so we are now recording after I've given the class who was here today all the answers to the first [Music] exam all right carbonal reactivity so here is a generic carbonal structure R is going to be anything could be a Benzene ring could be something carbon could be an alkal group and then why we're going to choose because we love BYU and it can be basically any number of things that I'll tell you in a little bit carbonal reactivity is dominated by the existence of this resonance structure in which you move the electrons the pi electrons from the carbon oxygen Pi Bond and you put them out on the oxygen with a negative formal charge on the oxygen and a positive formal charge on the carbon uh and that tell tells you that the carbon oxygen bond is polarized you should already expect that to be the case because oxygen is more electronegative than carbon uh but this other resonance structure is a is a minor but significant contributor to the overall reactivity of the carbonal compound it tells you that you expect the carbon to be electron poor which we're going to indicate with that little Greek letter Delta meaning a small amount increment of partial positive charge and the carbonal oxygen should have a partial negative charge on it understand you know this now that resonant structures are both accurate descriptions of the molecule but in and of themselves they're incomplete you need all of them to get the overall picture so you expect carbonal to be electron poor on the carbonal carbon but to be electron rich on the carbonal oxygen that's really important that's going to govern a lot about how these mole ules behave uh we're going to talk a lot about the influence of what this R Group sort of Y group is on the reactivity of the carbonal compound we're going to ask questions like is the Y group a good electron donor what do we mean by that well some groups are good at sharing electron density and others are not these are Concepts that you probably are already familiar with one way that you can be a good electron donor is via resonance so let me give you an example of something that y can be that would be a good resonance donor I'm going to draw for you the carbonal the structure of a carbonal molecule called an Esther where the Y group is this methoxy group here right and I'll just abbreviate that sometimes PE people abbreviate methoxy groups ch3o as just Meo hopefully you'll get used to that the oxygen has a lone pair on it and uh what I showed you above for the resonance structure of this Esther carbonal compound still holds there's still a resonant structure where a positive charge is on the carbonal carbon but now look what we can do that y group has lone pair electrons on it and they can donate into the positively charged carbon creating a new oxygen carbon Pi bond with now a positive formal charge on that oxygen and a negative formal charge on the carbonal oxygen what do you think that does does to the carbonal carbon what does that extra resonance structure tell you is that carbonal carbon more or less electron po than it would have been without the lone pair on that neighboring oxygen less electron poor yeah resonance electron donation makes the carbonal carbon less electron poor or less electrophilic so you would expect the Esther to be not as electrophilic I as a related carbonal carbon that lacks that lone pair uh as an example so we'll say the Esther is less electrophilic than uh an example of a carbonal compound that lacks a resonance electron donating group is the alahh where the Y group is just a hydrogen no lone pair no possibility of resonance donation of electron density into the carbonal carbon the carbonal carbon in the alahh experiences that the the full impact of that partial positive charge so you'd predict alahh would be more reactive than Esters and in fact that's the case in in chemistry and in biology all right um another example of electron donation is something we're going to call the inductive effect the inductive effect is related to electr negativity so how can you donate electron density ver via electr negativity well the thing that does the donating simply must be less Electro negative than the thing that does the accepting classic example of this would be a ketone so let me show you the structure of a ketone versus an alahh in a in a ketone that y group is something carbon based uh I'm going to draw that same resonance structure for you here and uh I want to talk about how the methyl group in the Ketone is an electron donating group the way to explain this is just to look at the hybridization of the carbonal carbon which is SP2 versus the hybridization of the methyl group carbon which is sp3 right which of those hybridizations has higher percent s character that is a 351 question go SP2 right 33% instead of 25% s orbitals hold electrons closer to the nucleus lower in energy SP2 orbitals are therefore more Electro netive because that's actually what electro negativity means how low in energy electrons are on that atom uh SP2 carbons are more elect negative than sp3 carbon so in a ketone the sp3 carbon actually donates electron density towards I'm