all right other questions about the acetal formation mechanism okay let's run through acetal hydrolysis uh this is just going to be the microscopic reverse of the formation mechanism so this should be review frankly I could send you all home and make you do this on your own but I kind of feel like walking you through it once uh so starting with the acetal again if you're worried about what to do first simply consult the formation mechanism start at the end and do the reverse so just as the last step was deprotonation of one of the O groups so the first step of acetal hydrolysis should be protonation of one of the O groups to turn it into a good leaving group that's going to lead us one step backwards to exactly the same intermediate as we saw previously now if we want to know what to do we can again consult the acetal formation mechanism the previous step was attack of an alcohol on an oxonium iion to give us this intermediate therefore the microscopic reverse of that should be kicking off of that alcohol as a leaving group to give us that same ox sonum ion and then of course the alcohol as a leaving group if we want to know what to do then we consult the formation mechanism noticing that in the previous step we have this intermediate and uh water got kicked off so the microscopic reverse of that is water attacks the carbonal carbon and breaks the pi Bond and this gives us that same intermediate with a positive formal charge on what used to be water if we need if we want to know what to do then we consult the previous formation mechanism the intermediate previous to that was the neutral Hemi acetal we can form that by uh simply removing a proton from the positively charged oxygen and that's going to give us our neutral Hemi acid and once you get there you know you're halfway through uh to figure out what to do next we consult the previous formation mechanism we need to get this to this intermediate where it's the alcohol o group that's protonated so we'll simply use the acid that was present and regenerated in the previous step to protonate that o group at this point you should sort of start to be able to see the finish line with the protonated O group we have converted that o group into a good leaving group relative to a neutral o kicker offer and so we will kick off that I don't like where that plus charge is so I'm going to move it sorry we can kick off the uh protonated o group as a leaving group that gets rid of our second equ equivalent of alcohol that takes us to this oxonium ion and then all that's left is to regenerate our acid Catalyst and our aldah in this case product because the reaction is acety hydrolysis normally if you wanted the hydrolysis reaction to occur you would do this reaction with aquous acid because a key step is adding water as a nucleophile to the oxonium ion so to summarize if you want the forward reaction to occur you start with the aldah you start with your alcohol and you need an organic acid uh and you need this to be run without any water and in fact you're going to need to remove water if you do that experimentally you'll get the acetal on the other hand if you start with the acetal and then you want to hydroly it you can use any aquous acid with an excess of water and that's going to get you to free the alcohol and go back to the aldah okay all right anything we need to say more about that yes please does it work on ketones works on ketones exactly the same only what's H attached to the carbon carbon would be another R Group yeah why does it need to be organic uh why does it need to be organic I just mean not aquous so some some acid i' I've given you some options toine sulphonic acid TSO or acetic acid just not like aquous HCL because if you add water that's going to take you back to the starting materials others yeah this doesn't work oners right doesn't work on Esters yeah we're going to learn what to do with Esters in chapter 16 but Esters generally you can hydroly Esters so stay tuned we are going to do this reaction on Esters and it is going to have an effect but we're not going to make acetals with Esters as starting materials there is such a thing it's kind of weird and it's not covered in your text so we're going to ignore it all right others so um this is an example we talked about protecting group strategies earlier and it's a group that gets rid of a problematic functional group but it's easy to install and easy to remove the acetal is actually a really great leaving group used in in a lot of cases I'm sorry a really great protecting group used in a lot of organic reactions and I want to just give you an example of uh a couple of them so I think this example is straight out of your text and maybe this is where the question about um the Esther comes from if I have this Ketone plus Esther molecule uh and suppose I wanted to do a reaction with the Esther but I wanted to leave the Ketone intact or at least do something different to the uh Esther than I want to do to the Ketone if I used just an Organo lithium reagent followed by aquous workup what would be problematic is I would expect the Ketone to react via an addition reaction and then I would expect the Esther to react via nucleophilic asil substitution first to give us the Ketone and then another equivalent to give us the tertiary alcohol that's a review of chapter 13 but I've got what I would call a selectivity problem uh what if I wanted to just react with with the Esther instead of the Ketone