Synthesis of Alkenes by Dehydrohalogenation of Alkyl Halides

When an alkyl halide is treated with a strong base such as sodium or potassium hydroxide (NaOH, KOH). Sodium methoxide (NaOCH3), sodium ethoxide (NaOC2H5) or potassium tertiary butoxide, (KOC(CH3)3) an elimination reaction takes place and one or more alkenes is formed.
H strong base C C -HX X X = Br, Cl, I C C

An Elimination Reaction

The E2 Mechanism of Dehydrohalogenation

?The mechanism is concerted i.e. bond making and bond breaking occur simultaneously. ?Rate of Reaction = k[base][alkyl halide]

B H C C X strong base ( B ) C C

BH

This type of elimination is referred to as a 1,2- elimination or as a ? -elimination. The hydrogen that is lost is attached to the carbon that is in the ? -position with respect to the halogen atom.

H C
2

C? Br

Stereochemistry of the E2 Mechanism

For the E2 mechanism to take place, the alkyl halide must adopt a conformation in which the halogen atom and the ? hydrogen are anti to each other.
H H X X

This is called the anti-periplanar or anti-coplanar conformation

Note!
Dehydrohalogenation reactions can also take place under conditions that favour an E1 mechanism. However, the synthesis of alkenes is better achieved by way of an E2 mechanism.

Dehydrobromination of 2-Bromopentane
H H3 C CH2 CH CH H CH2 B H 3C CH2 CH2 CH CH2

1-pentene (monosubstituted alkene) + H3C CH2 CH CH CH3

Br 2-bromopentane

2-pentene (disubstituted alkene)

Zaitsevs rule would dictate that the more highly substituted 2-pentene be the preferred product and this is so when bases such as sodium hydroxide, potassium hydroxide, sodium methoxide and sodium ethoxide are used.

The Hofmann Product

When potassium tertiary butoxide which is a much bulkier molecule than sodium or potassium hydroxide; sodium methoxide and sodium ethoxide, is used, the less substituted alkene, 1-pentene is the one that predominates and is referred to as the Hofmann product.

H CH3 H H C O H3C C H H C H

K
K

CH3O C
C

potassium tertiary butoxide H H

H potassium tertiary butoxide

Hofmann Product contd

Bulky bases abstract the least hindered H+ Least substituted alkene is major product.

Reactions of Alkenes

Reactivity of C=C
Electrons in pi bond are loosely held. Electrophiles are attracted to the pi electrons. Carbocation intermediate forms (typically). Nucleophile adds to the carbocation. Net result is addition to the double bond.

Addition Reactions
The typical mode of reaction of alkenes is that of addition. In addition reactions, two molecules combine to give a single molecule of product.

Notice the bonding changes that occur.

Addition Reactions Contd

The reaction is energetically favourable. The amount of energy released by the formation of two sigma bonds is in excess of that needed to break one sigma bond and one pi bond. As a result, addition reactions of alkenes are usually exothermic (heat is given off).

Energy Profile of Addition Reactions

C C ,A B G negative (exothermic reaction) G H T S

Energy

G A C C B

Reaction Coordinate

What is the Mechanism of Addition Reactions of Alkenes?

Remember that the term Reaction Mechanism refers to the sequence and timing of the bond breaking and bond making processes that bring about the conversion of starting materials into products.

The Reaction Mechanism tells us the order in which the following bond changes occur:
C C + A B A C C B

Bond Breaking One pi bond and one sigma bond are broken.

Bond Making Two new sigma bonds are formed

The Mechanism of Addition Reactions of Alkenes

Some addition reactions of alkenes are stepwise. They occur by way of a series of steps and involve the formation of intermediate species.

Some addition reactions are concerted. The conversion of starting material to product takes place in one step . Bonds are broken and formed simultaneously with no intermediate species being formed.

Electrophilic Addition
An alkene is a nucleophile by virtue of its pi bond. The two lobes of the pi bonding orbital above and below the molecular framework contain a pair of fairly loosely held electrons which can be donated to an electrophile. We say that the electrons are loosely held because the pi bond is weaker than the sigma.

lobes of pi bonding orbital above and below the molecular framework

Electrophilic Addition Contd

The addition is called Electrophilic Addition when the molecule, E Nu that adds to the alkene is highly polarized such that an electrophile E is provided.
?? ? ? E Nu

Nu

An electrophile is an electron deficient species that will accept an electron pair into an empty orbital to form a bond. The nucleophile is the electron rich species that will donate a pair of electrons to the electrophile

REMINDER! Representing Reaction Mechanisms on Paper

Use of Curly Arrows A curly arrow represents the movement of a pair of electrons. The arrow originates at the source of the electrons and terminates at the place where the electrons end up.

source of electrons

destination of electrons

Electrons usually end up either on an atom itself or in the gap between two atoms where a new bond is being formed.
B A

A C C C

A C

A C C

B C

A C

The Mechanism of Electrophilic Addition is a Stepwise Mechanism.

Step 1: Pi electrons attack the electrophile.

Step 2: Nucleophile attacks the carbocation.