going to use a little dipole symbol that you may have seen in general chemistry to indicate that the less electronegative sp3 carbon donates electron density through the sigma bonds to the SP2 carbon so comparing the aldah to the Ketone okay uh an sp3 carbon is less electr negative than a hydrogen so electron donation is better for the Ketone than it is for the aldah therefore you would predict that again the Ketone is less electrophilic than the alide and and uh and in fact you cans OB ve that all the time in in chemistry okay so the identity of that y group on the carbonal is going to be absolutely crucial um so with that in mind and before we talk a lot about reactivity or rather the kinds of reactions that can uh that these molecules can undergo I want to spend just a minute to survey most of the carbonal compounds you will encounter uh in this class and in biology and we're sort of going to rank them in terms of reactivity and I'm going to put them in three or four different groups starting with the most reactive most electrophilic to least electrophilic and some of this is going to set the foundation for things you're going to learn in Biochemistry reactions that you'll see in Biochemistry are going to make sense because of some of the things that we'll talk about today so if you were to put these things in rank order I've already uh done some of this for you already because we have alahh up here and we've put ketones a little bit down the list but let's let's just focus on alahh this is sort of group group one in group two you have Esters and I guess I'll show you the structure of an aldah now I'm going to show you group three which is a functional group where instead of an oxygen we put in a nitrogen this is a functional group called an Amid and sometimes we will call this portion of that functional group an amid Bond other times later on in the class we will call that a peptide bond now here's the first question well I've asked other question so the nth question of the class which is why did I put the amid as lower in reactivity than the Esther because I am the professor and I know everything and therefore it is true no why nitrogen is okay so that is a true observation a fact nitrogen is less electr negative I rarely have the patience to write out Electro negative in its entirety often I abbreviate it like that nitrogen is less electronegative than oxygen okay so what why should that make the amid less reactive yes leaving group is less stable okay the leaving group is less stable we haven't even gotten to leaving groups but you're you're right we're going to get there as we think about carbonal reactivity we're going to be paying special attention to where this y group could leave and be replaced by something you are right that o minus as a leaving group is a better leaving group than R NH minus for sure you can tell that just by thinking about o minus versus nhr minus then thinking about their conjugate acids as you learned to do in 351 as Seline Dion sings is it all coming back to you now you guys don't know that song that was a song from my day years and years and years ago look it up um stick to the Star Wars references Fly Boy uh yeah so you can tell that nhr minus is a poorer leaving group than o minus because uh it's nhr minus is less stable you can tell that by comparing the PKS of their conjugate acids make sense that's a 351 argument okay good what else something to you draw a res structure n will HB does it have to do with uh the hybridization of the nitrogen in the resonance structure not necessarily with its hybridization but you're on the right track to be thinking about resonance structures I'm going to go back to what I showed you on the earlier screen about how the oxygen donates electron density via this resonance structure and then I'm going to point out that nitrogen can do that too now I want you to think about whether you should expect nitrogen I'm not going to I'll just draw that other resonance structure oops and I'll do that for the Esther as well just so we can make a comparison which of those is a better resonance structure and how can you tell another way that's the same question is asking which is more willing to donate its electrons the oxygen or the nitrogen the nitrogen the nitrogen is less electronegative than oxygen that means its electrons are held a little bit higher in energy where they are more available for sharing okay nitrogen is a better donor because it's lower electr negativity that means that this resonant structure is a bigger contributor for the amid than it is for the Esther and therefore the amid is less reactive than the Esther better donor smaller Delta Plus on the carbonal carbon less electrophilic okay this is really important because the workhorses of biochemistry are proteins that are individual amino acids connected by this kind of bond they are actually made from precursors that are called Amino asil TRNA which are Esters biology uses an Esther a more reactive precursor to make a product Which is less reactive going downhill in energy okay all right um let's see and then fourth on the list we're going to put