1. Nucleophilic Substitution Swapping
Generic Equation: Swap R-X + Nu:  R-Nu + :X- The problem lies in the mechanism.

2. Importance of Alkyl Halides Precursor to many others

3. NUCLEOPHILIC SUBSTITUTION
Theory - nucleophile means ‘liking positive’
- a dipole is induced (by a Nu:) in the C-X bond and it is polar
polar bond, why is it polar with chlorine?
Answer: ∆E=0.4, electronegativity difference
OH¯ CN¯ NH H2O
These are the 4 Nu: NaOH, NaCN the 2 moleculars are as is

4. SN2 :NUCLEOPHILIC SUBSTITUTION
MECHANISM
MECHANISM: 2 Steps
The NU: electrons attacks the slightly positive carbon atom
The polar bond breaks unevenly (heterolytic) and Br- released
Back
attack
Polar Bond
Both e-
To halogen
2 products
Note/Points:
-attack from back (electronegative halogen will forces this)
-show the polar bond

5. SN2 All 10 (primary)halides react as SN2 reactions.
The 2 does NOT mean steps
S = substitution
N = Nucleophile
2 = second order (both reactants determine rate)
Note: this is for primary halides, tertiary will under go SN1 as we will see later, secondary will do both – but we are not responsible to know about secondary reactions

6. 1O Haloalkanes SN2

7. There are 4 Substitutions
1) WITH HYDROXIDE
C2H5Br(l) + OH- (aq) -->C2H5OH(l) +Br-(aq)
2) WITH A CYANIDE
C2H5Br(l) + CN- (aq/alc) —>C2H5CN + Br-(aq)
3) WITH 2 AMMONIAS
C2H5Br(l) + 2NH3(aq/alc)—> C2H5NH2 + NH4Br
4) WITH H2O (solvolysis) solvent and reactant at same time
C2H5Br(l) + H2O (l) —> C2H5OH(l) + HBr (aq)

8. SN2 Energy Diagram The SN2 reaction is a one-step reaction.
Transition state is highest in energy.
Chapter 6

9. Substitution Reactions : The Nu: will be one of these 4 reactants
OH¯ CN¯ NH H2O
These four reactants will be similar in result and mechanism
They will ALL be refluxed
Note: NaOH or KOH, NaCN etc is the source of
The OH¯ , and CN¯ above as they are ionic
But we can ignore the metals as spectators
NaOH ---> Na⁺ + OH⁻

10. NUCLEOPHILIC SUBSTITUTION AQUEOUS HYDROXIDE ALCOHOLS
Reagent Aqueous* NaOH or KOH (aq) (OH¯)
Conditions Reflux in aqueous solution (SOLVENT IS IMPORTANT)
Product Alcohol
Nucleophile hydroxide ion ( : OH¯)
Equation e.g. C2H5Br(l) Na OH-(aq) ——> C2H5OH(l) Na Br-(aq)
Spectator Spectator
Mechanism
STEP Nu: attack
STEP :Br- forms and leaves
* WARNING It is important to quote the solvent when answering questions.
Elimination takes place when ethanol is the solvent - SEE LATER

11. NUCLEOPHILIC SUBSTITUTION
CYANIDE makes Nitriles AND makes chain LONGER
Reagent Alcohol/ Aqueous, NaCN / KCN
Conditions Reflux in aqueous , alcoholic solution
Product Nitrile (cyanide)
Nucleophile cyanide ion (CN¯)
Equation e.g. C2H5Br + Na CN (aq/alc) ——> C2H5CN Na CN-(aq)
Mechanism
1-bromoethane propanenitrile Br-
Importance extends the carbon chain by one carbon atom,
called propanenitrile .

12. NUCLEOPHILIC SUBSTITUTION
AMMONIA makes an amine
Reagent Aqueous, alcoholic ammonia (in EXCESS, or 2 Ammonia’s)
Conditions Reflux in aqueous , alcoholic solution under pressure
Product Amine
Nucleophile Ammonia (NH3 (aq/alc) )
Equation e.g. C2H5Br NH3 (aq / alc) ——> C2H5NH NH4Br
(i) C2H5Br NH3 (aq / alc) ——> C2H5NH HBr
(ii) C2H5NH NH3 (aq / alc) ——> C2H5NH2 + NH4Br
_______________________________________________
C2H5Br NH3 (aq / alc) ——> C2H5NH2 (l) + NH4Br (aq/alc)
Mechanism
Ethaneamine Bromide

13. NUCLEOPHILIC SUBSTITUTION
AMMONIA
Why excess ammonia?
The second ammonia molecule ensures the removal of the H to make an amine. A large excess ammonia ensures that further substitution doesn’t take place.
Problem
Amines are also nucleophiles (lone pair on N) and can attack another molecule of haloalkane to produce a 2° amine. This too is a nucleophile and can react further producing a 3° amine and, eventually an ionic quarternary ammonium salt. ..
C2H5NH C2H5Br ——> HBr (C2H5)2NH diethylamine, a 2° amine
(C2H5)2NH + C2H5Br ——> HBr (C2H5)3N triethylamine, a 3° amine
(C2H5)3N C2H5Br ——> (C2H5)4N+ Br¯ tetraethylammonium bromide
a quaternary (4°) salt

