MCAT Organic Chemistry: Aldehydes and Ketones Part Two

hello everybody my name is Iman welcome back to my YouTube channel today we&#39;re going to continue our MCAT organic chemistry playlist this is chapter 7 alahh and ketones part two I want to first and foremost apologize for not uploading as much content in the past two weeks grad school has frankly been kicking my ass I am wrapping up a couple of projects and in the writeup phase and at the same time working on brand new projects and trying to work out the details of those experiments and that data analysis so it has been super hectic I plan in the next few weeks especially during Thanksgiving break to hopefully get very near if not finish the MCAT organic chemistry playlist I also intend on completing the last two chapters for MCAT physics and also refilm two videos for MCAT General chemistry because the audio quality was really poor and so I hope on making a lot of MCAT content in the next few weeks please please just be patient with me I I am a one woman show here and I am trying my very best and I do not want to disappoint any of y&#39;all so hopefully expect a lot more content for me starting now so let&#39;s go ahead and get started in the pre previous chapter so alahh and ketones part one we took a look at a couple of few properties and reactions of alahh tides and ketones and we saw that these molecules they have highly predictable chemistry centered on their electrophilic positively charged carbonal carbon all right in this chapter we&#39;re going to take a look at several more properties of alahh and ketones and we&#39;re really going to focus here on this chapter on the reactivity of the alpha hydrogen of these carbonal containing compounds and so the main objectives of this chapter are going to be first we&#39;re going to talk about some general principles we&#39;re going to talk about the acidity of alpha hydrogens we&#39;re going to talk about steric hindrance then we&#39;re going to move into the second objective which is enolate chemistry here we&#39;re going to talk about keto enal tariz we&#39;re going to talk about kinetic versus thermodynamic enolates we&#39;re even going to briefly mention enamines and then in our third objective and forgive me if I mispronounce enamines and I mindes I always have trouble with that and English is not my first language so do forgive the third objective will be Al doll condensation all right so those are our three big objectives for this chapter let&#39;s go ahead and get started again in the previous chapter we talked about and we really focused on how the electr negativity of the oxygen atom in a carbonal pulls electrons away all right pulls electrons away from that carbonal carbon making it partially positive now in this chapter we&#39;re also going to take we&#39;re going to take the electron withd drawing characteristics of oxygen one Bond further and we&#39;re going to start focusing on these Alpha carbons in an aldah or ketone and of course saying that the first thing we should do is properly Define what an alpha carbon is and Alpha carbon is adjacent to the carbonal carbon and the hydrogens connected to that Alpha carbon are going to be ter Alpha hydrogens you see that right here so this is an alpha carbon right here and the hydrogens that are attached to that Alpha carbon are called Alpha hydrogens now through induction oxygen pulls some of the electron density out of these carbon hydrogen bonds weaken weakening them and this makes it relatively easy to deprotonate the alpha carbons of an alahh or Ketone now the acidity of alpah hydrogens is is augmented by resonance stabilization of the conjugate basos specifically when the alpha hydrogen is removed an extra electron the extra electrons that that remain can resonate between the alpha carbon the carbonal carbon and the carbonal oxygen all right so we can see that we can see that if we draw if we draw this out okay so that&#39;s what we&#39;re going to do if we have for example this right here this uh this Ketone all right here is our carbonal carbon here&#39;s our carbonal oxygen this carbon right here would be an alpha carbon all right if we had say a hydroxide ion that comes in swoops and takes that hydrogen right the hydrogen would dump its electrons here all right you would have electrons right there so you can think of it as a negative charge you have these two electrons right here and what you can have is some resonance that happens again between the alpha carbon the carbonal carbon and the carbonal oxygen now what does this do this increases the stability of the enolate intermediate all right and we&#39;re going to talk about that here in just a second as well but through this resonance the negative charge what you notice is it can be distributed to the more electron negative oxygen atom and the electron withd drawing oxygen atom thereby helps stabilize the carbo anion all right carbo is just a molecule with a negatively charged carbon atom which is what we see here in what we drew now when in basic Solutions Alpha hydrogens will easily deprotonate all right and that&#39;s what we saw when we drew this this scheme right here deprotonation of an alpha carbon forming a carbo anion all right our hydroxides a base here and you see that it deprotonated all right that Alpha hydrogen was easily deprotonated now the alpha hydrogens of ketones they tend to be they tend to be slightly less acidic than those of aldah eyeses if we were to compare and that&#39;s due to the electron donating properties of the additional alkal groups in a ketone so this was a ketone all right it has these it has two R groups two variable groups whereas in an aldah you&#39;d have one R Group and you would you know this is one R Group this is a second for Ketone in an aldhy you&#39;d have one R Group one variable group and then a hydrogen all right so it makes sense that the alpha hydrogens of ketones they tend to be slightly less acidic than those of alahh because of the electron donating properties of having additional alkal groups R groups in a ketone and this property is the same reason that alkal groups help to stabilize carbocations ions all right in this case though they destabilize the carboanion now something else else that you should Ponder is steric hindrance in this regard so in reactions alahh are slightly more reactive