and so one strategy to sidestep that and and I guess I'll put in parenthesis it's helpful to know for this example maybe what my desired product is suppose I want to get out this but I don't want the Organo lithium reagent to react with the Ketone uh I'm going to Sid step that with a protecting group strategy so I want to make an acetat out of the Ketone now I can do this because ketones are more reactive than Esters so if I'm careful I can add an organic acid and again uh let's just say for our purposes this is acetic acid maybe let's say TSO I know that one scares you that's why I'm exposing you to it so you can get over your fears now go look it up it's from 351 and it's just an organic soluble acid and then for an alcohol I could choose basically any uh alcohol I want though it should be cheap and the reaction should be high yielding one interesting choice is this diol and the reason we choose that diol illustrate this in a little bit is it comes with both alcohols in the same molecule and it makes making the acetal really efficient um so if we do that first that will make the acetal out of the Ketone and not the Esther so at this stage I know I've drawn something that looks like a little guy um maybe a bird of some sort I don't know there's like two eyeballs um why how did that happen let me draw for you an intermediate oxonium ion that would have been made if you draw the mechanism this is after um after we protonate the Ketone then one of the alcohol oxygen attacks we do some proton transfer and water leaves as a leaving group the intermediate that would be formed would look like this this is exactly analogous to if we scroll out for a moment uh this oxonium ion where now we're ready for a second equivalent of alcohol to come back in and attack the only difference is now the second equivalent of alcohol is right there in the same molecule and in organic chemistry and all chemistry actually int molecular reactions are fast so it's actually really fast to attack the carbonal carbon and uh if you follow that through this acetal is the product I know that when you're not used to seeing something like that your brain sees this your brain sees the little guy and says I don't know what to do with that and then you forget everything you ever learned about acetals don't do that if you can't stand the fact that those two R groups are connected to each other simply do this surprising how much better that makes it right suddenly you know what you're doing okay one of the skills you need to get in oam is the ability to simplify more complicated structures into things that you recognize so to sort of increase your ability to tolerate this kind of thing I'm going to leave it drawn there but you are totally welcome to abbreviate and draw it as the much friendlier that okay all right fine um I will also pause to point out that there's a whole area of well there's a group at the at Rice University in Houston that attempted to get people interested about 20 years ago in chemistry by making what they called anthropomorphic molecules involving acetes because when you draw them they look like heads so I kid you not go look this up we're not going to do this it's not worth our time in class but it is kind of fun go Google nanop nanop so named for the lilipan of guler's travels and their molecules that look like people if you squint and try not to ask too many questions all right with the acetal installed one of the neat properties of acetals is that they are stable to basic conditions there's no acidic prot protons and because the carbon oxygen Sigma bonds are strong they are um resistant to nucleophilic attack the thing that made the Ketone problematic to begin with was this low energy pie star that a nucleophile could attack acetes don't have a piie star there's no Pi Bond there so now that we've installed the acetal we can proceed with a reaction involving uh step a the organolithium reagent and step B aquous workup and as long as that aquous workup is neutral and not acidic that should allow us to convert the Esther into the tertiary alcohol without doing anything to the acetal and then how do we remove the acetal group to get our desired product yeah that's just acid and water that hydes the acetal again if you want to really push yourself you could be like okay I want to draw the mechanism for hydrolysis of that acetal to make sure I can withstand the alluring eyes of the head headlike creature on this molecule I don't know um go ahead and try to do it you you should totally be able to do it but if you can't it's fine just abbreviate the alcoh those alcohols as o groups and it should be a lot more straightforward okay so that's an example of an acetal as a protecting group for a ketone there are other cases is not from your text but maybe I'll just give you a brief example um there are some cases in organic chemistry where we need to tell the difference between various alcohols um oh shoot do I dare do this probably not so uh I'm going to abbreviate some things here e here stands for some protecting group R there stands for an alcohol it is pretty easy in organic chemistry to tell a primary alcohol from these other secondary alcohols and the way you can distinguish between those two is ster so it's pretty easy to take say the starting material that I've drawn here which is glucose it's pretty easy to uh modify that primary Hydro oxal group with some kind of protecting Group which I'm just abbreviating as