in Chapter 17 we're going to be paying attention to the alpha carbon on our carbonyl compounds both aldehydes and ketones from chapter 16 and carboxylic acids and derivatives from chapter 15 because on this carbon that's adjacent to our carbonyl we have a whole second site of reactivity that we didn't discuss in chapter 15 and 16 those earlier chapters we just looked at a nucleophile coming in and attacking the carbonyl carbon which it certainly can do right we can do a nucleophilic acyl substitution that's what a lot of chapter 15 was about we can do a nucleophilic addition or an addition elimination like we saw in chapter 16 but a base can also come in and pull a proton off of the alpha carbon itself and that extra acidity that we have at the alpha carbon changes a lot of the reactivity that we might expect so the question we need to think about first is why is that hydrogen acidic because we've never considered hydrogen's on sp3 carbons to be acidic they typically have a PKA higher than 60 it's a relatively non-polar bond between carbon and hydrogen and so we have no reason to think that acidic especially when we're sp3 hybridized we know as we go to sp2 and then SB we can get more acidic but here we're still looking at sp3 hybridization so why is this hydrogen on the alpha carbon of a carbonyl compound in fact acidic and that lower PKA you see here a range of 16 to 20 on aldehydes and ketones and 25 on esters why are they so much lower than that 60 that we saw before well that alpha carbon right obviously must be acidic based on the acidity basicity principles we've always been discussing right it must have a more stable conjugate base and I hope you're already thinking all right it must have something to do with that carbonyl and in fact that it does if we do have one definition down there at the bottom if we have something that has an acidic hydrogen on an sp3 carbon which we have in this situation that's called a carbon acid in this next table table 17.1 from your textbook has examples of a lot of carbon acids you see lower PK's here for hydrogen's that are bonded to sp3 carbons so let's get into that business why is it well previously if it's just an sp3 hybridized carbon nothing else is going on if I'm to deprotonate that compound the electrons that are left behind go directly on to carbon they're localized on to an element that's not electronegative right carbon doesn't like to be a carbon ion like that but here with the alpha carbon on my carbonyls when I D protonate in the Alpha position those lone pair electrons that are left behind get delocalized right throughout the system and we've seen several times now D localization increases stability and in fact not only are they deal o close in this pi system here but they get delocalized onto oxygen which is inherently electronegative and happier to accommodate those electrons then carbon was right so two factors that are increasing the acidity at this position even though it's an sp3 hybridized carbon it's acidic because those electrons that are left behind are delocalized and oxygens happy to accept them but the next question we need to think about is why we're aldehydes and ketones more acidic than esters at those aldehydes and ketones 16 to 20 esters about 25 and the reason for that is when we have an ester we have some competition here this is showing deprotonation of in these are over here deprotonation in the Alpha position right but we compete with electrons being delocalized from the ass itself so notice there's two different contributors on the left and the right side there so because of that competition right it's less readily able to bear that electron pair so esters are less acidic than aldehydes and ketones are and we have other things that can form carbon acids as well all right with a nitro group or a nitrile or with an amid as long as we have the ability to delocalized the electrons that get left behind in the Alpha position something will serve as a carbon acid in in all three of these situations we get delocalized onto an electronegative atom and if we have two groups that we can delocalized onto we get even more acidic so if we have a beta die ketone or a beta Akito ester these compounds over here right so we've got in one position and then another carbonyl in the beta position that's what beta comes from here that alpha carbon that's between the two of them i've is incredibly acidic notice how low these values are now eight point nine ten point seven these are even more acidic than just having an aldehyde or a ketone or an ester because those electrons that get left behind can be delocalized two ways now on to two different oxygens that's shown right here okay deprotonate I can delocalized to my left eye candy' localized to my right so that gives me a lot of electron density on my oxygens up top it gives me an incredible incredibly acidic hydrogen there in the middle so we're gonna use those ideas to think about a couple of reactions that's what a lot of this chapter is about starting first by jumping back ten chapters to something we first introduced in Chapter seven the idea of ketones and enols and specifically keto enol tautomerization and if you recall from Chapter seven tautomers the keto tautomer in the enol tautomer here differ in the location of their hi bond and a hydrogen right from the Quito to the enol our hydrogen moves up our PI bond has moved down and in most situations we said the keto tautomer was more stable than the enol here we saw that tautomerization back in Chapter 7 and noticed the difference at a ninety nine point nine two point one percent but now that we've got this idea of Dai ketones to think about one thing you should have on your radar is that hydrogen bonding can stabilize in enol tautomer i in one of those positions right