to nucleophiles than ketones all right alahh are slightly more reactive than ketones to nucleophiles all right this is this is due in part to steric hindrance in the Ketone which arises from again the additional alkal groups that ketones contain all right so when the nucleophile approaches the Ketone or alahh in order to react the additional alkal groups on the Ketone are kind of in the way all right more so than just the single hydrogen of the aldah and so this makes for a higher energy more crowded intermediate step and remember higher energy intermediates mean that the reaction is going to be less likely to proceed all right so a couple of things to note here all right keep ketones tend to be slightly less acidic than alahh all right and then because of steric hindrance alahh are slightly more reactive to nucleophiles than ketones all right that is our first objective talking about the general principles now we want to talk about enolate chemistry so due to the acidity of the alpha hydrogen ald hides and ketones exist in solution as a mixture of two isomers all right the familiar keto form all right and the enal form so the enal form it gets its name from the presence of a carboncarbon double bond and an alcohol all right so the carbon carbon double bond the N comp that&#39;s the N component en component and an alcohol that&#39;s the o l component of the name now the two isomers which if you look at them right they differ in the placement of a proton and the double bond all right notice all right these are called ters the equilibrium between the ters it lies far to the keto side so there will be many more keto isomers in solution the process of interconverting from the keto to the enal toer is called enolization or more generally t ptimization so by extension any alahh or Ketone with a chyal alpha carbon will rapidly then become a rasmic mixture as the keto and the enal forms inter convert all right this is a phenomena known as Alpha uh rization all right so uh you have now a racemic mixture you have a rmic mixture of of the keto and the enal forms the keto and the enal forms and they interconvert all right now enols are really important intermediates in many reactions of aldhy and ketones the enolate carbo anion results from the deprotonation of the alpha carbon by a strong base right we described that earlier and some common strong bases include like the hydroxide ion which is what we use to to show how um a hydrogen can be uh deprotonated the alpha hydrogen can be easily deprotonated now you have this pair of electrons and you can have resonance that happens between Alpha carbon the carbonal carbon and the carbonal oxygen all right so hydroxide ion is a as a common strong base you also have um lithium diisopropyl commonly known as LDA you also have potassium hydride KH all right um a 13 dicarbon for example um this is a particularly uh a acidic compound because there are two carbonal to delocalize negative charge and for this reason it&#39;s often used to form enolate carbo ions and once it&#39;s formed the nucleophilic carbo anion react readily with electrophiles we&#39;re actually going to see one example of this shortly when we talk about alol condensation but another example of this type of reaction we&#39;re going to scroll down here all right is Michael addition that&#39;s shown right here in Parts A and B all right this this is Michael Edition in which the carbo anion attacks an alpha beta unsaturated carbonal compound all right and this is a molecule with multiple bonds between the alpha and beta carbonal that are next to uh Alpha and beta carbons next to a carbonal all right so this reaction it proceeds as shown all right due to the resonance stabilization of the intermediates all right and the better you understand the resonance forms of molecules the more you&#39;ll be able to predict the specific locations on a molecule where a reaction will occur so if we look here this these are examples of Michael Edition here if we look at part A what you notice is that the base deprotonates the alpha carbon all right this Alpha hydrogen gets swept up by the base that hydrogen dumps its electrons there all right dumps its electrons between here all right to form a double bond and you break that double bond in the carbonal so those that those electrons go to the o oxygen you form this first intermediate right here right you have a double bond right here all right now oxygen has an extra lone pair hence it has a negative charge but this can also interconvert because look at this this is a this is that example of a 13 dicarbon here right it has the ability to delocalize negative charge all right because there&#39;s two carbonal all right and so it is often used to form enolate carbon ions so if we look look at this intermediate we we formed right here all right what you what you notice is you can reform this double bond all right you can reform this double bond um this double bond can move over here and then you can break this double bond as well all right and so you get this form in addition all right so this base that that that deprotonates the alpha hydrogen all right that&#39;s that that is located at the alpha carbon you can form these two you can form this intermediate that has two resonance stabilized forms all right so the base deprotonates the alpha carbon making it a good nucleophile um and you see the intermediate that&#39;s formed now Part B here um the carbo anion attacks the double bond okay and this results in a Michael addition so we have this small molecule right here all right and here is our intermediate okay because we have these two resonance forms what this really looks like is that there is partial double bond character around this region okay you can depict it as so because we have these two resonance structures what happens here is that this can attack all right the double bond in this molecule for example and that is going to result in a Michael addition so it packs right here we break this double bond and we we we move this double bond to this location which breaks the double bond of our carbonal dumping the electrons on the oxygen all right and that way we have a Michael addition all right what you notice is that these two molecules have been added together to form one larger molecule all right so this is an example of a Michael addition