8.8 Unimolecular Nucleophilic Substitution S N 1

Tertiary alkyl halides are very unreactive in substitutions that proceed by the S N 2 mechanism. Do they undergo nucleophilic substitution at all? Yes. But by a mechanism different from S N 2. The most common examples are seen in solvolysis reactions. A question...

+ + H Br.... : O : : HH C CH 3 Br C OH : Example of a solvolysis. Hydrolysis of tert-butyl bromide.

+ + H Br.... : O : : HHC + + O : HH Br.... : : – CH 3 C Br C OH : Example of a solvolysis. Hydrolysis of tert-butyl bromide.

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

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

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

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

+ Br –.. : :.. unimolecular slow C CH 3 Br.... : C H3CH3CH3CH3C + Mechanism

bimolecular fast C H3CH3CH3CH3C CH 3 + O : : HH C + O : H H Mechanism

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

first order kinetics: rate = k[RX] unimolecular rate-determining step carbocation intermediate rate follows carbocation stability rearrangements sometimes observed reaction is not stereospecific much racemization in reactions of optically active alkyl halides Characteristics of the S N 1 mechanism

8.9 Carbocation Stability and S N 1 Reaction Rates

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

RBr solvolysis in aqueous formic acid Alkyl bromideClassRelative rate CH 3 BrMethyl1 CH 3 CH 2 BrPrimary2 (CH 3 ) 2 CHBrSecondary43 (CH 3 ) 3 CBrTertiary100,000,000 Table 8.5 Reactivity toward substitution by the S N 1 mechanism

CH 3 Br CH 3 CH 2 Br (CH 3 ) 2 CHBr (CH 3 ) 3 CBr Decreasing S N 1 Reactivity

8.10 Stereochemistry of S N 1 Reactions

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

R-(–)-2-Bromooctane HC CH 3 Br CH 3 (CH 2 ) 5 (R)-(–)-2-Octanol (17%) HC CH 3 OH CH 3 (CH 2 ) 5 C H CH 3 HO (CH 2 ) 5 CH 3 (S)-(+)-2-Octanol (83%) H2OH2OH2OH2O Stereochemistry of an S N 1 Reaction

Ionization step gives carbocation; three bonds to stereogenic center become coplanar + Figure 8.8

Leaving group shields one face of carbocation; nucleophile attacks faster at opposite face. + Figure 8.8

More than 50% Less than 50% +

8.11 Carbocation Rearrangements in S N 1 Reactions

carbocations are intermediates in S N 1 reactions, rearrangements are possible. Because...

CH 3 C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%) Example

C H CHCH 3 CH 3 C CHCH 3 CH 3 C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%) + H + Example

8.12 Solvent Effects

S N 1 Reaction Rates Increase in Polar Solvents In general...

SolventDielectricRelative constantrate acetic acid 61 methanol334 formic acid585,000 water78150,000 Table 8.6 S N 1 Reactivity versus Solvent Polarity

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

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

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

SolventTypeRelative rate CH 3 OHpolar protic1 H 2 Opolar protic7 DMSOpolar aprotic1300 DMFpolar aprotic2800 Acetonitrilepolar aprotic5000 CH 3 CH 2 CH 2 CH 2 Br + N 3 – Table 8.7 S N 2 Reactivity versus Type of Solvent

Mechanism Summary S N 1 and S N 2

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