1. Nucleophilic Substitution Reactions: SN1 Mechanism12

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

3. 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

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

5. 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

6. 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

7. 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

8. 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

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

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

12. carbocation formation carbocation capture
proton transfer
ROH RX
ROH2 + 21

13. 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

14. 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

15. 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

16. Carbocation Stability and SN1 Reaction Rates20

17. 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

18. 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

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

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

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

22. Stereochemistry of SN1 Reactions23

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

25. Stereochemistry of an SN1 ReactionBr
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

26. 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

27. 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

28. +
More than 50%
Less than 50% 25

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

30. Carbocation Rearrangements in SN1 Reactions26

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

32. Example CH3 C H CHCH3 Br H2O OH CH2CH3 (93%) CH3 C H CHCH3 + H2O CH3 C27

33. Effect of Solvent on the Rate of Nucleophilic Substitution28

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

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

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

37. 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

38. 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

39. 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

40. Mechanism Summary SN1 and SN224

41. 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

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

43. 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.

44. Various Functions from Substitution Reactions

45. Calibrated Peer Review / Lab Experimentation