Organic
Synthesis
Notation
Chemistry
Advanced Higher
Organic molecule synthesis
 The
construction of compounds via organic
reactions.
 All chemical reactions involve the breaking
and making of bonds.
 Curly arrows give an impression of bonds
breaking and bonds being made.
 Curly arrows are specifically used to show the
movement of electrons, both singly and in
pairs.
 Curly arrows should not be used for any other
purpose.
Curly arrows
 In
order to represent the movement of an
electron pair, this arrow is used:
 In
order to represent the movement of a
single electron, this arrow is used:
Curly arrows
 The
arrow tail starts from where the electron
pair/electron originates.
 The arrow head points to where the electron
pair/electron finishes.
 The reaction between ethene and hydrogen
bromide below illustrates this:
C2H4 + HBr
CH3CH2Br
Curly arrows
H2C
H
CH2

Br

H
H2C

C+
H
H
Br -
Two electrons move from the
double bond in ethene and a new
bond forms with the hydrogen from
the hydrogen bromide.
At the same time the pair of
electrons in the hydrogen bromide
bond move to the bromine atom.
Note that the head of the arrow
points between the carbon and
hydrogen, as that is where the
new bond is formed.
Curly arrows

+
H2C
C
H
.. -
H

H
Br

The second stage of this reaction
allows us to illustrate how to use
curly arrows for a lone pair of
electrons.
The first stage of the reaction has
left us with a positive charge on
the carbon and a negative bromide
ion.
Notice the head of the arrow is
pointing to a place between the
carbon and the bromide ion since
this is where the bond is formed.
Bond fission
 Bond
breaking is also known as bond fission.
 There are two ways in which bond fission can
happen
Homolytic
Heterolytic
Homolytic bond fission
 The
two shared electrons forming the bond
separate equally, one going to each atom.
 In the case of hydrogen bromide:
H
:
Br
 Remember
H• + •Br
the single-headed arrow shows
movement of only one electron.
Homolytic bond fission
H
 The
:
Br
H• + •Br
dot (•) beside each atom represents the
unpaired electron.
 The atoms are electrically neutral because each
has equal numbers of protons and electrons.
 However, the atoms are highly reactive because
the unpaired electron has a strong tendency to pair
up with an electron from another atom or molecule.
Homolytic bond fission
 Highly
reactive atoms or groups of atoms
containing unpaired electrons are called free
radicals.
 Because of their high reactivity free radicals
only exist as reaction intermediates.
 Free radicals are most likely to be formed
when the bond being broken is non-polar, ie
has electrons that are more or less equally
shared.
Free-radical chain reaction
 The
reaction between methane and chlorine
in which one of the hydrogen atoms in
methane is replaced by one chlorine atom.
 This reaction is known as a free-radical chain
reaction and has three distinct steps:



initiation
propagation
termination.
Free-radical chain reaction
 Initiation
UV light is required to split the chlorine
molecules into two chlorine free radicals:
UV
Cl . : . Cl
Free-radical chain reaction
 Propagation
(two steps)
Firstly, a chlorine radical can collide with a
methane molecule, resulting in removal of a
hydrogen atom, forming a methyl radical:
H
C
H
H
.
.
ClCl
H
.
H
H
Free-radical chain reaction
 Propagation
(two steps)
In the second step, the methyl radical collides
with another chlorine molecule, producing
more chlorine radicals, which keeps the
reaction repeating:
H
.
C
Cl Cl
H
Cl
H
H
H
Free-radical chain reaction
 Termination
(three possible steps)
Each of these steps removes the radicals
from the process.
i. Two chlorine radicals form a chlorine
molecule.
ClCl. . Cl
Free-radical chain reaction

Termination (three possible steps)
Each of these steps removes the radicals from the
process.
ii. A methyl radical joins a chlorine radical to form
chloromethane.
H
C.
H
H
.Cl
Cl
Free-radical chain reaction
 Termination
(three possible steps)
Each of these steps removes the radicals
from the process.
iii. Two methyl radicals form ethane.
HH
HH
HC C
H
HH
.
CHC H
HH
H
Heterolytic bond fission
 If,
when the bond breaks, one atom retains
both of the electrons from the former covalent
bond then an ion pair is formed.
H
:
 Note
Br
H+ + Br -
the double-headed arrow showing
movement of two electrons.
Heterolytic bond fission
 Heterolytic
fission is more likely when a bond
is already polar.
 Bromomethane contains a polar carbon-tobromine bond and under certain conditions
this can break heterolytically.
H
C
H
H

