Increase in Polar Solvents

SN 1 Reactivity versus Solvent Polarity Solvent Dielectric Relative constant rate acetic acid methanol formic acid water Most polar Fastest rate

transition state stabilized by polar solvent R X R+ energy of RX not much affected by polarity of solvent RX

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

In general. . . SN 2 Reaction Rates Increase in Polar Aprotic Solvents An aprotic solvent is one that does not have an —OH group.

SN 2 Reactivity versus Type of Solvent CH 3 CH 2 CH 2 Br + N 3– Solvent Type Relative Rate CH 3 OH polar protic 1 H 2 O polar protic 7 DMSO polar aprotic 1300 DMF Acetonitrile polar aprotic 5000

Mechanism Summary SN 1 and SN 2

When. . . primary alkyl halides undergo nucleophilic substitution, they always react by the SN 2 mechanism tertiary alkyl halides undergo nucleophilic substitution, they always react by the SN 1 mechanism secondary alkyl halides undergo nucleophilic substitution, they react by the SN 1 mechanism in the presence of a weak nucleophile (solvolysis) SN 2 mechanism in the presence of a good nucleophile

SN 1 vs. SN 2 – The Leaving Group The most commonly used leaving groups are halides and sulfonate ions. CONCEPTUAL CHECKPOINT 7. 28.

SN 2 vs. SN 1 – Solvent SN 2 reaction, use a polar, aprotic solvent To promote an SN 1 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

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