p and you don't need to worry about what that is it's also pretty easy to take care of this o group because as you notice in glucose what I've drawn here is an acetal the glucose structure itself as we learn about carbohydrates comes as a Hemi acetal it is really easy to convert a Hemi acetal into an acetal so we can also modify that o group but then what about the three uh other protecting groups how can you tell um one from the other and it actually is pretty easy I wouldn't expect you to predict that this would happen uh I would this was not a fair predict products question I'm just showing you something organic chemists do you can actually take a ketone or an aldah uh in this case let's see uh I think the key tone of CH or the alahh of choice is this benzal deide and use some again organic acid maybe toine sulfonic acid and you can selectively modify two of the secondary alcohols without touching the third and the reason for this has to do to some extent with Steris I kind of screwed up but whatever I don't like that but it's okay don't ever don't anybody write that down but basically you can um because I'm pulling this out of my head and I'm trying to remember what's actually done but basically you can use do you see what the the approach here was not to protect a ketone it was to protect some alcohols so in this case the alcohols above we were trying to protect the Ketone and using the alcohols as the protecting group now we're trying to protect the alcohols using the Ketone as the protecting group but there is your acetal uh as I said that's that's not you don't I wouldn't expect you to do this in a predict the products question it's not a fair question that way but it's designed to illustrate that you can use acetals both as protecting groups for ketones and alcohols okay so with that I'm going to erase all the evidence that I ever talked about that from the video it'll still H I'll just leave it there what have I got to hide um as I said I don't know if when I write down things like this someone always comes to my office and says do I actually need to know that and my response is yes everything I say is of equal importance but so I'm going to add a disclaimer here don't worry about the specifics here the thing to understand is that you can use acetals to protect alcohols and that's what I want you to get out of it and I'm signing here in Blood and there's little drip marks so you can tell all right you can hold me to that all right um that's acetals anything more you want to say about that yes yeah okay good your text points out and I've said that uh Hemi acetals thank you for pointing that out i' sort of forgotten that Hemi acetals are not very stable and they are intermediates you either go backwards to the carbonal starting material or forwards to the acetal the except ception to that is that cyclic Hemi acetals are often stable so uh as an example I'm going to draw the structure of an alcohol this is actually an alcohol that has an alahh in it I'm drawing it in this pseudo chair orientation for a reason this is D glucose and as I said you don't need very much acid to catalyze formation of acetes and Hemi acetes so it turns out that even at physiological pH or ph7 there is enough um acid to catalyze the interconversion of glucose into a h acetal and this is the stuff of nightmares if you don't know how it ends up because as you look at that molecule glucose is both an alahh so I'm going to highlight the carbonal carbon as we've done previously here is the uh Carbon on one side the proton on the other here is the carbonal oxygen all the important ingredients for the Hemi acetal and the alcohol is in the same molecule so what we're going to be doing here is called int molecular that means in the same molecule Hemi acetal formation and when you do this you make a cyclic acetal the question is of all the alcohols which is the right one I know you detest uncertainty and I'm here to tell you that it is going to be a feature of the rest of your life so you got to get used to it but for fortunately there are some guiding principles here for the cyclic Hemi acetals and the idea is you're going to form the most stable ring now we know some things about rings from 351 right that ring strain makes three and four membered rings somewhat less stable than five and six membered rings uh and that six membered rings are great because you can adopt a chair structure where there isn't any angle strain and there's also not a lot of torsional strain so if you can form a six membered ring for a Hemi acetal that's probably the more stable one so all we're going to do is start counting from o groups to the Hemi acety carbon to the carbon carbonal carbon to see what size ring we could form start with this one oxygen is one 2 3 three membered ring I mean if you want to force me to but let's see if we got better choices this one one two 3 4 better but not great one two three four five okay five might be okay I'm going to write a number five by this o group just to have in my mind the size of the Ring what about this one one two 3 4 five six Bingo that's the magic number for ring size because again as you learned about chair confirmations a six-membered ring can minimize ring and minimize angle strain and torsional strain what about this other one this would be a 1 2 3 4 four five six seven membered ring if six is great is seven better and the answer is no six is The Sweet Spot there's a lot of reasons behind this