A traditional method for the reduction of alkynes to trans-alkenes is to dissolve metal reduction using sodium or lithium in ammonia. However, we can also use Zinc as a metal to reduce alkynes.
In this specific case, by changing the proton source in the reaction, the dissolving Zinc metal reduction of ethyl phenylpropiolate to the corresponding cinnamate ester can be stereochemically controlled.
The product of the reaction will be a mixture of cis and trans ester. By this reaction, we can see the efficiency of Zinc in the reduction of alkynes.
The picture above shows a few of the steps in the creation of amphetamines. In these steps, tosyl chloride is added to (2,5-dimethoxyl-4-methylphenyl)-2-propanol to create the tosylate. After this step, the reaction can proceed in one of two ways. If the chirality of the amphetamine is not important, ammonia is added to the tosylate to give 2,5-dimethoxy-4-methylamphetamine. This reaction has an 80% yield, but has a racemic mixture of products because it is thought to be an SN1 reaction. If the chirality is important, the tosylate is converted into an azide with sodium azide, then hydrogenated using a paladium catalyst to form 2,5-dimethoxy-4-methylamphetamine. Forming the amphetamine using this method gives a final yield of about 77%. The chirality of the original alcohol is inverted by the tosylation, so reacting an (S)-alcohol with the tosyl-azide-hydrogen sequence would give an (R)-amphetamine, and vice versa.
The above reaction is an example of a Williamson synthesis of an ether. It is one the earlier steps in the reaction mechanism resulting in the octaethylene glycol derivative of 1,1,1,3,5,5,5-heptamethyltrisiloxane. Such an initial Williamson synthesis reaction had to be carried out so that later steps in the reaction—that is, ones involving material types not readily accessible—could successfully yield the derivative product. The resultant glycol derivative is an example of a defined surfactant. This particular journal article focused on the correlation between surfactant constituents and the effect on properties such as spreading performance.
The Williamson synthesis involves an SN2 reaction in which a halogen, sulfonyl, or sulfate group is replaced by an alkoxide ion, which can itself be prepared by a reaction of the alcohol with an active metal such as sodium or its hydride (i.e. NaH). The resultant alkoxide salt then reacts with the alkyl halide (must be primary) to produce an ether via the SN2 mechanism.
Other examples of Williamson synthesis of ethers can be found in this same reaction mechanism used to produce the surfactant.
