you can review content from Crash Course organic chemistry with the crash course app available now for Android and iOS devices hi I'm deoki chakeri and welcome to crash course organic chemistry cows produce methane and that's a concern because of global heating but their diet really affects how much methane they burp out in 2014 researchers showed that feeding them a diet containing 1 to 2% red seaweed reduced their methane emissions by over 90% the problem with this exciting research is that there's not enough water seaweed to feed all the cows and this seaweed hasn't been commercially farmed yet but people are working on it in the meantime to better understand red seaweed chemists have been looking closely at its chemical makeup one of the minor components is bromoacetone a substance that can be made in the lab by combining bromine with acetone in the presence of an acid Catalyst this reaction works because the acetone analizes in the presence of the acid what does that mean exactly well we're about to find out out as we dive into enols and [Music] enolates if you're thinking that the word enol sounds familiar it is we first met enol in episode 18 when we learned about alkin molecules with a carboncarbon triple bond alkes react in similar ways to alkenes they undergo addition reactions makes sense if you think about it there's a nice juicy electron dense Center where the triple bond is so anything that's even a little bit electrophilic is going to head straight there a particularly important set of addition reactions involve water adding an O group to an alen produces a straightforward alcohol but alkin do something funky we get a ketone well to be more specific we get an enol A molecule with an alcohol attached to a carbon carbon double bond and the enol tzes to a Ketone it's the same story if we carry out hydroboration oxidation of an alkine except this time our enol atomizes to an alahh if you want to know more about these alkine chemical reactions check out episode 18 because this episode is all about enols and their cousins enolates we'll get to them in a bit enols are ters which is a word that comes from the Greek Toto the same in meos part ters are a specific kind of isomer where the only difference between the two compounds are the positions of the hydrogens and the electrons the carbon skeleton is the same when I say skeleton the carbon atoms are the bones even though a carbonal and an enol might look different at first glance they have the same basic structure of three carbons bonds are just shared electrons they're more like the tendons and muscles on top of skeleton when a carbonal oxygen atom is protonated we get an intermediate cation then this intermediate loses a proton from its Alpha carbon which is the carbon adjacent to the carbonal creating a neutral enol we know this atomization happens because we can observe it with certain enol if we pop everything into an NMR spectrometer we can think of an enol as a type of alkine and because of the resonance electron donation from the lone pair on the oxygen to the pi Bond enols are more electron rich and better nucleophiles than alkenes without an electron donating group attached but we can make an even better nucleophile from something closely related to enols here's a useful organic chemistry rule of thumb the conjugate base of a substance is always a better nucleophile just look at water for example water is a nucleophile but its conjugate base hydroxide is a much better nucleophile we talked about nucleophilicity in episode 21 the conjugate base of an enol is called an enolate ion and it has a resonance stabilized negative charge and enolate ions which we often call enolates for short are great nucleophiles to make enolates we take a carbonal compound like a ketone and add a strong base like hydroxide ions instead of forming a neutral enol the Ketone reacts with hydroxide to become a negatively charged enolate the key to this reaction are the hydrogens on the alpha carbon remember that's the neighbor to the carbonal group these Alpha hydrogens are acidic while the other hydrogens in carbonal aren't acidic enough to be removed by a base when the alpha hydrogen is deprotonated the annion that forms is resonance stabilized let's look at the relative acidity of alpha hydrogens in different molecules for a moment because this is going to introduce fun new compounds remember the lower the pka value the more readily the substance donates a proton and the more readily an enolate will form the pka of the alpha hydrogens in simple alkal substituted alahh and ketones like acetal dhide and acetone are in the High Teens but the pka of the alpha hydrogens in compounds with two carbonal are lower so those protons are more acidic which makes sense with two carbonal groups flanking them to stabilize the negative charge in the annion however the alpha hydrogens and Esters have a higher PKA than their Ketone cousins this is because there's residence donation from the oxygen of the AL coxy group towards the carbonal this makes the carbonal more electron Rich already and it's harder to stabiliz an enolate and it's a similar story with amides the nitrogen donates its electrons to the carbonal through resonance so again the oxygen of the carbonal has quite a bit of negative character the pka of dimethyl acetamide or dma is a whopping 30 we're not going to get enolates very easily from these so overall if we react a carbonal compound with an appropriate strong base we get resonance stabilized anion called enolates which are great nucleophiles even better than enols which are pretty good themselves we can see the nucleophilic power of enolates if we look at halogenation reactions both alahh and ketones will react with a diatomic hallogen like bromine at the alpha position in the presence of a base it doesn't even have to be a super strong base because as soon as even a tiny bit of enolate is formed as an intermediate the hogen reacts and uses