Tosylate, alcohols, epoxides

[00:00:14]do you hear this here look at listen to this real real quick that you hear that that's those are ice cubes chilling in a glass crackling and i've been in the house too long with the kids and the in-laws and they finally left well the in-laws laughter kid's still here anyway i'm going to have a sip i'm very parched anyway let's do this i'm snow bound it's crazy outside i have no idea what the is going on anymore okay tosylates means lights triflates all right so we were talking about this when we ended off the the lecture last time and um we use tosulates and these things to you know when we want to make um alcohol is better leaving groups why because oh h is a horrible leaving group an sn2 reaction so we have to convert the oh to a better leaving group somehow okay this is one of the ways to do it is to take your o-h convert to an o-toss or an o-mesolate and it will be a a better leaving group because as it leaves as the nucleophile comes in and kicks off the toss light or the mesolate this o group here which was formerly on the oh right is now on the o tosyl or o measle here and this is now engaged in resonance so this resonance here can be well let me just see if i can get on to the do some pen work here have some lone pairs lone pairs all right lone pairs there there there and there and you can dump those lone pairs into there and there and so forth and so on and have all kinds of nifty resonance uh to make this a great leaving group okay so sample mechanism for sulfonylation all right so you want to sulfonylate something um you want to you want to you know toss like something let's just do a typical thing you have um you know we'll use appropriately we'll use ethanol all right there's that so cheers all right so take that guy here and we'll use for the toss for for sulfonylation like for tosylation and measilation or or even triflation we use the chloride version of this okay so you take a toss-up group a tosyl chloride which is going to be your part in the drawing i'm using this drawing pad on my lap here and my lap is i don't know what's going on my lap all right there's that that's wrong that's completely wrong so let me just let me erase can i use the eraser i don't know if i have an eraser i have an erase pen that work oh well thanks that's nothing okay all right let me try this again all right take two all right i got so crazy about the chloride talking about it i just ignored science there you go sulfonyl this is an s all right there's a chlorine there and this is a toss group so we're going to put a tile so para para tall toluene sulfonyl chloride or tosyl chloride we use use tulsa chloride with pyridine all right you take your benzene ring there and put a nitrogen right in the benzene ring and there's your lone pair for that so this is pyridine and tosochloride roughly in a one to one mixture one to one to one mixture roughly okay so what's the mechanism pretty pretty straightforward it's not a non-sn2 not an sn1 it's like an addition elimination so now you're adding your oxygen here you're attacking from your oxygen to your sulfur that is going to kick that up all right now let's just draw our our intermediate here all right that's the oxygen there there's your hydrogen there your new bond here is your sulfur and let's just try to accommodate everything that we've done so far so there's your o minus from from there there's your double bond still there there's your chlorine right still attached all right and there is i'm going to abbreviate this off to keep on drawing it i'm going to abbreviate this toluel or tol right this is for the toluene group t o l all right so there is this intermediate okay oopsie forgot this charge remember you keep if it's a neutral species to begin with or set of them keep them overall neutral you know these are charged separated they are still a negative and a positive when you add them together are still going to be a neutral species all right so you have that species right there all right which then you can then collapse down to get rid of this chlorine here right so this guy here will swing on down so i'm trying to iron the lone pairs with this pen but it's hard all right so there all right this will kick off this chlorine you say well wait a minute why did you kick off the chlorine you could have just kicked off the o h plus well if you do that then you then you're back to this then you're back to starting materials and that's not productive we want to be productive we want to go forward in the reaction so even though there is i am sure there is a little bit of reversal i am sure this is acid-based chemistry so why wouldn't there be a little bit of reversal right but since we have some we have the ability to have some reversal that's fine we understand that but let's go forward and assume that we have a reaction that is a positive a positive thing that that actually occurs that's like that's a good i should do i should drink this more often all right um okay good let's do this now let's always keep track of what we're getting rid of and stuff okay so we're getting rid of that chlorine so we're going to hit this with a minus cl right minus cl musk because when we leave when chlorine leaves it's going to leave us as a chloride ion all right sulfur your original double bond from there your newly formed sulfur oxidable bond right chair the chlorine is gone but the toluene is still there so we'll say tall no i'm tall t-o-l notice that this is a tall tall group t-o-l group tall group but this whole thing is a toss a this is a toluene here but this is a toluene sulfonyl or a toss group all right so this is a tall but this is a toss this whole thing here is a toss all right we still have this here to contend with all right and now of course we have still a system that looks like it's inbounds for charge but we have a minus here and a plus here so it is actually pretty still balanced all right but we still have this chart to take care of here because we don't want this species here being that that higher energy right so i'm going to have our handy little chlorine here that's just floating around cl minus come in and rip off that proton right here giving us our i'm just going to draw oh i'll draw i'll draw it mostly out tall okay this whole thing here i just want to remind you this is a toss group all right plus hcl hcl now the important part is here is now where the where the protein comes in this pyridine here now your book says that the pyridine comes in here pulls off that proton and does all kinds of hijinks and or it does it pulls it off here or here either way i don't like it it doesn't work that way it's pyridine doesn't abstract protons it absorbs protons it's not that strong a base it's going to abs absorb it's going to absorb that acid right there all right so let's assume even though we know this is quarter this is sort of and doesn't have a covalent bond here we're going to take pyridine all right and it's going to zoop it's going to pull off that proton right there kick off sort of that and what you're going to have here is on the side reaction where you actually have pyridinium that's a nitrogen nitrogen all right there's your pyridinium right because the nitrogen is protonated hydrochloride so this guy here is pyridinium hydrochloride right which falls out of solution as a solid so you have protein hydrochloride and you have this otosyn so why the hell do you need the pyridine here if in case you don't remember from last semester or if you're new to this class the reason why you need to have this have pyridine around is to absorb hcl because if you don't and you just keep on generating hcl this hcl will go back and attack your starting material and