Experiment 21 – The Wittig Reaction

Introduction:

Wittig Reaction, the reaction of an aldehyde or ketone with a triphenyl

phosphonium ylide (the Wittig reagent) to produce an alkene and triphenylphosphine

oxide, is of great use in forming carbon-carbon bond between reactants. The Wittig

reaction was discovered in 1954 by Georg Wittig, for which he was awarded the

Nobel Prize in Chemistry in 1979. 1 The development of Wittig Reagents were

examined in a recent general review by Eisch, in which the author discussed Georg

Wittig’s discovery of the reaction along with his other significant contributions in

organic chemistry.2

In this experiment, methyl (triphenylphosphoranylidene) acetate (1) was used to

react with 2-nitrobenzaldehyde (2), with the application of heat from microwave

radiation, to produce both (Z)-methyl 3-(2-nitrophenyl) acrylate (3) and (E)-methyl 3-

(2-nitrophenyl) acrylate (4), with (E)-methyl 3-(2-nitrophenyl) acrylate as the major

product, and triphenylphosphine oxide (5) (Scheme 1).

Scheme 1. Wittig Reaction of methyl (triphenylphosphoranylidene) acetate with

2-nitrobenzaldehyde.

The mechanism of this reaction (Scheme 2) involves the nucleophilic addition of

the phorphorus ylide (1) to the carbonyl carbon in 2-nitrobenzaldehyde (2), forming a

new carbon-carbon bond and providing the intermediate (6). Addition from the

electron rich oxygen to the positively charged phosphorus could then produce either

the (E) oxaphosphetane (7) or the (Z) oxaphosphetane (8). Upon breaking of the ring,

triphenylphosphine oxide (5) and either the (Z)-methyl 3-(2-nitrophenyl) acrylate (3)

or the (E)-methyl 3-(2-nitrophenyl) acrylate (4) could be produced.

Scheme 2. Mechanism of the Wittig Reaction.

Experimental Section:

．(Z)-methyl 3-(2-nitrophenyl) acrylate (3).

．(E)-methyl 3-(2-nitrophenyl) acrylate (4).

．Triphenylphosphine oxide (5).

Solid 2-nitrobenzaldehyde (80 mg,0.50 mmol), methyl (triphenylphosphoranylidene)

acetate (175 mg, 0.52 mmol), and silica gel (104 mg) were combined in a 1-dram vial.

The evenly distributed mixture was heated with microwave radiation at power level

four for two minutes. The solid mass was mixed again and cooled to room

temperature. A chromatography column was packed with 10 mL of 50:50 ethyl

acetate: hexane solution and 0.65 g of silica gel. The reaction mixture was then added

directly to the packed column. Subsequently, column chromatography was used to

separate the products. 4 fractions of 1.5 mL of solution was collected as well as a fifth

fraction of the remaining solution. Solutions of triphenylphosphine oxide and the five

fractions were each spotted in a lane on TLC pates. The plates were developed in

50:50 hexane: ethyl acetate and visualized using UV lamp. Fractions determined to

contain only the alkene product were combined in a tared 25-mL filter flask. Yellow

particle-like crystals of the alkene product were collected by evaporating the solvent

with air and pulling a vacuum on the system. Product of 0.0990g (0.478 mmol,

90.3%) impure (Z)-methyl 3-(2-nitrophenyl) acrylate (3) and (E)-methyl 3-(2-

nitrophenyl) acrylate (4) crystalline solid were obtained, with the (E) alkene isomer

determined to be the major product, mp 54.8 – 64.2 °C (lit3 72 – 74°C). 1H NMR

(400 MHz, CDCl3) δ 3.82 (s, 3H), 6.36 (d, J = 15.8 Hz, 1H), 7.55 (d of d, J = 2.16 &

J = 1.56, 1H), 7.64 (d of d, J = 5.71 & J = 2.23, 1H), 7.66 (d, J = 6.94 Hz, 1H), 8.03

(d, J = 8.0 Hz, 1H), 8.1 (d, J = 15.9 Hz, 1H). 13C NMR (100.6 MHz, CDCl3) δ

166.2, 148.2, 140.1, 133.5, 130.5, 130.3, 129.1, 124.9, 122.8, 52.01.

References:

1) Gericke, D. 1979 Nobel Prize in chemistry for the Wittig reaction as the source of

multiple syntheses. Georg Wittig the sixtieth German Nobel Prize recipient.

Fortschritte der Medizin 1979, 97(43), 1958-1964.

2) J. J. Eisch, Organometallics, 2002, 21, 5439–5463.

3) Methyl (2E)-3-(2-nitrophenyl)acrylate

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