organic reactions a detailed study of the following: dehydration synthesis addition free radical...

Organic Reactions

A detailed study of the following:Dehydration Synthesis

AdditionFree Radical Reactions

Substitution (SN1 & SN2)Elimination (E1 & E2)

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.

What can be made using this process?

• Alcohol + alcohol Ether*• Alcohol + acid Ester*• Alcohol + ammonia Amine• Alcohol + Acid Amide

• * These are discussed further

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:

OH + CH3-OHH3O+

heatO

O

+

+ O

OH + OH

H3O+

heatO + H2O

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

OH +

HO

H

HO

H

H

+H

OH

OH

H

OH + +H

OH

O

H

+ HO

HO

HO +

HO

H

H

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.

Products of combustionComplete combustion produces:

carbon dioxide water vapour

while incomplete may produces a combination of :carbon monoxide

carbon water vapour

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.

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.

Free Radical Substitution reaction

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.

UV2Br 2Br

or

UV2Br Br : Br

UV3 2 2 2 2 3 2 3 2 2 2 2 2CH CH CH CH CH CH Br CH CH CH CH CH CH Br HBr

1-bromohexane

.

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


• 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.

UV3 2 2 2 2 3 2 3 2 2 2 2 2CH CH CH CH CH CH 2Br CH CH CH CH CH CHBr 2HBr

1,1 dibromohexane


Cl Cllight

2 : Cl..

...

CH3 H + : Cl..

...

..:

..H Cl + . CH3

. CH3 +

..

..

..

..: :Cl Cl

..

..:CH3 Cl + : Cl

...

..

..

..

..

..: :

1. Initiation

2. Chain Propagation (first step)

3. Chain Propagation (second step)

a free radical

methyl radical

feeds back intostep two

REPEAT ING

STEPS

Mechanism of chlorination of methaneCHAIN REACTION

“hydrogen abstraction”

“dissociation”

4. Termination Steps

Cl Cl2 : Cl..

...

. CH3CH3

..

..

..

..: :

. + CH3CH3

: Cl..

... . CH3+ : Cl

..CH3

..

These steps stopthe chain reaction

“recombinations”

Mechanism of chlorination of methane

1414

Reactions of Alkenes: Addition ReactionsHydrogenation of Alkenes – addition of H-H (H2) to theπ-bond of alkenes to afford an alkane. The reaction must becatalyzed by metals such as Pd, Pt, Rh, and Ni.

C C

H

H H

H

H H+ C C

H

H H

HH H

Pd/C

EtOH

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.

1515

H2, PtO2

ethanol

O O

OCH3

O

H2, Pd/C

ethanolOCH3

O

CN

CN

H2, Pd/C

ethanol

C5H11 OH

O

Linoleic Acid (unsaturated fatty acid)

H2, Pd/CCH3(CH2)16CO2H

Steric Acid (saturated fatty acid)

• 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 CN are not easily reduced by catalytic hydrogenation. The C=C bonds of aryl rings are not easily reduced.

1616

Heats of Hydrogenation -an be used to measure relative stability of isomeric alkenes

H3C CH3

H H

H3C H

H CH3

cis-2-butene trans-2-butene

H°combustion : -2710 KJ/mol -2707 KJ/mol

H3C CH3

H H

H3C H

H CH3

cis-2-butene trans-2-butene

H2, Pd H2, PdCH3CH2CH2CH3

H°hydrogenation: -119 KJ/mol -115 KJ/mol trans isomer is ~4 KJ/mol more stable than the cis isomer

trans isomer is ~3 KJ/mol more stable than the cis isomer

The greater release of heat, the less stable the reactant.

1717

H3C CH3

H H

H3C H

H CH3

H3C H

H H

136

125 - 126

117 - 119

114 - 115

116 - 117

112

110

H3C H

H3C H

H3C CH3

H3C H

H3C CH3

H3C CH3

tetrasubstituted

trisubstituted

disubstituted

monosubstituted

H2C=CH2

Alkene H° (KJ/mol)

Heats of Hydrogenation of Some Alkenes

1818

Electrophilic Addition of Hydrogen Halides to Alkenes

C-C -bond: H°= 368 KJ/molC-C -bond: H°= 243 KJ/mol

-bond of an alkene canact as a nucleophile!!

