SUBSTITUTION AND ELIMINATION

REACTIONS OF ALKYL HALIDES

SN1, SN2, E1 & E2 REACTIONS

1
 Reactions of Alkyl Halides (R-X): [SN1, SN2, E1, & E2 reactions]
d d
H3C F EN (F-C) = (4.0 2.5) = 1.5
d d
H3C Cl EN (Cl-C) = (3.0 2.5) = 0.5
d d
H3C Br EN (Br-C) = (2.8 2.5) = 0.3
H3C I
EN (I-C) = (2.5 2.5) = 0.0
The -carbon in an alkyl halide is electrophilic (electron accepting) for either
or both of two reasons
a) the C to X (F, Cl, Br) bond is polar making carbon d+

b) X (Cl, Br, I) is a leaving group

decreasing basicity, increasing stability
The best The poorest
leaving leaving
pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7
groups are groups are
I- Br - Cl - F- HO - the strongest
the weakest
30,000 10,000 200 1 0 bases.
bases.

increasing leaving ability 2

 Reactions of Alkyl Halides (R-X): [SN1, SN2, E1, & E2 reactions]

When a nucleophile (electron donor, e.g., OH-) reacts with an alkyl halide, the
halogen leaves as a halide

.. ..
Nu: R .. :
Br : Br
.. :

There are two competing reactions of alkyl halides with nucleophiles.

1) substitution H
H
+ X-
Nu: -
C C C C
+

X Nu

2) elimination The Nu:- replaces the halogen on the -carbon.

H

Nu:- + C C C C + X- + Nu H
b
X The Nu:- removes an H+ from a b-carbon &
the halogen leaves forming an alkene.
3
 2nd Order Nucleophilic Substitution Reactions, i.e., SN2 reactions

There are two kinds of substitution reactions, called SN1 and SN2.
As well as two kinds of elimination reactions, called E1 and E2.
Lets study SN2 reactions first. SN2 stands for Substitution,
Nucleophilic, bimolecular. Another word for bimolecular is 2nd
order.
Bimolecular (or 2nd order) means that the rate of an SN2 reaction is
directly proportional to the molar concentration of two reacting
molecules, the alkyl halide substrate and the nucleophile:
Rate = k [RX] [Nu:-] (This is a rate equation and k is a constant).
The mechanism of an SN2 reaction is the one shown on slide #2:

H H

- C C + X-
Nu: + C C

X Nu

Note that the nucleophile must hit the back side of the -carbon.
The nucleophile to C bond forms as the C to X bond breaks.
No C+ intermediate forms. An example is shown on the next slide.
4
 2nd Order Nucleophilic Substitution Reactions, i.e., SN2 reactions

H H
.. H .. .. .. .. ..
:O H + C Br : H ..O C Br : H C + : Br :
..
H
.. .. ..O ..
H
H HH H
transition state

The rate of an SN2 reaction depends upon 4 factors:

1. The nature of the substrate (the alkyl halide)
2. The power of the nucleophile
3. The ability of the leaving group to leave
4. The nature of the solvent
1. Consider the nature of the substrate:
Unhindered alkyl halides, those in which the back side of the -carbon is
not blocked, will react fastest in SN2 reactions, that is:
Me >> 1 >> 2 >> 3
While a methyl halides reacts quickly in SN2 reactions, a 3 does not react.
The back side of an -carbon in a 3 alkyl halide is completely blocked.

5
 Effect of nature of substrate on rate of SN2 reactions:
H3C H3C
CH Br H3C C Br
H3C Br H3C CH2 Br
H3C H3C

methyl bromide ethyl bromide isopropyl bromide t-butyl bromide

SPACE FILLING MODELS SHOW ACTUAL SHAPES AND RELATIVE SIZES

Back side of -C Back side of -C of a Back side of -C of a Back side of -C of a

of a methyl halide 1 alkyl halide is 2 alkyl halide is 3 alkyl halide is
is unhindered. slightly hindered. mostly hindered. completely blocked.