Typical Highly Polarized Molecules that add to Alkenes

?? ?? H X ?? H

Hydrogen halides, (X= Br, Cl, I)

?? OSO3H H O

Sulfuric acid (H 2SO4)

?? H

Hydronium ion

Mechanism of Addition of HBr to Alkenes

H C C Br Fast C C H

Br

H Slow C C C Br

H C

Br

Electrophilic Addition Reactions

When a symmetrical alkene undergoes electrophilic addition of an unsymmetrical molecule, HY, only one product is possible regardless of the direction in which HY adds.

H C
2

H C
1

H HY H C Y
2

H C H H H

H C
2

H C H

ethene, symmetrical alkene

Regioselectivity in Electrophilic Addition Reactions Contd

If the alkene is unsymmetrical, for example propene, the addition of HY can in theory lead to two different products I and II which are structural or constitutional isomers

H3C C H C

H HY H H

CH3 H C Y I C H H + H

CH3 H C H II C Y H

The Two Possible Carbocations

H3C C H C H Y H H Y H HY H C C H CH3 H + + H CH 3 H C C H

II

CH3 H H C C H carbocation A H

Compound I

CH3 H H C C H

Y Compound II

H carbocation B

Markovnikovs Rule (The Modern Statement)

When an unsymmetrical reagent adds to a double bond by way of an ionic mechanism, the positive portion of the reagent (the electrophile) attaches itself to a carbon atom of the double bond so that the more stable of the two possible carbocations is formed as the intermediate.

Markovnikovs Rule Obeyed

CH3 H H HY H3C C H C H H H A secondary carbocation Y H Compound I formed preferentially from more stable carbocation C C H H CH3 H C C H

HY CH3 H H C H B primary carbocation C H Compound II Not formed or formed in a minor amount

The Markovnikov Product is formed by way of the energetically more favorable route.

AntiMarkovnikov product

Markovnikov product

Markovnikovs Rule (The Original Statement)

In the addition of HX to an alkene, the hydrogen atom adds to the carbon atom of the double bond that already has the greater number of hydrogens.
H3 C C H C H X I H H II H HX H C C H CH3 H + H CH 3 H C C H

When a reaction such as the one above has the potential to produce two or more constitutional isomers and yet only one is formed or a mixture in which one predominates, the reaction is said to be regioselective.

Electrophilic Addition With Rearrangement

CH3 H3 C CH CH CH2 HCl H3C CH3 CH CH Cl 3-methyl-1-butene 2-chloro-3-methylbutane CH3

+
CH3 H3C C Cl 2-chloro-2-methylbutane CH2 CH3

The Expected Outcome

Cl CH3 H3C C H C H H C H H H3C CH3 Cl C H C H H C H H

Carbocation formed in keeping with Markovnikov's Rule

2-chloro-3-methylbutane

H CH 3 H 3C C H C H C H H

Cl

Rearrangement
CH3 H 3C C H C H
1 2 3

H C
4

CH 3 H H 1,2-hydride shift H3C C C H

H C H H

Cl

CH3 H H 3C C Cl C H

H C H H

2-chloro-2-methylbutane

Addition of HBr to alkenes

Sometimes the expected Markovnikov addition was observed, yet at other times the regioselectivity was just the opposite.
H3C C H C H H CH3 H

HBr

Br H Markovnikov Product

H 3C C H C

CH3 H

HBr
H

(under certain circumstances)

Br II Anti-Markovnikov Product

Anti-Markovnikov addition of HBr to alkenes

H3C C H C H H CH3 H

HBr (under certain circumstances)

Br II Anti-Markovnikov Product

It was discovered that the anti-Markovnikov addition occurred when there happened to be organic peroxides present in the reaction mixture.

Anti-Markovnikov Addition of HBr to Alkenes contd.

Organic peroxides have the following structures:
R O O R

alkyl peroxide alkyl hydroperoxide

H3C C H C

CH 3 H

HBr
H

ROOR or ROOH

Br II Anti-Markovnikov Product

Anti-Markovnikov Addition of HBr to Alkenes contd.

In the presence of organic peroxides, addition of HBr proceeds by way of a Free Radical Mechanism. STEP 1 (Initiation) The weak oxygenoxygen bond in the organic peroxide undergoes homolysis to produce alkoxy radicals.

R O O R

heat

R O

O R

Anti-Markovnikov Addition of HBr to Alkenes contd.

STEP 2 (Propogation)

An alkoxy radical abstracts a hydrogen atom from H-Br thus producing a bromine radical.

R O

+ H Br

R O H

+ Br

Electrophile

Anti-Markovnikov Addition of HBr to Alkenes contd.

STEP 3 (Propogation) The bromine radical then adds to the double bond of the alkene in such a way as to give the more stable secondary alkyl radical.
H3 C C H C H H H CH3 H C C Br H

Br

2 alkyl radical

Anti-Markovnikov Addition of HBr to Alkenes contd.

STEP 4 (Propogation) In the product forming fourth step, the secondary radical abstracts a hydrogen atom from HBr to give an alkyl bromide.
CH3 H CH3 H H C C Br H H Br Br H H C C H + Br

Electrophile

Anti-Markovnikov ??
CH3 CH3 C CH CH3

CH3 CH3 C CH CH3 + Br

Br

CH3 CH3 C CH CH3 Br

Tertiary radical is more stable, so that intermediate forms faster.