GRIGNARD REAGENTS

ALKYLMAGNESIUM HALIDES, R-Mg-X, ARE

KNOWN AS GRIGNARD REAGENTS.
GRIGNARD REAGENTS ARE PREPARED BY
REACTING ALKYL HALIDES WITH EXCESS
MAGNESIUM METAL IN DRY ALCOHOL-FREE
DIETHYL ETHER OR TETRAHYDROFURAN
(THF). DIETHYL ETHER AND THF ARE
SOLVENTS.
CH3CH2 O CH2CH3
diethyl ether

O
tetrahydrofuran
(THF), a cyclic ether

GRIGNARD REAGENTS
PREPARATION
R-X + Mg R-Mg-X
(radical mechanism)
Ease of formation follows the trends shown below
R-I > R-Br > R-Cl.
CH3X > C2H5X >C3H7X
Grignard reagents are usually closely associated
with two molecules of the ethereal solvent in which
Et
they have been prepared.
O Et
R
Mg
X

O Et
Et

REACTIONS OF GRIGNARD REAGENTS

Most reactions of Grignard reagents fall into
one of two categories.
1. Reactions with compounds containing
active hydrogen, e.g. H2O, ROH.
2. Addition to epoxides and to multiply
bonded groups.
C C
EPOXIDE
O

C O

C S

S O

N O

N
3

REACTIONS OF GRIGNARD REAGENTS

1.

Reactions with compounds containing active hydrogen,

e.g. H2O, ROH.
The Mg-C bond in a Grignard reagent,
e.g. methylmagnesium bromide, is polarized as shown.
H
H

MgBr

The carbon attached to Mg bears a partial negative charge.

This carbon is NUCLEOPHILIC, and is subject to attack by
electrophiles.
An ELECTROPHILE is a chemical species which seeks
electrons.
4

REACTIONS OF GRIGNARD REAGENTS

1.

Reactions with compounds containing active H, e.g. H2O, ROH.

The carbon bonded to Mg in Grignard reagents is nucleophilic. The
hydrogens on the O-H groups in H2O and alcohols (ROH) are effective
ELECTROPHILES.
n-octylmagnesium bromide + H2O:
O
H
H
CH3(CH2)6

C
H

H
H
Mg Br

CH3(CH2)6

H
CH + MgBr

A similar reaction occurs with alcohols, e.g. ethanol:

O
H
H
CH3(CH2)6

Et
H
Mg Br

What would the reaction be with D2O?

CH3(CH2)6

Et
CH + MgBr

REACTIONS OF GRIGNARD REAGENTS

2. Addition to epoxides and to carbonyl groups
(aldehydes, ketones, esters, CO2).
Experimental procedure
(i)

A solution of the epoxide/aldhyde/ketone/

ester in anhydrous Et2O or THF is added
to the Grignard reagent in Et2O or THF.

(ii)

After a short time, dilute acid or aqueous

NH4Cl (a proton source) is added to the
reaction mixture. The product of the
6
reaction is then isolated.

REACTIONS OF GRIGNARD REAGENTS

2. (a)

Addition to epoxides.

Epoxides, also known as oxiranes, are three-membered

cyclic compounds. The ring consists of two carbon atoms
and one oxygen atom. The simplest epoxide is
ethylene oxide. H
H
C C
H
O H
The carbons of the ring can bear substituents other than
hydrogen, e.g.
H
CH
H

C C
O H

The three-membered ring is highly strained, as the angles

between the oxygen and carbon atoms are significantly less
than the tetrahedral angle of ~ 109o. Epoxides therefore
7
open readily, and are quite reactive.

REACTIONS OF GRIGNARD REAGENTS

2.

(a)

Addition to epoxides
n-octylmagnesium bromide + ethylene oxide

H2C CH2
O
H
(i) CH3(CH2)6 C
Mg Br
H

H
CH3(CH2)6 C CH2-CH2-O-MgBr
H

H
H3O
(ii) CH3(CH2)6 C CH2-CH2-O-MgBr
H

H
CH3(CH2)6 C CH2-CH2-O-H
H
+ Mg(OH)Br

The product is a 1o alcohol. The carbon chain of the alcohol

is two carbons longer than the carbon chain of the alkyl
group in the Grignard reagent.
Grignard reagents react with epoxides 1o alcohols,
with 2 carbon homologation.
8

REACTIONS OF GRIGNARD REAGENTS

2. Addition to carbonyl compounds
The difference in electronegativity between oxygen
and carbon causes the carbon-oxygen bond of
carbonyl groups to be polarized as shown.

