Reactions Of alkyl substituents

1. 1
Reactions of alkyl substituents
NBS = N-bromosuccinimide

2. 2
Halo substituted alkyl groups undergo elimination reactions by using a bulky base.
Substituents with double and triple bonds can be reduced by catalytic hydrogenation

3. 3
Benzene can be reduced only under extreme conditions.
Alkyl groups can be oxidised to carboxyl groups, regardless of the length of
the alkyl substituent.

4. 4
If the alkyl group does not have a benzylic hydrogen, the reaction will not occur.
Strong oxidising agents will oxidise benzylic alcohols to benzoic acid

5. 5
Mild oxidising agents, e.g. MnO2 oxidises benzyl alcohols to
aldehydes or ketones.

6. 6
Reducing a nitro substituent
Selective reduction of one nitro group

7. 7
Effect of substituents on reactivity
some substituents make the ring more reactive and some make it less
reactive than benzene toward electrophilic substitution.
Rate determining step of electrophilic aromatic substitution:
attack of a +ve electrophile on a nucleophilic aromatic ring.
What would happen if the electron density of the ring is increased?
This will increase its attractiveness to an electrophile.
Conclusion:
substituents capable of donating e-s into the ring will increase the rate of
substitution (called ACTIVATING substituents).
Substituent that withdraw electrons from the ring will decrease the rate
of substitution (called DEACTIVATING substituents).
Donation and withdrawal can occur by induction or by resonance.

8. 8
RESONANCE ELECTRON DONATION AND WITHDRAWAL
Non bonded e-s can be delocalised onto the ring through through p orbital
overlap, e.g. NH2, OH, OR and Cl.
If the atom is doubly or triply bonded to a more e-ve atom, then e-
s can
be withdrawn by resonance, e.g C=O, nitrile and NO2.
Can you predict where the electrophile will go in each case ?

9. 9
Strongly activating substituents
will donate e-
s into the ring by resonance
Note that N and O withdraw e-s from the ring inductively
but electron donation into the ring is more significant.

10. 10
They donate e-s by resonance in two competing directions
Moderately activating substituents

11. 11
Weakly activating substituents
Donates e-s inductively compared to H
Resonance donation is stronger than withdrawal.
Weakly deactivating substituents
e.g. halides. are electronegative atoms
Withdraw e-s inductively more strongly than they
donate e-s by resonance

12. 12
Moderately deactivating substituents
have C=O groups directly attached to benzene ring - withdraw e-
s
both inductively and by resonance.
Strongly deactivating substituents
Powerful e-
withdrawers by both induction and resonance.

13. 13
The effect of substituents on orientation
All activating and weakly deactivating substituents are
ortho/para directors.
All moderately and strongly deactivating substituents are meta
directors.
Inductive electron donation - the indicated resonance contributors
are most stable because the substituent is directly bonded to the +ve
C, which it can stablise by inductive e- donation.
Substituents that donate e-s inductively are o-/p- directors

14. 14

15. 15
Electron donation by resonance and orientation
- the indicated resonance contributors all have complete octets.
Substituents that donate electrons by resonance are o-/p-
directors.
What about the halogens? They donate e-s by resonance
and hence are o-/p- directors

16. 16
Electron withdrawal by induction and resonance
- the indicated resonance contributors are the least stable because they
have +ve charges on adjacent atoms.
- most stable carbocation formed when the electrophile is directed
toward the meta position.
Summary: All o-/p- directors have at least one lone pair on the atom
directly attached to the ring with the exception of alkyl, aryl and
alkene groups.
All meta directors have a +ve or partial +ve charge on the atom
attached to the ring.
Try and rationalise the list given.

17. 17
The ortho-/para- ratio
Bulky group favours para

18. 18
With activating substituents, milder conditions can be used.

19. 19
Friedel Crafts reactions are most sluggish - will not go with moderate to
strong deactivators - ring will be too unreactive.
Amines and substituted amines cannot undergo Friedel Crafts reactions
nor can it undergo nitration, because of the reactivity of the amine
group.
The lone pair complexes with the
Lewis acid and converts it to a
meta director

20. 20
Aniline cannot be nitrated because HNO3 is an oxidising agent and
will oxidise NH2 to NO2
Tertiary amines however can be nitrated under milder conditions.

