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Ch. 13 - Alcohols and Carbonyl CompoundsWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Ch. 26 - Transition Metals
Oxidizing and Reducing Agents
Oxidizing Agent
Reducing Agent
Nucleophilic Addition
Preparation of Organometallics
Grignard Reaction
Protecting Alcohols from Organometallics
Organometallic Cumulative Practice
Additional Guides

Concept #1: Use of Protecting Groups


Now that we understand organometallics a little bit better, hopefully, you're aware of one of the major limitations that they have. And that limitation is that they tend to cross react with acidic hydrogens. So how do we prevent that from happening? Well, let's go ahead and talk about a strategy for that which is called protecting groups.
As I've explained before, organometallics are very powerful bases. They can obviously react as nucleophiles and attack electrophiles, but they can also react as bases and deprotonate things. What kind of things can they deprotonate? Well, they tend to just react with any acidic protons available and that ruins the reagent. What we've talked about already is that those acidic protons are usually stuff like carboxylic acid, very acidic; alcohol, pretty acidic; and water. These are all examples of protons that are so acidic that they're going to mess with the reagent instead of letting it react with an electrophile.
Let me give you an example. Let's say that I was trying to do a substitution reaction on this molecule. Notice that it has an alkyl halide on one side and an alcohol on the other. Now, notice that my reagent here is a Grignard. I've got my Grignard reagent. We know that the way that we like to draw Grignard reagents is as a CH3-. That tells my I've got a negative charge, it's going to attack some positive.
Alkyl halides, do CH3-'s or Grignards react with an alkyl halide? Absolutely. Remember that the alkyl halide happens to have a partial positive there. So I would expect to get an SN2 reaction on that alkyl halide.
But wait, we've got a problem. We've also got an alcohol on this molecule. That alcohol is going to be very acidic. What that means is that – notice I put pKa of 16. That's acidic enough to react with my Grignard. So what winds up happening is that instead of reacting in an SN2, that doesn't happen. It winds up reacting with the proton as an acid/base reaction. What we wind up getting is CH4 because now we've got the CH3 plus the H, and then you wind up getting a negative charge on the O. Now, by the way, the MgBr positive is just a spectator ion that happens to associate with the O.
This is considered ruined. This is not good. No bueno. Because now the Grignard can't react with the electrophile that I intended it to, which was this carbon right here.
So how do we prevent this from happening? Well, it turns out that alcohols can be protected. There are some strategies that we've used before to protect alcohols and this part is going to require a little bit of prior knowledge. If you've already learned about using protecting groups for alcohol, then we're going to review that right now. If you don't know how to use protecting groups for alcohol, then I would recommend going back to my lessons on protecting groups in the alcohol section and that will give you a better understanding, so you can understand this better.
But basically, there's two different ways, there's two different type of reagents that we can use to protect alcohols. Either we can use t-butyl ethers or silyl ethers. Both of them are two different ways to protect an alcohol from reaction. When you protect it, that means it's not going to be deprotonated by the organometallic. Instead, it's going to be locked up in that ether.
Just so you guys know, a really common acid that's used for protection is para-toluenesulfonic acid, which is kind of a long name, bit it's actually a very common acid in your book, but it's usually abbreviated. Instead of spelling it all like that, they usually say it that it's TsOH or that it's pTSA. Either way, both of them, just know that they're a source of H+ because this is an acid. An acid is used in protection. In a protection reaction, we always use one of these. We make an ether and the way we make it is through the reaction of an acid, like H+, and a double bond.
So for this problem, I'm going to go ahead and ask you guys to try to solve it on your own and try to get the final product. Now if you already have reviewed protecting groups from alcohol, then go ahead and try to solve it now. If not, if you have no clue what I'm talking about with protecting groups, then don't worry, just sit back and I'll explain the whole reaction in a second. So go ahead and try it out. 

Example #1: Provide mechanism and final product of transformation.


Alright guys so you can see that I have an organometallic here but I've got an issue my issue is that this organometallic if it gets exposed to that alcohol it's going to react with it and that's going to be a really bad cross-reaction it's going to mess up my organometallic so what can we do? We can use a protecting group, how does a protecting group work? Well in this case what I would do is I would take my isobutylene which is a molecule it looks like this, a double bond on a four carbon chain and what I would do is I would use PTSA which is a source of H plus, OK? So what that's going to do is it's going to protonate and I'm going to wind up getting a carbocation that looks like this according to this would be a markovnikov addition in case you're familiar with that term, OK? Now that carbocation winds up getting reacted by the alcohol, the alcohol grabs that carbocation so what we now get is an alcohol that looks like this, OH but now it's got a tert butyl ether on one side and a positive charge, OK? Cool OK that positive one's getting deprotonated, OK? So I would use the conjugate of that which is on the conjugate of PTSA but I could also just in this case I'll just use water, Ok? So I'm going to use water to deprotonate that and what I wind up getting is my T-butyl ether, OK? Now this alcohol it used to be an alcohol now this is considered a protected alcohol the reason it's protected is because ethers don't really react with anything, OK? So now I want to introduce my organolithium reagent I'm going to write a negative there because this is that's the best way to synthetically draw the product I'm going to take that negative and then attack the carbonyl, Ok? So I'm going to attack the carbonyl push the electrons up and notice that I don't have to worry about the organolithium reacting with the T-butyl ether or reacting with the alcohol, why? Because this entire thing is non-reactive, it's protected right now that's what protective means it's nonreactive because it's an ether and ethers really don't react with anything so they react with very little, Ok? So now I'm going to go ahead and draw my tetrahedral intermediate which is O negative now I've got a stage 2 stage 3 coming off of that and I still have my T-butyl ether, OK?

In my last step I'm going to use acid and what does acid do? Well What acid is going to do over water it's going to do two things first of all it's going to protonate, OK? So now this becomes and alcohol, second of all it's doing to deprotect this T-Butyl ether what I mean by deprotect is it takes it completely off and goes in the reverse direction, OK? So now instead of having a T-butyl ether you're going to want to getting the alcohol again, OK? And that just has to do with the fact that this whole thing that we've been drawing is a reversible reaction, OK? So this actually has an arrow going back, this part here actually has an arrow going backwards now the organometallic is a forwards reaction once we get to the organometallic it moves forwards but all I'm trying to say is that if you expose this to acid it can go back and regenerate that alcohol which is the whole definition of a protecting group that's why we use protecting groups because we can easily remove them afterwards so now my final product for this reaction is going to be OH here, ethyl group here and alcohol here and notice that I'm sorry I'll get out of the way so you guys can see so notice that now I have this alcohol back and I never reacted with it so the whole point of using protecting groups is that we can avoid ruining our own organometallic and react somewhere else on the reaction instead and then we can go back and deprotected and get that alcohol back, alright? Just so you guys know the one we just used is called a T-butyl ether but there's also another type of protective called a Silyl ether some professors require that you know it some professors don't so if you don't know about it it's fine but I'm just letting you know that's an alternative method to protect and you should know about it if I covered it in your lessons then you should know about if I didn't cover it and then don't worry about it. Alright guys so I hope that makes sense kind of an intro on protecting groups and an application of it in organometallics, alright? So hopefully that makes sense let's go ahead and move on.