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ALKYL HALIDES
by
Parinya Theramongkol
Department of Chemistry
Khon Kaen University
Structure : The Functional Group
R-X
Alkyl group
Halogen atom
เป็ นตัวกำหนดลักษณะเชิงโครงสร้ ำง
และควบคุมคุณสมบัตขิ องสำร
The Functional Group
Classification & nomenclature
แบ่งตามชนิดของอะตอมคาร์บอนที่แฮโลเจนเกาะอยู่
H
R
C
R
R
X
R
C
X
R
C
X
H
H
R
P rim ary
(1 o )
S ec o n d ary
(2 o )
T e r ti a r y
(3 o )
Common vs IUPAC names
common
C H 3C H 2C H 2C H 2B r
(1o)
Cl
C H 3C H C H 3
(2o)
CH3
C H 3C H C H 2C l
(1o)
IUPAC
n-Butyl bromide
1-Bromobutane
Isopropyl chloride
2-Chloropropane
Isobutyl chloride
1-Chloro-2-methylpropane
(2o)
C H3
C H 3C H 2C H C H C H
3-Chloro-2-methylpentane
3
Cl
(3o)
CH3 CH3
C H 3C H 2C C H 2C H C H
3
4-Bromo-2,4-dimethylhexane
Br
CH
3
C H 2C H
C H 3C H C H C H 2C H C H
I
3
3
?
PREPARATION
1. From alcohols
R -O H
H X or PX 3
R -X
c o n c .H B r
OH
n -P r o p y l a lc o h o l
Br
n -P r o p y l b r o m id e
OH
Br
P B r3
1 -P h e n y le t h a n o l
1 -B r o m o -1 -p h e n y le t h a n e
2. Halogenation of certain hydrocarbons
X2
R -H
H 3C
CH
R -X + H X
3
C l 2 , h e a t o r lig h t
H 3C C H 3
N e o p e n ta n e
CH
T o lu e n e
3
H 3C
CH
H 3C
C H 2C l
3
N e o p e n t y l c h lo r id e
B r 2 , r e f lu x , lig h t
C H 2B r
B e n z y l b r o m id e
3. Addition of hydrogen halide to alkenes
HX
C
C
C
H
C
X
4. Addition of halogens to alkenes and alkynes
X2
C
C
C
X
2X 2
C
C
X
C
X
C
X
X
C
X
5. Halide exchange
R -X
+
I
R -I + X
Notes on preparation :
•The most general and practical way to make RX is to
prepare from alcohols.
•RXs are almost never prepared by direct halogenation
of alkanes.
•RI is often prepared from the corresponding bromide or
chloride by treatment with a solution of NaI in acetone.
REACTIONS
1.Nucleophilic aliphatic substitution
R -W + : Z
S u b str a te
N u c le o p h ile
R
R -Z
C
Electrophilic site
d+ C
W
+
L e a v in g g r o u p
d-
X
Nucleophilic site
Nucleophilic substitution
R -X
+
:O H
+
H 2O
+
:O R '
-
-
+ -C C R '
-
+
:I
+
:C N
-
R -O H
+
X
-
A lc o h o l
R -O H
A lc o h o l
R -O R '
E th e r
R C CR'
A lk y n e
R -I
A lk y l io d id e
R -C N
N it r ile
See more examples on text p.174
2. Dehydrohalogenation : elimination
b a se
C C
H X
C C
3. Preparation of Grignard reagent
d r y e th e r
R -X
+
M g
R M gX
4. Reduction
R -X + M
+ H
RH + M ++ X
+
M = Li , Na, K
Br
Br
N a , C H 3O H
7 ,7 -d ib r o m o n o r c a r e n e
N orcaren e
M g
Cl
t-B u t y l c h lo r id e
D 2O
M gC l
D
2 -D e u t e r o -2 -m e t h y lp r o p a n e
The SN2 Reaction: substitution nucleophilic bimolecular
C H 3B r
+
OH
-
C H 3O H + B r
-
Kinetics :
the reaction rate a the concentrations of both reactants
r a t e = k [C H 3 B r ][O H - ]
Second - order kinetics
Mechanism & stereochemistry of SN2 reaction
HO
-
C Br
d
HO
C
d
Br
HO C
Br
-
tr a n s itio n s ta te
p e n t a v a le n c e c a r b o n a t o m !