The carbon atoms of carbonyl groups are

ELECTROPHILIC, and will be attacked by the
nucleophilic carbons of Grignard reagents.
9

REACTIONS OF GRIGNARD REAGENTS

2.

Addition to carbonyl compounds

ALDEHYDES react with Grignard reagents to yield 2o
alcohols. An example is this reaction is shown.
n-octylmagnesium bromide + propanal
H
CH3CH2
H
CH 3(CH 2)6 C
H

O
(i)

CH3CH2 C
H
CH 3(CH2)6

Mg Br

H
CH3CH2 C
H

CH 3(CH2)6

C
H

OH

C Mg Br
H

(ii) H3O

+ Mg(OH)Br
10

REACTIONS OF GRIGNARD REAGENTS

2. Addition to carbonyl compounds
ALDEHYDES react with Grignard reagents to
yield 2o alcohols. The general reaction is:
H
R-MgX +

R'

R' H
C O Mg X
R

(i)

(ii) H3O

R' H
C OH
R
+ Mg(OH)X

KETONES add to Grignard reagents to produce 3o

alcohols. The general reaction is shown.
R''
R-MgX +

R'

R''

(i)

R'
R

C O Mg X

R''
(ii) H3O

R'

C OH
R

11
+ Mg(OH)X

REACTIONS OF GRIGNARD REAGENTS

2.

Addition to carbonyl compounds

An example of the reaction between ketones and Grignard
reagents is the addition of
methylmagnesium bromide to 3-hexanone.
CH3CH2

C
O
CH3CH2CH2
H
H C
Mg I
H

CH3CH2
(i)

CH3CH2CH2 C
H3C

O
Mg

(ii) H3O
CH3CH2
CH3CH2CH2 C OH + Mg(OH)I
H3C

12

REACTIONS OF GRIGNARD REAGENTS

2.

Addition to carbonyl compounds esters

The addition of Grignard reagents to esters is illustrated
by the reaction between
ethyl acetate and n-propylmagnesium bromide.

CH3

C
CH3CH2O

CH3
C
EtO

ethyl acetate

H
CH3CH2 C MgBr
H
n-propylmagnesium bromide

13

REACTIONS OF GRIGNARD REAGENTS

2. Addition to carbonyl compounds esters
ethyl acetate+ n-propylmagnesium bromide

CH3

C
EtO
H
CH3CH2 C
Mg Br

CH3

CH3
EtO C
H
C
CH3CH2 H

EtO

MgBr

Pr

O
MgBr

electrophilic
fairly good
leaving group

14

REACTIONS OF GRIGNARD REAGENTS

2.

Addition to carbonyl compounds esters

ethyl acetate+ n-propylmagnesium bromide
The initially formed adduct reacts with a second equivalent of the
Grignard reagent. After workup a 3o alcohol is obtained.
Two of the alkyl groups on the 3o alcohol are identical, and
originate from the Grignard reagent.
CH3

CH3
EtO

C
Pr

Br

O
MgBr

H
Mg
C CH2CH3
H

O
H3O
H MgBr
C CH2CH3
H
+ EtOMgBr

Pr

CH3
Pr C OH
Pr
+ Mg(OH)Br

15

REACTIONS OF GRIGNARD REAGENTS

2.

Addition to carbonyl compounds

carbon dioxide (dry ice or CO2 gas)
The addition of methylmagnesium iodide to CO2
is illustrative. The product is a carboxylic acid.

H
H

C
H

Mg I

O
(i)

C
H3C

O
Mg I

(ii) H3O

OH

+ Mg(OH)I

H3C

The general reaction is:

RMgX

(i) CO2
(ii) H3O

RCOOH + Mg(OH)X
16

CARBONYL COMPOUNDS
1. Acyclic aldehydes and ketones with saturated
carbon chains have the general formula
CnH2nO. They contain the oxo,
C O
or carbonyl group.
R
C O
2. In aldehydes,
one of the
H
available valencies of the carbonyl carbon is
occupied by a hydrogen, therefore the
aldehyde group always occurs at the end of a
chain.
R
3. In ketones, R' C O R and R are alkyl groups,
so the keto group occurs within a chain.
17

CARBONYL COMPOUNDS
4.

Bonding
The carbonyl carbon is sp2 hybridized.