you could learn more in a grad level organic chemistry class or you could actually try to build some models and test it for yourself but in general when you have the choice you're going to form the most stable Hemi atile ring okay yes seven and difference seven and five there is a difference not one that I expect you to predict yeah okay yes yes the carbonal carbon the blue and the orange atoms are going to be bonded together that close the ring and the pink atom is going to be an O group yep good so you can see now why I drew it this way because I knew which way this was going to go I'll highlight the new bond that we form in Orange you can draw the mechanism for this if you want to but this is the alcohol that does the attacking of the oxonium ion the other O's are less reactive because they lead to less stable products um now it turns out for glucose you could imagine depending on the confirmation of the molecule that o group uh in our Hemi acetal product might be oriented in one of two directions in other words imagine if I rotated around this carbon carbon bond between the carbonal carbon and the alpha carbon I might have had a confirmation in which the proton is here and the O group is down there I'm not going to draw that but can you imagine that and if that o group if that carbonal oxygen had been pointed downward I might have gotten this stereoisomer as product I'm drawing it kind of quickly sorry about that again here is the new Bond that we made here's the what used to be the alcohol here's the carbonal carbon the oops there we are proton and the R Group and then the O group um in one of these Hemi acetes they're both Hemi acetes they're both viable products in one of them the O group is in the equatorial position in the other the O group is in the axial position uh it turns out that the ratio of these is about 67 to 33 that's from your text and it's not worth memorizing uh something you will learn later in 352 we call this the beta animer or the beta stereoisomer animer is a new term which I will Define later so don't worry about it now and the other one is called the alpha animer again animer a term referring to two stereoisomers that differ at in configuration at a Hemi acety carbon 351 review what is the stereochemical relationship between those two molecules are they the same compound in antier or diasteromers or are they not even isomers options a through D dumers good you know their dumers how they're different at one but not all stereo centers good yeah so the relationship between these two we call them diamer uh incidentally the beta animer forms in larger amount you can tell it's more stable but it's not as much more stable as you would expect based on some stuff you learned in 351 and that is a story for another day uh the point you need to realize is that cylic Hemi acetals uh you can make when you have an alcohol and an aldah in the same molecule um one other thing that's worth just saying in an about 40 seconds is your text will have you do this in some problems if you have a very simple cylic chemi acetal you can use an acid Catalyst and an Al alcohol to go from the cyclic Hemi acetal to the complete acetal I don't know there we go um sorry getting ahead of myself some I'm nervous now somebody's timing me I told you 40 seconds and I think I'm already beyond that so you can convert a Hemi acetal into an acetal the way that works is the same way as it works in acetal formation mechanism you proteinate the O group to turn it into a good leaving group then the ring oxygen does the kicking off of the good leaving group to make an oxonium ion like we've done before and then the alcohol attacks the pie star of the oxonium ion as you've seen before that's all I'm going to draw for you I'm going to expect you to be able to draw the next intermediate and the next proton transfer step and that'll get you to the acetal all right so it looks like our uh time in chapter 14 isn't over as soon as I thought it was there's one more thing you need to know from this chapter I've saved it to the end because it's weird it's kind of out of place relative to the other reactions we've talked about so far what we've done is involved acid catalysis on a carbonal oxygen so that we can have something attack the carbonal carbon this reaction fits in this chapter because it's a reaction on ketones and aldah it's included here because it's a reaction that was awarded its Discoverer gorg viig was awarded the 1979 Nobel Prize for it and it's still used in organic Labs today because it's a reaction that in one step will make two carboncarbon bonds a sigma Bond and a pi Bond so it's highly useful but it's totally out of place it's not related to a lot of the other things we've talked about in this chapter so that's why I've left it to the end um we're going to talk about the reaction we're going to draw the mechanism we'll talk about some of the features you will need to know how to predict products and provide reagents and use the reaction in a synthesis so behold the viig reaction uh we organic chemists pronounce the W like the German speakers would if you want to call it the whittig reaction we will smirk at you a little bit but we will try to be polite so just whatever you want okay so here's the reaction I'll show you the reaction that I need to show you how to prepare the reagent that is used for the reaction I'm going to be as general as I can to start with it works on on alahh and ketones we're