1. Organic Reactions A detailed study of the following:
Dehydration Synthesis
Addition
Free Radical Reactions
Substitution (SN1 & SN2)
Elimination (E1 & E2)

2. Dehydration Synthesis
A reaction involving the formation of a single product through the formation & removal of water.
These reactions usually involve reactions between an alcohol and something else.

3. What can be made using this process?
Alcohol + alcohol  Ether*
Alcohol + acid  Ester*
Alcohol + ammonia  Amine
Alcohol + Acid  Amide
* These are discussed further

4. Dehydration of Alcohols to form Ethers
Simple, symmetrical ethers can be formed from the intermolecular acid-catalyzed dehydration of 1° (or methyl) alcohols (a “substitution reaction”)
2° and 3° alcohols can’t be used because they eliminate (intramolecular dehydration) to form alkenes
Unsymmetrical ethers can’t be made this way because a mixture of products results:

5. Mechanism of Formation of Ethers from Alcohols
First, an alcohol is protonated by H3O+
Next, H2O is displaced by another alcohol (substitution)
Finally, a proton is removed by H2O to form the product

6. Combustion of alkanes
Alkanes are unreactive as a family because of the strong C–C and C–H bonds as well as them being nonpolar compounds. At room temperature alkanes do not react with acids, bases, or strong oxidizing agents.
Alkanes do undergo combustion in air (making them good fuels):
2C2H6(g) + 7O2(g)  4CO2(g) + 6H2O(l) H = –2855 kJ
Complete combustion produced carbon dioxide and water while incomplete may produces a combination of carbon monoxide, carbon and water in addition to carbon dioxide. Carbon dioxide contributes to global warming while carbon monoxide is toxic; hemoglobin binds to carbon monoxide in preference to oxygen causing suffocation and even death.

7. Products of combustion
Complete combustion produces:
carbon dioxide
water vapour
while incomplete may produces a combination of :
carbon monoxide
carbon
carbon dioxide.
Carbon dioxide contributes to global warming.
Carbon monoxide is toxic; hemoglobin binds to carbon monoxide in preference to oxygen causing suffocation and even death.

8. Alkane Substitution Reaction
In the presence of light alkanes undergo substitution reaction with halogens.
RH + Br2  RBr + HBr
In a substitution reaction, one atom of a molecule is removed and replaced or substituted by another atom or group of atoms.
Mechanism of subtitution reaction involves free radicals.

9. Free Radical Substitution reaction
1-bromohexane
For a reaction between an alkane and bromine to occur, C-H and Br-Br bonds must break.
The C-H bond is stronger than Br-Br bond
Therefore, the reaction proceeds by first the breakage of Br-Br bond, which is brought about by UV light.
Br-Br bond can be broken in one of two ways. . or

10. Free Radical Substitution reaction
When the bond is broken, either
the bond pair can be equally shared between the two atoms producing two bromine atoms (called free radicals), or
The bond pair goes with one atom producing a positive and a negatively charged ions of bromine.
The first type of bond breakage producing free radicals is referred to as a homolytic fission and the second heterolytic fission.
Homolytic fission because the bond pairs are equally distributed, or particles that are the same in every way is produced.
homolytic fission of the halogen takes place.
In the next step, the free radical removes a hydrogen atom from the alkane forming hydrogen bromine and a free radical of the alkane.
CH3CH2CH2CH2CH2CH2-H + Br•  CH3CH2CH2CH2CH2CH2• + HBr

11. Free Radical Substitution reaction
The free radical goes on to react with a molecule of chlorine and regenerate another chlorine free radical.
CH3CH2CH2CH2CH2CH2• + Br2  CH3CH2CH2CH2CH2CH2Br + Br•
And so on.
Because this reaction, once initiated, can keep itself going is referred to as a chain reaction.
The reaction can conducted with any halogen and the mechanism would be the same.
Not only that, more than one hydrogen can be substituted.
1,1 dibromohexane