you're saying yeah but big deal why what does it matter well here's what happens if you attack your star material you have alcohol here here's what you don't want to happen all right you have your alcohol there right and then you have your hcl that you made all right if you have hcl you know this is going to protonate that oxygen of that alcohol giving you this weird this protonated protonated alcohol right plus cl minus now two things two things can't happen thing one that can happen is chlorine can attack the back side of that carbon here giving you the ethyl chloride so that's an untoward or an unwanted reaction that's one way of doing it all right but at the very least when you have this species so the one thing is that you have you have potentially a and not a good sn2 type of reaction that you don't really want so that you don't want that don't no one all right or the other thing is that this guy here should be involved in a nucleophilic attack of that sulfur but this can't do that because now this is no more nucleophilic when you're a nucleophilic you have an excess of electron density to use to be able to attack something right this guy here is going to use this partial delta negative to attack this delta positive it can do that because it's delta negative this guy here is no more delta negative it is it is a full positive there's no reason for it to want to do any sort of nucleophilic attack because it is all full up it doesn't it has no more impetus to be a nucleophile all right so this this is good here because you have um you know you have the this is the sulfonyl procedure for tosal measle or or the triflate i believe trifluoros trifluorosulfonyl all right so this is all one thing you just change out the different r groups on the sulfur okay that's all you got to do all right so um ether is by intramolecular dehydration of alcohol i'll drink to that again let's every time i'm gonna say alcohol i'm gonna drink no i don't still not a bad idea okay okay so so here's the thing so you already know how to do this sort of okay um you take your alcohol here and you heat the bejesus out of it and sulfuric acid and you end up making ethylene gas all right but if you don't do that if you don't if you don't heat it up if you don't heat it up as high as this and you get a little bit lower you can make um acid catalyzed um symmetrical ether bonds okay and so you could do that all right and so that's that's just one way to do it okay but there's multiple ways to be able to do this kind of thing all right and we'll go over the mechanism in a minute okay and we have some time over here yeah i guess we'll talk about the mechanism now okay so we will do that let's take this ethanol here heat it up with a little bit of acid and heat and make diethyl ether okay so take one more and now here notice we're not talking about any stoichiometry here at all we're just talking about as much alcohol as we need to be able to do the chemistry all right so let's just do that you use h plus because we know we know what sulfuric acid is and we'll say heat now we know what's going to happen here all right we're going to do this we're going to protonate so like the thing that we didn't want to do last time we want to do now because we actually want to make some substitution so use sulfuric acid make up protonated uh protonated the people in the background are my my my wife and children having trying to my wife trying to bathe the kids let's see how that works out for her all right she needs she should get some help having kids is hard anyway so um so you have this protonated alcohol over there right and let's say another alcohol is floating around all right now this guy here now where do i pull this other alcohol from because we have an enough of this we have q b we have q b a that is that is um quanto basta that's that's latin essentially for enough we have enough that we need to do the reaction all right we have qb of that so we're going to protonate one mole of it we'll take another mole of it and then have that mole attack the back side of that kicks that off like so and gives you your protonated dye in this case here diethyl ether plus your water that's kicked off okay that's pretty that seems to be pretty efficient right that's not that's not that bad oh by the way then you have to deal with this business okay so let's have our water come on in pull off that proton right here okay right there and give us our diethyl ether plus now no more water but h3o plus which is convenient because hbo plus is our catalyst or our catalyst catalan oh jesus i'll stop i'll stop all right um is our catalyst right for this so we get some of that back which is not then fulfills the role of the catalyst okay so this is pretty good it's pretty efficient it's cheap as all hell which means i love it but the bad thing about it is that it's limiting how is it limiting well you have to have if you want to make use this procedure to make ethers you have to make sure that the ethers that you want to make are symmetrical that means this the left side is the same as the right side you can't make like an isopropyl on this side and then have an ethyl on that side doesn't work that way you can you can do that by using a different method okay but this is the not a bet this is this acid catalyzed method is not a bad way to make highly symmetrical ethers okay so that's not a bad thing to know okay enter in the williamson ether synthesis now this might be somewhat of a review for many of you from last semester but still go over it again okay the williamson ether synthesis is a synthesis of asymmetric or symmetric ethers by way of an sn2 reaction wherein you have one of your r groups here is let's just say it could be like an alkyl halide or an alkyl tosylate and one of your other species there is going to be an alkoxide species okay and so that guy there can be a nucleophile to attack in to this electrophile over here because this guy here is very nucleophilic and this guy here is very is very electrophilic okay and so that's how that's going to happen all right and this happens via an sn2 reaction and but the r is limited to a primary and secondary right why because this is still even though it's a new it's a new name reaction right it is still an sn2 reaction which is still you know to the to the uh it still has to fall under the structures of being an sn2 which means you can't do an sn2 like like on a tertiary structure on a on a tertiary substrate for example you know so let's just talk about a simple and very simple um williamson synthesis you know what let's use a tricky one let's use a tricky one let's make let's make this guy let's make methyl let's make methyl terbutyl ether all right methyltripetal ether alright that's an ether we can't make it by the acid catalyze method so we have to use another method that we would use to be able to attach both this methyl side and this terp-butyl side right now we can start with one of these alcohols and i'm going to start off with with this being the alcohol i'm going to start off with tert-butanol right tert-butanol right there right and i say this is going to be this is going to be the alcohol that we start with because what happens is that once we have this guy here we can treat it with a good base a good strong base we'll use in this case here we use sodium hydride now i'm not using an ethoxide or an alkoxide base because the alkoxide bases are the pkas are too close to to what this would be so the sodium hydride here is a nice strong base way up there in the in the pka range okay uh and so i'm going to be using that i'll probably be using a good a good a good solvent maybe dmf is a good solvent for for that right all right and so that's