Ether Reactions
Ether Reactions
Ethers are pretty unreactive functional groups. Although they are fairly unreactive, they do undergo reactions in the presence of strong acids. What part of an ether would react with H+ from an acid? What is the most negative part of an ether? Of course, the most negative site is the juicy lone pairs of electrons on the oxygen atom. Once the oxygen atom of an ether is protonated, half of the molecule becomes a great leaving group, an alcohol. The protonated ether can then be attacked by a nucleophile in an SN2 type reaction.
Ether cleavage with HBr, HI
HBr and HI can both protonate the ether and makes Br- and I-. Br- and I- are excellent nucleophiles, and they are weak bases. Think about that for a moment. If HBr and HI are strong acids, that means they want to give away H+. They do this because Br- and I- are quite stable anions because they are so large. That means Br- and I- are terrible bases because they do not want to grab an H+. So, in this reaction, Br- and I- will not deprotonate the ether, but will attack it as a nucleophile.
Overall:
HBr and HI with phenyl ethers
A phenyl group, because it is sp2 hybridized, cannot undergo an SN2 reaction with the halide. Therefore, phenyl ethers make phenol as a product and not a phenyl halide!
Overall:
3. What are the major organic products of the following reaction?
Beware of autooxidation!
Ethers, over time, slowly react with oxygen. They can oxidize and form explosive peroxides. This process takes months. Solvents like diethyl ether, THF, and dioxane should not be stores for long periods of time. One should only purchase an amount that can be used in about six months.
If you ever come across an old bottle of an ether, be very careful. Look carefully at the cap of the bottle to see if there is any white, crusty powder. This is an indication the ether has been peroxidized. If the lid to the bottle is twisted, it could generate a spark right next to the fuel, the ether, which is in the bottle. This can be very dangerous. Get professional help from your local fire department/bomb squad instead of taking this matter into your own hands.
One must also be careful when distilling ethers. Most ethers that have been peroxidized are not explosive until the peroxides have been concentrated. Imagine what could happen if you are in a lab and think you have an ether compound that is not pure. Perhaps you would think it is a good idea to distill this ether. You begin heating the ether using distillation glassware. The purified ether boils and condenses into your receiving flask giving you pure ether. But, there is less ether in the impure flask. The peroxidized compounds get more and more concentrated. Eventually, the flask with peroxidizable compounds boils uncontrollably, explodes, and sends glass shrapnel everywhere. Think twice before distilling ethers.
Sulfide Reactivity
Ethers are quite unreactive unless they react with a strong acid. Thioethers, on the other hand, are a little more reactive. Since sulfur is below oxygen in the periodic table, we know that sulfur is larger and less electronegative than oxygen. The sulfur atom of a thioether holds its electrons less tightly than the oxygen atom of an ether. There is a larger cloud of negative electrons around the sulfur atom of a thioether. These fluffy, lone pairs of negative electrons can act as nucleophiles and perform SN2 reactions by attacking alkyl halides. The thioethers, or sulfides, are alkylated to make a sulfonium salt.
Sulfonium salts are good alkylating agents. They are great electrophiles because they contain a very stable leaving group, a neutral thioether compound. Any weak nucleophile can attack a sulfonium’s alkyl group.
SAM
Sulfonium salts are biochemical agents that perform alkylating reactions in living things. For instance, in human adrenal glands, a molecule called SAM, S-adenosenylmethionine, is used as a methylating agent to transform norepinephrine into epinephrine (adrenaline).
Sulfide oxidation
Sulfur can expand its valence beyond the normal octet rule. Sulfides are therefore also easily oxidized. Sulfides can oxidize to sulfoxides which can oxidize to sulfones. The oxidation of dimethyl sulfide with hydrogen peroxide results in dimethyl sulfoxide (DMSO), which is a common solvent and used in drug delivery. DMSO can carry products through skin into the blood stream. Dimethyl sulfoxide can be further oxidized to a sulfone.
We have seen the oxidation of DMS to DMSO previously in the ozonolysis reaction of an alkene. Three oxygen atoms make up ozone. Dimethyl sulfide is oxidized to make DMSO using up one of the oxygen atoms. The other two oxygen atoms are used to make the two carbonyl groups.
Answers
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