12. Mechanism of chlorination of methane
CHAIN REACTION
“dissociation”
R E P E A T I N G S
T E P S
“hydrogen abstraction”

13. Mechanism of chlorination of methane
4. Termination Steps
“recombinations”
These steps stop
the chain reaction

14. Reactions of Alkenes: Addition Reactions
Hydrogenation of Alkenes – addition of H-H (H2) to the
π-bond of alkenes to afford an alkane. The reaction must be
catalyzed by metals such as Pd, Pt, Rh, and Ni.
H°hydrogenation = -136 KJ/mol
C-C π-bond H-H C-H
= 243 KJ/mol = 435 KJ/mol = 2 x -410 KJ/mol = -142 KJ/mol
• The catalysts is not soluble in the reaction media, thus this
process is referred to as a heterogenous catalysis.
• The catalyst assists in breaking the -bond of the alkene and
the H-H -bond.
• The reaction takes places on the surface of the catalyst. Thus,
the rate of the reaction is proportional to the surface area
of the catalyst. 14

15. • Carbon-carbon -bond of alkenes and alkynes can be reduced
to the corresponding saturated C-C bond. Other -bond bond
such as C=O (carbonyl) and CN are not easily reduced by
catalytic hydrogenation. The C=C bonds of aryl rings are not
easily reduced. 15

16. H°combustion : -2710 KJ/mol -2707 KJ/mol
Heats of Hydrogenation -an be used to measure relative stability of isomeric alkenes
trans isomer is ~3 KJ/mol
more stable than the
cis isomer
H°combustion : KJ/mol KJ/mol
H°hydrogenation: -119 KJ/mol KJ/mol
trans isomer is ~4 KJ/mol more stable than the cis isomer
The greater release
of heat, the less
stable the reactant. 16

17. Heats of Hydrogenation of Some Alkenes17

18. Electrophilic Addition of Hydrogen Halides to Alkenes
C-C -bond: H°= 368 KJ/mol
C-C -bond: H°= 243 KJ/mol
-bond of an alkene can
act as a nucleophile!!
Electrophilic addition reaction
Bonds broken Bonds formed
C=C -bond KJ/mol H3C-H2C–H KJ/mol
H–Br KJ/mol H3C-H2C–Br KJ/mol
calc. H° = -84 KJ/mol
expt. H°= -84 KJ/mol 18

19. Reactivity of HX correlates with acidity:
slowest HF << HCl < HBr < HI fastest
Regioselectivity of Hydrogen Halide Addition:
Markovnikov's Rule
For the electrophilic addition of HX across a C=C bond, the H (of
HX) will add to the carbon of the double bond with the most H’s
(the least substitutent carbon) and the X will add to the carbon of
the double bond that has the most alkyl groups. 19

20. Mechanism of electrophilic addition of HX to alkenes
Regioselectivity determined by Markovnikov’s rule – which can be explained by comparing the stability of the intermediate carbocations 20

21. For the electrophilic addition of HX to an unsymmetrically
substituted alkene:
• The more highly substituted carbocation intermediate is
formed.
• More highly substituted carbocations are more stable than
less substituted carbocations. (hyperconjugation)
• The more highly substituted carbocation is formed faster
than the less substituted carbocation. Once formed, the
more highly substituted carbocation goes on to the final
product more rapidly as well. 21

22. Note that the shifting atom or group moves with its electron pair.
Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes - In reactions involving
carbocation intermediates, the carbocation may sometimes rearrange if a
more stable carbocation can be formed by the rearrangement. These involve hydride and
methyl shifts.
Note that the shifting atom or group moves with its electron pair.
A MORE STABLE CARBOCATION IS FORMED. 22

23. Free-radical Addition of HBr to Alkenes
Polar mechanism
(Markovnikov addition)
Radical mechanism
(Anti-Markovnikov addition)
The regiochemistry of
HBr addition is reversed
in the presence of
peroxides.
Peroxides are radical
initiators - change in
mechanism 23