Nucleophile attacks on the back-side of the C-X bond
Bond-making and bond-breaking occur simultaneously
Product has a complete inversion of configuration
C 6H
H
C
CH
13
Br
3
(-)-2 -B r o m o o c t a n e
[ a] = - 3 9 .6 o
N aO H
SN2
HO
C 6H
13
C
H
CH
3
(+ )-2 -o c t a n o l
[ a] = + 1 0 .3 o
SN2 Reactivity. Steric hindrance
R -B r
r e la t iv e
r a te
(S N 2 )
+
Cl
-
DM F
R -C l +
H
H
CH3
H C B r > H 3C C B r > H 3C C B r
H
H
H
Br
-
CH3
> H 3C C B r
CH3
M e th y l
E th y l
I so p r o p y l
te r t-B u t y l
37
1 .0
0 .0 2
0 .0 0 0 8
Reactivity :
CH3W > 1o > 2o > 3o
The SN1 Reaction: substitution nucleophilic unimolecular
H 3C
H 3C
Br +
OH
-
H 3C
H 3C
H 3C
O H + Br
-
H 3C
Kinetics :
the reaction rate a the concentration of alkyl halide
r a t e = k [R B r ]
First - order kinetics
Mechanism & stereochemistry of SN1 reaction
H 3C
H 3C
s lo w
Br
H 3C
H 3C
Br
-
(1 )
H 3C
r e a c tiv e in te r m e d ia te
c a r b o c a t io n
CH3
H 3C
CH3
+ OH
-
fa st
H 3C
H 3C
H 3C
OH
H 3C
Step 1 : ionization = rate determining step
Step 2 : combination
(2 )
CARBOCATION
A reactive intermediate which is a group of
atoms that contains a carbon atom bearing
only 6 electrons.
H 3C
H 3C
io n iz a tio n
H 3C
Br
CH3
Br
H 3C
te tr a h e d r a l
-
H 3C
t r ig o n a l
Structure of carbocation
sp2
empty p-orbital
CH3
H 3C
120o
CH
3
Mechanism & stereochemistry of SN1 reaction
Ionization of the C-X bond to generate a carbocation
is the rate determining step.
Reaction proceeds with racemization.
CH
R
CH
3
C
W + C H 3O H
C 2H
5
Optically active
R
3
C
OCH
C 2H
5
3
+ W
-
+ H +
Opposite configuration ;
Lower optical purity
SN1 : racemization plus inversion
H 2O
R
H
X
H 3C
io n iz a tio n
H2O
b
a
R
H
+
X
CH
c a r b o c a t io n
-
3
R
HO
R
H
CH
H
3
(a) Inversion
(predominates)
OH
H 3C
(b) retension
SN1 Reactivity. Ease of formation of carbocation
R -W
+ C F 3C O O H
CH3
H 3C C W
CH3
Relative
Rate
(SN1)
O
R -O C C F 3 + H -W
t-B u t y l
6
> 10
Reactivity in SN1 :
CH3
> H 3C C W
H
I so p r o p y l
1 .0
H
> H 3C C
H
W
H
> H C
H
E th y l
-4
< 10
3o > 2o > 1o > CH3W
Rate of formation of C+ : 3o > 2o > 1o > CH3+
M e th y l
-5
< 10
W
Stabilization of C+ : Polar effects
Polar effects : ผลทีเ่ กิดขึน
้ ตรงจุดเกิดปฏิกริยา อันเนื่องมาจาก
การให้ หรื อรับอิเล็คตรอนของกลุ่มข้ างเคียง
Charge dispersion
G
C
stability
G
C
G = e- donating group
G = e- withdrawing group
Disperses charge
Stabilizes cation
intensifies charge
Destabilizes cation
Rearrangement of carbocations
A less stable C+ can rearrange itself in order to
become a more stable C+.
O C 2H 5
Br
C 2H 5O H
SN1
C 2H 5O
SN2
rearrangement
-
Br
O C 2H 5
No rearrangement
O C 2H 5
C 2H 5O H
SN1
rearrangement
Migratory mode : 1,2-shifts
Two common migrations are a hydride shift and
an alkyl shift
A hydride shift
+
C
H
C
C
C
C
C
H
C
C
R
H
An alkyl shift
+
C
R
C
C
C
R
SN2 vs. SN1
SN2
(a) second-order kinetics
(b) complete stereochemical inversion
(c) absence of rearrangement
(d) the reactivity sequence CH3W > 1o > 2o > 3o
SN1
(a) first-order kinetics
(b) racemization
(c) rearrangement
(d) the reactivity sequence 3o > 2o > 1o > CH3W