Me>> 1 >> 2 >> 3

decreasing rate of SN2 reactions

6
 Effect of the nucleophile on rate of SN2 reactions:

The -carbon in vinyl and aryl halides, as in 3 carbocations, is completely

hindered and these alkyl halides do not undergo SN2 reactions.

H2C CH Br Br

vinyl bromide bromobenzene

Nu:- Nu:-
H2C CH Br Br

The overlapping p-orbitals that form the p-bonds in vinyl and aryl halides
completely block the access of a nucleophile to the back side of the
-carbon.

7
 Effect of nature substrate on rate of SN2 reactions:

2. Consider the power of the nucleophile:

The better the nucleophile, the faster the rate of SN2 reactions.
The table below show the relative power or various nucleophiles.
The best nucleophiles are the best electron donors.

Reactivity Nu:- Relative Reactivity

very weak HSO4-, H2PO4-, RCOOH < 0.01
weak ROH 1

increasing
HOH, NO3- 100
fair F- 500
Cl-, RCOO- 20 103
NH3, CH3SCH3 300 103
good N3-, Br- 600 103
OH-, CH3O- 2 106
very good CN-, HS-, RS-, (CH3)3P:, NH2- ,RMgX, I-, H- > 100 106

8
 Effect of nature of the leaving group on rate of SN2 reactions:

3. Consider the nature of the leaving group:

The leaving group usually has a negative charge
Groups which best stabilize a negative charge are the best leaving groups,
i.e., the weakest bases are stable as anions and are the best leaving groups.
Weak bases are readily identified. They have high pKb values.

pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7 pKb = -2 pKb = -21

I- Br - Cl- F- HO- RO- H2N-
30,000 10,000 200 1 0 0 0

Increasing leaving ability

Iodine (-I) is a good leaving group because iodide (I-) is non basic.
The hydroxyl group (-OH) is a poor leaving group because hydroxide (OH-)
is a strong base.

9
 Effect of the solvent on rate of SN2 reactions:

4. Consider the nature of the solvent:

There are 3 classes of organic solvents:
Protic solvents, which contain OH or NH2 groups. Protic solvents
slow down SN2 reactions.
Polar aprotic solvents like acetone, which contain strong dipoles but no
OH or NH2 groups. Polar aprotic solvents speed up SN2 reactions.
Non polar solvents, e.g., hydrocarbons. SN2 reactions are relatively
slow in non polar solvents.

Protic solvents (e.g., H2O, MeOH, EtOH, CH3COOH, etc.) cluster around the
Nu:- (solvate it) and lower its energy (stabilize it) and reduce its reactivity via
+ -
H-bonding. d d
H OR
+ d-
d A solvated anion (Nu:-) has reduced nucleophilicity,
RO H X: -
H OR reduced reactivity and increased stability
- +
d d A solvated nucleophile has
H OR difficulty hitting the -carbon.
+ d-
d
10
 : O:
CH3 C N:
Effect of the solvent on rate of SN2 reactions: H3C C CH3
acetonitrile
acetone

Polar Aprotic Solvents solvate the cation counterion of the nucleophile but
not the nucleophile.
Examples include acetonitrile (CH3CN), acetone (CH3COCH3),
dimethylformamide (DMF) [(CH3)2NC=OH], dimethyl sulfoxide, DMSO
[(CH3)2SO], hexamethylphosphoramide, HMPA {[(CH3)2N]3PO} and
dimethylacetamide (DMA).

:O : : O: :O:
.. CH3 .. .. .. CH3
H C N H3C S CH3 [(CH3)2N]3P O.. H3C C N
..
CH3 CH3
HMPA DMA
DMF DMSO
- +
d d
Polar aprotic solvents solvate metal cations N C CH3
..
leaving the anion counterion (Nu: -) bare and
thus more reactive + - :O:
d d .. _
+
:O: H3C C N: Na : N C CH3 + CH3C O
..
:
- +
.. _ CH3CN : d d
: +
CH3C O
.. Na ..
N C CH3
- +
d d
11
 Effect of the solvent on rate of SN2 reactions:

Non polar solvents (benzene, carbon tetrachloride, hexane, etc.) do not

solvate or stabilize nucleophiles.