going to do some simple acid-base chemistry all right this hydra is going to pull off that proton right there when it pulls off that proton right there this pair of electrons will go right back here to the to the oxygen making this sodium sodium terpetoxide all right this guy here is now going to be a good nucleophile to then be able to add in this other piece here now this other piece here now we can just simply use another alkyl you know group here with a good leaving group let's use since we're only going to do methyl let's just use almond methyl iodide that's cheap to buy and i'm going to see if i can just draw the methyl pretty straight pretty obvious right so you can see and there's your iodine right there right so this this ethox this uh triputoxide here right we'll attack the backside of that carbon right there kicking off that iodine right there giving you your final product plus what um sodium iodide plus sodium plus sodium iodide okay so it's acid based chemistry fall by and this is where your sn2 comes in it's right there okay that's where your sn2 is right and so once you once you have that you know this is how you make this is how you can make your your you know your asymmetric ethers notice you cannot make this by the acid catalyze method all right it seems pretty specific that i chose to make this ether this mtbe by this method what would happen if i do the opposite way what about if i use this as the alcohol to deprotonate well let's let's try that and see what where we end up let's use methanol same hydride this this chemistry works fine right okay so we'll do this guy here well now we'll make sodium methox and using the same exact using the same exact method as we did before right is that does that all right all right so now you have your sodium methoxide now instead of using now because we've already made this side of the molecule here what happens if we just use this as the we'll bring this in as a is the thing that is the electrophile well i think you see what the problem is right what you have right here is that you have an sn2 reaction set up that you like to do but you have a you have a a good a good nucleophile a good small nucleophile that's very strong and very hard and very willing to do the substitution but now you have an electrophile which is this is a good electrophile but not for an sn2 why because this is now this is a this is a tertiary substrate and tertiary substrates do not undergo nucleophilic substitution very quickly or at all let's just say for what we need to okay so as you all know when you have an sn2 when you have an sn2 setup but you can't do an sn2 well the next best thing is going to be a competing e2 all right so you will have a bimolecular elimination when this happens so you have your tributary iodide that will that will be attacked right in the beta position this one of these protons will be abstracted by your methoxide that will swing on down take off that iodine over there and what you'll make is you know you'll get back your methanol which is going to be a sort of a wash but also you will make isobutylene which is hey it's all well and good but it's not what you wanted to make it's it's this guy here right it is the 2-methyl2 methylpropane which is also isobutylene so this is not a successful reaction for for to make this ether okay so be very wary when you do williamson ethers that you choose to write meant the right methods to do the right methods to use okay or the right choice in substrate okay all right oh this is i so this is one of my favorite ways to make epoxides right um we talked we touched upon this last semester a little bit okay so here you have what do you have here you have this sodium hydroxide in water and you do this intermolecular sn2 reaction to give you an epoxide right how does that work well pretty straightforward you take this hydroxide here you pull off that proton right there this guy here swings back to that oxygen and what you end up making is um there's your iodine and here's now your alkoxide side of it right all right then when you have that then this undergoes an intermolecular reaction where attacks that that carbon there and kicks off that iodine giving you your desired epoxide that you want okay now this doesn't work all the time because you have to have the correct stereo relative stereochemistry here and here this has to be trans it has to be opposite each other on the ring right this here doesn't work because these guys here are not on this these are guys here on the same side of the of the cyclohexane ring no epoxide is observed okay um let me draw out the active intermediate the active you know the reactive intermediate for this to show you why this has to why this has to work that way all right all right so let me just see if i can quickly guess at the right if i can guess at the right um you know what i'll probably use the other other contour so i it'll be able to easily be seen i hope okay oh yes this worked out just fine um i think right no i was probably right the first time let me just use this other to use this other isomer yeah this so this was right the first time i don't know why i screwed up all right so use this is one chair confirmation of this and here is so this iodine here can be down here like this guy here can be down here like so so this iodine is going to be right there now your eyeball is going to be right up say so my eyeball here is looking at the screen right but your eyeball here when you turn when you flip this guy here you flip it 90 degrees your eyeball is going to be looking down on the on the molecule right uh here's your eyelashes right there here's your this here's your here's your bloodshot because of the because uh because of whatever you're doing because i'm not judging you i'm not judging you you're looking right down at the right down at the ring there right the iodine is going away from you so the iodine is going away from you the alkoxide is now coming up at you just like so there's your o minus right there all right and that's happening right like so you see how this oxygen this alkoxide here has a straight shot at that the back side of that carbon that's exactly what it needs it needs to have boom right there to have a perfect intermolecular sn2 reaction to give you your yours your well yours essentially your cis epoxide all right now you draw a quick sketch of this and you'll see immediately how this can't work let me draw the same exact structure except change up the star chemistry of this and you tell me if it would you think it would work i'll draw out even the deprotonated version and tell me what you think okay all right all right and so the iodine's still going to be going down but now instead of the alkoxide coming up it's going to be cis to this iodine all right which means while your your hydrogen here your hydrogen here would be here and your alkoxide would be right there there's no way there's no way that this guy here even if you do a chair flip that this alkoxy would ever give get a straight backside attack you know like this is a nice straight backside attack because it's an sn2 reaction there's no backside attack on this alkoxide species so you can't it can't ever really be done all right so that's not going to be the reactive that won't that this species here will not give you the cis epoxide that you so desire okay so just keep that in mind so even though it's a straightforward thing you know you can make epoxides this way and you can make you know if you have if you have a chain you know essentially and you have you know if you have you know this guy there and here's like a straight chain here for example and i'm just drawing in start chemistry but with a straight chain as long as