Hi everyone, this is lecture 12-3 and we're going to be looking at a new multi-step reaction called the Grignard reaction. This is probably one of the most important multi-step reactions that we're going to see because it leads to the formation of a new carbon-carbon bond. And those types of reactions are really hard to come by, at least those that are really successful. Another important outcome. of this reaction, of this multi-step synthesis, other than the fact that you get a new carbon-carbon covalent bond, is that the products are alcohols, either a primary, a secondary, or a tertiary.
So the three-step series of reactions first includes a rather unusual one that we have not seen before, and it involves a metal, magnesium, inserting in between a carbon and a halogen. So in the reaction, the general reaction you see below, you have an alkyl bromide reacting with magnesium. The solvent is ether. And notice that the magnesium has inserted itself right in between the carbon and the bromine, or the carbon and the halogen.
This is referred to as an organometallic. The bond here that's formed is not an ionic bond. This is actually a coordinate covalent bond. It is partially covalent, although most of the electron density is very close to the carbon.
That's why we show the carbon with a negative charge and the magnesium bearing a positive charge. This organometallic product that's formed in this first step is referred to as the Grignard reagent, named after the discoverer, Professor Grignard, and the importance of the Grignard reagent. is that it now reacts with some type of an oxygen-containing compound, either an aldehyde, a ketone, an ester, or an epoxide, producing a new carbon-carbon bond and an alcohol of some type. So I want to go through very quickly and in general terms the three steps of this multi-step reaction and then look at each step in a little more detail right after this. So in step one, we have an alkyl halide, typically an alkyl bromide or an alkyl chloride, and it reacts with magnesium metal in ether.
So you literally have pieces of magnesium metal floating around in the ether. The magnesium inserts itself in between the carbon and the bromine, giving you this organometallic Grignard reagent. That is reaction step number one. Step number two.
you add in some oxygen compound, aldehyde, ketone, ester, or epoxide. And what happens is that the carbon of the R group acts like a nucleophile. It adds to the carbon of the oxygen-containing compound.
And in the case of the carbonyl, the electrons in the double bond get pushed up onto the oxygen. So the new carbon-carbon bond you're forming is between the carbon of the R group and the carbon of the oxygen-containing compound. So in the product from reaction step number two, here is the new bond that was formed between the R group and the carbon of this oxygen compound.
This is, by the way, a ketone, and the two methyl groups of the ketone are right here. The electrons in the pi bond went on to the oxygen, and that now forms a regular ionic salt. with magnesium bromide. The last step of this multi-step synthesis is to do an acid-base step to protonate this intermediate, and that gives us the alcohol product and some salts, and the little squiggly red line is to show the new bond that was formed. All right, let's now look at each step in a little bit more detail.
Okay, so step one. part 1, step 1. Okay, the carbon, for the carbon to be aimed to act as a nucleophile, which is pretty rare, it is activated by forming the Grignard reagent. Okay, so that is the purpose of doing this Grignard reaction, to turn carbon, a carbon atom, into a nucleophile.
This is done with magnesium and the solvent is ether. You see the Grignard reagent and how the magnesium has inserted itself right in between. the R group and the halogen.
In terms of the scope of the reaction, the alkyl halide can be primary, secondary, or tertiary. The alkyl halide can be a vinyl halide. In other words, the halogen can be bonded to an sp2 carbon.
And the halogen can even be bonded to a benzene ring. In other words, a phenyl halide. So, so far, there are absolutely no limitations. This is a very straightforward reaction.
very versatile. The ether solvent is needed because we have to keep water away from this reaction. We'll talk about that in just a minute.
And we form the Grignard reagent and basically a negative charge on carbon or a carbon anion. Step 2. Alright, we're going to talk a little bit about what the Grignard Reagent is. First off, the Grignard Reagent, more than anything else, is a strong base. You have a carbon with a negative charge on it. Even though our preference, or the role, the goal of the Grignard Reaction is to use carbon as a nucleophile, if there are any acidic protons around, that will be the preferential reaction.
So if water is contaminating your reaction mixture, the Grignard reagent will react with water first. You'll end up putting a proton on the R group and simply getting an alkane. We have no need to synthesize alkanes.
So it's very important when you're doing this reaction in lab that your glassware must be absolutely dry. The same thing with the chemical reagents you're using. They must be dry. So you don't want to go handling things with your fingers.
The second thing that a Grignard reagent is, is a great nucleophile. And this is the role of the Grignard reaction. We want the carbon nucleophile to be able to add to the carbonyl carbon of some oxygen-containing compound.
That forms this intermediate, which is getting us on our way to forming an alcohol product. Now, in terms of the types of oxygen-containing compounds, if you have an aldehyde, where you have a carbonyl group bonded to a R group and a hydrogen. The product here will be a secondary alcohol.
Notice that the dipole here is showing that there's more positive charge on the carbon and more negative charge on the oxygen. That's why the Grignard reagent is attracted to that particular carbon, and the electrons eventually end up on the oxygen. So aldehydes will give you a secondary alcohol.
A ketone with two R groups bonded to the carbonyl will give you a tertiary alcohol. And ester, and ester is a little strange. We'll talk about those in the next lecture. Esters always give you tertiary alcohols. And the reason that happens is that actually two Grignard reagents, two of these R groups, must add to this carbon.
One breaks the spawn. The other R group pushes a pair of electrons on the oxygen. Esters always give tertiary alcohols.
And finally, epoxides. Epoxides can give you primary, secondary, or tertiary alcohols. With epoxides, the Grignard reagent must add to the least substituted carbon atom.
More examples of this on the next lecture. ok the final step part three is simply an acid based step all we want to do is to neutralize this oxygen so we use a weak very weak aqueous acid usually it's actually actually the usual thing we use is is a solution of ammonium chloride a very weak acid and that gives you your substituted alcohol and that is the end of this lecture