now another important thing that we we want to talk about all right so this is two parts to the Michael Edition we saw how we can have a base that deprotonates the alpha carbon for this molecule all right it&#39;s making get a good nucleophile we saw the intermediate that formed its resonance stabilized that resonance stabilized intermediate can then attack all right the double bond of another molecule that you have in the mix okay and now you get a Michel addition something else that&#39;s important to talk about in this in this section about enolate chemistry is kinetic and thermodynamic enolates so given a ketone that has two different alkal groups for example Each of which may have Alpha hydrogens two forms of the enolate can form with the carbon carbon double bond between the carbonal carbon and either the more or less substance stituted carbon right we kind of see this here all right what we have here okay uh a a ketone all right now the equilibrium between these forms so from this um this this K this molecule you can have it form two different enolates all right you can have one where the double bond forms between what was the carbonal and this methyl group right here or the double Bond can form on the other side of the carbonal group right because you have two different Alpha uh Alpha carbons so you have two different Alpha hydrogens that can be deprotonated hence you can form two different enolates all right and that&#39;s the example that we see with this molecule so if we had a base all right the base can deprotonate the hydrogen at this location we&#39;ll call it location one or it can deprotonate the hydrogen in location two location one one gives us this enolate and location two gives us this enolate and what you notice is that one is titled the thermodynamic enolate and the other one is titled the kinetic enate so the equilibrium between these forms is really dictated okay by the kinetic and thermodynamic control of the reaction the kinetically controlled product is formed more rapidly but it is less stable right this form has the double bond to the less substitute Ed Alpha carbon all right this is the less substituted Alpha carbon right here that&#39;s why it&#39;s called all right and this is the kinetic enolate all right as expected this product is formed by the removal of the alpha hydrogen from the less substituted Alpha carbon which is position two because it offers less steric hindrance there&#39;s not another there&#39;s not a methyl group here in position two like there is in position one hence it&#39;s less hysterically hindered and for that reason it is the kinetic enolate forms more rapidly but again the co the caveat is that it&#39;s less stable because you form all right because you form the less substituted you you form the less substituted double bond all right this form has the double bond to the less substituted Alpha carbon I should say all right now the thermodynamically controlled product it&#39;s formed more slowly but it is more stable all right and it features the double bond being formed with the more substituted Alpha carbon which is position one all right so when the base deprotonates the alpha hydrogen in position one we get the thermodynamic enolate which is this right here you notice it&#39;s formed at the more substituted Alpha carbon position it forms more slowly but this is the more stable form so in short the kinetic enolate forms more quickly because of less steric hindrance but it&#39;s less stable than the thermodynamic enolate all right so each of these two products as you notice is going to be it&#39;s going to be favored by different conditions the kinetic product is favored in reactions that are rapid irreversible at low temperatures and with strong sterically hindered base all right but if the reaction if the reaction isse rible all right if the reaction is reversible the kinetic product can actually revert to the original reactant and react again to form the thermodynamic product the thermodynamic product is favored with higher temperatures slow reversable reactions and weaker smaller bases all right so we can we can take a look at this and we can make a list of when each of these enolates will be the more favored all right product all right because each of these two products is favored under different conditions the kinetic enolate all right we said is favored in reactions that are rapid irreversible low temperature all right and with strong sterically hindered bases the thermodynamic enolate though it&#39;s formed and it&#39;s favored at high temperatures all right slow reversible reactions and with weaker and smaller bases all right so that is how you want to think about kinetic and thermodynamic enolates now just as enals are ters of carbonal enamines are toomer of amines all right an amine is a compound that contains a carbon to nitrogen double bond all right the nitrogen in the amine that right you see right here all right may or may not be bonded to an alkal group or other substituent and through toiz right so the movement of a hydrogen and a double bond amines can be converted into enamines all right kind of like what you see here so on the right is the amine form which is thermodynamically favored over the enamine form which is on the left right here so again tolerization can happen also with nitrogen containing compounds these enamines and amines fantastic with that being said all right those are all the main parts of objective two all right now what we can do is move into objective three our final objective and talk about aldol condensation so this is another really important reaction you should know for the MCAT this reaction follows the same general mechanism of nucleophilic addition to a carbonal that we&#39;ve seen in previous chapters so in this case however an alahh or a ketone acts both as an electrophile in its keto form and a nucleophile in its enolate form and the end result is the formation of a carbon carbon Bond now what you see here all right what you see here um is the aldol condensation reaction we&#39;re going to take it step by step so when an acetal alahh also known as ethanol is treated with a catalytic amount of base and enolate is produced now the enolate is more nucleophilic than the enal because it is negatively charged this nucleophilic enolate ion can react then with the