something that uh actually you've seen before this is the conjugate base of a carboxilic acid this is called a carox oxalate why would this be less reactive than the amid go ahead get the oxygen does have a full negative charge on it that's going to be a better donor than the neutral amid or than the neutral oxygen right and in fact you've grown up in organic chemistry learning to draw this alternative resonance structure you should already be used to thinking of that negative charge is delocalized equally on both of those carbons the carboxilate is not very reactive at all it's sort of an it's sort of an end point okay um let's scroll up the list a little bit more we'll have some more to say about the conjugate acid of a carboxilate but the reason which is a carboxilic acid the reason I'm showing you the carboxilate is that is the form of a carboxilic acid at the physiological iCal pH of seven so in biology if you've got a carboxilic acid it's usually in this form and that's that's an important thing to realize we'll have some some more to say about uh carboxilic acids in organic chemistry in a little bit on the at the top of the list I want to include some other things that are very highly reactive some of which are uh found a lot in biology others of which are only found really in the lab that we use from a synthetic point of view we'll stick with the biological ones to begin with I'm going to just for now if it's okay I'm going to include alahh highes and ketones in the same category even though you know and I know that alahh and ketones are different and that the alahh is a little bit more reactive than the Ketone whoops let's see need to rearrange I wanted that no that there we go slide it down a little bit sorry if the notes aren't aesthetically pleasing it's sort of hard to do this on the Fly uh right so another molecule that you'll encounter in biology not so much in the textbook but you'll encounter it a lot uh later on when we start talking about metabolism is something called a thioester a thioester is the sulfur version of the Esther but notice I didn't put it down with the Esther in terms of reactivity put it next to the alahh why do you think the thioester might be more reactive than the Esther your instinct is going to be to say it has to do with electr negativity that's the wrong way actually sulfur is less Electro negative than oxygen right so if it were about electro negativity you'd think oh maybe that sulfur isn't pulling so hard against that uh carbon maybe it's more a able to donate its electrons uh why is the thester up so high in reactivity yeah go ahead my guess would be what someone else was talking about with leaving groups leaving group ability the the Su group okay right we've talked before we've talked a little bit you learned a lot actually in 351 about leaving group ability and though I haven't said a lot about it today it is also one way that you can rank the reactivity of carbonal compounds or or related ones uh the argument here is Sr minus whose conjugate acid is a thol and if you look this up would have a PKA of8 is a better leaving group than o minus which you saw with the Esters conjugate acid is the alcohol pka of 16 remember PKA units are factors of 10 so you're looking at a 100 million times better of a leaving group Sr minus is than o minus so that's part of it why why is Sr minus a better leaving group than o minus yeah go ahead aery yep sulfur is a bigger atom than oxygen size is bigger for sulfur as you go down a column of the periodic table in the same column size increases the larger an atom is the more space it spreads out its electrons electron delocalization is a favorable thing oh if you want to know more about that we could go down a rabbit hole but um when I try to do this people tell me to stop it has to do with electron kinetic energy and the second derivative of the wave function doesn't that sound exciting um nerd alert if you want to know more about that there's a optional Theory study guide that you can read on the content page of Learning Suite that delves into that yes in general the larger an atom is that holds electrons the more those electrons are spread out that's a stabilizing effect um the size also makes it so that sulfur is not as good the size makes it so that sulfur is not as good of an electron donor and the real explanation for that is a little bit more complicated than we need to delve into today the larger an atom is relative to another atom the more poorly their orbitals overlap resonance actually is about orbital overlap so the sulfur is not as good of a resonance electron donor and that makes uh the thioester less stable than the Esther okay um also on the list uh for things that are highly sort of reactive about the same extent as aldah tides and festers are a class of molecules called AAL phosphates you won't encounter these until we get to metabolism really but I mention them here um as to and it's a tossup at ph7 as to whether both of those oxygens are negatively charged or one of them's an O group um this is reactive for the same reason that the thioester is reactive is because what I'm