24. The regiochemistry of free radical addition of H-Br to alkenes
reflects the stability of the radical intermediate.

25. Acid-Catalyzed Hydration of Alkenes
The addition of water (H-OH) across the -bond of an alkene to give an alcohol; opposite of dehydration
This addition reaction follows Markovnikov’s rule The more
highly substituted alcohol is the product and is derived from
The most stable carbocation intermediate.
Reactions works best for the preparation of 3° alcohols

26. p. 91a

27. Mechanism for this reaction is the reverse of the acid-catalyzed dehydration
of alcohols:

28. Bonds broken Bonds formed C=C -bond 243 KJ/mol H3C-H2C–H -410 KJ/mol
6.11: Thermodynamics of Addition-Elimination Equlibria
Bonds broken Bonds formed
C=C -bond KJ/mol H3C-H2C–H KJ/mol
H–OH 497 KJ/mol (H3C)3C–OH KJ/mol
calc. H° = -50 KJ/mol
G° = -5.4 KJ/mol H° = KJ/mol S° = KJ/mol
How is the position of the equilibrium controlled?
Le Chatelier’s Principle - an equilibrium will adjusts to any stress
The hydration-dehydration equilibria is pushed toward hydration (alcohol) by adding water
and toward alkene (dehydration) by removing water.

29. The acid catalyzed hydration is not a good or general method for
the hydration of an alkene.
Oxymercuration: a general (2-step) method for the Markovnokov
hydration of alkenes
NaBH4 reduces the C-Hg
bond to a C-H bond

30. Addition of Halogens to Alkenes X2 = Cl2 and Br2
(vicinal dihalide)
Stereochemistry of Halogen Addition - 1,2-dibromide has the anti stereochemistry

31. Substitution Reaction with Halides
(1)
(2)
bromomethane
methanol
If concentration of (1) is doubled, the rate of the reaction is doubled.
If concentration of (1) and (2) is doubled, the rate of the reaction quadruples.
If concentration of (2) is doubled, the rate of the reaction is doubled.

32. Substitution Reaction with Halides
(1)
(2)
bromomethane
methanol
Rate law:
rate = k [bromoethane][OH-]
this reaction is an example of a SN2 reaction.
S stands for substitution
N stands for nucleophilic
2 stands for bimolecular

33. Mechanism of SN2 Reactions
Alkyl halide
Relative rate
1200 40 1
≈ 0
The rate of reaction depends on the concentrations of both reactants.
When the hydrogens of bromomethane are replaced with methyl groups the reaction rate slow down.
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of only one stereoisomer

34. Mechanism of SN2 Reactions
Hughes and Ingold proposed the following mechanism:
Transition state
Increasing the concentration of either of the reactant makes their collision more probable.

35. Mechanism of SN2 Reactions
Steric effect
activation
energy: DG2
Energy
activation
energy: DG1
reaction coordinate
reaction coordinate
Inversion of configuration
(R)-2-bromobutane
(S)-2-butanol

36. Factor Affecting SN2 Reactions
The leaving group
relative rates of reaction pKa HX
HO- + RCH2I RCH2OH + I
HO- + RCH2Br RCH2OH + Br
HO- + RCH2Cl RCH2OH + Cl
HO- + RCH2F RCH2OH + F
The nucleophile
In general, for halogen substitution the strongest the base the better the nucleophile.
pKa
Nuclephilicity

37. SN2 Reactions With Alkyl Halides
an alcohol
a thiol
an ether
a thioether
an amine
an alkyne
a nitrile

38. Substitution Reactions With Halides
1-bromo-1,1-dimethylethane
1,1-dimethylethanol
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a SN1 reaction.
S stands for substitution
N stands for nucleophilic
1 stands for unimolecular
If concentration of (1) is doubled, the rate of the reaction is doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.