electrophilic carbonal group of another acetyl alahh molecule all right and the key to this reaction is that both species are in the same flask so the product is three hydroxy butanol which is an example of an aldol an aldol is a molecule that contains both alahh and alcohol functional groups all right and note that this mechanism it&#39;s still called an aldol reaction even when the reactants are ketones so here what we see is the aldol condensation the first step which is forming the aldol all right and just like we worked through this right we have an acetyl alahh it&#39;s treated with a catalytic amount of base and we have an enolate that is produced all right and then the enolate is morec nucleophilic than the enol because it&#39;s negatively charged all right and then this nucleophilic enolate ion can react with the electrophilic carbonal group of another acetal alahh molecule okay and what we get when that happens is a final product all right this final product is three hydroxy butanol which is an aldol now with a strong base and high temperatures all right dehydration occurs by an E1 or E2 mechanism so we kick off a water molecule and then form a double bond which produces an alpha beta unsaturated carbonal which we see right here so this next step is dehydration of the alol so the O group all right is removed as water hence the dehy hydration and instead there is a double bond that forms between the alpha carbon and the beta carbon now aldol condensations are most useful if we only use one type of alahh or Ketone because if there are multiple alahh or ketones we actually we we can&#39;t easily control which will act as the nucleophile and which will act as an electrophile and the consequence of that is a mixture of products all right we&#39;re going to get a mixture of products as the end result now this could be prevented if one of the molecules has no Alpha hydrogens because the alpan carbons are quinary all right like benzal deide now this reaction is referred to as a condensation reaction because two molecules are joined with the loss of a small molecule so this type of reaction is also a dehydration reaction because the small molecule that&#39;s lost is you guessed it water now to that note of of of aldol of a of an alol condensation reaction we can also talk about a retroaldol reaction the reverse of this reaction you guessed it is called a retroaldol reaction to to push um the reaction in the retroaldol direction aquous base is added and also heat is applied and the retroaldol reaction is useful for breaking bonds between the alpha and beta carbons of a carbonal um and this reaction is facilitated if the intermediate can be stabilized in the inate form just as in the forward reaction so we can see that right here the bond between the alpha and beta carbons of a carbonal is broken all right so we have covered a lot of very very important information let&#39;s quickly review before we end this video and move on to the problem set all right so speed round of everything we covered we said that the carbon adjacent to the carbonal carbon is termed an alpha carbon and so then the hydrogens that are attached to an alpha carbon are called alpha hydrogens alpha hydrogens are relatively acidic and can be removed by a strong base the El the electron withdrawing o oxygen of the carbonal weakens the carbon hydrogen bonds on an alpha carbon the enolate that&#39;s result that results from deprotonation can then be stabilized by resonance with the carbonal we also said that ketones are less reactive towards nucleophiles because of steric hindrance and Alpha carbo anion destabilization then we moved into objective uh two which is all about enolate chemistry we said alahh and ketones exist in the traditional keto form form where there&#39;s a double bond between the carbon and oxygen so there&#39;s a carbonal group and then they also exist in the less common form which is the enal form there&#39;s a double bond and a hydroxy group toomer are just isomers that can be interconverted by moving a hydrogen and a double bond so what we can say is that the keto and Eno forms are toomer of each other the enil form can be deprotonated in addition to form an enolate and enolates are good nucleophiles we saw an example of this in the Michael Edition an enolate attacks in Alpha Beta unsaturated carbonal creating a bond all right something else that we made mention of is the the difference and and the comparison between kinetic and thermodynamic enolates kinetic enolate is formed by fast irreversible reactions at low temperatures with strong sterically hindered bases and thermodynamic inal are favored by slower reversible reactions at higher temperatures with weaker smaller bases we also said like hey by the way it&#39;s not just alahh and and ketones that have the toomer forms enamines are toomer of iines and like enols enamines are the less common toer last but not least we covered aldol condensation in the aldol condensation the alahh or Ketone act as both nucleophile and electrophile resulting in the formation of a carbon carbon bond in a new molecule that&#39;s called an aldol an aldol contains both alide and alcohol functional groups and the nucleophile is the enolate formed from the deprotonation of the alpha carbon the electrophile is going to be the alahh or Ketone in the form of the keto toomer and then first you&#39;re going to have a condensation reaction that occurs in which the two molecules come to together and and then after the aldol is formed a dehydration reaction occurs you have a loss of a water molecule this results in an alphabet unsaturated carbonal you can also have the opposite reaction happen this is called a retroaldol reaction just the reverse of an aldol condensation reaction and it&#39;s catalyzed by heat and a base and in these reactions the bond between the alpha and beta carbon is cleaved all right with that we have covered chapter 7 alahh and ketones part two in the next video we&#39;re going to tackle a problem set together let me know if you have any questions comments concerns down below other than that good luck happy studying and have a beautiful beautiful day future doctors