highlighting in green is a good leaving group and in general carbonal compounds where we have good leaving groups attached to the carbonal carbon are reactive uh AAL phosphates you stay tuned you'll encounter those a little bit later we can also include on this list since we're dealing with Biology uh things like ATP and ADP they're not exactly carbonal but they're they sure look like it and act like it and they act like they're carbonal with good leaving groups attached I'll have more to say on this later don't worry about it for now but we'll come back to it and you'll see that they fit in this same category um finally on the list we can include things that are more uh sort of Labon type chemicals uh and now if you were to shout out leaving groups you would come up with good answers if we let the Y group be CL minus that's an acid chloride and that's very reactive uh and it turns out if we let the Y group be something like this a carboxilate which can leave as a negatively charged conjugate base of a carboxilic acid that's called an anhydride an hydride and that's B basically on the same level of reactivity as the acid chloride we're going to see that it's really easy in 352 to take a more reactive carbonal compound and convert it into a less reactive one it's more challenging to go the other way all right questions about that overall ranking yeah could it be said that bigger molecules in are are bigger molecules in general better leaving groups no when we're talking about leaving group ability it's always about the atom that has the negative charge so you focus in on that atom and in this case the sulfur versus the oxygen size does matter for sulfur versus oxygen but we're focused in on the atom that has the negative charge not necessarily everything else okay others yes a lot ofes Theory uh are there there's a lot of things in this top category are there going to be things later on where we need to rank them um not necessarily the thioester or the AAL phosphate um however you could predict pretty easily that the acid chloride would be that the chloros a better leaving group than the carboxilate I feel like that's a fair comparison but yeah yes less eliv more re um yeah you're you're summarizing what we're talking about based on the principle of electr negativity thinking about the Y group better donors better donating electron donating y groups lead to less reactive carbonal compounds okay poorer donating groups lead to more reactive carbonal compounds so in the case of the amid versus the Esther the reason they're similar in terms of their resonance structures both the oxygen and the nitrogen are electron donating groups nitrogen's better than oxygen because nitrogen's more willing to share it's less electronegative yeah would a carboxilic acid be basically about the same as an Esther um no and I'm going to tell you why not the carboxilic acid is weird the carboxilic acid is the conjugate acid of the carboxilate its chemistry is dominated by that acidic proton whose PKA is four in just a second we're going to talk about what happens when a nucleophile encounters a carbonal compound and we're going to talk about what that nucleophile does for most of these the nucleophile is going to go where the partial positive is that is it's going to attack the carbonal carbon however for the carboxilic acid youve got another tempting Choice you've got this very acidic proton and often nucleophiles will remove that proton first often if we want to do chemistry with carboxilic acids we're going to have to do something to deal with this proton first and we'll get into that later all right let's talk about um carbonal compounds reacting as electrophiles we've set this up already by telling you about resonance and the partial positive charge that is on the carbonal carbon and that's good enough for some people and some people stop there I find it useful to take one step further and try to understand what the orbitals in the molecule are doing if you took 351 with some of my colleagues or or from me you may have some background in molecular orbital theory if you didn't that's okay we're not going to go too in depth but what we do talk about Will be useful and will help you remember reaction mechanisms so for molecules in organic chemistry we care a lot about what the highest energy electrons are in the molecule and what the lowest energy electrons are in the molecule and all of 351 was was designed to help you get some intuition for that if you were to look at this aldah what are the highest energy electrons in this molecule ah there's controversy good some of you are saying the pi electrons presumably you're saying that because you know Pi bonds are less stable than Sigma bonds so electrons in pi bonds should be higher energy than electrons in Sigma bonds good those of you that said lone pair are thinking hey those are in an atomic orbital not even invol involved in bonding bonding always moves electrons down in energy therefore electrons that are not involved in bonding must be higher in energy than are the electrons that are involved in bonding and that's right so lone pair electrons there's