going to start with the alahh just to keep things simple and the reaction involves uh what is called a viig reagent thank you for that that tells me a whole lot about the situation A viig reagent for a viig reaction what does the viig reagent look like well you're going to hate this even more it is something called a phosphonium ID those are two new words this is what is this Duolingo can you use it in a sentence phosphonium refers to a phosphorus with a positive formal charge on it a phosphorus bonded to four things ID refers to a molecule where there's a positive and negative formal charge on adjacent carbon so behold the phosphonium illid there's the phosphorus uh in a lot of examples in your text the phos phosphorus is bonded to three fennel groups there's the positive formal charge on the phosphorus and then the adjacent carbon we'll put another R Group here the adjacent carbon uh is negatively charged this is the phosphonium ID now the trick with the phosphonium illid is that sometimes people don't like to draw plus and negative charges and they remember that atoms that are from the third row and Below on the periodic table can actually accommodate or be surrounded by more than eight electrons the octet rule doesn't really hold for atoms that are from the third row and Beyond of the periodic table uh and so you can draw the structure of the phosphonium illid as this sort of resonance structure where you move the electrons on that negatively charged oxygen to form a pi bond with the phosphorus blasphemy I know that's why I yeah go ahead and if you have pearls you can clutch them in in horror um but uh I like to draw it as the fos as this resonance structure just because it's a little bit easier to follow what's going on it's useful uh to color code things as you're learning this will'll color code the carbonal carbon uh blue will color the carbonal oxygen uh uh Pink and then let's color the negatively charged carbon uh orange in the product we make a new Pi Bond a new Sigma Bond and a new Pi bond between the blue carbonal carbon of the alahh and the orange carbon of the phosphonium illid so I'm going to illustrate that here here is the orange carbon and there is the possib possibility for stereo isomers so you would expect to get in some ratio both the Cy and the trans isomer uh your text may or may not explore that in a lot of detail there are subsequent developments in organic chemistry that allow you to have some control over the stereochemical outcome as to whether or not you get the e or the Z is I simply want you to be aware of both of them the other thing you need to know is what happens to the carbonal oxygen and that is it ends up bonded to the phosphorus and uh this is called triphenol phosphine and it is very stable actually phosphorus oxygen bonds are quite stable you can choose to draw triphenol phosph oxide sorry I said that wrong Tri I'm not going to write down the name you don't need to know it trienal phosphine oxide is very stable and its formation is a major driving force for the reaction you can draw it either as I've done on the left or here on the right but that's where the carbonal oxygen ends up okay so that's the what you can tell how useful this reaction is in a synthesis because it's what we call a convergent reaction that word means you're taking two parts I'm going to illustrate those parts with highlighting because yay colors and uh the green portion and then uh I need a new color um the other green portion let's go purple only problem is purple and pink appear same on the screen anyway uh you're bringing two two separate things together two simpler pieces together and connecting them to a more complicated molecule So This is highly useful in organic synthesis um questions about the reaction so far yes the phosphonium is the reent the phosphonium ID is the vidic reagent yep um right what else yes could you use something else like silicone ORF could you use something else from the third row be phos phosphorus works well I don't actually know the answer to that question it's good question and I don't know from what I've seen phosphorus is the atom of choice others okay so I'll show you mechanism I'll show you example of synthesis and then I need to show you how to prepare the vidic reagent because you can actually do that using the stuff from the text and your text in synthesis problems will expect you to do that um so mechanism really quick it actually is easy to draw there's a lot of things going on at once the easiest thing to do is um to draw the phosphorus here and the carbon here of the phosphonium ID and then I'll just abbreviate the fenel groups like that and there's the positively charged phosphor us so um what you might predict if you know about carbonal chemistry is the negatively charged oxyen whoa I going to do that you might predict that the negatively charged oxygen of the phosphonium illid would be a nucleophile and attack the carbonal carbon so that happens attack the pi star and break the pi Bond at the same time lone pair electrons on the oxygen attack the phosphorus so that's sort of three things going on once if you follow those arrows and look at the consequences I'm going to continue to highlight in red the new bonds that we made as part of this process we've made our three we've made two new Sigma bonds one between the carbonal carbon and the negatively charged carbon of the phosphonium illid and then the other between the carbonal oxygen