21. 21
Designing a synthesis
As the number of reactions increases, there are more reactions to choose from
when designing a synthesis.
The synthesis of 2-phenylethanol can be carried out very differently.
The first is more preferred: the second uses excess benzene, has a radical
reaction that can produce side reactions, yield of elimination is not high as some
subsitution occurs as well and hydroboration-oxidation is not an easy reaction
to carry out.

22. 22
The order in which the substituents are placed is very important.
Whether you brominate or sulphonate first has a bearing
on the product formed because halides and sulphonyl
groups direct to different positions.

23. 23
NO2 groups are more deactivating and must be put on last.
At which point do we chemically modify a substituent ?
CH3 is a o-/p- director
but COOH is a m-
director

24. 24
Straight chain propyl group must be put on by acylation
reduction because of carbocation rearrangement.
SO3H must be put on after the alkyl group because it is
deactivating and meta-directing.
Reduction must be carried out before sulphonation because acyl
groups are deactivating and meta directing.

25. 25
Synthesis of tri-substituted benzenes
The directing effect of all substituents need to be considered.

26. 26
Strongly activating substituents will win over weakly activating
or deactivating substituents.
OH is more activating than
methyl
If substituents have similar properties, neither will dominate
and a mixture will result.

27. 27
SYNTHESIS OF SUBSTITUTED BENZENES USING
ARENEDIAZONIUM SALTS
HNO2 is created in situ because it is unstable.
N2 is such a good leaving group that it must be synthesised at 0o
C and used
immediately.
The drive to form a stable molecule of N2 causes the diazonium ion to be easily
displaced by a wide variety of nucleophiles.

28. 28
The Sandmeyer reaction
The reaction of an
arenediazonium salt with a
cuprous salt is known as a
Sandmeyer reaction.

29. 29
How could you synthesis p-chloroethylbenzene without getting any
ortho product ?
For I, use KI

30. 30
fluoro subsitution occurs when heated with fluoroboric acid - known as
Schieman reaction.
If allowed to warm up to room temperature in aqueous solution, phenols
result.

31. 31
A hydrogen will replace a diazonium group if the diazonium salt is
treated with hydrophosporus acid (H3PO2).
This is a good way of getting rid of an amino group.

32. 32
Arenediazonium ions can act as electrophiles only with strong
activating groups because the reaction needs to be carried out well
below room temperature. (phenols, anilines and N-alkyl anilines can
undergo electrophilic substitution with these ions.)
Because the electrophile is so large, substitution takes place at the
less sterically hindered para position.

33. 33
If the para position is blocked, substitution will occur at the ortho
position.
Mechanism is the same as that for other electrophiles.

34. 34
Mechanism for diazonium formation
First step is the generation of the nitrosonium ion

35. 35
What do you think happens when 2o
and 3o
amines react with
nitrosonium ion ?
The 2o
amine does not have the second proton for the formation of the
diazonium ion.

36. 36
π electron clouds repel the
approach of a nucleophile
benzene does not undergo
nucleophilic substitution (SN)
substituted benzenes can undergo
SN type reactions if there is a
substituent that strongly withdraws
e-s from the ring by resonance and
a good leaving group such as a
halogen.
e- withdrawing group must be
positioned ortho or para to the
leaving group.
The greater the no. of e-
withdrawing groups, the easier to
carry out the reactions.
Nucleophilic aromatic substitution

37. 37
General mechanism for nucleophilic aromatic substitution
The electron withdrawing substituent must be ortho or para to the site of
nucleophilic attack because the e-s of the attacking nucleophile can be
delocalised onto the substituent only if the substituent is in one of these
positions.

38. 38
A variety of substituents can be placed on a benzene ring by means of
nucleophilic aromatic substitution reactions.
The only requirement is that the incoming group be a stronger base
than the group that is being replaced.

39. 39
Electrophilic substitution reactions of naphthalene and
substituted naphthalenes.
Naphthalene is more reactive than benzene toward electrophilic
aromatic substitution. A Lewis acid is not needed for bromination
or chlorination.

40. 40
Under conditions which are not reversible, sulphonation occurs at the
1-position, the kinetic product - easier to form.
Under conditions which are reversible, sulphonation occurs at the 2-
position, the thermodynamic product - more stable.

41. 41
In substituted naphthalene, the nature of the substituent determines which ring
will undergo electrophilic substitution.
If the substituent is deactivating, the electrophile will attack at the 1-position of
the ring without the substituent, because that ring is more reactive than the
deactivated ring.
If the substituent is activating, substitution will occur on the ring with the
substituent. It will occur ortho or para at the 1-position.