SN2 reactions are relatively slow in non polar solvents similar to that
in protic solvents.
Cl

C CH3CH2CH2CH2CH2CH3
Cl Cl
Cl
benzene n-hexane
carbon
tetrachloride

12
 1st Order Nucleophilic Substitution Reactions, i.e., SN1 reactions

CH3 CH3
rapid
3 C I Na+ Br-
H3C C Br + Na+ I- H3C +
CH3 CH3

3 alkyl halides are essentially inert to substitution by the SN2 mechanism

because of steric hindrance at the back side of the -carbon.
Despite this, 3 alkyl halides do undergo nucleophilic substitution reactions
quite rapidly , but by a different mechanism, i.e., the SN1 mechanism.
SN1 = Substitution, Nucleophilic, 1st order (unimolecular).
SN1 reactions obey 1st order kinetics, i.e., Rate = k[RX].
The rate depends upon the concentration of only 1 reactant, the
alkyl halide-not the nucleophile
The order of reactivity of substrates for SN1 reactions is the reverse of SN2
3 > 2 > 1 > vinyl > phenyl > Me
R3C-Br R2HC-Br RH2C-Br CH2=CH-Br -Br H3C-Br

increasing rate of SN1 reactions

13
 Mechanism of SN1 reactions

The mechanism of an SN1 reaction occurs in 2 steps:

CH3 CH3 rapid CH3

3 .. 1. 2. ..
.. : ..I : Na+ Br-
H3C C H3C C+ C
Br
- Br - .. H3C +
Na+ :I :-
CH3 CH3 .. CH3
3 C+

Reaction Steps
1. the slower, rate-limiting dissociation of the alkyl halide forming a C+
intermediate
2. a rapid nucleophilic attack on the C+

Note that the nucleophile is not involved in the slower, rate-limiting step.

14
 The Rate of SN1 reactions

The rate of an SN1 reaction depends upon 3 factors:

1. The nature of the substrate (the alkyl halide)
2. The ability of the leaving group to leave
3. The nature of the solvent
The rate is independent of the power of the nucleophile.
1. Consider the nature of the substrate:
Highly substituted alkyl halides (substrates) form a more stable C+.

increasing rate of SN1 reactions

more less
stable stable
CH3 CH3 CH3 H

H3C C+ H3C C+ H C+ H C+

CH3 H H H
tertiary > secondary > primary > methyl
3 2 1

15
 Stability of Carbocations

Alkyl groups are weak electron donors.

They stabilize carbocations by donating electron density by induction
(through s bonds)
CH3
Inductive effects:
Alkyl groups donate (shift) electron
H3C C+ density through sigma bonds to
electron deficient atoms.
This stabilizes the carbocation.
CH3

They stabilize carbocations by hyperconjugation (by partial overlap of the

alkyl C-to-H bonds with the empty p-orbital of the carbocation).
vacant p orbital overlap (hyperconjugation)
of a carbocation

sp 2 Csp 3-Hs
hybridized sigma bond
carbocation H orbital
..
+
C C H
H

HYPERCONJUGATION
16
 Stability of Carbocations

Allyl and benzyl halides also react quickly by SN1 reactions because
their carbocations are unusually stable due to their resonance forms
which delocalize charge over an extended p system

+ HC CHR
H2C CH +
CH2 H2C+ HC CH2 H2C CH +
CHR H2C

1 allyl carbocation 2 allyl carbocation

2 benzylic
H H 1 benzylic H H
+ + H
C C C C +
H H H H C
R
+ +

17
 Relative Stability of All Types of Carbocations

Increasing C+ stability and rate of SN1 reaction

+ +
C HR C H2

1 benzylic
+ 2 benzylic
C R2

3 C + 2 C + 1 C + H
3 benzylic
+
CH3 CH3 H + H C+
> > CH2 CH > >
CH3 C+ > CH3 C+ CH3 C+ H
> + +
H H vinyl C
CH3 phenyl m ethyl C
+
+ +
CH2 CH CR2
CH2 CH CHR CH2 CH CH2
3 allylic 2 allylic 1 allylic

