Grignard Reagent
Introduction of Organometallic Compound
Organometallic compounds are the
organic compound in which a metal atom
is directly to carbon atom through covalent
bond or ionic bond.
For example C-M or C- M+
Eg R-MgX, R2CuLi, R2Zn
(Where C is a carbon atom of an organic
Molecule and M is a metal atom)
If the metal atom is attached to oxygen ,
nitrogen , sulphur etc ,then organic compound is
not regarded as an organometallic compounds .
RONa ,
CH3COONa , CH3COOAg, RSK ,RNHK
(N-Alkylpotassiumamide), (CH3COO)4Pb etc
Note
It should be noted that (CH3)4Si
Tetramethylsilane is also not an organometallic
compound because silicon is a non metal.
Most important examples of organometallic
compounds are Grignard’s reagent.In Grignard
reagent ,the carbon and magnesium atoms are
bonded with each other through polar covalent
bond and magnesium is attached to halogen by
ionic bond.
C-Mg+X- (Functional part of Grignard
reagent molecule)
In organomettalic compounds, the metal
atom can be bonded to carbon atom of a
hydrocarbon radical(Saturated,
unsaturated , aliphatic,alicyclic or
aromatic) or carbon atom of heterocyclic
radical
Saturated Aliphatic Griganard
,s Reagent
R-MgX (Alkyl magnesium halide)
CH3MgX (Methyl magnesium halide )
Aromatic Grignard’s Reagent
C6H5MgX (Phenyl magnesium halide)
C6H5CH2MgCl (Benzyl magnesium halide)
Preparation
RX + Mg RMgX
Dry and pure ether
Ether is used as a solvent because it is a
Lewis base that donates its lone pair of
electrons to electron deficient magnesium
atom , therefore providing stability to the
Grignard’s reagent by completing the
octet on magnesium atom
14.6
Synthesis of Alcohols Using
14_06_10.html.ppt
Grignard Reagents
Grignard reagents act as nucleophiles
toward the carbonyl group
d+ diethyl
d– R R C
C ether
MgX O •• •• O •• + MgX
•• •• –
H3O+
two-step sequence
R C
gives an alcohol as
the isolated product •• OH
••
Grignard reagents react with:
formaldehyde to give primary alcohols
aldehydes to give secondary alcohols
ketones to give tertiary alcohols
esters to give tertiary alcohols
Grignard reagents react with:
formaldehyde to give primary alcohols
Grignard reagents react with formaldehyde
H
H d+ H diethyl
d– R R C H
C ether
•• O ••
+
MgX O •• MgX
•• •• –
H3O+ H
product is a R C H
primary alcohol
•• OH
••
Example
Mg
Cl MgCl
diethyl
ether
H
C O
H
H3O+
CH2OH CH2OMgCl
(64-69%)
Grignard reagents react with:
formaldehyde to give primary alcohols
aldehydes to give secondary alcohols
Grignard reagents react with aldehydes
H
H d+ R' diethyl
d– R R C R'
C ether
MgX O •• •• O •• + MgX
•• •• –
H3O+ H
product is a R C R'
secondary alcohol
•• OH
••
Example
Mg
CH3(CH2)4CH2Br CH3(CH2)4CH2MgBr
diethyl
ether H3C
C O
H
H3O+
CH3(CH2)4CH2CHCH3 CH3(CH2)4CH2CHCH3
OH OMgBr
(84%)
Grignard reagents react with:
formaldehyde to give primary alcohols
aldehydes to give secondary alcohols
ketones to give tertiary alcohols
Grignard reagents react with ketones
R"
R" d+ R' diethyl
d– R R C R'
C ether
•• O •• +
MgX O •• MgX
•• •• –
H3O+ R"
product is a R C R'
tertiary alcohol
•• OH
••
Example
Mg
CH3Cl CH3MgCl
diethyl
ether O
HO CH3 ClMgO CH3
H3O+
(62%)
14.7
Synthesis of Alcohols
Using Organolithium Reagents
Organolithium reagents react with
aldehydes and ketones in the same
way that Grignard reagents do.
Example
O
H2C CHLi + CH
1. diethyl ether
2. H3O+
CHCH CH2
OH
(76%)
14.8
Synthesis of Acetylenic Alcohols
Using Sodium Salts of Acetylenes
NaNH2
HC CH HC CNa
NH3
O HO C CH
1. NH3
HC CNa +
2. H3O+
(65-75%)
Using Acetylenic Grignard Reagents
CH3(CH2)3C CH + CH3CH2MgBr
diethyl ether
CH3(CH2)3C CMgBr + CH3CH3
1. H2C O
2. H3O+
CH3(CH2)3C CCH2OH
(82%)
14.9
Retrosynthetic Analysis
Retrosynthetic analysis is the process by
which we plan a synthesis by reasoning
backward from the desired product (the
"target molecule").
Retrosynthetic Analysis of Alcohols
OH
Step 1 Locate the carbon that bears the
hydroxyl group.
Retrosynthetic Analysis of Alcohols
OH
Step 2 Disconnect one of the groups
attached to this carbon.
Retrosynthetic Analysis of Alcohols
OH
Retrosynthetic Analysis of Alcohols
MgX
What remains is the combination of Grignard
reagent and carbonyl compound that can be
used to prepare the alcohol.
Example CH3
C CH2CH3
There are two OH
other
possibilities.
Can you see
them? CH3MgX
C CH2CH3
Synthesis
Mg, diethyl ether
CH3Br CH3MgBr
1. C CH2CH3
2. H3O+
CH3
C CH2CH3
OH
14.10
Preparation of Tertiary Alcohols
From Esters and Grignard Reagents
Grignard reagents react with esters
•• R'
R' d+ OCH diethyl
d– R ••
3 ••
C ether R C OCH3
••
MgX O •• •• O •• + MgX
•• •• –
but species formed is
unstable and dissociates
under the reaction
conditions to form a ketone
Grignard reagents react with esters
•• R'
R' d+ OCH diethyl
d– R ••
3 ••
C ether R C OCH3
••
MgX O •• •• O •• + MgX
•• •• –
–CH3OMgX
this ketone then
goes on to react with R R'
a second mole of the C
Grignard reagent to
give a tertiary O ••
••
alcohol
Example
O
2 CH3MgBr + (CH3)2CHCOCH3
1. diethyl ether
2. H3O+
Two of the groups
OH attached to the
tertiary carbon
(CH3)2CHCCH3
come from the
CH3 Grignard reagent
(73%)
