Symmetrical aliphatic ethers may be prepared from the simpler primary and secondary alcohols by heat — Organic Chemistry Chemistry Question
The Williamson Synthesis of Ethers
Symmetrical aliphatic ethers may be prepared from the simpler primary and secondary alcohols by heating with sulphuric acid, but dehydration to the alkene is an important competing reaction. The sulphuric acid process is unsuited to the preparation of ethers from tertiary alcohols and of unsymmetrical ethers.
The Williamson synthesis, using an alkyl halide and a metal alkoxide, is of broader scope and can be used to obtain symmetrical or unsymmetrical ethers. For the latter type, either of two combinations of reactants is possible.
The proper choice depends mainly upon the structure of the alkyl halides involved. Competition arises between the substitution reaction (SN2) to an ether ( 1° > 2° >> 3° halides ) and the elimination of HX to form an alkene ( 3° >> 2° > 1° halides ). Therefore 3° halides are not suitable for the reaction, but ethers having a 3° alkyl group can be prepared from a 3° alkoxide and a 1° halide.
The Williamson synthesis is an excellent method for the preparation of alkylaryl ethers – 1° and 2° alkyl halides react readily with sodium or potassium phenoxides.
In this experiment benzyl chloride is reacted with 4-chlorophenol under basic conditions to produce an ether.
The use of a fume cupboard protective clothing including gloves is essential for this experiment.
[VISUAL]
Chemicals
* benzyl chloride (*), liquid
* 4-chlorophenol, solid
* potassium hydroxide, solid
* lithium iodide, solid
* diethyl ether, liquid
* petroleum ether (*), liquid
* absolute ethanol, liquid
(*) This compound will not be used at the IChO competition
Experimental
a) Add absolute ethanol (50 cm3) to potassium hydroxide pellets (0.87 g) in a 100 cm3 round bottomed flask with a ground-glass joint.
b) Add 4-Chlorophenol (2 g) followed by benzyl chloride (1.8 cm3) and lithium iodide (approx. 20 mg - the end of a micro-spatula).
c) Add a boiling stick, fit the flask with a condenser and heat under gentle reflux for 1 hour (an isomantle is recommended but keep careful control of the heating to maintain gentle reflux otherwise vigorous bumping can occur).
d) Allow the reaction mixture to cool and pour onto ice/water (150 cm3) with swirling.
Isolate the crude product by suction filtration and wash with ice-cold water (3 × 10 cm3). Press dry on the filter.
f) The crude product should be recrystallised from aqueous ethanol. This entails dissolving your compound in the minimum volume of boiling ethanol and then adding water dropwise until the first crystals appear. Then set the hot solution aside to cool in the usual manner.
g) Record the yield of your product and run a thin layer chromatogram on a silica plate using ether/petroleum ether 2:8 as the eluent. Record the Rf value.
h) Measure and record the m.p.
What is the role of the lithium iodide added to the reaction mixture?
Model Answer
Lithium iodide transfers benzyl chloride to more reactive benzyl iodide.
Substantial increases in the rate of reaction are often observed if SN2 reactions are carried out in solvents such as dimethylformamide (DMF) or dimethylsulphoxide (DMSO). Suggest why this is so.
Model Answer
This is true for those SN2 reactions where transition state is more polar (better stabilised by polar solvent) than reactants. Williamson synthesis of ethers uses alkoxide as anionic nucleophile, it has less polar transition state than reactants and therefore will be retarded in more polar solvent.