there's no hint there's no rotation hindrance there you can this it almost doesn't even matter what the stereochemistry is here but it will give you whatever the stereochemistry is at the very end you know resulting in it all right but this guy here there's no ring here to to worry about rotation but as long as you have sort of a a good straight you know straight uh you know straight shot at the alpine you know the epoxide that's going to be overall a good thing for you okay and what i will do here is i will not translate that going going towards you to now this going towards you and this going away from you to this going away from you okay that's how you can do that very simply all right so it's a nice that's one of my favorite ways to make epoxides all right and so we've talked about this last semester synthesis of ethers by alcoxy mercuration demercuration all right and so what we use here is that we use this this um mercuric trifluoroacetate and normally we'd use it with just some water right to give you the the um the thing that you need let's just see real quick here yeah normally we would use we would use um this guy here to give you the the um what's going on here hold on one second all right we are back to to doing this because all right good all right um sorry i had to take a little bit of a break to deal with some dad stuff oh dad all right we're over here um okay so coccyx recreation demon recreation okay and so so last semester we did put this back to pen um this was an alcohol this wasn't this is a water before and this is a way to do to give us um markovnikov edition without rearrangement okay but if you don't use water and you use you know a decent selection actually of alcohols here you can say instead of using instead of making alcohols here you can make ethers right so imagine if this was a guy this guy here was a was a water this guy here would be a this guy here would be a an alcohol if you use this roh or whatever this this alkyl group is here you can make a you can make a in a regular um ether which is a very you know a very versatile way to use to to adapt this ox you know this alkoxy recreation de mercuration all right um just make sure you have both the both of the regions that you know that you know that you need we talked about the mechanism of this and the only thing that you're responsible for is let's just go through the first step here okay the first step that you only really have to know is like this last step here is two is a little bit too much so what we're normally going to be doing here is we're going to say we're going to say this hg is pretty much attached right that's a carbon all right there's an oxygen there there's a carbon here there's that and this is what cf3 all right cf3 fine cf3 pardon the penmanship thing is the pad and and and what other other factors as well c f 3. all right all right so this is what this is what this is except drawing out all right so what we do here is that we're we're going to assume that one of these trifluoroacetates are liberated right from that from that merc from that um mercury salt all right and that's going to give you i'm going to just draw it down here it's going to give you this this hg we'll say h yep hg uh o2 c f 3 but plus all right and that guy here is going to is going to pretty much this guy here has some lone pairs of electrons on it we don't normally draw lots of lone pairs on transition metals all right but for now we'll just do this okay and your book doesn't talk about a mechanism and this is about as far as i want to go with it this here swings on up in between that mercury and that carbon and this lone pair here swings on down like so giving you this mercurian bridge right that's an r group there and here's your mercurian bridge all right and once you have that hg there's that and then you have your o your trifluoroacetate group on that side all right cf sorry cf3 cf3 all right and there's your mercurial bridge right there okay and then what happens there is then then your alcohol from here comes in and attacks this side all right so you have whatever that alcohol is here comes in and attacks pretty much the most hindered side of this guy here because what you what it's attacking it's not attacking this carbon that's on the interior because it loves to attack hinted carbons it's attacking the carbon you might remember from last semester that has a greater partial positive charge well why does this have a greater partial positive charge than that the reason why that one has a greater has a greater partial positive charge because it is a this guy here if you were to think about this in terms of a carbocation and imagine this car this r group here was a carbon if you think about this carbon here is a carbocation this would be a secondary carbocation which has a greater positive character this guy here would be a positive carbocation right a a primary carbocation which would have less positive character because it's a primary you have less hyperconjugation here you have more hyperconjugation because it's a second it would it would be it would act like a secondary carbocation this guy has a primary it would act like a primary carbocation all right so this guy here has a more developed a more developed delta positive charge right there all right to give you this and then there you're from here we don't we don't talk about the mechanism because it's just a little bit too much for this course but here's and then your this is your reduction step so oxygen recuration here alkoxy migration deregulation to give you your final overall ethereal product okay all right all right and so this is um this i love how your book talks about this actually this is a really wonderful thing um it's not just about how to make ethers from alkenes and alcohols and acids to give you a a you know a certain ether which is what it is but they're talking about this ether that they're making specifically as a protecting group which is sort of sort of wonderful all right sort of wonderful right um there's you know you always need a good a a a really you know a nice selection of prison groups for alcohols right and this is just one of them all right and so how this thing happens is that this is a this is as straightforward as it as as it comes you take your alcohol you take your isobutylene or your two methylpropane you hit it with some acid and then you end up getting this protected alcohol here which then you can do some chemistry on the other side of your molecule to and not worry about this getting involved like for example let's say i'm doing some base chemistry or some nucleophile chemistry on like this side of the molecule right and um that's all well and good but i really can't you know i can't do base chemistry or nucleophile chemistry if i have a free proton around so let's get rid of that proton well i can either use tassel if i want to or i could use this guy here right this guy here removes that proton gives you this guy here you can do all your chemistry or over on this other side of the molecule and then remove this later to get your alcohol back which is pretty great right so this is a protecting group just like just like the tosyl group or the measle group or the triphala group is a protecting group all right so it's not just an ether it's that too but it's using in in it's employed as a protecting group so it's great it's easily removed by treating it with with um with the with a dilute aqueous acid all right all right you know what let's talk and ah let me just i want to talk about that mechanism actually all right let me talk about this this mechanism okay very very simple very simple mechanism all right i'm going to leave that there i'm going to take this guy