CHEM 334L
Organic Chemistry Laboratory
Revision 1.0
“Green” Wittig Reaction
Preparation of (3E)-4-phenyl-3-buten-2-one
In this experiment (3E)-4-phenyl-3-buten-2-one, obtained through a “Green” Wittig
reaction of benzaldehyde with a stable phosphonium-ylid (methyl (triphenylphosphoranylidene)acetate) will be synthesized.
Green Chemistry
Green chemistry, also called sustainable chemistry, is a philosophy of chemical research
and engineering that encourages the design of products and processes that minimize the
use and generation of hazardous substances. Whereas environmental chemistry is the
chemistry of the natural environment, and of pollutant chemicals in nature, green
chemistry seeks to reduce and prevent pollution at its source. In 1990 the Pollution
Prevention Act was passed in the United States. This act helped create a modus operandi
for dealing with pollution in an original and innovative way. It aims to avoid problems
before they happen. (source: http://en.wikipedia.org/wiki/Green_chemistry)
Why water?
Over the last two or three decades it could be demonstrated that water as a solvent can
significantly increase the rates and the selectivities of several chemical reactions.
Besides this, there are many more reasons why we should consider using water as an
alternative solvent for organic reactions.
1.) There is no cheaper solvent available than water.
2.) Water, in contrast to many organic solvents is not inflammable, not explosive, not
carcinogenic and/or mutagenic.
3.) The use of water can reduce the problem of pollution by organic solvents.
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4.) For many reactions it is not necessary to perform tedious protection-deprotection
steps, which saves time, money and many steps in the synthetic process.
In 1998, Paul T. Anastas and John C. Warner published the so called “Twelve Principles
of Green Chemistry”
1. Prevention
It is better to prevent waste than to treat or clean up waste after it has been
created.
2. Atom Economy
Synthetic methods should be designed to maximize the incorporation of all
materials used in the process into the final product.
3. Less Hazardous Chemical Syntheses
Wherever practicable, synthetic methods should be designed to use and generate
substances that possess little or no toxicity to human health and the environment.
4. Designing Safer Chemicals
Chemical products should be designed to effect their desired function while
minimizing their toxicity.
5. Safer Solvents and Auxiliaries
The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be
made unnecessary wherever possible and innocuous when used.
6. Design for Energy Efficiency
Energy requirements of chemical processes should be recognized for their
environmental and economic impacts and should be minimized. If possible,
synthetic methods should be conducted at ambient temperature and pressure.
7. Use of Renewable Feedstocks
A raw material or feedstock should be renewable rather than depleting whenever
technically and economically practicable.
8. Reduce Derivatives
Unnecessary derivatization (use of blocking groups, protection/ deprotection,
temporary modification of physical/chemical processes) should be minimized or
avoided if possible, because such steps require additional reagents and can
generate waste.
9. Catalysis
Catalytic reagents (as selective as possible) are superior to stoichiometric
reagents.
10. Design for Degradation
Chemical products should be designed so that at the end of their function they
break down into innocuous degradation products and do not persist in the
environment.
11. Real-time analysis for Pollution Prevention
Analytical methodologies need to be further developed to allow for real-time, inprocess monitoring and control prior to the formation of hazardous substances.
12. Inherently Safer Chemistry for Accident Prevention
Substances and the form of a substance used in a chemical process should be
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chosen to minimize the potential for chemical accidents, including releases,
explosions, and fires.
Source: http://www.epa.gov/greenchemistry/pubs/principles.html
Wittig Reaction
The Wittig reaction is a reaction between an aldehyde or a ketone with a triphenyl
phosphonium ylide (Wittig reagent) to yield the corresponding alkane and
triphenylphospine oxide. The Wittig reaction is a very powerful method for the
stereoselective synthesis of alkenes from aldehydes and ketones.
Georg Wittig (June 16, 1897 – August 26, 1987) was born in
Berlin, Germany. He was a German chemist working on a
method to synthesize alkenes from aldehydes or ketones by
using so called phosphonium ylides (Wittig reaction).
In 1979 he obtained the Nobel Prize in Chemistry for his work
in the field of phosphorous containing compounds. He shared
this Nobel Prize with Herbert C. Brown who worked in the
field of boron containing compounds.
Source:
http://bioinorganic.disav.unipmn.it/nobel_chemistry.html
C O
+
(C6H5)3P C
C C
Ylide
Alkene
Aldehyde
or ketone
+
(C6H5)3P O
Triphenylphosphine oxide
The Wittig Reaction
If not commercially available, the preparation of the phosphorous ylides can be
accomplished in a two-step sequence. The first step is the nucleophilic displacement of
halide by triphenylphosphine to furnish an alkyltriphenylphosphonium salt.
R
(C6H5) 3P
Triphenylphosphine
CH2 X
X = Cl, Br, I
RCH2P(C6H5)3 X
An alkyltriphenylphosphonium halide
Phosphonium Salt Synthesis
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In the second step, deprotonation of the alkyltriphenylphosphonium halide using bases
such as alkoxides, sodium hydride, or butyllithium, gives the ylide.
Ylide Formation
The Wittig reaction is a valuable addition to our synthetic arsenal because it forms
carbon-carbon double bonds. In contrast with eliminations, it gives rise to alkenes in
which the position of the newly formed double bond is unambiguous.
Mechanism of the Wittig Reaction
Mechanism of the Wittig Reaction
Stereoselectivity of the Wittig Reaction
The stereoselectivity of the Wittig Reaction depends on the structure of the ylide.
Stabilized ylides: They have a group (like carbonyl) that can help stabilize the carbon’s
negative charge. These ylides form primarily E alkenes
Unstabilized ylides: They don’t have a group which stabilizes the carbon’s negative
charge. These ylides form primarily Z alkenes.
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Pre-Lab Questions
1.
Propose syntheses of 3-methylenecyclohexene from
(a) 2-cyclohexenone
(b) 3-bromocyclohexene
using Wittig reactions.
2.
Draw the structure of (3E)-4-phenyl-3-buten-2-one and (3Z)-4-phenyl-3-buten-2one. Why will you obtain mainly the E alkene?
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Procedure
(3E)-4-phenyl-3-buten-2-one
1.
In a 50 mL flask, combine 531 mg (5 mmol, 1.0 eq) benzaldehyde with 2 g (6
mmol, 1.2 eq) methyl (triphenylphosphoranylidene)acetate and 25 mL of water.
Add a magnetic stir-bar to the reaction mixture and stir vigorously for 1h at room
temperature.
2.
Extract the reaction mixture with dichloromethane (CH2Cl2) and dry over
anhydrous magnesium sulfate.
3.
Add sodium sulfate or magnesium sulfate to dry the solution and stir for 10 min.
Gravity filter into a second 125 mL Erlenmeyer flask to remove the drying agent
and evaporate the dichloromethane using a rotary evaporator.
Spectroscopy
1.
Obtain a NMR spectrum of the product. Consult with your laboratory instructor
about how to do this.
2.
Assign all the NMR peaks in the spectrum. Determine the E,Z-ratio of the obtained
alkenes.
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Post-Lab Questions
1.
What carbonyl compound and what phosphonium ylide are needed to synthesize the
following compounds?