hello everybody my name is Iman welcome back to my YouTube channel today we&amp;#39;re going to continue our MCAT organic chemistry playlist this is chapter 7 alahh and ketones part two I want to first and foremost apologize for not uploading as much content in the past two weeks grad school has frankly been kicking my ass I am wrapping up a couple of projects and in the writeup phase and at the same time working on brand new projects and trying to work out the details of those experiments and that data analysis so it has been super hectic I plan in the next few weeks especially during Thanksgiving break to hopefully get very near if not finish the MCAT organic chemistry playlist I also intend on completing the last two chapters for MCAT physics and also refilm two videos for MCAT General chemistry because the audio quality was really poor and so I hope on making a lot of MCAT content in the next few weeks please please just be patient with me I I am a one woman show here and I am trying my very best and I do not want to disappoint any of y&amp;#39;all so hopefully expect a lot more content for me starting now so let&amp;#39;s go ahead and get started in the pre previous chapter so alahh and ketones part one we took a look at a couple of few properties and reactions of alahh tides and ketones and we saw that these molecules they have highly predictable chemistry centered on their electrophilic positively charged carbonal carbon all right in this chapter we&amp;#39;re going to take a look at several more properties of alahh and ketones and we&amp;#39;re really going to focus here on this chapter on the reactivity of the alpha hydrogen of these carbonal containing compounds and so the main objectives of this chapter are going to be first we&amp;#39;re going to talk about some general principles we&amp;#39;re going to talk about the acidity of alpha hydrogens we&amp;#39;re going to talk about steric hindrance then we&amp;#39;re going to move into the second objective which is enolate chemistry here we&amp;#39;re going to talk about keto enal tariz we&amp;#39;re going to talk about kinetic versus thermodynamic enolates we&amp;#39;re even going to briefly mention enamines and then in our third objective and forgive me if I mispronounce enamines and I mindes I always have trouble with that and English is not my first language so do forgive the third objective will be Al doll condensation all right so those are our three big objectives for this chapter let&amp;#39;s go ahead and get started again in the previous chapter we talked about and we really focused on how the electr negativity of the oxygen atom in a carbonal pulls electrons away all right pulls electrons away from that carbonal carbon making it partially positive now in this chapter we&amp;#39;re also going to take we&amp;#39;re going to take the electron withd drawing characteristics of oxygen one Bond further and we&amp;#39;re going to start focusing on these Alpha carbons in an aldah or ketone and of course saying that the first thing we should do is properly Define what an alpha carbon is and Alpha carbon is adjacent to the carbonal carbon and the hydrogens connected to that Alpha carbon are going to be ter Alpha hydrogens you see that right here so this is an alpha carbon right here and the hydrogens that are attached to that Alpha carbon are called Alpha hydrogens now through induction oxygen pulls some of the electron density out of these carbon hydrogen bonds weaken weakening them and this makes it relatively easy to deprotonate the alpha carbons of an alahh or Ketone now the acidity of alpah hydrogens is is augmented by resonance stabilization of the conjugate basos specifically when the alpha hydrogen is removed an extra electron the extra electrons that that remain can resonate between the alpha carbon the carbonal carbon and the carbonal oxygen all right so we can see that we can see that if we draw if we draw this out okay so that&amp;#39;s what we&amp;#39;re going to do if we have for example this right here this uh this Ketone all right here is our carbonal carbon here&amp;#39;s our carbonal oxygen this carbon right here would be an alpha carbon all right if we had say a hydroxide ion that comes in swoops and takes that hydrogen right the hydrogen would dump its electrons here all right you would have electrons right there so you can think of it as a negative charge you have these two electrons right here and what you can have is some resonance that happens again between the alpha carbon the carbonal carbon and the carbonal oxygen now what does this do this increases the stability of the enolate intermediate all right and we&amp;#39;re going to talk about that here in just a second as well but through this resonance the negative charge what you notice is it can be distributed to the more electron negative oxygen atom and the electron withd drawing oxygen atom thereby helps stabilize the carbo anion all right carbo is just a molecule with a negatively charged carbon atom which is what we see here in what we drew now when in basic Solutions Alpha hydrogens will easily deprotonate all right and that&amp;#39;s what we saw when we drew this this scheme right here deprotonation of an alpha carbon forming a carbo anion all right our hydroxides a base here and you see that it deprotonated all right that Alpha hydrogen was easily deprotonated now the alpha hydrogens of ketones they tend to be they tend to be slightly less acidic than those of aldah eyeses if we were to compare and that&amp;#39;s due to the electron donating properties of the additional alkal groups in a ketone so this was a ketone all right it has these it has two R groups two variable groups whereas in an aldah you&amp;#39;d have one R Group and you would you know this is one R Group this is a second for Ketone in an aldhy you&amp;#39;d have one R Group one variable group and then a hydrogen all right so it makes sense that the alpha hydrogens of ketones they tend to be slightly less acidic than those of alahh because of the electron donating properties of having additional alkal groups R groups in a ketone and this property is the same reason that alkal groups help to stabilize carbocations ions all right in this case though they destabilize the carboanion now something else else that you should Ponder is steric hindrance in this regard so in reactions alahh are slightly more reactive to nucleophiles than ketones all right alahh are slightly more reactive than ketones to nucleophiles all right this is this is due in part