Electrophilic addition reaction

C C

H

H H

H

+ H-Br C C

Br H

H HH H

nucleophile electrophile

Bonds broken Bonds formedC=C -bond 243 KJ/mol H3C-H2C–H -410 KJ/molH–Br 366 KJ/mol H3C-H2C–Br -283 KJ/mol

calc. H° = -84 KJ/molexpt. H°= -84 KJ/mol

1919

Regioselectivity of Hydrogen Halide Addition: Markovnikov's Rule

Reactivity of HX correlates with acidity:

slowest HF << HCl < HBr < HI fastest

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.

R CC H

H

H

R CC H

R

H

R CC H

R

R

H-Br

H-Br

H-Br

C C

Br

H

R

H

H

H C C

H

H

R

Br

H

H+

C C

Br

R

R

H

H

H C C

H

R

R

Br

H

H+

C C

Br

R

R

H

H

R C C

H

R

R

Br

H

R+

none of this

H CC H

R

R'

H-BrC C

Br

H

R

H

H

R C C

H

H

R

Br

H

R'+

Both products observed

none of this

none of this

2020

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

2121

For the electrophilic addition of HX to an unsymmetricallysubstituted 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.

2222

Carbocation Rearrangements in Hydrogen Halide Addition to Alkenes - In reactions involvingcarbocation intermediates, the carbocation may sometimes rearrange if a more stable carbocation can be formed by the rearrangement. These involve hydride andmethyl shifts.

C C

C

H3C

H3C

H

H

H

H

H-ClC C

C

H3C

H3C

H

H

H

H

Cl

H

+C C

C

H3C

H3C

Cl

H

H

H

H

H

~ 50% ~ 50%expected product

Note that the shifting atom or group moves with its electron pair. A MORE STABLE CARBOCATION IS FORMED.

C C

C

H3C

H3C

CH3

H

H

H

H-ClC C

C

H3C

H3C

CH3

H

H

H

Cl

H

+C C

C

H3C

H3C

Cl

H

H

H

H3C

H

2323

Free-radical Addition of HBr to AlkenesPolar mechanism

(Markovnikov addition)

Radical mechanism(Anti-Markovnikov addition)

H3CH2C CC H

H

H

H-BrC C

Br

H

H3CH2C

H

H

H C C

H

H

H3CH2C

Br

H

H+

none of this

H3CH2C CC H

H

H

H-BrC C

Br

H

H3CH2C

H

H

H C C

H

H

H3CH2C

Br

H

H+

peroxides(RO-OR)

none of this

R CC H

H

H

R CC H

R

H

R CC H

R

R

H-BrC C

Br

H

R

H

H

H C C

H

H

R

Br

H

H+

C C

Br

R

R

H

H

H C C

H

R

R

Br

H

H+

C C

Br

R

R

H

H

R C C

H

R

R

Br

H

R+

none of this

H CC H

R

R'C C

Br

H

R

H

H

R C C

H

H

R

Br

H

R'+

Both products observed

none of this

none of this

ROOR

H-Br

ROOR

H-Br

ROOR

H-Br

ROOR

(peroxides)The regiochemistry of HBr addition is reversedin the presence of peroxides.

Peroxides are radicalinitiators - change inmechanism

24

The regiochemistry of free radical addition of H-Br to alkenesreflects the stability of the radical intermediate.

C

H

H

R

Primary (1°)

C

R

H

R

Secondary (2°)

C

R

R

R

Tertiary (3°)< <

• • •

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

C CH2

H3C

H3C

H2SO4, H2O

H3C

OHC

H3C

H3C

This addition reaction follows Markovnikov’s rule The more highly substituted alcohol is the product and is derived fromThe most stable carbocation intermediate.

Reactions works best for the preparation of 3° alcohols

p. 91a

27

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

28

6.11: Thermodynamics of Addition-Elimination Equlibria

C OHH3C

H3C

H3CH3C

C

H3C

CH2+ H2O

H2SO4

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 waterand toward alkene (dehydration) by removing water.