it up remember lat's principle it's the idea that equilibria in chemical reactions shift to minimize the effect of a change like a temperature change or an increase or decrease in the amount of one of the substances so when we use up the tiny bit of enolate that forms it drives the equilibrium towards making more enolate and the reaction keeps going and here we run into a little problem the AL the hydrogen on the now halogenated carbonal is more acidic than it was in the starting carbonal so it reacts too and yes the third hydrogen reacts as well it's really hard to stop this halogenation reaction at the monosubstituted product okay so you might be thinking why is this a problem maybe this trip halogenated compound is fun and cool and useful but the trouble is in basic conditions the triple hallogen product doesn't stick around it's cleaved in something called a Halo form reaction and we end up with a carboxylic acid and a Halo form chbr3 the most famous Halo form is chloroform chcl3 which has all sorts of uses from anesthetic to solvent so Halo forms can be interesting in fact bromoform is in that red seaweed from the intro and it's thought to be one of the bioactive compounds that reduce cow's methane emissions and this is great if we want a Halo form but not if our goal is to get a single hallogen atom next to a carbonal group that's all messed up if we go about halogenation this way thankfully we almost always have options like let's do our halogenation reaction in an acidic solution instead using bromine and acetic acid this reaction is much easier to control because there's no super nucleophilic enolate we can just work with the slightly less nucleophilic enol since we've got protons floating about the carbonal oxygen gets proteinated next the conjugate base of the acid nabs an acidic hydrogen from the alpha carbon giving us an enol intermediate like I said this enol acts as a less aggressive nucleophile than our enolate last time so an electron pair attacks the bromine and forms a resonance stabilized cation finally the carbonal group loses its proton and leaves us with the alpha halogenated product we wanted no outof control halogenations here yay now halogens are nice and all but as you know by now we organic chemists love to see carbon carbon Bond formation if we introduce enolates to an alkal or a tosilate they undergo an alation reaction joining the two smaller pieces into one bigger molecule what's happening is that the nucleophilic enolate ion is reacting with the electrophilic alkal haly in an sn2 reaction and the leaving group is displaced by a backside attack but because of this we run into the usual issues that we have with sn2 reactions namely the alkal group should be primary or methyl this reaction isn't great with secondary alkal groups because we start to get a competing E2 reaction and with tertiary the E2 reaction is all we get there's one more thing we have to look out for in these alul reactions with enolates because they're resonance hybrids they kind of have a dual identity and two different ways of reacting one part of the hybrid is a vanilla Al coxide that is a carbon carbon double bond with a negatively charged oxygen attached in this situation enolates react at the oxygen and we end up with an enol derivative but the other part of the hybd is the alpha keto carban ion that is a carbonal group bonded to a negatively charged carbon in this situation enolates react at the carbon giving us an alpha substituted carbonal we can often favor the reaction at Carbon by carefully choosing our reaction conditions but all these complications with enolates and alkal could lead to something that really annoys chemists mixtures of products if only we had a more reliable way to add sub carbons to our carbonal never fear aceto AIC alkal is here this reaction effectively converts an alkal halide into a Methyl Ketone with three more carbons without so many potential side products as the name suggests it involves aceto AIC Esther which is also called ethyl acetoacetate when we were comparing PKA we saw that Alpha hydrogens surrounded by two carbonal groups are much more acidic than plain old carbonal so this compound we have here is completely converted into its enolate ion when reacted with a base like sodium eox oxide next that can be alculated with an alkal halide making the carbon carbon Bond we know and love in fact because there were two acidic Alpha hydrogens we can even do a second alkal if we want to add two different alkal groups we can perform the alkal as separate steps carefully adding one molar equivalent of Base in each reaction now we're not quite done because this weird aceto AIC Ester thing is hanging around in our product not bashing it it was really helpful for this reaction but we want a plain old Ketone and for that we have to lose CO2 and the ethyl group from this molecule so we'll heat the alculated or dialated aceto AIC Esther with some hydrochloric acid solution then the Esther portion is quickly hydrolized to a carboxilic acid called a beta keto acid which loses CO2 in decarbox reaction these are easy to decarbox because when we lose CO2 from a beta keto acid the electrons have somewhere to go we get an enol first that atomizes into the more stable Ketone and with that we're done for now in this episode we learned that the alpha hydrogens in carbonal compounds are acidic enol and enolates are good nucleophiles we can carry out halogenation reactions with enols and enolates but enols are easier to control and we can alcate enols in enolates and the aceto AIC eser alcal is especially useful there's more enals and enolates coming up in the next episode when we take a look at aldol and claz and reactions and return to our mold medicine map of penicillin V synthesis until next time thanks for watching this episode of Crash Course organic chemistry if you want to help keep all crash course free for everybody forever you can join our community on patreon