Note that 1 allylic and 1 benzylic C+s are about as stable as 2alkyl C+s.
Note that 2 allylic and 2 benzylic C+s are about as stable as 3 alkyl C+s.
Note that 3 allylic and 3 benzlic C+s are more stable than 3 alkyl C+s
Note that phenyl and vinyl C+s are unstable. Phenyl and vinyl halides do not
usually react by SN1 or SN2 reactions
18
 Effect of nature of the leaving group on rate of SN1 reactions:

2. Consider the nature of the leaving group:

The nature of the leaving group has the same effect on both SN1 and SN2
reactions.
The better the leaving group, the faster a C+ can form and hence the faster will
be the SN1 reaction.
The leaving group usually has a negative charge
Groups which best stabilize a negative charge are the best leaving groups,
i.e., the weakest bases are stable as anions and are the best leaving groups.
Weak bases are readily identified. They have high pKb values.

pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7 pKb = -2 pKb = -21

I- Br - Cl- F- HO- RO- H2N-
30,000 10,000 200 1 0 0 0

Increasing leaving ability

Iodine (-I) is a good leaving group because iodide (I-) is non basic.
The hydroxyl group (-OH) is a poor leaving group because hydroxide (OH-) is
a strong base.
19
 Effect of the solvent on rate of SN1 reactions:

3. Consider the nature of the solvent:

For SN1 reactions, the solvent affects the rate only if it influences the
stability of the charged transition state, i.e., the C+. The Nu:- is not
involved in the rate determining step so solvent effects on the Nu:- do not
affect the rate of SN1 reactions.
Polar solvents, both protic and aprotic, will solvate and stabilize the
charged transition state (C+ intermediate), lowering the activation energy
and accelerating SN1 reactions.
Nonpolar solvents do not lower the activation energy and thus make SN1
reactions relatively slower

The relative rates of an SN1 reaction due to solvent effects are given

(CH3)3C-Cl + ROH (CH3)3C-OR + HCl

H2O 20% EtOH (aq) 40% EtOH (aq) EtOH

100,000 14,000 100 1
reaction rate increases with polarity of solvent
20
 Effect of the solvent on rate of SN1 reactions:

Solvent polarity is usually expressed by the dielectric constant, , which

is a measure of the ability of a solvent to act as an electric insulator.
Polar solvents are good electric insulators because their dipoles surround
and associate with charged species.
Dielectric constants of some common solvents are given in the following
table
name dielectric constant name dielectric constant
aprotic solvents protic solvents
hexane 1.9 acetic acid 6.2
benzene 2.3 acetone 20.7
diethyl ether 4.3 ethanol 24.3
chloroform 4.8 methanol 33.6
HMPA 30 formic acid 58.0
DMF 38 water 80.4
DMSO 48

21
 Effect of the nucleophile on rate of SN1 reactions:

Consider the nature of the Nucleophile:

Recall again that the nature of the nucleophile has no effect on the rate of
SN1 reactions because the slowest (rate-determining) step of an SN1
reaction is the dissociation of the leaving group and formation of the
carbocation.
All carbocations are very good electrophiles (electron acceptors) and even
weak nucleophiles, like H2O and methanol, will react quickly with them.
The two SN1 reactions will proceed at essentially the same rate since the
only difference is the nucleophile.
CH3 CH3
3 C I Na+ Br-
H3C C Br + Na+ I- H3C +
CH3 CH3

CH3 CH3
3 K+ F- C F K+ Br-
H3C C Br + H3C +
CH3 CH3

22
 Elimination Reactions, E1 and E2:

We have seen that alkyl halides may react with basic nucleophiles such as NaOH
via substitution reactions.
H H
.. H .. .. .. .. ..
:O H + C Br : H ..O C Br : H C + : Br :
..
H
.. .. ..O ..
H
H HH H
transition state

Also recall our study of the preparation of alkenes. When a 2 or 3 alkyl halide
is treated with a strong base such as NaOH, dehydrohalogenation occurs
producing an alkene an elimination (E2) reaction.