Bonds broken Bonds formedC=C -bond 243 KJ/mol H3C-H2C–H -410 KJ/molH–OH 497 KJ/mol (H3C)3C–OH -380 KJ/mol

calc. H° = -50 KJ/mol

G° = -5.4 KJ/mol H° = -52.7 KJ/mol S° = -0.16 KJ/mol

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

H3C OC

O

Ac= acetate =NaBH4 reduces the C-Hg bond to a C-H bond

C4H9 CC 1) Hg(OAc)2, H2O

C4H9 CC

H

Hg(OAc)

H

OHHH

H

H 2) NaBH4

C4H9 CC

H

H

H

OHH

30

Addition of Halogens to Alkenes X2 = Cl2 and Br2

C C C C

XX

1,2-dihalidealkene

X2

+ Br2

Br

Br

+

Br

Br

not observed

(vicinal dihalide)

Stereochemistry of Halogen Addition - 1,2-dibromide has the anti stereochemistry

CH3 CH3Br

BrH

Br2

Substitution Reaction with Halides

If concentration of (1) is doubled, the rate of the

reaction is doubled.

bromomethane

(1)(2)



If concentration of (1) and (2) is doubled, the rate of the reaction quadruples.

methanol

Substitution Reaction with Halides

bromomethane

(1)(2)

methanol

Rate law:

rate = k [bromoethane][OH-]

this reaction is an example of a SN2 reaction.S stands for substitutionN stands for nucleophilic 2 stands for bimolecular

Mechanism of SN2 Reactions

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

Alkyl halide Relative rate

1200

40

1

≈ 0


Hughes and Ingold proposed the following mechanism:

Transition state

Increasing the concentration of either of the reactant makes their collision more probable.


activationenergy: DG1

activationenergy: DG2

Steric effect

Inversion of configuration

(R)-2-bromobutane (S)-2-butanol

Ener

gy

reaction coordinate reaction coordinate

Factor Affecting SN2 Reactions

relative rates of reaction pKa HX

HO- + RCH2I RCH2OH + I- 30 000 -10

HO- + RCH2Br RCH2OH + Br- 10 000 -9

HO- + RCH2Cl RCH2OH + Cl- 200 -7

HO- + RCH2F RCH2OH + F- 1 3.2

The leaving group

The nucleophile

In general, for halogen substitution the strongest the base the better the

nucleophile.

pKa Nuclephilicity

SN2 Reactions With Alkyl Halidesan alcohol

a thiol

an ether

a thioether

an amine

an alkyne

a nitrile

Substitution Reactions With Halides



If concentration of (2) is doubled, the rate of the reaction is not doubled.

Rate law:

rate = k [1-bromo-1,1-dimethylethane]

this reaction is an example of a SN1 reaction.

S stands for substitutionN stands for nucleophilic 1 stands for unimolecular

1-bromo-1,1-dimethylethane 1,1-dimethylethanol


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

Alkyl halide Relative rate

≈ 0 *

≈ 0 *

12

1 200 000

* a small rate is actually observed as a result of a SN2


C-Br bond breaks

nucleophile attacks the carbocation

Proton dissociation

slow

fast


DG

Rate determining stepCarbocation intermediate

R++ X-

R-OH2

+

R-OH


Same configuration as the alkyl halide

Inverted configuration relative

the alkyl halide

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

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

Reactivity order:methyl > 1o > 2o > 3o

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 elimination2 stands for bimolecular

The E2 Reaction

A proton is removed

Br- is eliminatedThe mechanism shows that an E2

reaction is a one-step reaction

Elimination Reactions



If concentration of (2) is doubled, the rate of the reaction is not doubled.

Rate law:

rate = k [1-bromo-1,1-dimethylethane]

this reaction is an example of a E1 reaction.

E stands for elimination1 stands for unimolecular

1-bromo-1,1-dimethylethane 2-methylpropene

The E1 Reaction

The alkyl halide dissociate, forming a

carbocation

The base removes a proton

The mechanism shows that an E1 reaction is a two-step reaction

Products of Elimination Reaction

2-bromobutane

2-butene

1-butene

80%

20%

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

30% 50%

Competition Between SN2/E2 and SN1/E1

rate = k1[alkyl halide] + k2[alkyl halide][nucleo.] + k3[alkyl halide] + k2[alkyl halide][base]

SN1 SN2 E1 E2

• 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

Competition Between Substitution and Elimination

• SN2/E2 conditions:In a SN2 reaction: 1o > 2o > 3o

In a E2 reaction: 3o > 2o > 1o

90% 10%

25% 75%

100%

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%)

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

organic reactions a detailed study of the following: dehydration synthesis addition free radical...

Documents