to steric hindrance in the Ketone which arises from again the additional alkal groups that ketones contain all right so when the nucleophile approaches the Ketone or alahh in order to react the additional alkal groups on the Ketone are kind of in the way all right more so than just the single hydrogen of the aldah and so this makes for a higher energy more crowded intermediate step and remember higher energy intermediates mean that the reaction is going to be less likely to proceed all right so a couple of things to note here all right keep ketones tend to be slightly less acidic than alahh all right and then because of steric hindrance alahh are slightly more reactive to nucleophiles than ketones all right that is our first objective talking about the general principles now we want to talk about enolate chemistry so due to the acidity of the alpha hydrogen ald hides and ketones exist in solution as a mixture of two isomers all right the familiar keto form all right and the enal form so the enal form it gets its name from the presence of a carboncarbon double bond and an alcohol all right so the carbon carbon double bond the N comp that&amp;#39;s the N component en component and an alcohol that&amp;#39;s the o l component of the name now the two isomers which if you look at them right they differ in the placement of a proton and the double bond all right notice all right these are called ters the equilibrium between the ters it lies far to the keto side so there will be many more keto isomers in solution the process of interconverting from the keto to the enal toer is called enolization or more generally t ptimization so by extension any alahh or Ketone with a chyal alpha carbon will rapidly then become a rasmic mixture as the keto and the enal forms inter convert all right this is a phenomena known as Alpha uh rization all right so uh you have now a racemic mixture you have a rmic mixture of of the keto and the enal forms the keto and the enal forms and they interconvert all right now enols are really important intermediates in many reactions of aldhy and ketones the enolate carbo anion results from the deprotonation of the alpha carbon by a strong base right we described that earlier and some common strong bases include like the hydroxide ion which is what we use to to show how um a hydrogen can be uh deprotonated the alpha hydrogen can be easily deprotonated now you have this pair of electrons and you can have resonance that happens between Alpha carbon the carbonal carbon and the carbonal oxygen all right so hydroxide ion is a as a common strong base you also have um lithium diisopropyl commonly known as LDA you also have potassium hydride KH all right um a 13 dicarbon for example um this is a particularly uh a acidic compound because there are two carbonal to delocalize negative charge and for this reason it&amp;#39;s often used to form enolate carbo ions and once it&amp;#39;s formed the nucleophilic carbo anion react readily with electrophiles we&amp;#39;re actually going to see one example of this shortly when we talk about alol condensation but another example of this type of reaction we&amp;#39;re going to scroll down here all right is Michael addition that&amp;#39;s shown right here in Parts A and B all right this this is Michael Edition in which the carbo anion attacks an alpha beta unsaturated carbonal compound all right and this is a molecule with multiple bonds between the alpha and beta carbonal that are next to uh Alpha and beta carbons next to a carbonal all right so this reaction it proceeds as shown all right due to the resonance stabilization of the intermediates all right and the better you understand the resonance forms of molecules the more you&amp;#39;ll be able to predict the specific locations on a molecule where a reaction will occur so if we look here this these are examples of Michael Edition here if we look at part A what you notice is that the base deprotonates the alpha carbon all right this Alpha hydrogen gets swept up by the base that hydrogen dumps its electrons there all right dumps its electrons between here all right to form a double bond and you break that double bond in the carbonal so those that those electrons go to the o oxygen you form this first intermediate right here right you have a double bond right here all right now oxygen has an extra lone pair hence it has a negative charge but this can also interconvert because look at this this is a this is that example of a 13 dicarbon here right it has the ability to delocalize negative charge all right because there&amp;#39;s two carbonal all right and so it is often used to form enolate carbon ions so if we look look at this intermediate we we formed right here all right what you what you notice is you can reform this double bond all right you can reform this double bond um this double bond can move over here and then you can break this double bond as well all right and so you get this form in addition all right so this base that that that deprotonates the alpha hydrogen all right that&amp;#39;s that that is located at the alpha carbon you can form these two you can form this intermediate that has two resonance stabilized forms all right so the base deprotonates the alpha carbon making it a good nucleophile um and you see the intermediate that&amp;#39;s formed now Part B here um the carbo anion attacks the double bond okay and this results in a Michael addition so we have this small molecule right here all right and here is our intermediate okay because we have these two resonance forms what this really looks like is that there is partial double bond character around this region okay you can depict it as so because we have these two resonance structures what happens here is that this can attack all right the double bond in this molecule for example and that is going to result in a Michael addition so it packs right here we break this double bond and we we we move this double bond to this location which breaks the double bond of our carbonal dumping the electrons on the oxygen all right and that way we have a Michael addition all right what you notice is that these two molecules have been added together to form one larger molecule all right so this is an example of a Michael addition now another important thing that we we want to talk about all right so this is two parts to the