KOH in ethanol + KBr + H2O

Br
-HBr

bromocyclohexane + KOH cyclohexene (80 % yield)

Substitution and elimination reactions are often in competition. We shall

consider the determining factors after studying the mechanisms of elimination.

23
 E2 Reaction Mechanism

There are 2 kinds of elimination reactions, E1 and E2.

E2 = Elimination, Bimolecular (2nd order). Rate = k [RX] [Nu:-]
E2 reactions occur when a 2 or 3 alkyl halide is treated with a strong
base such as OH-, OR-, NH2-, H-, etc.

H
C C + Br- + HO H
OH- + C C
b
Br
The Nu:- removes an H+ from a b-carbon &
the halogen leaves forming an alkene.

All strong bases, like OH-, are good nucleophiles. In 2 and 3 alkyl halides
the -carbon in the alkyl halide is hindered. In such cases, a strong base
will abstract (remove) a hydrogen ion (H+) from a b-carbon, before it hits
the -carbon. Thus strong bases cause elimination (E2) in 2 and 3 alkyl
halides and cause substitution (SN2) in unhindered methyl and 1 alkyl
halides.

24
 E2 Reaction Mechanism

In E2 reactions, the Base to H s bond formation, the C to H s bond breaking,

the C to C p bond formation, and the C to Br s bond breaking all occur
simultaneously. No carbocation intermediate forms.

B:- d
+
B
H R H R R R
C C R C C C C + B H + X-
R R R R
R X R R
X-
d

Reactions in which several steps occur simultaneously are called concerted

reactions.
Zaitsevs Rule:
Recall that in elimination of HX from alkenes, the more highly substituted
(more stable) alkene product predominates.
Br CH3CH2O-Na+
CH3CH2CHCH3 CH3CH CHCH3 + CH3CH2CH CH2
EtOH 2-butene 1-butene

major product minor product

( > 80%) ( < 20%)
25
 E2 Reactions are antiperiplanar

E2 reactions, do not always follow Zaitsevs rule.

E2 eliminations occur with anti-periplanar geometry, i.e., periplanar

means that all 4 reacting atoms - H, C, C, & X - all lie in the same
plane. Anti means that H and X (the eliminated atoms) are on opposite
sides of the molecules.

Look at the mechanism again and note the opposite side & same plane
orientation of the mechanism:

B:- d
+
B
H R H R R R
C C R C C C C + B H + X-
R R R R
R X R R
X-
d

26
 Antiperiplanar E2 Reactions in Cyclic Alkyl Halides

When E2 reactions occur in open chain alkyl halides, the Zaitsev

product is usually the major product. Single bonds can rotate to the
proper alignment to allow the antiperiplanar elimination.
In cyclic structures, however, single bonds cannot rotate. We need to
be mindful of the stereochemistry in cyclic alkyl halides undergoing E2
reactions.
See the following example.

Trans 1-chloro-2-methylcyclopentane undergoes E2 elimination with

NaOH. Draw and name the major product.

H H3C H
H3C H Na+ OH- NaCl
+
H H3C
H H + HOH H
H E2 H
H
Cl
Little or no Zaitsev (more stable)
Non Zaitsev product product is formed.
is major product.

3-methylcyclopentene 1-methylcyclopentene
27
 E1 Reactions

Just as SN2 reactions are analogous to E2 reactions, so SN1 reactions have

an analog, E1 reaction.
E1 = Elimination, unimolecular (1st order); Rate = k [RX]

CH3 CH3
slow H
rapid CH3
CH3 C Br CH3 C+ -
C C + B H + Br
- Br-
CH3 H C H
CH3 H
H B:-

E1 eliminations, like SN1 substitutions, begin with unimolecular

dissociation, but the dissociation is followed by loss of a proton from the
b-carbon (attached to the C+) rather than by substitution.
E1 & SN1 normally occur in competition, whenever an alkyl halide is
treated in a protic solvent with a nonbasic, poor nucleophile.
Note: The best E1 substrates are also the best SN1 substrates, and
mixtures of products are usually obtained.