+

Br
H
-
C
H
H
+
+ Br -
Heterolytic bond fission
H
C
H

+

H



It should be noted the CH3+ ion contains a
positively charged carbon atom.
The CH3+ ion is an example of a
carbocation (also called a carbonium
ion).
Heterolytic fission can lead to the formation
of ions containing a negatively charged
carbon atom.
These ions are called carbanions.
Both these types of ions tend to be unstable
and highly reactive. Consequently, they only
exist as short-lived reaction intermediates.
Heterolytic bond fission
o In reactions involving heterolytic bond fission, attacking groups
are classified as nucleophiles or electrophiles.
Nucleophiles






Nucleophile means ‘nucleusloving’.
Electron-rich species that seek
out electron-deficient sites.
Examples: OH− , Cl−, Br−, CN−,
NH3, H2O.
Atoms or groups of atoms that
are attracted to atoms bearing a
positive charge.
Capable of donating and
sharing electrons to form a new
bond.
May be uncharged molecules or
negative ions, but must have at
least one lone pair of electrons.
Electrophiles





Electrophile means ‘electronloving’.
Electron-deficient species that
seek out electron-rich sites.
Examples: H+, Cl+, Br+, I+, NO2+,
CH3+, CH3CO+, SO3.
Usually positive ions or
uncharged molecules with one
atom that has a slightly positive
charge.
Capable of accepting and
sharing electrons to form a new
bond.
Heterolytic bond fission
o The terms electrophile and nucleophile do not apply only to ions.
o Partial negative and positive charges can be found in polar
compounds. These partial charges can also act as electrophilic
or nucleophilic centres.
H
C
H

+
Nucleophile

-
Br
H
Electrophile
Nucleophilic substitution reactions
 Nucleophilic
substitution reactions involve an
attacking nucleophile replacing a leaving
group.
 Such substitution reactions fall into two
categories: SN1 or SN2 (S = substitution, N =
nucleophilic).
 In order to determine which mechanism
applies to an organic compound we must look
at the structure of the carbon skeleton.
Which mechanism, SN1 or SN2?



If the compound can form a relatively stable
positive ion (cation) then the more favoured
reaction will be via the SN1 mechanism, while
more unstable cations will react via the SN2
mechanism.
The more heavily substituted the cations are, the
more stable they will be.
In the case of haloalkanes, tertiary and some
secondary haloalkanes react via the SN1
mechanism because of the bulky groups
surrounding the carbon atom.
SN1 mechanism

HO-
H3C
CH3 Br+
C

Br 3
CH
CH3


The reaction of 2-bromo-2methylpropane with hydroxide
ions.
The slow first step of this
mechanism only involves one
species (the haloalkane) reacting.
This is why it is referred to as an
SN1 reaction.
The ‘1’ also means it is a firstorder reaction (see the unit on
physical chemistry).
SN1 mechanism

HO-
CH3 Br+

C
HH3O
C
CH3
CH3

This mechanism forms a true
intermediate carbocation, as the cation
itself is relatively stable.
Once the carbocation is formed it will
quickly react with the attacking
nucleophile, as its electrons will be highly
attracted to the carbocation itself.
The carbocation is planar, which
suggests that the substitution of the
nucleophile could happen on either side,
but there is some steric hindrance from
the departing bromide ion so the
hydroxide slightly favours the opposite
side.
SN1 mechanism summary
HO-
H3C
CH3
HO-
CH3 Br-
CH3 Br+
Br
CH3
C
H3C
CH3
C
HO
CH3
CH3
SN2 mechanism

CH3

C
H
Br
H

In an SN2 mechanism there
are two species involved in
the rate-determining step.
This type of mechanism is
more likely to occur with a
primary haloalkane such as
bromoethane, as used here.
The ‘2’ also means it is a
second-order reaction (see
the unit on physical
chemistry).
SN2 mechanism
 The
CH33
CH
HO-
HO
H
HO
C
C
: Br
Br
Br
H
H
H
H
-
hydroxyl group
approaches from the side
away from the bromine.
 A five-centred transition
state is formed.
 However, it is a one-step
reaction to the product.
SN2 mechanism summary
CH3
-
-
Br
HO
HO-
CH3
H
CH3
H
C
H
Br
H
: Br
C
HO
H
H
-