hydrogen bonding there between the carbonyl oxygen and that hydrogen so that changes our ratio from ninety nine point nine point one to eighty-five 15 makes the enol tautomer much more stable okay but the keto tautomer still predominates the one situation we're gonna be looking out for immediately is phenol with phenol over here the enol tautomer is actually more stable and predominates because in the enol we've established aromaticity right that aromatic pi bond there in benzene okay so know that for short right aromaticity trumps everything if there's a way that we can get something to be aromatic it will always be more stable which is why the enol tautomer dominates in this situation so now knowing that and knowing what we know about the alpha carbon we're gonna think about that conversion again tautomerization which can be acid or base catalyzed and then we'll see how some other things in the pot can change the substituents we can put at the alpha carbon these are things we've seen before in chapter 7 ok but you can get them in your notes again it's probably been a while so the keto tautomer now how does that become the enol here we see it being base catalyzed this tautomerization our hydroxide pulls a proton right off of the alpha position what should make a lot more sense now right previously we hadn't discussed why this is acidic right that forms an enolate anion right here right different resonance contributor and then we protonate our oxygen we formed the enol that's base catalyzed how about acid catalyzed well we can do that by protonating the carbonyl yep then water comes in pulls hydrogen off of our alpha carbon and we form the enol tautomer but that tautomerization keto enol interconversion what it's calling it up here it can be altered in the presence of other species and that's what we're thinking about these kind of reactions in chapter 17 this shows acid catalyzed halogenation of the alpha carbon this is known as an alpha substitution reaction we took a hydrogen in the Alpha position and substituted it for something else an alpha substitution reaction these can be acid or base catalyzed and effectively you're using bromine chlorine or iodine to replace one or more alpha hydrogen's when you have a carbonyl compound so what does that mechanism look like well the good news is it's pretty much the exact same as the tautomerization but the enol ization part looking at the acid catalyzed first i protonate my carbonyl okay water pulls off a proton in the Alpha position to form my enol that but then that ena reacts with the halogen it's electrophilic right I kick my PI bond reform this one that this pi density picks up a bromine you protonate the carbonyl and I formed my substituted product so very similar mechanism just a different electrophile that's been introduced down here base catalyzed we can do it as well that's our base promoted I actually should say the hydroxide ion is not acting as catalyst because it's not regenerated notice it goes from hydroxide to h2o so it's a promoted reaction not catalyzed how does it work hydroxide pulls a proton off of the Alpha position for my ena late ion over here kicks back down right same exact thing we saw before just nothing left to protonate but notice the difference if I have something that's base promoted I switch all of my alpha hydrogen's for the halogen all of the alpha hydrogen's are substituted for the halogen whereas over here when I was acid catalyzed I only did it once and that's a key idea to take away from this video for these reactions so why the difference yeah those halogens are electronegative right so they're electron withdrawing they're pulling electron density away so after we've done the reaction one time it increases the acidity of our alpha hydrogen's so for base catalyzed it's gonna make them easy even easier to pull off but they're also decreasing the basicity of the carbonyl oxygen which is making that protonation step less favorable so it's all about the first step jumping backward again right here if it's acid catalyzed it makes this first step more difficult which is why for an acid catalyzed alpha substitution with a halogen we only do it once okay but it makes the deprotonation here easier which is why we replace all of those alpha hydrogen's last thing we'll think about in this video is carboxylic acids okay and trying to substitute at the Alpha position here those aren't as easy to do because I've got an acidic hydrogen over here on my carboxylic acid as well right so I can't just do a quick alpha substitution like before I need special conditions and those are achieved in the hell will hard cywinski also known as just the hvz another named reaction that uses pbr3 and br-2 and then water workup to replace a single alpha hydrogen of a carboxylic acid bromine how does that work well first it converts our carboxylic acid to a aisa bromide that acyl bromide is in equilibrium with the enol form and then when we're in the enol form look that should look similar kick that down bump over I formed this species over here water takes me back to the keto form which in this situation is the Alpha brominated carboxylic acid hydrolyze it back easy stuff now once I've done that an alpha substitution in the previous condition or using the HvZ reaction these have synthetic utility if I want to replace something in the Alpha position with a weak base I can do that and I can't use a strong base because remember from chapter 9 and 10 strong bases favor elimination which would put a PI bond in this situation because it's conjugated with the other forms a conjugated system there so if I've got a halogen in the Alpha position I can only replace it with a weak base next we'll look at situations where we need to form an enolate ion specifically but we'll save that for video 2