28
 E1 Reactions

As with E2 reactions, E1 reactions also produce the more highly

substituted alkene (Zaitsevs rule). However, unlike E2 reactions where no
C+ is produced, C+ rearrangements can occur in E1 reactions.
e.g., t-butyl chloride + H2O (in EtOH) at 65 C t-butanol + 2-methylpropene

CH3 H2O, EtOH CH3 CH3 H

CH3 C Cl CH3 C OH + C C
65C
CH3 CH3 CH3 H
36%
64%
E1
S N1
product
product

In most unimolecular reactions, SN1 is favored over E1, especially at low

temperature. Such reactions with mixed products are not often used in
synthetic chemistry.
If the E1 product is desired, it is better to use a strong base and force the
E2 reaction.
Note that increasing the strength of the nucleophile favors SN1 over E1.
Can you postulate an explanation?

29
 Predicting Reaction Mechanisms

1. Non basic, good nucleophiles, like Br- and I- will cause substitution not
elimination. In 3 substrates, only SN1 is possible. In Me and 1
substrates, SN2 is faster. For 2 substrates, the mechanism of
substitution depends upon the solvent.
2. Strong bases, like OH- and OR-, are also good nucleophiles.
Substitution and elimination compete. In 3 and 2 alkyl halides, E2 is
faster. In 1 and Me alkyl halides, SN2 occurs.
3. Weakly basic, weak nucleophiles, like H2O, EtOH, CH3COOH, etc.,
cannot react unless a C+ forms. This only occurs with 2 or 3
substrates. Once the C+ forms, both SN1 and E1 occur in competition.
The substitution product is usually predominant.
4. High temperatures increase the yield of elimination product over
substitution product. (G = H TS) Elimination produces more
products than substitution, hence creates greater entropy (disorder).
5. Polar solvents, both protic and aprotic, like H2O and CH3CN,
respectively, favor unimolecular reactions (SN1 and E1) by stabilizing
the C+ intermediate. Polar aprotic solvents enhance bimolecular
reactions (SN2 and E2) by activating the nucleophile.

30
 Predicting Reaction Mechanisms

- - - -
good Nu good Nu good Nu very poor Nu
alkyl nonbasic strong base strong bulky base nonbasic
halide e.g., bromide e.g., ethoxide e.g., t-butoxide e.g., acetic acid
- - -
(substrate) Br C2H5O (CH3)3CO CH3COOH

Me SN2 SN2 SN2 no reaction

1 SN2 SN2 E2 (SN2) no reaction

2 SN2 E2 E2 SN1, E1

3 SN1 E2 E2 SN1, E1

Strong bulky bases like t-butoxide are hindered. They have difficulty hitting
the -carbon in a 1 alkyl halide. As a result, they favor E2 over SN2
products.

31
 Predicting Reaction Mechanisms

The nucleophiles in the table on slide 30 are extremes. Some

nucleophiles have basicity and nucleophilicity in between these extremes.
The reaction mechanisms that they will predominate can be interpolated
with good success.
Predict the predominant reaction mechanisms the following table.
-
v. gd. Nu-
.. v. gd. Nu-
.. ..
fair Nu HI
alkyl . .base
moderate .. base
moderate ..
weak base alcohol HBr
halide e.g., cyanide e.g., alkyl sulfide e.g., carboxylate (substrate)
- - - - HCl
(substrate) CN RS , also HS RCOO
4.7
pkb = 6.0 / 7.0
pkb = 9
pkb =

Me SN2 SN2 SN2 Me SN2

1 SN2 SN2 SN2 1 SN2
2 SN2 SN2 E2 2 SN1
3 E2 E2 E2 3 SN1

HCl, HBr and HI are assumed to be in aqueous solution, a protic solvent.

32
 Alkylation of Alkynides

Recall the preparation of long alkynes.

