Oxymercuration/Demercuration
Oxymercuration/Demercuration -
with water -
A triangle reaction
A good, gentle way to make Markovnikov alcohols is oxymercuration in water followed by demercuration. This is an example of what I call a Triangle Reaction. If you have not yet read about Triangle reactions and the analogy we use for them, go do that first here.
Oxymercuration in water
To perform the oxymercuration, mercuric acetate, Hg(OAc)2, is used. There are two common oxidation states of mercury, 1+ and 2+. Mercuric refers to the higher oxidation state, Hg2+. Acetate (OAc) is CH3CO2-. There needs to be two of these acetates with -1 charge to balance the 2+ charge of the mercury. The key first step in the oxymercuration of an alkene is the breaking apart of the mercuric acetate to form the electrophilic +HgOAc.
The negative pi-electrons of the alkene eagerly attack the positively charged, electrophilic +HgOAc. The pi-electrons attack to form the triangular mercurium ion. The two electrons from the pi bond go towards the Hg+, and two electrons return towards the pi bond. This causes the oxidation state of the mercury not to change so it remains Hg+. These triangles are formed when very large, soft atoms like mercury are used in the electrophile. The mercury atom is so large, it takes both carbon atoms to hold up. The victim in our triangle analogy is now holding a “+” over his head indicating he has money.
When the reaction is run in water, a weak nucleophile is present. Water is a stable, happy molecule. It will not attack a triangle compound unless it is coaxed in by money in some bags. In this case, the positive charge is shared over the two carbon atoms of the triangle. The more substituted carbon atom (on the right) carries a greater partial positive charge. Water then attacks the carbon atom with the greatest partial positive charge. In our criminal/victim analogy, the right carbon atom of the triangle is holding more bags and the + money is kept on the right carbon atom of the triangle under the bags. From what direction will the water attack the triangle? The large HgOAc blocks the topside of the mercurium ion triangle from attack, so the water must attack from the backside. It attacks, and the electrons go up onto the positive mercury. The neutral mercury acetate that is formed is a good leaving group—even though it is still attached to the left triangle carbon of our molecule. Finally, another water molecule cleans up the protonated alcohol to give us a mercury-alcohol compound.
Demercuration
The final step is demercuration, where HgOAc is replaced with H. Sodium borohydride (NaBH4) is a source of hydride (H-). This H- directly replaces the HgOAc. Don’t worry about the mechanism of this step. The mechanism will only confuse you at this state, so this is one of those instances where you should simply memorize this.
The benefits of oxymercuration and demercuration are:
1) a regular carbocation is not formed, so there is no chance for rearrangements.
2) the reaction is gentler than using sulfuric acid.
3) the reaction tends to go in high yield.
Are there any drawbacks to the oxymercuration/demercuration reaction? You may have already guessed it. Any time a reaction uses mercury, we need to be careful. Mercuric acetate and our mercury-containing products are toxic. We need to be very careful using them and be careful that we properly dispose of our waste.
Oxymercuration/Demercuration -
with alcohol -
a Triangle Reaction
Oxymercuration in alcohol
Once again, mercuric acetate is used to make the triangular mercurium ion. If water is not used as our solvent, it cannot react as the nucleophile. If alcohol is used as the solvent, the lone pair of electrons on the alcohol can act as a weak nucleophile and attack the mercurium. Again, it attacks the carbon atom of the mercurium triangle with the greatest partially positive charge. The electron bond goes up onto the mercury cation to make a good, neutral mercury leaving group. The protonated –OR group is deprotonated with another molecule of solvent to make a mercury-ether containing compound. Many different Markovnikov ethers can be made depending on the alcohol used as the solvent. R = CH3 for methanol, R = CH2CH3 for ethanol, etc.
Demercuration
Sodium borohydride (NaBH4) is once again used to replace HgOAc with H- making a Markovnikov ether.
Markovnikov hydration of alkyne
Alkynes, with their two pi-bonds, can also react in an oxymercuration-demercuration reaction. The reaction is very similar to that for an alkene with a twist at the end. Instead of mercuric acetate, the oxymercuration of alkynes usually involves mercuric sulfate and aqueous sulfuric acid. Like with alkenes, this results in the addition of water across a pi-bond resulting in a Markovnikov alcohol. Only one pi-bond of the triple bond reacted, so alkene remains. This vinyl alcohol is called an enol (pronounced “een-awl”). The “enol” name comes from this compound being an alkene (ene) and an alcohol (ol).
Enols tend to be unstable. Enols are in equilibrium with their isomer, the ketone. These isomers differ only in the location of one proton and a double bond. Such isomers are called tautomers (pronounced “taw-toe-mers”). The ketone and enol are called keto-enol tautomers. The transformation of one into another is called a keto-enol tautomerization. The process itself is called keto-enol tautomerism. In the equilibrium of the two, the keto form predominates. Take careful notice of the transformation. The hydrogen atom moves from the alcohol of the enol to the alpha carbon. The pi-bond of the alkene of the enol moves to make a carbonyl (a ketone).
Keto-enol tautomerization
Overall Reaction
The tautomerization is acid-catalyzed since sulfuric acid is used in the reaction. H+ is available because of the acid. To write the mechanism of the acid-catalyzed keto-enol tautomerization, protonate the enol at the alpha-carbon, draw resonance forms, and clean it up to make a ketone.
Acid-catalyzed keto-enol tautomerization
3. Draw the products of the following reactions.
a)
b)
c)
d)
Answers
3.
a)
b)
c)
d)