two of them I'm only drawing one of them on the oxygen are the highest energy electrons in the molecule those of us that uh talk about molecular orbital Theory know that those electrons are held in an atomic orbital on that oxygen what is it it actually doesn't matter that much you can think of it as an SP2 hybridized orbital if you want that one of those lone pairs is sitting in uh there are other ways to think about it too uh so we'll call those highest energy electrons they are in the highest occupied molecular orbital of the molecule or for abbreviation h m o homo the homo of the molecule is the lone pairs on the car caral oxygen that means that if this molecule is going to react as a Lewis base or a nucleophile or an electron donor the most reactive electrons react first so you already know looking at this molecule if it's going to be a nucleophile it's the lone pairs on the oxygen that do the attacking right the the first and great commandment of 351 was and of all organic chemistry is nucleophiles attack electrophiles the second is like unto it home Mo attacks lumo highest energy electrons on one molecule attack a low energy empty orbital on another molecule now um so if the carbonal were to act as a nucleophile what's it going to do the lone pairs on the oxygen are going to do the chemistry an example of this would be a simple proton transfer reaction that we'll see uh later on this semester bring an acid into proximity to a carbonal compound the thing that happens first is the carbonal oxygen attacks the proton Breaking the Bond between the proton and the a group whatever it is and that gives you a new bond between oxygen and hydrogen and then you got the conjugate base over here okay that's an acid base reaction but you know where the proton's going to go it's going to go where the highest energy electrons are does that make sense this protonated carbonal is called an oxonium ion uh and protonating a carbonal is one thing we're going to do when we need to soup up the reactivity of a molecule when we need it to be even more electrophilic the reason protonation increases how electrophilic this carbonal is is because it makes this resonance structure even more reasonable right once the carbonal is protonated you got the oxonium ion positive formal charge on the oxygen I can draw a resonance structure where I take the pi electrons from that carbon oxygen Bond I move them out onto the oxygen now the full positive charge is on the carbonal carbon oxonium ions are more reactive than their conjugate bases because they increase the amount of positive charge that's felt on the carbonal Carbon Let's talk about carbonal as electrophiles all right so we've talked about their nucleophilic character now let's talk about carbonal as electrophiles when we come to electrophiles or leis acids we are concerned about what is the lowest unoccupied or empty molecular orbital in the molecule you may not be used to thinking about empty orbitals if you're not uh you should look at that optional emo Theory study guide to get up to speed but the basic con concept is anytime I mix two Atomic orbitals together to get a new Bond I get a lower energy bonding orbital but I also get a higher energy antibonding orbital and that anti-bonding orbital isn't occupied but it is a place where electrons could go if they became available filling an anti-bonding orbital breaks a bond you've seen this before in the 351 substitution reaction where you learn to draw that uh if you had an electrophile with a leaving group a nucleophile could do a substitution reaction and break the bond and you learned by the way that the sn2 reaction happens via backside attack the reason for that is the antibonding orbital of the carbon chlorine bond actually points in this direction so when you drew this arrows previously you actually were drawing What organic chemists knew all along which is a nucleophile dumps its electrons into the antibonding orbital associated with the carbon chlorine Sigma Bond when you fill an anti-bonding orbital you break the corresponding Bond okay that's we don't have time to talk about it in a lot more detail if you had if you've been with some of my colleagues or me for 351 you might this might sound familiar if it doesn't go check out that optional Theory study guide skim skip all the nerd math and just get to the part about the anti-bonding orbitals and and you should be good to go for the carbonal molecule the lumo the lowest unoccupied molecular orbital is what we're going to call the pi star this is the anti-bonding orbital associated with the pi Bond how do we know it's the lowest energy orbital well Pi bonds are less stable than Sigma bonds are right a pi bond is closer is higher in energy than a sigma bond is in a similar way the pi star is lower in energy than all of the sigma star antibonding orbitals and again if you want to know more about that you should uh you should go to the review study guide and and check it out what is the pie star look like we'll take a couple of different views of it I'm going to draw the alahh again here's the overhead view and then here's the view of the alahh