here i'm going to you know we're going to imagine that this sulfuric acid is always just h plus all right so we're going to swing on out grab that proton over there very markovnikov style all right and so now i'm going to redraw this carbon skeleton this proton here because it's a markovnikov style of addition will go to the exterior there on the the distal or the distant carbon here where it already has lots of protons on it because it wants to expose a tertiary carbocation all right so that's sort of the thing that we talked about last semester if you know it's not this doesn't go to the end of the of the olefin because of a markovnikov's rule that's a rule that a guy thought up the reason why it happens is because it's exposing the most stable carbocation so notice i'm not drawing the primary carbocation i'm drawing the tertiary carbocation all right tertiary carbocation very very very stable okay all right so i have that there and now let's let's now reintroduce our alcohol group there okay let's take our alcohol group there all right and it's going to do what it does with its bad new nucleophile itself pop right there giving us our do do do oh positive charge positive charge there okay so now you have this guy here then from there to there essentially all it is is then you take um this is this is not just h plus this is h2so4 but if you remove one h plus from here it's hso4 minus so one might imagine hso4 minus one might imagine that the minus that the so4 must pulls off that proton to give you back your neutral species or you can just have water pull it off because plenty of water in there to them you know i'm sure as well all right all right so that's another thing so so that's that's how to that is how to um add on this this this tert beetle group too and and we've talked about this a little bit last semester but we've never talked about it as a protecting loop but i really love the fact that your book does talk about it okay so why don't you make sure and pause the video here and copy this all down because i have to i don't i didn't leave myself another page after this to talk about it but we got to talk about how to remove remove this guy here with aqueous dilute acid okay so pause it and take this down or print it off or do whatever the hell you want to do all right you ready all right erase all right now let's go let's go backwards and go backwards all right now we want to remove we want to remove this thing here using aqueous acid all right let's take an arrow there let's put a little bit of h plus here with some water all right we need the aqueous aqueous acid because the aqueous this is this oh here's part of it okay this guy here dude gets coordinated all right there's that and now what do you think happens this guy here why did i just let labs in the journey what do you think happens who are these people all of a sudden i'm jerry seinfeld all right this water here who eat who eats all these peanuts on an airplane right how do i need okay so hey take your water right there this guy here attacks the back side of that carbon right so and now you have your alcohol back plus your trip butyl alcohol trap butyl alcohol okay see does that attack the backside of that carbon over here all right giving you that species right right there okay so there's your aqueous dilute acid now you have to be use aqueous because if you don't use aqueous you won't you need to have the water there to do this and you know this this this um sn2 reaction okay so stick that in your pipe all right um silo ether protecting groups here are probably the most beloved protecting groups of um pretty much everybody both students and practitioners of the art itself okay because they go off very easy they go on very easily and they come up just as easily all right and there's almost there's almost no mechanism to it okay so um butyl butyl dimethyl silane trip butyl chloro dimethyl silane very popular um chlorocylene that we can be adding on here silo silene is the car is the atom right underneath carbon so it shares a lot of properties of carbon actually um but what it does doesn't have the carbon what what carbon doesn't have that cell does have is that the ability to be able to to be able to expand its valence temporarily to be able to do some chemistry all right let me show you what i mean all right so this guy here comes on remember you know this alcohol here is that alcohol all right so take this guy here attacks this this silene right there and what you have is this all right it's an addition again similar to before it's an additional elimination all right uh methyl methyl and turt butyl okay i know it looks a little bit weird all right ugh i'm making it worse i'm making it work just not but just a positive here negative all right so there's your two methyls your tert-butyl your chloro and there's all that business there okay all right so what happens is that this guy here just pops off spontaneously it's temporarily expanded its valence right it's not the cylinder is not in the 2p orbital so it doesn't have to follow the octet rule right the cylinder here pulls off right it pops off chlorine pop all right and when that happens you end up making that guy there which again should look very familiar to you in terms of like all these protecting groups they all have they also go on very similarly our chlorine here pulls off there pulls off that proton over there and gives you the thing that we talked about okay imidazole is another is an is a is a pyridine-like molecule that had that does the same exact role that uses the same exact role as you know pyridine it absorbs hcl right so there's that all right very useful very easily easy to go on and just as easy to take off it's so sweet to take off actually okay so here's one protecting group there and you use something called t-bath right tetrabutyl ammonium fluoride or t-bath t-bath tetrabutyl ammonium fluoride tetrabutyl ammonium fluoride in thf you do that and it's pretty much a straight a straight shot right what happens here is that your t-bath all it is is a source of nucleophilic fluorine the same way you can also by the way use use um use aqueous hf2 is but h aqueous hf is is an evil is a bad actor it's terrible actually it's very bad for you hf um oh yeah it was featured prominently in breaking bad for example it dissolves people um not just people in new mexico but people people's everywhere all right persons everywhere all right so aqueous hf is something you can use or tea baff tbaf is a nice salt that you can pretty much almost handle with your hands which is sort of nice but you still don't want to do that be very careful with tbaf all right anyway it's a source of nucleophilic fluorine and fluorine is like i ca i just can't wait to get into the limelight and here i am finally i you would norma i i remove groups that's fine i'm still still a player so attacks the attacks into into silene again zoop oh i want to watch better call saul that that spin-off show of breaking bad i can't wait to see that i think i missed the first few episodes of it i don't know what's supposed to be on i'm going to see all right r-o-s-i methyl methyl methyl methyl toy butyl here's your floral all right and so now you have this guy right here right which has this negative charge here and this is going to break down just like it broke down before when you were just adding on the alcohol onto the chlorocylene so this breaks off here spontaneously as this just snaps off giving you your giving you your um bitter r o minus n h four plus so this your textbook here is is wrong in this respect because it asked me to do it do it this way this is not right because what you add you have no source of protons here so you actually have