Michael Edition we saw how we can have a base that deprotonates the alpha carbon for this molecule all right it&amp;#39;s making get a good nucleophile we saw the intermediate that formed its resonance stabilized that resonance stabilized intermediate can then attack all right the double bond of another molecule that you have in the mix okay and now you get a Michel addition something else that&amp;#39;s important to talk about in this in this section about enolate chemistry is kinetic and thermodynamic enolates so given a ketone that has two different alkal groups for example Each of which may have Alpha hydrogens two forms of the enolate can form with the carbon carbon double bond between the carbonal carbon and either the more or less substance stituted carbon right we kind of see this here all right what we have here okay uh a a ketone all right now the equilibrium between these forms so from this um this this K this molecule you can have it form two different enolates all right you can have one where the double bond forms between what was the carbonal and this methyl group right here or the double Bond can form on the other side of the carbonal group right because you have two different Alpha uh Alpha carbons so you have two different Alpha hydrogens that can be deprotonated hence you can form two different enolates all right and that&amp;#39;s the example that we see with this molecule so if we had a base all right the base can deprotonate the hydrogen at this location we&amp;#39;ll call it location one or it can deprotonate the hydrogen in location two location one one gives us this enolate and location two gives us this enolate and what you notice is that one is titled the thermodynamic enolate and the other one is titled the kinetic enate so the equilibrium between these forms is really dictated okay by the kinetic and thermodynamic control of the reaction the kinetically controlled product is formed more rapidly but it is less stable right this form has the double bond to the less substitute Ed Alpha carbon all right this is the less substituted Alpha carbon right here that&amp;#39;s why it&amp;#39;s called all right and this is the kinetic enolate all right as expected this product is formed by the removal of the alpha hydrogen from the less substituted Alpha carbon which is position two because it offers less steric hindrance there&amp;#39;s not another there&amp;#39;s not a methyl group here in position two like there is in position one hence it&amp;#39;s less hysterically hindered and for that reason it is the kinetic enolate forms more rapidly but again the co the caveat is that it&amp;#39;s less stable because you form all right because you form the less substituted you you form the less substituted double bond all right this form has the double bond to the less substituted Alpha carbon I should say all right now the thermodynamically controlled product it&amp;#39;s formed more slowly but it is more stable all right and it features the double bond being formed with the more substituted Alpha carbon which is position one all right so when the base deprotonates the alpha hydrogen in position one we get the thermodynamic enolate which is this right here you notice it&amp;#39;s formed at the more substituted Alpha carbon position it forms more slowly but this is the more stable form so in short the kinetic enolate forms more quickly because of less steric hindrance but it&amp;#39;s less stable than the thermodynamic enolate all right so each of these two products as you notice is going to be it&amp;#39;s going to be favored by different conditions the kinetic product is favored in reactions that are rapid irreversible at low temperatures and with strong sterically hindered base all right but if the reaction if the reaction isse rible all right if the reaction is reversible the kinetic product can actually revert to the original reactant and react again to form the thermodynamic product the thermodynamic product is favored with higher temperatures slow reversable reactions and weaker smaller bases all right so we can we can take a look at this and we can make a list of when each of these enolates will be the more favored all right product all right because each of these two products is favored under different conditions the kinetic enolate all right we said is favored in reactions that are rapid irreversible low temperature all right and with strong sterically hindered bases the thermodynamic enolate though it&amp;#39;s formed and it&amp;#39;s favored at high temperatures all right slow reversible reactions and with weaker and smaller bases all right so that is how you want to think about kinetic and thermodynamic enolates now just as enals are ters of carbonal enamines are toomer of amines all right an amine is a compound that contains a carbon to nitrogen double bond all right the nitrogen in the amine that right you see right here all right may or may not be bonded to an alkal group or other substituent and through toiz right so the movement of a hydrogen and a double bond amines can be converted into enamines all right kind of like what you see here so on the right is the amine form which is thermodynamically favored over the enamine form which is on the left right here so again tolerization can happen also with nitrogen containing compounds these enamines and amines fantastic with that being said all right those are all the main parts of objective two all right now what we can do is move into objective three our final objective and talk about aldol condensation so this is another really important reaction you should know for the MCAT this reaction follows the same general mechanism of nucleophilic addition to a carbonal that we&amp;#39;ve seen in previous chapters so in this case however an alahh or a ketone acts both as an electrophile in its keto form and a nucleophile in its enolate form and the end result is the formation of a carbon carbon Bond now what you see here all right what you see here um is the aldol condensation reaction we&amp;#39;re going to take it step by step so when an acetal alahh also known as ethanol is treated with a catalytic amount of base and enolate is produced now the enolate is more nucleophilic than the enal because it is negatively charged this nucleophilic enolate ion can react then with the electrophilic carbonal group of