from the side sort of occupying this this plane with the carbon hydrogen bond pointing out at us and the carbon carbon Bond pointing away from us and the carbon oxygen bond in the plane of the page if we were to look at this anti-bonding orbital I'm going to draw it here there is a lobe of the orbital on the carbonal carbon another lobe of the orbital on the oxygen the lobe is actually bigger on the carbon than it is on the oxygen uh there is a node in between the carbon and the oxygen the node is a place where electron density or wave function squared goes to zero um we're going to use color for different wave function signs of the molecular orbital the sign switches because the wave function goes to zero in between the two there's another node in the plane of the carbon uh in the plane of the SP2 hybridized carbon and so there there will be lobes below the plane of the page as well with a change in wave function sign there I'm using Color to indicate sign of the wave function if we were to draw this orbital over here there would be a large lobe on the carbonal carbon and a smaller lobe on the carbonal oxygen again a node in between the two atoms where wave function goes to zero and then we'll use color again pink and orange to indicate switches in wave function sign uh that's what it would look like sometimes that drawing isn't helpful to people so we'll go to another program called Spartan where I will draw a carbonal for you it's a simple alahh oops that wasn't it by the way I've spent probably the equivalent of multiple years of my life waiting after a child has done something and said wait that wasn't it so if you have to spend a lot of time with me erasing things and say wait doesn't wait that isn't it I'm just preparing you for your future anytime a child wants to show you a trick on a trampoline that they've already done and then you show up to watch it it is a guarantee that the next 15 minutes of your life are going to be taken up by someone telling you no no no no no that wasn't it so uh if we look at what the lumo of this molecule is is just going to turn it off again here is the carbonal carbonal carbon in in Gray oxygen in red hydrogen's in white you have a large lobe on the carbon a small lob on the oxygen a node in between the two nuclei and then the side view shows you there's a node in the plane of all the atoms this is the empty this is the lowest energy empty orbital for this molecule and when a nucleophile attacks it's going to attack to put its electrons in the lowest energy spot that's possible let me show you how this works for a carbonal molecule here is a nucleophile we're going to be generic about it something with extra electron density it's going to dump its electrons into the lumo into the piie star notice that the lumo is on both the carbon and the oxygen why do you think it goes for the carbon instead of the oxygen because the carbon has that positive partial positive charge on it right now what happens when I fill an antibonding orbital what happens when I fill a piie star the pi bond has to break so if you know what the orbital is and you have The nucleophile Dumping into that orbital the next Arrow you don't have to memorize it just comes out of that analysis automatic Ally you have to break the carbon oxygen Pi Bond those arrows then become the instructions for drawing the next intermediate in this reaction which was a nucleophile attacking the carbonal compound now notice that nucleophile attacked I went from a carbon here that was SP2 hybridized now my carbonal carbon is sp3 hybridized because of that we are going to call this intermediate which you predicted based on your understanding of carbonal reactivity we're going to call it the ti or the tetrahedral intermediate this is a common intermediate in all the carbonal reactions that we're going to talk about you need to be paying attention to the idea that a nucleophile attacks at the carbonal carbon to give you a tetrahedral intermediate okay I have one minute left and we need every minute desperately this semester so I want to do one more thing and that is ask you how this reaction might be different if instead of using the aldah I used the acid chloride now remember the acid chloride is about as reactive as the aldah but the difference is you got the chlorine on there and you no chlorine is a good leaving group so by analogy to what we did with the alahh nucleophile attacks the lumo on the acid chloride you should get a tetrahedral intermediate what do you think's going to happen next chloro is a leaving group the next thing that can happen is called the collapse of the tetrahedral intermediate El Rons on the oxygen can kick back down break the carbon chlorine bond we could analyze the orbitals here if we wanted to I found it generally not necessary to help students to understand this chemistry so I'm not going to if you want to know more feel free to stop by and we can chat leaving group leaves and you end up with this which is a substitution product okay that's the beginning you have a steady guide for chapter 13 that you need to start working on good luck and I will see you Friday