the ammonium the ammonium alkoxide plus your s i oh i'm such a stickler where can i just leave your poor textbook alone all right there's your tert-butyl dimethylfluorosilane here is your alkoxy and ammonium salt if you treat this guy here with water or whatever the hell you know whatever some proton source then you get you know pro h plus this is h plus h plus in water there you go there's your alcohol back as soon as you're done with it if you don't treat it like that then you have your ammonium salt back which is a big mess all right all right so my question to you is that why the hell does it go this why does this reaction go this way why does it kick off the or versus the s why is kick off the sio bond versus the sif bond all right what i'd like you to do and you can just google this on the interwebs look at the look at the um the bond strength between silicon and fluorine silicon and fluorine are one of these bonds that are like made in history um silicon let's give you an example to to harden the enamel in your teeth you use you use toothpaste with sodium fluoride in it right well your teeth are made essentially made of silicon oxides and fluorine here if fluorine in the toothpaste is very much attracted to the silicon bond because the fluorine silicon bond here is one of the strongest polar covalent bonds known to organic chemistry so this is a very very very short bond and very energetic and it will kick off anything else to maintain the silicon fluorine bond here so this guy here is very is a very favorable bond all right so that's why they're given a choice it will kick off the next best thing because it is not breaking that bond again silicon flooring uh very strong so strong that we use it that we use fluorine in our toothpaste to harden the enamel of our of our silicon-based teeth all right um that water there you go okay all right so this is something um that i might save until afterwards to talk about um in terms of the you know why why would we use this you know why would we use these can you know kinds of things and these procedures in the synthesis um you know why do we use these uh you know the these protecting groups here so for example here i want to make this molecule here from that guy here and this guy here well if you if you just take this guy here you treat it with from here to here you won't make this right you won't make this you will deprotonate sorry you will deprotonate this guy here before you'll displace that so this will happen right to give you one two three four right plus you know that sodium alkoxide bond here will in this will be made before long before that's made because this is this all acid-base chemistry as you know is faster all right than anything nucleophilic all right so there's that you want to make sure that you understand that all right so so what do you do to make this what how can you how can you treat this problem well this is where you can either use tbs chloride you can use oh what the hell you want to use one is tbs chloride you can use you can use isobutylene and acid you can use tosyl chloride whatever you want to use right but for tbs it's so but but um but tbs is is uh tbs chloride is so you know any of the solid chlorides are so easy to use and so readily taken off then you know this is the best way to go take tbs chloride treat it with this guy here this tbs chloride this tbs will go on to this oxygen here protecting it you can do all the sn2 sn2 like chemistry that you want to do without worrying about anything else and then at that point there this guy here attacks the back side of that carbon over here kicking off that iodine giving you that guy right there and then t baff it and then you can get this guy here right so you need to use this step this step here even though it's a protective group here is one of the most important steps in doing any of this chemistry if you don't have that then there's no way that you can actually produce the chemistry all right um reactions of ether we've talked about this a little bit before if we've taken an ether here we hit it with hbr or especially hi um they end up cleaving all right they end up breaking it breaking in half okay so here if you take it with hbi hbr here you make an oxonium salt all right um again very nucleophilic very or or very or or basic that will attack with anything that is either electrophilic or acidic all right that's what this is so all acid-base chemistry is here like this isn't this is a base this is an acid right period but if you look at it a different way this is actually sort of a nucleophile this is actually sort of an electrophile right it makes that's how that's why you know i make such a big deal about acid-base chemistry in the very beginning not because i'm sort of a weirdo wonk about acid base i could give a i just want you to know that acid base is the reason why everything ever happens at all all right so there's that so um all right let us talk about the cleavage of ethers okay but where instead of using hbr you know we'll just use hi i'm gonna do two i'm going to do two of these guys here i'm gonna do this guy here first hi hydroionic acid a very very strong acid all right this guy here grabs that proton right here all right all right and then there is your iodine right there there's your oxonium species there pressure iodide right there your iodide there there's no very good nucleophile which will attack the back side of that carbon right there because this guy here is a good leaving group right so this carbon right there is is a it has a slightly positive charge which attracts that iodine we're like yeah but big deal this has a full positive charge why doesn't that attack that charge over there again not productive there's nothing you can do with that chart with that it could it could because this can't because it's acid-based chemistry it could certainly go backwards so it could pull off that proton then go backwards because it's acid base chemistry and whenever we draw acid base equations we should draw the double arrow but in this case here we didn't because we we know we want to go forward to do the chemistry so just shy of going backwards let us attack nucleophilically this carbon over here because it's now electrophilic because if it's electrophilic because it knows if this oxygen gets this pair of electrons it will then no longer be positive which is its which is the oxygen's motive to help this reaction to go okay so this reaction attack so this iodine attacks that carbon over here like so bloop all right i don't know if it actually makes a bloop sound that just might be me being a foley artist i don't know i'm a former i should be a foley artist all right let's draw exactly what we draw we draw there like so all right this and we'll put the iodine over there okay so but we're not done we're not done right because this now we've made one ethyl iodide but we still have this alcohol lying around and the way this reaction goes is that this guy here you have to have all the equivalents of ethyl iodide okay so let's just attack it with one more mole of zoop zoop and just like the foe attacks the back side of that guy over there like so kicks that off the same exact reason for that right and it gives you another mole of ethyl iodide so now overall you have you have your overall reaction mechanism the overall scheme using hydroionic acid is that two moles of that stoichiometry wise and whatever the house do we make we made a map oh we made water right plus water we made one mole of water right yep one mole of water so one mole of diethyl ether plus one mole of hi gives us two moles of ethylene plus one mole of water okay that is the full mechanism for the cleavage of standard regular simple