and the phosphorus so if I want to keep our highlighting consistent with what we did above blue and whatever orange that's where the sigma Bond comes from then what happens next is is something that we don't need to spend a ton of time explaining uh electrons and there's actually two ways to draw it you just have to pick one electrons from the carbon phosphorus Bond are going to kick down to form the new carbon carbon Pi Bond at the same time the carbon ox oygen uh Sigma bond is going to shift over here to form a new oxygen phosphorus Pi Bond that's going to result in the triphenol phosphine oxide product here and then the alken product here and because I don't want to I'm not going to draw the Z stereoisomer okay so that's the mechanism you form a four membered ring and then it breaks apart driving force for this is probably release of ring strain along with formation of the very stable oxygen phosphorus uh Sigma and Pi bonds yes does still have uh in the intermediate here yes phosphorus still has a positive formal charge um let's see what did I miss five bonds no you're right four bonds to phosphorus thank you I got a minus minus one formal charge mistakes are usually minus one so minus one for me put put that on my tab end of semester reviews minus one for formal charge for me okay yes the phosphorus there with five bonds should only have should be neutral you can do the math if you see the periodic table other questions okay I told you we needed to figure out the phosphonium how to make the phosphonium illid uh so you start out with if this is your end goal if you want this phosphonium [Music] illid then uh you're going to start out with if that's your goal you're going to start out with the corresponding and I'll continue to label the negatively charged carbon the phosphonium illid there you're going to start out with the corresponding alkal halide so the carbon that your um is bonded to the phosphorus Begins by being bonded to a haly as a leaving group the first reaction uses triphenol phosphine P phosphorus bonded to three feny groups as a nucleophile in an sn2 reaction essentially this is just backside attack kicking off the um leaving group The Hali leaving group to create this intermediate now notice that we're almost to the phosphonium illid only the orange carbon is neutral and and fully saturated the bromo leing group sort of sticks around as the counter ion this is sometimes called a phosphonium salt notice that this sn2 reaction is fast for primary alkal halides it's going to be slower for secondary alkal halides more on that in a little bit but that's a review from 351 then to make the ID you got to remove a proton from the orange carbon you need a really strong base to do this and the base of choice is called nbal lithium or alternatively it's an organolithium reagent like that that just happens to be fairly inexpensive to get we're using it not as a nucleophile now but in its capacity as a very strong base to Simply remove the proton and generate the phosphonium ID so generating a viig reagent you can do that from the corresponding alkal halide in two steps first the sn2 reaction with trienal phosphine then remove the proton with NB lithium to make the phosphonium ID and that is the viig reagent now I said something about that sn2 reaction and this is important sometimes the fact that you have to do often the fact that you have to do the sn2 reaction to make the viig reagent influences your choice of synthesis so as an example suppose your target is this molecule let's e okay fine let's methyl groups are boring let's make it an ethyl group now we're very much more interested okay so there when you do retrosynthesis you break the molecule up conceptually in your head into two different starting points or or into two simpler starting materials so I would see this Sigma and the pi Bond and I would say I can make that via a viig reaction the only thing is now I have to decide which side do I think was my carbonal and which side do I think was my viig reagent uh you might say okay one strategy would be to use this as a ketone and then use uh and then the viig re agent would be the remaining portion right A3 carbon and then there's the phosphonium illet so that would be one way to do this alternatively you might ask could I not have the Ketone be on or or the aldah be on the sort of shorter upper half and then on the lower half of the molecule could I not have that be the phosphonium illid uh and it turns out that this method up top is preferred and this is UN preferred not preferred worser worser is what we will say the the reason has to do with the reaction you do to get the phosphonium illid here as I showed you you could start out with a primary alkal halide you could do the sn2 reaction very fast and super efficient starting with the primary alkal halide uh and then use as I showed you above nbal lithium to make the viig reagent as opposed to here you would have to start with a secondary alkal halide and as I told you the sn2 reaction is less efficient there and so that's why the top method is preferred that's important it's actually ridiculously easy for me to ask an exam question about that issue so I have fully disclosed that here just review it make sure you know how to do it now this puts us maybe one full day behind fortunately I wasn't ever going to spend two days on chapter 15 anyway so next time come prepare to be done with chapter 15 and we'll move on have a great Monday