Williamson ether synthesis

one way to make ethers is to use the Williamson ether synthesis which is where you start with an alcohol and you add a strong base to deprotonate the alcohol once you deprotonate the alcohol you add an alkyl halide and primary alkyl halides work the best we'll talk about why in a minute and what happens is you end up putting the R prime group from your alkyl halide onto what used to be your alcohol to form your ether that so let's look at the mechanism for the Williamson ether synthesis where you start with your alcohol we know that alcohols can function as weak acids so if you're if you react an alcohol with a strong base so then like sodium hydride alright so we know that the hydride portion of the molecule is going to function as a strong base this lone pair of electrons is going to take that proton which is going to kick these electrons off onto the oxygen so if we're drawing the product of that acid-base reaction we now have an oxygen with three lone pairs of electrons around it giving it a negative 1 formal charge we call that an alkoxide anion which would interact with the positively charged sodium ion floating around right so there's some electrostatic or ionic interaction between those opposite charges and here's where you introduce your alkyl halide so if we draw our alkyl halide it would look like this alright and we know that there's an electronegativity difference between our halogen and our carbon where our halogen is going to be partially negative and our carbon is going to be partially positive partially positive carbon means that that carbon wants electrons it's going to function as an electrophile on the next step of the mechanism and a lone pair of electrons and the oxygen is going to function as a nucleophile so opposite charges attract lone pair of electrons on our nucleophile are going to attack our electrophile our carbon at the same time the electrons in the bond between the carbon the halogen are going to kick off onto the halogen like that so this is an sn2 type mechanism alright so this is an sn2 type mechanism which is why a primary alkyl halide will work the best because that has the decreased steric hindrance right compared to other alkyl halides so what will happen is after the nucleophilic attack we're going to attach our oxygen to our carbon like that and we form our ether so if we wanted to we could just rewrite our eat our ether like this right to show it as as we add it on an R prime group like that let's look at an example of the Williamson ether synthesis so if I start with if I start with molecule over here on the left and it's kind of interesting looking molecules called beta naphthol and so beta naphthol has two rings together like this and then there's an O H coming off of one of the rings like that so that's beta naphthol and in the first part we're going to add potassium hydroxide so in the first step potassium hydroxide as our base now potassium hydroxide is not as strong of a base as sodium hydride is but in this case it's okay to use a little bit weaker base so the lone pair of electrons on the hydroxide I'm going to take that proton leaving these electrons behind on the oxygen so when we draw the conjugate base to beta naphthol alright we can go ahead and show that we're going to take off that proton alright which is going to leave that oxygen there with three lone pairs of electrons and giving it a negative 1 formal charge all right so this is our alkoxide anion and this alkoxide anion is resonance stabilized so a resonance stabilized conjugate base right stabilizes the conjugate base which makes beta naphthol a little bit better acid than then other alcohols that we will talk about so since beta naphthol is a little bit more acidic that's why it's okay for us to use a weaker base for this example so potassium hydroxide is is strong enough to take away the acidic proton on beta naphthol because the conjugate base debated naphthol is resonance stabilized so in the second step once we formed our once we have formed our alkoxide anion this is where we add our alkyl halide right so if I add my alkyl halide in my second step let's see if we can have enough room here I'm going to use methyl ayuh died as our alkyl halide so methyl iodine looks like that and once again we know this carbon is going to be the electrophilic carbon so nucleophile electrophile alright so a lone pair of electrons on the oxygen attacks the carbon kicks these electrons off onto the iodine and we form our product so let's go ahead and draw the ether product that will result so these rings are going to stay the same like that and we're now are going to have our oxygen attached to a methyl group which came from the methyl iodide like that so we formed our product this product is called Nealon which is a fixative used in perfume so this has an interesting smell to it so if you ever get a chance to do this Williamson ether synthesis it's it's just interesting to see to see what Nederland smells like what it looks like and to think about it as being a component of some perfumes let's let's think about synthesizing and ether so if you were if you were given a problem where the questions is something like okay here is the ether that you want to synthesize you know what would you need in order to do so so you need to think about okay there's my ether and I'm going to make it from some other things over here and if I analyze the alkyl groups attached to my ether all right I have a methyl group over here and just be like a cyclohexyl group over here and one of those two groups I'm going to use for my alkyl halides you want to use the group that's the least sterically hindered since it's an sn2 type mechanism so you want to go you want to go with the methyl group right so and their second step you would like you would need to add something like methyl iodide right that's the least sterically hindered so that's going to improve your yield on this reaction so that's the second step and in the first step you'd have to add a strong base so we'll use a sodium hydride here and your alcohol therefore must must be it must come from this right so this must be where your alcohol comes from so if I'm going to show my starting alcohol all right it would have to look like this okay so if I had that alcohol in first step sodium hydride I take off that proton form an alkoxide that alkoxide nucleophilic attacks the methyl iodide to add the methyl group on and to form the ether on the right so that's how to think about using the Williamson ether synthesis right so think about retro synthesis and think about think about which alkyl group is the best one to use for your alkyl halides