ethers there's a there's a little catch right remember all the steps here there's nothing special about the cleavage of ethers that make it like well that has to go this way no all this is is acid based chemistry sn2 reactions acid-base chemistry sn2 reactions boom there you go there's nothing special about this reaction this this overall scheme that's a that makes it more special than anything else all right so it's still governed by the other strictures of standard substitution chemistry what do i mean by that all right let me show you an example you take you take phenyl phenylethyl phenyl ethyl ether hit it with hi hit it with hi all right wow that doesn't that doesn't even look like oh hi all right so there's that all right there's that there's that let me turn up my phone because i have a funny feeling i'm gonna be getting some messages all right okay plus all right so there's that there's that first acid-base reaction that happens right now you have iodine here that attacks the back side of this carbon species right there like so giving us this guy right there oh h okay all right and so now plus this guy here all right all right now normally if this isn't if this is a regular ether i'd say well now you go and do it again now you protonate this guy here and the whole thing but this is where the reaction stops why is that the reason why is because you cannot protonate this phenol and then do a new then do another backside attack of this why that carbon is sp2 hybridized there's no such thing as an sp as an sp2 hybridized carbon undergoing an sn2 reaction on something like this or in anything actually for that for that matter okay so either the reaction is done is done right here again nothing special because of ethyl phenyl ethers or whatever it's just the chemistry doesn't allow it to go forward all right that's all it is okay all right let's go forward come on uh under the reaction it was carbon okay so we talked about that's just a cleavage or cleavage of the ethers okay and so you can use that with hi or hbr if you want to no no big deal and i don't know if hcl is strong enough but i know hi is so anyway and there's a mechanism if you don't want to see me on my scrolling although i do think my drunken scrolling is fun epoxide okay epoxides we love those um they're very they're very um straightforward to make more or less and they're very nicely reactive okay to remember a ring containing an oxygen all right how do you make them well you can make them with a peroxy acid what's a peroxy acid well if this if you had a regular benzoic acid this would be a benzoic acid which is a regular it's a regular carboxylic acid right and it just has two oxygens and one carbon it makes of the a carboxylic acid but if you have a a per acid per means more or peroxy acid just means more oxygens that means you take your regular carboxylic acid then you add on one more oxygen in in between the carbon and the oh so these this extra oxygen makes it a per a per acid or peroxy acid okay like mcpba or this regular methyl parasitic this this per acetic acid acetic acid comes from the acetate ion right here the per comes from this so here's your perceived gas right there and here's your metachloroperoxybenzoic acid okay the mechanism for from from this perox from this olefin to this peroxide is one of my favorites you are going to love this all right all right so we will talk about oh come on give me a clean oh okay okay well let's talk we'll talk about the star chemistry and then we'll give you one quick mechanism okay so here is if we have a trans olefin or trans alkene and use mcpba then when you have a trans epoxide why it's not because what's going to happen is that this oxygen is going to come from one face of the double bond instead of drawing the trans bond like this let's let me just draw it like this let's try it like where it's it's flat like so and if i'm pivoting this towards me where this is a little flatter where this is in the plane of the paper and i pivot this towards me and then that away from me what happens it looks sort of like like this guy here like so all right all right so this is going away from you this is coming towards you and you are lowering pretty much the oxygen in the plane of the paper to give you this guy here right so if you start with a trans olefin you end up with a trans epoxide you stop with cess olaf and you end up with a cis epoxide all right um and just keeps in mind more electron rich double bonds react faster so if you have if you have two double bonds and use mcpba which is the standard reagent to do epoxidations then you will have the m the approximation happening on the more electron rich side this side here is more electron rich than this side because you have methyls here dumping some electron density into that olefin side okay okay so let's talk about the mechanism finally of this beautiful reaction you're going to love this all right and we will actually use the trans epoxide to start with okay and we use mcpba but let me talk about mtpb for one second here's medical or proxy benzoic acid um here's how you normally draw it metachlorial orthometa so here is all right and how we're going to draw this though we're not going to draw it this way when we look at the mechanism i'm going to probably just do this i'm probably just going to say this guy here is going to be fennel because i'm just going to abbreviate this because our transition state is going to be so very clogged up it'll be very congested because i care about the the configuration or the or the confirmation believe it or not of these one two three four five atoms right here we will not be drawing them that way we will we'll be drawing it and i'll just do one so i'll put that as fennel now we'll be can be drawing them in a very certain very specific way we're gonna be drawing them such that they look almost like a five-membered ring one two three four five i want them to draw in this way right why because i want to get at that oxygen right there this suction right over there and i also need that oxygen to be close to that proton right there because this is going to help us be the linchpin of this entire reaction mechanism okay let's start off with a very simple olefin all right start off with just ethylene ethylene gas our ethylene gas hitting it with m mcpba will give us straightforward epoxide right oxarine all right the mechanism all right i believe it's methylene chloride all right so i'm gonna draw it out a little bit on the you know what i'm gonna draw it a little bit on the big side all right i'm gonna draw it on the big sign there and you know what all right so copy this all down all right i'm going to i'm going to use a clean page because i want to make sure that we have a nice clean palette to work with here right so here's here's our overall reaction mechanism all right cp ba give us give this oxide okay so what's the what's the reaction mechanism nice and big nice and big all right so there's our expanded olefin and here's our mcpb but drawn in that really weird way where we have the oxygen right isolated right all right and so i'm going to do that i'm going to do that all right and have that there i'm going to have that right there and i'm going to abbreviate again the funnel for that all right i i drew this auction here outsized for some reason because just because all right now what's going to happen here is that the this pair of electrons here is going to help me out here right this guy here is going to help me to pull off that proton here which will help break this bond this pair of electrons here will attack that side of that carbon-carbon double bond here when it does that this bond here will flip on up and attack that oxygen