39. Mechanism of SN1 Reactions
Alkyl halide
Relative rate
≈ 0 * 12
The rate of reaction depends on the concentrations of the alkyl halide only.
When the methyl groups of 1-bromo-1,1-dimethylethane are replaced with hydrogens the reaction rate slow down.
The reaction of an alkyl halide in which the halogen is bonded to an asymetric center leads to the formation of two stereoisomers
* a small rate is actually observed as a result of a SN2

40. Mechanism of SN1 Reactions
nucleophile attacks the carbocation
slow
C-Br bond breaks
fast
Proton dissociation

41. Mechanism of SN1 Reactions
Rate determining step
Carbocation intermediate DG
R++ X- +
R-OH2
R-OH

42. Mechanism of SN1 Reactions
Inverted configuration relative the alkyl halide
Same configuration as the alkyl halide

43. Factor Affecting SN1 reaction
Two factors affect the rate of a SN1 reaction:
The ease with which the leaving group dissociate from the carbon
The stability of the carbocation
The more the substituted the carbocation is, the more stable it is and therefore the easier it is to form.
As in the case of SN2, the weaker base is the leaving group, the less tightly it is bonded to the carbon and the easier it is to break the bond
The reactivity of the nucleophile has no effect on the rate of a SN1 reaction

44. Comparison SN1 – SN2 SN1 SN2 A two-step mechanism A one-step mechanism
A unimolecular rate-determining step
A bimolecular rate-determining step
Products have both retained and inverted configuration relative to the reactant
Product has inverted configuration relative to the reactant
Reactivity order:
3o > 2o > 1o > methyl
methyl > 1o > 2o > 3o

45. Elimination Reactions
1-bromo-1,1-dimethylethane
2-methylpropene
Rate law:
rate = k [1-bromo-1,1-dimethylethane][OH-]
this reaction is an example of a E2 reaction.
E stands for elimination
2 stands for bimolecular

46. The mechanism shows that an E2 reaction is a one-step reaction
The E2 Reaction
A proton is removed
Br- is eliminated
The mechanism shows that an E2 reaction is a one-step reaction

47. Elimination Reactions
1-bromo-1,1-dimethylethane
2-methylpropene
Rate law:
rate = k [1-bromo-1,1-dimethylethane]
this reaction is an example of a E1 reaction.
E stands for elimination
1 stands for unimolecular
If concentration of (1) is doubled, the rate of the reaction is doubled.
If concentration of (2) is doubled, the rate of the reaction is not doubled.

48. The E1 Reaction The base removes a proton
The alkyl halide dissociate, forming a carbocation
The mechanism shows that an E1 reaction is a two-step reaction

49. Products of Elimination Reaction
30%
50%
80%
2-butene
2-bromobutane
20%
1-butene
The most stable alkene is the major product of the reaction for both E1 and E2 reaction
The greater the number of alkyl substituent the more stable is the alkene
For both E1 and E2 reactions, tertiary alkyl halides are the most reactive and primary alkyl halides are the least reactive

50. Competition Between SN2/E2 and SN1/E1
rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] + k2[alkyl halide][base]
SN2 and E2 are favoured by a high concentration of a good nucleophile/strong base
SN1 and E1 are favoured by a poor nucleophile/weak base, because a poor nucleophile/weak base disfavours SN2 and E2 reactions

51. Competition Between Substitution and Elimination
SN2/E2 conditions:
In a SN2 reaction: 1o > 2o > 3o
In a E2 reaction: 3o > 2o > 1o
10%
90%
75%
25%
100%

52. Competition Between Substitution and Elimination
SN1/E1 conditions:
All alkyl halides that react under SN1/E1 conditions will give both substitution and elimination products (≈50%/50%)

53. Summary of Elimination & Substitution Reactions
Alkyl halides undergo two kinds of nucleophilic subtitutions: SN1 and SN2, and two kinds of elimination: E1 and E2.
SN2 and E2 are bimolecular one-step reactions
SN1 and E1 are unimolecular two step reactions
SN1 lead to a mixture of stereoisomers
SN2 inverts the configuration od an asymmetric carbon
The major product of a elimination is the most stable alkene
SN2 are E2 are favoured by strong nucleophile/strong base
SN2 reactions are favoured by primary alkyl halides
E2 reactions are favoured by tertiary alkyl halides