Synthesis of Alkenes

Synthesis of Alkenes

Major approaches to the synthesis of alkenes:

Dehydrohalogenation of Alkyl HalidesE2 mechanism – most useful E1 mechanism

Dehalogenation of Vicinal Dibromides

Dehydration of Alcohols


Dehydrohalogenation can occur via either an E2 or E1 mechanism. Loss of H+ and X- ions from adjacent

carbons, forming a new pi bond

CH3CCH

2CH

3

(CH3CH

2)

3N

C

CH3

Br

CH

3C

H3C

H

CH3

NaOH


The most synthetically useful dehydrohalogenation reactions occur under E2 reaction conditions. 3o or bulky 2o alkyl halide strong bases

strong bulky bases are best when using 2o alkyl halides

less likely to undergo substitution reactions


Common strong bulky bases

CH3CCH

3

(CH3CH

2)

3N

C

or Et3N

(CH3)

2CH

or t-BuO-

CH3

O-

CH

3C

H3C

H

CH3

N(CH3)

2CH H

N CH3H

3C

CH3CCH

3

(CH3CH

2)

3N

C

or Et3N

(CH3)

2CH

or t-BuO-

CH3

O-

CH

3C

H3C

H

CH3

N(CH3)

2CH H

N CH3H3C

CH3CCH

3

(CH3CH

2)

3N

C

or Et3N

(CH3)

2CH

or t-BuO-

CH3

O-

CH

3C

H3C

H

CH3

N(CH3)

2CH H

N CH3H3C

CH3CCH

3

(CH3CH

2)

3N

C

or Et3N

(CH3)

2CH

or t-BuO-

CH3

O-

CH

3C

H3C

H

CH3

N(CH3)

2CH H

N CH3H3C

triethylamine

t-butoxide ion

diisopropylamine

2,6-dimethylpyridine

Synthesis of Alkenes Mechanism of E2 Dehydrohalogenation

concerted reaction

anti-coplanar transition stateB

C

H

C

X

C C + B H + X-

C CPh

H3C

H

Ph


E2 elimination reactions can take place in cyclohexanes only when proton and leaving group can get into a trans-diaxial arrangement corresponds to anti-coplanar


Strong, less hindered bases (MeO-, EtO-, etc) generally give the most substituted alkene (Saytzeff’s rule) as the major product.

Synthesis of Alkenes Strong, bulky bases usually give the

Hoffmann product (least highly substituted alkene) as the major product bulky bases often abstract a proton from

a less hindered carbon


Example: Predict all elimination product(s) of the following reactions. Which one is the major product?

CH3CHCH

2CH

3

KOH

C2H

5OH,

Br

CH3CHCH

2CH

3

KOH

C2H

5OH,

NaOCH3

CH3OH,

Br

H

CH3

BrH

HD


Example: Predict all possible elimination products for the following reaction. Which one will be the major product?

Et3N

CH3Br


Dehalogenation of Vicinal Dibromides two possible reagents

NaI (E2 mechanism)Zn/HOAc (redox reaction)

C

Br

C

Br

C C + I Br + NaBrNa+ I -


Dehalogenation using I- takes place via a concerted, stereospecific E2 mechanism

Anti-coplanar conformation required

Trans-diaxial conformation required for cycloalkanes


Example: Predict the major elimination product formed in the following reactions.

NaI

acetone

Br

Br

CNaI

acetoneC

Br

BrCH

3

HH

H3C

Synthesis of Alkenes Dehydration of Alcohols

removal of water

equilibrium processdrive reaction to completion by removing alkene as formed (LeChatelier’s Principle)

C

CH3

CH2

+ H2O

C

C

CH3

CH3

OH CCH

3

CH3

H2SO4


Typical reaction conditions alcohol substrate

Order of reactivity:3o > 2o > 1o alcohol

acid catalystconc. H2SO4

conc. H3PO4

heat

Synthesis of AlkenesMechanism of Dehydration (E1) Step 1: Protonation of the hydroxyl group (fast)

Step 2: Ionization (RDS)

+


Step 3: Proton abstraction (fast)

Rearrangements to form more stable carbonium ions are common in dehydration reactions.

Saytzeff’s product preferred.


Example: Propose a mechanism for the following reaction.

CH3CCH

2OH C=CHCH

3

H2SO

4

150o

CH3

CH3

H3C

H3C

C


Step 1: Protonation of OH group

Step 2: Ionization with Methyl Shift


Step 3: Abstraction of proton


Example: Predict the major product formed in the following reaction.

OH H2SO4

heat

conc.

Reactions of Alkenes

The most common reactions of alkenes are addition reactions: the addition of a reagent to the pi bond

with subsequent formation of new sigma bondsnumber of elements of unsaturation decreases

Reactions of Alkenes The electrons in the bond of C=C are

delocalized above and below the sigma bond more loosely held

In the presence of a strong electrophile, the double bond acts as a nucleophile, donating the electrons to the electrophile and forming a new bond.

Reactions of Alkenes Most reactions of alkenes are

electrophilic addition reactions.Step 1: Attack of electrophile on pi bond forming a carbonium ion:

Step 2: Nucleophile attacks carbonium ion giving product.


Addition of H-X to Alkenes

C + H CC X C

H X


In the previous example, the proton added to the secondary carbon, forming the most stable carbonium ion.

Markovnikov’s Rule: Asymmetric reagents such as H-X add

to a C=C so that the proton adds to the carbon (in the double bond) that already has the greater number of hydrogen atoms.“The rich get richer”


Markovnikov’s Rule (extended): In an electrophilic addition to an

alkene, the electrophile adds in such a way as to give the most stable intermediate.


Example: Predict the product formed in each of the following reactions.

HBr

CH3

HBr

HI

CH3


Anti-Markovnikov Addition of HBr In the presence of peroxides, HBr adds

to C=C via a free radical mechanism giving the “Anti-Markovnikov” product.

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3 H3C BrH

Works only with HBr (not HCl or HI) due to relative bond strengths.


Some common peroxides:

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3CO-OCCH3

CH3 H3C BrH

O O

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3CO-OCCH3

CH3 H3C BrH

O O

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3CO-OCCH3

CH3 H3C BrH

O O

O O

Acetyl peroxide

Di-t-butyl peroxide

Diethyl peroxide

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3CO-OCCH3

CH3 H3C BrH

O O

O O

COOCO O

COOC

O OBenzoyl peroxide


Example: Predict the product of the following reaction.

HBr

HI

CH3CH

2O-OCH

2CH

3

CH3CO-OCCH3

CH3 H3C BrH

O O

HBr

Synthesis of Alkenes

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