Download 4 Nucleophilic substitution reactions. Cleavage reaction (elimination).

TASHKENT MEDICAL ACADEMY
Department of Bioorganic and Biological Chemistry
Bioorganic chemistry
I COURSE
SUBJECT: nucleophilic substitution reactions. Cleavage reaction
(elimination)
LECTURE№4
LECTURER :
PROFESSOR
A.D.DZHURAEV
PURPOSE OF LECTURES:
Develop the ability to predict the reactivity of
alcohols and halogen derivatives of hydrocarbons in
the competitive nucleophilic substitution and
elimination depending on the structure of the
substrate and the type of reagent.
The questions of:
– 1. Common definitions of biologically important
compounds such as R-X (alcohols, halides,
amines, thiols, etc.)
2. Familiarize with finding the reaction centers in
compounds such as R-X
3. Consider the reaction proceeds by unimolecular
and bimolecular mechanism
4. Consider the cleavage reaction (elimination)
5. Teach to predict in advance the reaction in
compounds such as R-X on the mechanism of
nucleophilic substitution or elimination
Derivatives of saturated hydrocarbons
involved in the reactions SN
1.
2.
3.
4.
5.
Halogenated R – Hal
Alcohols R – OH
Thiols R – SH
Amines R – NH2
Ethers R – OR
The reaction takes place at SN mechanism
R-Cl + Na – OH
R-Br + Na – SH
R-Cl + Na – OR
R – OH + Na – Cl
R – SH + Na – Br
R – OR + Na – Cl
Reaction centers in compounds such as R-X
electrophile. center
acid sites
(Н)
+
С
+
СН acid sites
С
+
Х
(Н) +
..
basic center
Nucleophile. center
Framework mechanism nucleophilic
substitution reactions
Nu - +
C
+
X
-
C
Nu + X
The leaving group
Leaving group (X), compared with a nucleophile (: Nu-) should be
more sustainable, has less energy.
Good leaving group : I-> Br-> Cl-> F->.
Bad leaving group: HO-, RO-, NH2-, CH3-, H
1. For primary alkyl halides, alcohols and amines (R-CH2X)
character SN2- Mechanism:
R
CH2 Br
+
NaOH
R
R
R
-
H O
C
+
H
Nu- - attack
B r
H
H O
R
 -
C
H
CH2 OH + NaBr
B r
H
transition state
C
H
O H
H
+
B r
-
2. For tertiary alkyl halides, alcohols and amines Character SN1
Mechanism :
R
R' C
R ''
R
R' C
R ''
B r + N aO H
Br
slowly
R
R' C
R ''
R
R' C
R ''
- -O H
Br
quickly
O H + N aB r
R
R' C
R ''
O H + Br
SN1 MECHANISM
For tertiary alkyl halides, alcohols and amines
CHARACTERISTIC SN1 :
R
R'
C
R
B r
R '
+ N aO H
R ''
C
R ''
O H
+ N aB r
R ''
R
R'
C
R
R'
B r
slowly
C
R ''
-
B r
- O H
quickly
R
R'
C
R ''
O H
+ B r
for secondary connections character/ SN1-, SN2/ :
In these compounds, depending on the nature of the
leaving group and the solvent reaction proceeds via two
mechanisms/ SN1-, SN2- /
R CH X
R
R CH Hal
R
Elimination reaction (Cleavage) Е
In the split-off halogenated alkyl halides proceeds in an alkaline medium(-ОН, OR)


C
C
H
X ( J)
C C
 --
+
H X
Weaned water in alcohol departure from the acidic environment of ( end. H2SO4
or H3PO4)


C
C
H
OH (-J)
-
C C
+
H OH
EXAMPLES:
R CH2 CH2 Br + NaOH
R CH2 CH2 OH + NaBr
+ H2O
+ R'
OH
2CH2 CH2 + NaBr + H OH
CH 3 CH
CH 3 CH
Br
CH 2 CH 3
+K
+ R'
OH
CH
CH 3
80 %
+
OH 20 %
CH 2 CH
CH 2
CH 3
2 HBr Правило
Зайцева