over there when it does that that oxygen will then at that point be breaking the octet rule so it has to fulfill the octet rule by breaking this oxygen oxygen peroxy bond over here then when that happens here that one here comes flipping out there and then that kicks up like like so okay let's show you what this means okay so that pair of electrons here grabs that proton right there this privilege here slides on down crashes into the other side of that now this already has as many electrons as it likes all right so that means one of these double bonds here cannot cannot be that way all right so this will then flip on up like so and the way the style is i'm going to put i'm going to put this pointing to like almost nothing like you'll see here where it looks like i'm not pointing to anything well i am pointing to the imaginary bond that will be formed when we make the epoxide okay that's a style of this mechanism all right all right so that swings on non-crushing into that this swings on up between that oxygen and carbon bond over here if i form this carbon oxygen bond up here i am breaking down the octet rule for this oxygen so i have to break this peroxy bond here all right when i do that i'm just going to dump this pair of electrons in between that oxygen and carbon bond over here and when i do that that will be great because because as you remember from the beginning this auction here is protonated so that o is going to be an o plus and that o plus does not want to be that way that oxygen does not want to be electron deficient so if i were to dump these electron dens this electron density in between this oxygen carbon bond here then i can swing this up here and make that oxygen neutral again let's now unravel this mess and see what we have we have it's almost like the the unexciting part is the epoxide so there's our epoxy that we've just formed and now i'm gonna i'm just gonna draw this as per you know just written just like that all right so here's your fennel all right so now the bond comes out now this carbon carbon bond over here is not going to be a carbon i'm sorry carbon oxygen bond has been carbon oxygen bond here but it's going to be a double bond because this bond here is a double bond and then this carbon oxygen bond here carbon dioxide is going to be a single bond and then this oxygen here now has a hydrogen on it it's going to be that hydrogen right there all right so now we've made with mcpba and ethylene gas we've now made oxarin and benzoic acid and this benzoic acid can be washed away using acid-base chemistry acid-base washes in a sub-funnel all right so that's how it so this this is the mechanism for mcpba there's only one crazy little transition state you know thing um and that's what that and that's what this is what it is okay so here's what i need to do i need you to practice and practice and practice this it's not immediately obvious to you but once you start doing a few more a few you know just practice this mechanism and then when you start doing a few more you'll see where you'll see how it'll ultimately make sense to you it's like oh yeah now i see how this guy here helps this bond here to form this guy here you know for example right because this guy here pulls off that proton makes this nucleophilic then crashes into that and then this this is already filled up with electron density it's already obeying the octet rule here and swings on up this can start to help to break the octet rule with that auction over there and you see how that's not going to work out all right so again practice practice practice practice practice okay this is all it is all right how many times so for you new people how many times should you practice this some of you get it on the first 30 tries some of you get it on the first 75 tries right but keep on trying frustration's a part of it right you have to make sure you give yourself the frustration if you don't if you're not frustrated you're not trying hard enough okay for those of you who who have got it make sure that you can use as many you know you know do as many problems as you need to feel comfortable with it okay i love me some mcpba it's one of my favorite reactions all right so high strain three-membered ring of epoxides makes them much more active towards nucleophilic substitution than than ethers uh you know than other ethers all right so here's an acid-catalyzed ring opening of an epoxide that you might imagine so you have an epoxide that you've made by either way either by mcpba or by the you know the the base chemistry using your you know using your iodine hydroxide thing so either this way here or or this way using mcpba okay so either way all right so now you've made your epoxide now you want to open it up and do something with it okay fine so let's take our epoxide and hit it with some hit it with some acid and once you do that this guy here right will so this guy here will protonate right from that acid there then these guys here become very electrophilic why because that oxygen here wants to does not want to be a have a have a positive charge so this guy here of course you have two your two you have you have an alternative you can either go backwards right but we've talked about not being productive or you can go forwards which is what we're going to do because we want to make the reaction go all right so we have our water attacking one side of this epoxy versus the other one as long as you break that carbon oxygen bond here to fulfill you know to have oxygen have its its octet of electrons back that it wants all right so once that happens water will then come in and pull off one of the protons from the from the from the resultant nucleophilic attack so this water here attacks the backside of that carbon over there all right so keep an eye on this water right there that water right there is that water right there another mole of water comes in grabs a proton from there neutralizing it and making a making this diol this diol is has a very specific category of diol it's called a vicinal invisible dial invisible diol is a dial in which you have a one two dial situation you have a you have two alcohols on adjacent carbons okay vicinal diol vicinal meaning in the vicinity or close it's also abbreviated as as a okay so here's your vistil thing okay you can even do a base catalyze ring opening of an epoxide right this guy here your book chose to use an alkoxide version of this but you don't really have to you can use either an alkoxide or you can even use a hydroxide there's no reason why you can't do that to give you another vicinal diol but yeah this is just straightforward straight up attacks one of those sides one of those carbons here of course there's no protonation because it's a base catalyzed and then once you do that then this guy here you know opens up right giving you the alkoxide there and then you have the alkoxide here that can't just be this way forever because it's unstable that way so you have to protonate this in some way the other only proton source you have there is from is from some some alcohol source that is maybe your solvent perhaps all right so there is your so for example like here if you're using if this is like methoxide you probably run the reaction in methanol right then this would be the methanol that you would use okay to be able to pull off that proton there to give you your vital well it would be your your alcohol ether but again if you use you know hydroxide here then you'll have a vicinal diol with your alkoxide there okay okay folks i think uh my my kids my kids i have to go to sleep and so my my wife told me i can't be blathering on anymore anyway thank you for this uh for this nighttime edition of organic after dark anyway you