In a ketone, it is connected by
two (sigma) bonds to the
C
adjacent carbon atoms
O
by sp2 (C) sp3 (C) overlap.
A third bond connects the
C
carbonyl carbon to the oxygen
atom by by sp2 (C) 2p (O) overlap.
The bond is formed by 2p(C) 2p(O) overlap.
Carbonyl groups are flat. The electrons are above and
below the trigonal plane formed by the sp2 orbitals of the
carbonyl carbon.
18

CARBONYL COMPOUNDS
6.

The electronic configuration of oxygen is

1s2, 2s2, 2p4. Oxygen has six outer sphere electrons,
two of which are involved in covalent bonding to carbon;

the remaining four electrons comprise two unshared

(non-bonded) pairs.
7(a) Oxygen is much more electronegative than carbon.
The carbonyl group is polarized.

19

CARBONYL COMPOUNDS
7 (b) It is also possible to draw a dipolar
resonance form of a carbonyl group.

The structures on either side of a straight

two-headed arrow are resonance forms of the
same chemical entity; they differ only the
location of electrons, and can be interconverted
by the movement of curly arrows.
A carbonyl group is a HYBRID of the two
resonance forms shown.
20

CARBONYL COMPOUNDS
8. As a result of the high electron density on
the oxygen atom of carbonyl groups,
carbonyl compounds participate in
hydrogen bonding with compounds which
contain active hydrogen.
O

C
R

R'

Aldehydes and ketones of low molecular

weight are therefore soluble in water. 21

CARBONYL COMPOUNDS - nomenclature

To name an aldehyde using the IUPAC system,
the final e in the name of the parent alkane is
replaced by al
CH3

C O

ethanal (acetaldehyde)

H
Cl
H3C

H
C

2-chloropropanal
C O

H
CH3CH CHCHO 2-butenal

22

CARBONYL COMPOUNDS - nomenclature

Ketones are named by replacing the e in the
name of the parent alkane with one. If necessary,
the position of the oxo group is indicated by a number.
O
CH 3
cyclohexanone

CH 3

O
C

CH 2CH 2CH 3

2-pentanone

CH 2CH 3

butanone
(methyl ethyl ketone)

CH 3

O
C

CH 3
CH 3
propanone
(acetone)
O
H
C
CH 3
C

H
2,4-pentanedione
the 'e' is retained in dione names
23

PREPARATION OF CARBONYL COMPOUNDS

A. Preparation of aldehydes
1.Aldehydes may be prepared by oxidation
H
H
of 1o alcohols
[O]
R

C OH
H

C O + "2H"

1o alcohol

aldehyde

2.Reduction of acyl chloride yields aldehydes

R

R
C O + "H "
Cl
an acyl chloride,
also known as
an acid chloride

C O + Cl
H
aldehyde
24

PREPARATION OF ALDEHYDES
1.

Oxidation of 1o alcohols: RCH2OH RCHO

In general, aldehydes are more easily oxidized than
alcohols.
RCHO RCOOH occurs more readily than
RCHO.
RCH2OH
Therefore, very mild oxidizing agents must by used for
the transformation RCH2OH RCHO.
Examples of mild oxidizing agents are:
(a) chromium trioxide-pyridine complex,
CrO3 . 2
CrO3.2py;
(b) manganese dioxide, MnO2

N
25

PREPARATION OF ALDEHYDES
1.

Oxidation of 1o alcohols: RCH2OH RCHO

H
Mild oxidizing agents
CrO3.2py
R C OH
are used.
H
R

H
C OH

MnO2

H
C O
R
H
C O
R

You are not required to know the mechanisms of these

reactions.
With strong oxidizing agents, e.g. KMnO4, H2CrO4,
1o alcohols are oxidized to carboxylic acids.
R

H
C OH

H
1o alcohol

KMnO 4

R
C O
HO
26

carboxylic acid

PREPARATION OF ALDEHYDES
2. Reduction of acyl chlorides: RCOCl RCHO
Lithium tri-t-butoxyaluminum hydride is often used
for this reduction.
CH3
H3C C O

Li

CH3
Al O C CH3

O
CH3
CH3
H3C C CH3
CH3

LiAlH[OC(CH3)3]3 or LiAlH(OtBu)3;
this is a mild hydride reducing agent.

27

PREPARATION OF ALDEHYDES
2. Reduction of acyl chlorides
R

LiAlH(OtBu)3

C O

.
R
C O
H

Cl

A partial, simplified mechanism for this reaction:

R
C
Cl

C
Cl

O Li

R
C O
H

+ LiCl

"H "
28