Wittig ReactionPresentation1

• In Organic Chemistry, a Witting reaction is used to prepare an alkene by reacting an aldehyde or ketone with an ylide. An ylide is a compound that has two bound atoms that are oppositely charged. • This compound is known as an organo-phosphorous or phosphonium

salt. Because of phosphorus's chemical prosperities, the phosphonium salt has two charged particles bound together and a resonance structure can form (fig. 1), making a reaction possible.

• The Wittig synthesis reaction is preferable over elimination reactions when the regional-selectiveness of the double bond is desired for higher yields. The mechanism replaces the carbonyl’s double bonded O with a double bonded C without producing constitutional isomers.

• The Wittig reaction is named after the German scientist, Georg Wittig, who discovered it and in 1979 he was awarded a Nobel Prize.

OCH3 CH2

Ph3P CH2

• The three step mechanism of the Wittig reaction is:• The negatively charged C atom of the ylide acts as the nucleophile, attacking

the partial positive charged C atom of a carbonyl. This displaces the π electrons to the O atom.

• The lone pair then re-bonds to the P atom of the salt.

• The thermodynamic drive of the intermediate continues the reaction forward in a single step, reducing the carbonyl to an alkene while oxidizing the salt.

O O

H2C PPh3

O

H2C PPh3

CH2

Ph3P OH2C PPh3

• Two examples of the Wittig reaction can be experimentally achieved by the synthesis of:

4-Methoxybenzealdehyde to4-Methoxystyrene (Fig. 2)

2,4-Dimethoxybenzealdehyde to 2,4-Dimethoxystyrene (Fig. 3)

• 4-Methoxybenzealdehyde 4-Methoxystyrene

• 2,4-Dimethoxybenzealdehyde 2,4-Dimethoxystyrene

2.04 g 4-Methoxybenzealdehyde

136.148 M 4-Methoxybenzealdehyde

Theoretical: (134.178 4-Methoxystyrene)

= 2.01g

2.49 g 2,4-Methoxybenzealdehyde

154.167 M 2,4-Methoxybenzealdehyde

Theoretical: (152.193 2,4-Methoxystyrene)

= 2.01g

1.7 g 4-Methoxystyrene

2.01g

Actual: (100%)

= 84.6%

1.94 g 2,4-Methoxystyrene

2.458g

Actual: (100%)

= 78.9%

There are slight differences between the spectrum of the two products.

Can you guess why?

------?????????------

O O

O

Synthesis of the products can be evaluated using 1H NMR.

O

Original Product ~R-CHO

Impurities

Impurities

Solvent CDCL3

Before Colum Chromatography

CDCL3

JcisJtrans

R R

H H

O

R R

H H

H

R R

H

HJcis

Jtrans

R R

O

H3C

R R

O

After Colum Chromatography

Impurities

Solvent CDCL3

O

O

Impurities

No original product peak

Before Colum Chromatography

CDCL3

JcisJtrans

Impurities

O

R R

H H

O

OR

R

H3C

H3C

R R

O H

O

O

After Colum Chromatography

H

R R

O

H

H

R R

O

The extra Methoxy group gives a different spectrum reading because

of the shielding effect from the donation of electrons from the

oxygen.

In these NMRs, there is ashift in the Benzene peaks

as well as distortionfrom the different hydrogens.

O O

O

There are slight differences between the spectrum of the two products.

QUESTIONS?

• 4-Methoxystyrene┼ 1H NMR (CDCl3, 300 MHz) δ 3.828 (s, 3H); 5.141 (d, J = 10.8, 1 H); 5.627 (d, J = 17.4,

1H); 6.682 (dd, J = 11.1, 17.7, 1H); 6.880 (d, J = 8.7, 2H); 7.367 (d, 8.7, 2H)• 2,4-Methoxystyrene┼

1H NMR (CDCl3, 300 MHz) δ 3.833 (d, J = 3.6, 6H); 5.157 (d, J = 11.1, 1H); 5.64 (d, J = 17.7, 1H); 6.48 (m); 6.962 (dd, J = 11.1, 17.7, 1H); 7.400 (d, J = 8.4, 1H)

┼ Denotes experimentally prepared products

References:Introduction to Organic Laboratory Techniques, A Microscale Approach, 4th Edition; Pavia, et al.Organic Chemistry, 4th Edition; Smith, et al.