another acetyl alahh molecule all right and the key to this reaction is that both species are in the same flask so the product is three hydroxy butanol which is an example of an aldol an aldol is a molecule that contains both alahh and alcohol functional groups all right and note that this mechanism it&amp;#39;s still called an aldol reaction even when the reactants are ketones so here what we see is the aldol condensation the first step which is forming the aldol all right and just like we worked through this right we have an acetyl alahh it&amp;#39;s treated with a catalytic amount of base and we have an enolate that is produced all right and then the enolate is morec nucleophilic than the enol because it&amp;#39;s negatively charged all right and then this nucleophilic enolate ion can react with the electrophilic carbonal group of another acetal alahh molecule okay and what we get when that happens is a final product all right this final product is three hydroxy butanol which is an aldol now with a strong base and high temperatures all right dehydration occurs by an E1 or E2 mechanism so we kick off a water molecule and then form a double bond which produces an alpha beta unsaturated carbonal which we see right here so this next step is dehydration of the alol so the O group all right is removed as water hence the dehy hydration and instead there is a double bond that forms between the alpha carbon and the beta carbon now aldol condensations are most useful if we only use one type of alahh or Ketone because if there are multiple alahh or ketones we actually we we can&amp;#39;t easily control which will act as the nucleophile and which will act as an electrophile and the consequence of that is a mixture of products all right we&amp;#39;re going to get a mixture of products as the end result now this could be prevented if one of the molecules has no Alpha hydrogens because the alpan carbons are quinary all right like benzal deide now this reaction is referred to as a condensation reaction because two molecules are joined with the loss of a small molecule so this type of reaction is also a dehydration reaction because the small molecule that&amp;#39;s lost is you guessed it water now to that note of of of aldol of a of an alol condensation reaction we can also talk about a retroaldol reaction the reverse of this reaction you guessed it is called a retroaldol reaction to to push um the reaction in the retroaldol direction aquous base is added and also heat is applied and the retroaldol reaction is useful for breaking bonds between the alpha and beta carbons of a carbonal um and this reaction is facilitated if the intermediate can be stabilized in the inate form just as in the forward reaction so we can see that right here the bond between the alpha and beta carbons of a carbonal is broken all right so we have covered a lot of very very important information let&amp;#39;s quickly review before we end this video and move on to the problem set all right so speed round of everything we covered we said that the carbon adjacent to the carbonal carbon is termed an alpha carbon and so then the hydrogens that are attached to an alpha carbon are called alpha hydrogens alpha hydrogens are relatively acidic and can be removed by a strong base the El the electron withdrawing o oxygen of the carbonal weakens the carbon hydrogen bonds on an alpha carbon the enolate that&amp;#39;s result that results from deprotonation can then be stabilized by resonance with the carbonal we also said that ketones are less reactive towards nucleophiles because of steric hindrance and Alpha carbo anion destabilization then we moved into objective uh two which is all about enolate chemistry we said alahh and ketones exist in the traditional keto form form where there&amp;#39;s a double bond between the carbon and oxygen so there&amp;#39;s a carbonal group and then they also exist in the less common form which is the enal form there&amp;#39;s a double bond and a hydroxy group toomer are just isomers that can be interconverted by moving a hydrogen and a double bond so what we can say is that the keto and Eno forms are toomer of each other the enil form can be deprotonated in addition to form an enolate and enolates are good nucleophiles we saw an example of this in the Michael Edition an enolate attacks in Alpha Beta unsaturated carbonal creating a bond all right something else that we made mention of is the the difference and and the comparison between kinetic and thermodynamic enolates kinetic enolate is formed by fast irreversible reactions at low temperatures with strong sterically hindered bases and thermodynamic inal are favored by slower reversible reactions at higher temperatures with weaker smaller bases we also said like hey by the way it&amp;#39;s not just alahh and and ketones that have the toomer forms enamines are toomer of iines and like enols enamines are the less common toer last but not least we covered aldol condensation in the aldol condensation the alahh or Ketone act as both nucleophile and electrophile resulting in the formation of a carbon carbon bond in a new molecule that&amp;#39;s called an aldol an aldol contains both alide and alcohol functional groups and the nucleophile is the enolate formed from the deprotonation of the alpha carbon the electrophile is going to be the alahh or Ketone in the form of the keto toomer and then first you&amp;#39;re going to have a condensation reaction that occurs in which the two molecules come to together and and then after the aldol is formed a dehydration reaction occurs you have a loss of a water molecule this results in an alphabet unsaturated carbonal you can also have the opposite reaction happen this is called a retroaldol reaction just the reverse of an aldol condensation reaction and it&amp;#39;s catalyzed by heat and a base and in these reactions the bond between the alpha and beta carbon is cleaved all right with that we have covered chapter 7 alahh and ketones part two in the next video we&amp;#39;re going to tackle a problem set together let me know if you have any questions comments concerns down below other than that good luck happy studying and have a beautiful beautiful day future doctors

Transcript for:MCAT Organic Chemistry: Aldehydes and Ketones Part Two

Transcript for:
MCAT Organic Chemistry: Aldehydes and Ketones Part Two