1. A terminal alkyne (pKa = 25) is deprotonated with a very strong base

R-C C-H + NaNH2 R-C C:- Na+ + NH3

2. An alkynide anion is a good Nu:- which can substitute (replace) halogen

atoms in methyl or 1 alkyl halides producing longer terminal alkynes

R-C C: - Na+ + CH3CH2-X R-C C-CH2CH3 + NaX

The reaction is straightforward with Me and 1 alkyl halides and proceeds

via an SN2 mechanism

Alkynide anions are also strong bases (pKb = -11) as well as good Nu:-s,
so E2 competes with SN2 for 2 and 3 alkyl halides
CH3(CH2)3CC:- Na+ + CH3-CH(Br)-CH3 CH3(CH2)3CCCH(CH3)2 (7% SN2)
+ CH3(CH2)3CCH + CH3CH=CH2 (93% E2)

33
 Preparation of Alkyl Halides from Alcohols

Alkyl halides can be prepared from alcohols by reaction with HX, i.e., the
substitution of a halide on a protonated alcohol.

3 - H2O
.. + ..
(Lucas Test) (CH3)3C Cl : + H2O
(CH ) C OH + H Cl (CH3)3C OH (CH3)3C + ..
SN1 33 .. .. 2
.. -
Rapid. 3 C+ is stabilized by protic sovent (H2O) : Cl :
..

OH- is a poor leaving group, i.e., is not displaced directly by nucleophiles.

Reaction in acid media protonates the OH group producing a better leaving
group (H2O). 2 and 3 alcohols react by SN1 but Me and 1 alcohols react
by SN2.
1
.. +
SN2 CH3CH2 OH + H Cl CH3CH2 OH2 CH3CH2Cl + H2O
.. .. -
: Cl :
..
Very slow. Protic solvent inhibits the nucleophile.

Draw the mechanism of the reaction of isopropyl alcohol with HBr.

What products form if concentrated H2SO4 is used in place of aq. HCl?

34
 Preparation of Alkyl Halides from Alcohols

Alternative to using hydrohalic acids (HCl, HBr, HI), alcohols can be

converted to alkyl halides by reaction with PBr3 which transforms OH- into
a better leaving group allowing substitution (SN2) to occur without
rearrangement.
Br
:P
Br
1
.. Br + PBr2
CH3(CH2)4CH2Br
SN2 CH3(CH2)4CH2 OH CH3(CH2)4CH2 O
.. ..
ether H
-
Br

35
 Preparation of Alkenes from Alkyl Halides

On Slide 22 we noted that 2 and 3 alkyl halides can be dehydrohalogenated

with a strong base such as OH- producing an alkene.

KOH in ethanol + KBr + H2O

Br
-HBr

bromocyclohexane + KOH cyclohexene (80 % yield)

Clearly, this is an E2 reaction.

Predict the mechanism that occurs with a Me or 1 alkyl halide.

Predict the products and mechanism that occur with isopentyl chloride and
KOH

36
 Summary of SN /Elimination Reactions

Alkyl Halide Substrate Reactivity:

methyl 1 2 3

H H CH3 CH3

H C Br CH3 C Br CH3 C Br CH3 C Br

H H H CH3

unhindered substrates favor S N2 hindered substrates. S N2 increasingly unfavorable, E2 is OK

do not form a stable C + form increasingly stable C +
do not react by S N1 or E1 favors SN1 and E1. E2 is OK

E2 reactions possible with strong bases

E2 reactions possible with strong bulky bases (t-butoxide)

37
 Summary of SN /Elimination Reactions

Reactivity of Nucleophiles:
HS- CN- I- CH3O- HO- NH3 Cl- H2O

125,000 125,000 100,000 25,000 16,000 1000 700 1

good nucleophiles which are good nucleophiles which are

weak bases favor SN reactions also strong bases favor elimination

Note that poor nucleophiles that are also weak bases (H2O, ROH, CH3COOH,
etc.) do not undergo any reaction unless a C+ is formed first. If a C+ can form
(as with a 2, 3, any benzylic, or any allylic halides), then E1 and SN1
generally occur together.
Leaving Group Activity:

pKb = 23 pKb = 22 pKb = 21 pKb = 11 pKb = -1.7 pKb = -2 pKb = -21

I- Br - Cl- F- HO- RO- H2N-
30,000 10,000 200 1 0 0 0

good leaving groups favor both poor leaving groups make both
substitution and elimination reactions substitution and elimination
reactions unfavorable
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