14. NUCLEOPHILIC SUBSTITUTION
WATER Makes Alcohols
Details A similar reaction to that with OH¯ takes place with water.
It is slower as water is a poor nucleophile.
Water may be looked at as HOH THE OH AND BR SWAP
Equation C2H5Br(l) H2O(l) ——> C2H5OH(l) HBr(aq)
We show the product as HBr and not just Br- because it is molecular and the H in the water is not an ion like Na+ or K+. As well, H3O+ forms, which we rewrite as
H+ and the water from the H3O+ is part of the (aq)

15. SN1 V SN2 There is very little difference in these reactions.
Both have 2 steps and the same product , the same reactants. Hard to see any difference
S = substitution (both will swap)
N= Nucleophile (both will use the same Nu:
1 =Rate of reaction (depends on 1 reactant)
called 1st order
2 =Rate of reaction (depends on 2 REACTANTS)
called 2nd order

16. Steric Hinderance
With a tertiary halogenoalkane, NU: attack is impossible. The back of the molecule is completely cluttered with CH3 groups.
It has to go by an alternative mechanism.

17. Tertiary Haloalkenes SN1
Steric hindrance means the Nu: cannot approach and has no effect on the reactions first step
The [Nu:] nucleophile has no effect. Only the [haloalkane] affect the reaction rate. Thus it is first order.
rate = k [haloalkane] 1

18. Mechanism for 3o Halides SN1
SLOW (RDS)
STEP
Carbocation Intermediate
FAST STEP

19. SN1 Energy Diagram Forming the carbocation is an endothermic step.
Step 2 is fast with a low activation energy.
Chapter 6

20. Film Clip 30 Haloalkanes SN2 (single step)

21. Secondary Halides
They undergo both SN1 and SN2 reactions so on an exam if you are given a secondary halide, either mechanism will receive full credit in marks

22. LAST REACTION
ELIMINATION

23. 3 WAYS to Favor Elimination
To favor elimination rather than substitution use:
1) More heat
2) More concentrated hydroxide in ALCOHOL
3) pure ethanol as the solvent

24. Elimination
The :OH- is a BASE, in alcohol and takes a hydrogen (H+) to form water. This sets off a cascade where a C=C forms and the halide ion is lost. (as always Reflux)

25. Elimination Via OH- BASE
Step 1: The :OH- is NOT a nucleophile, it is a BASE, and attacks H
Step 2: The H+ leave and e- pair make C=C
Step 3: The halogen (here as :Br-) leaves
GENERIC CASCADING REACTION
+ H2O + :Br-
An Example
+ H2O + :Br-

26. ELIMINATION Reagent Alcoholic sodium (or potassium) hydroxide
Conditions Reflux in alcoholic solution, ALL alcohol
Product Alkene
Mechanism Elimination
Equation C3H7Br NaOH(alc) ——> C3H H2O NaBr
Mechanism
the OH¯ ion acts as a base and picks up a proton
the proton comes from a carbon atom next to that bonded to the halogen
the electron pair left moves to form a second bond between the carbon atoms
the halogen is displaced
overall there is ELIMINATION of HBr.
Complication:Cis / Trans with unsymmetrical halalkanes, you get mixture of products

27. but-2-ene (Major Product) can exist as cis and trans isomers
ELIMINATION
Complication
If the haloalkane is unsymmetrical a mixture of isomeric alkene products is obtained.
but-1-ene (Minor Product)
2-bromobutane
but-2-ene (Major Product)
can exist as cis and trans isomers
2-bromobutane

28. ELIMINATION v. SUBSTITUTION
The products of reactions between haloalkanes and OH¯ are influenced by the solvent
SOLVENT
ROLE OF OH–
MECHANISM
PRODUCT
WATER
NUCLEOPHILE
SUBSTITUTION
ALCOHOL
BASE
ELIMINATION
ALKENE
Modes of attack
Aqueous soln OH¯ acts as a nucleophile
Alcoholic soln OH¯ acts as a base (A BASE IS A PROTON ACCEPTOR)
Both reactions take place at the same time but by varying
the solvent you can influence which mechanism dominates.

29. Elimination Clips
Franklychem

30. than alcohol (see chart)
The ability of solvents to stabilize ions through solvation is directly associated
with their polarity. Polar solvents, such as water, can stabilize the ions 3X more
than alcohol (see chart)
Methanol can stabilize ions through solvation, but water is best at controlling
ions. The :OH- is a super strong ion and needs controlling. Alcohol controls less
and is better to dissolve weak :Nu’s such as NH3 and CN, as they do not need
to be controlled like OH- as they are weak ions
Aprotic solvents ε
Protic solvents
Hexane
1.9
Acetic acid
6.2
Benzene
2.3
1-Methyl-2-propanol 11
Diethyl ether
4.3
Ethanol
34.3
Chloroform
4.8
Methanol
33.6
Hexamethylphosphoramide (HMPT) 30
Formic acid
58.0
Dimethyl formamide (DMF) 38
Water
80.4
Dimethyl sulfoxide (DMSO) 48