Aldehydes & Ketones: Nucleophilic Substitution
This is a modal window.
The media could not be loaded, either because the server or network failed or because the format is not supported.
Formal Metadata
| Title |
| |
| Title of Series | ||
| Part Number | 7 | |
| Number of Parts | 27 | |
| Author | ||
| License | CC Attribution - ShareAlike 3.0 USA: You are free to use, adapt and copy, distribute and transmit the work or content in adapted or unchanged form for any legal purpose as long as the work is attributed to the author in the manner specified by the author or licensor and the work or content is shared also in adapted form only under the conditions of this | |
| Identifiers | 10.5446/19403 (DOI) | |
| Publisher | ||
| Release Date | ||
| Language |
Content Metadata
| Subject Area | ||
| Genre | ||
| Abstract |
|
1
9
11
12
14
16
17
18
20
21
22
24
26
27
00:00
ChemistryColumbia RecordsMan pageMethylphenidateInternational Nonproprietary NameCigarInflammationBiosynthesisChemical reactionLithiumorganische VerbindungenHaloalkaneWalkingRetrosynthetic analysisChemical compoundCarbon dioxidePharmaceutical drugCarbon (fiber)HalideCarboxylateLithiumMetabolic pathwayAluminium hydrideGrading (tumors)AlcoholAcetyleneBromideWaterBromineGrignard-ReaktionProcess (computing)AldehydeFunctional groupAcidIonenbindungBranch (computer science)Complication (medicine)SteelTube (container)AgeingSeleniteCarboxylierungSong of SongsCadmium sulfideComputer animationLecture/Conference
08:22
TrihalomethaneInclusion (mineral)LymphangioleiomyomatosisChemistryAngular milColumbia RecordsPitting corrosionAldrinAlumNitrogen fixationSiltChemist11 (number)International Nonproprietary NameSetzen <Verfahrenstechnik>AlcoholChemical reactionCarbon (fiber)WaterHydrogenDipol <1,3->ÖlSense DistrictSolubilityHydrogen bondAmrinoneHydrateCamphorElectronic cigaretteCinnamonGlucosePerfumerBiosynthesisElektronenakzeptorStuffingWalkingMagnesiumMoleculeChain (unit)Economic sectorRadioactive tracerGrading (tumors)ThermoformingTrace elementChemical compoundAcetaldehydeSteroidChemical propertyAddition reactionAlkaliCyanideHydrideSodiumProcess (computing)Human subject researchPhysical chemistryBranntweinCyanidionAldehydeRiver sourceFunctional groupAlpha-1-RezeptorKlinisches ExperimentCarbonylverbindungenKetoneAlkeneComplication (medicine)EnantiomereGrignard-ReaktionOrganische ChemieAcidZimtaldehydBase (chemistry)ChemistryAminationElectron donorLithiumLithiumorganische VerbindungenComputer animation
16:44
Methyl iodideAngular milInternational Nonproprietary NameMultiple chemical sensitivityNucleolusChemistryWaterWalkingEpoxideReaction mechanismHydroxideAcidBase (chemistry)CobaltoxideCarbonylverbindungenChemical reactionGesundheitsstörungProtonationCommon landAcetoneHydrateSpeciesLactitolElectronFunctional groupDiolAlcoholCarbon (fiber)Separator (milk)Lone pairAldehydeHydroxylChemistryOreDiet foodActive siteHydro TasmaniaElectronegativityAgeingChemical plantChemical clockFlourComputer animationLecture/Conference
25:07
ChemistryResonance (chemistry)MethylgruppeAcidAldehydeCarbonylverbindungenGrading (tumors)Functional groupFluorineSteric effectsCarbon (fiber)BenzaldehydeReaction mechanismKetoneSetzen <Verfahrenstechnik>HydrateInduktiver EffektGeneric drugAcetaldehydeSense DistrictElectronReactivity (chemistry)HydroxideSlightingWaterBase (chemistry)SunscreenOctane ratingWalkingChemical compoundPeriodateAddition reactionFiller (materials)Human subject researchMetalMedical historyHybridisierung <Chemie>FullereneChemical structureOrlistatFood additiveStereoselectivityComputer animation
33:29
International Nonproprietary NameChemistryFluorineAcidKetoneBase (chemistry)Chemical reactionThermoformingCarbonylverbindungenSetzen <Verfahrenstechnik>CobaltoxideWalkingElectronReaction mechanismCarbon (fiber)HydroxylLone pairHydrateAcetaldehydeCombine harvesterAlkoxy groupFunctional groupMethoxygruppePhenyl groupProtonationGleichgewichtskonstanteAldehydeMethanolAlcoholChemical structureOrigin of replicationHybridisierung <Chemie>Impfung <Chemie>AreaOxideAcetoneStimulus (physiology)Ballistic traumaWine tasting descriptorsTopicityGap junctionComputer animationLecture/Conference
41:51
AlumWalkingRenewable resourceChemical structureMethanolPeriodateExplosionReaction mechanismHydroxylWursthülleLibrary (computing)SpeciesAlcoholMachinabilityProcess (computing)HydrateElectronFunctional groupCarbon (fiber)AcidResonance (chemistry)AcetoneAcetateSurface finishingEpoxidharzHydrogenChemical reactionChemical compoundHoneyCobaltoxideAgeingPeroxideKetoneMethoxygruppeEpoxideHydroxideAlkoxy groupProteinkinase AMethylgruppeCarbonylverbindungenCarbokationComputer animation
50:13
Computer animation
Transcript: English(auto-generated)
00:08
I hope you guys had a great weekend. Are there any questions? Alright, so my policy is the due date for sapling is two days after we finish it in lecture, so that means that I'm going to move the due date for chapter 22 Wednesday. Alright? So somebody
00:26
has to remind me though. I'm worried I'm going to forget because I'm going to be, I'm a judge at the Mr. Medicine competition today, so I might forget. So somebody has to send me an email to remind me, just you, not everybody please. Anyway, questions? Yes?
00:56
Wednesday morning at what time? Oh that one. Yeah. I need to follow up on that, yes. Okay.
01:08
Send me an email to remind me. My mind's on Mr. Medicine right now, so I'm going to forget. Okay, so we left off last time talking about synthesis and we had two different
01:30
routes and we decided that if we were going to use CO2 that it would be better not to use the lithium route. Better to use Grignard, so let's branch off here. Oh, what do
01:47
you mean? Oh, how about that? We decided that it would be better not to use the lithium route for CO2 because it will add twice, so we want it just to add once so
02:03
we're going to do Grignard instead if we're going to do the other pathway. So we're at a point now where there is going to be more than one pathway and so that makes grading trickier on exams so you really want to make sure when you get your exam back some people if they don't do well they won't look at their exam and you know
02:22
you might have things marked wrong that were correct. If you have a unique pathway that I didn't anticipate you might have got it marked wrong so you definitely got to make sure that you check it out. I want you to get the points that you deserve. Alright so then we do CO2 followed by H3O+, this is a little bit longer pathway but
02:54
we don't care as long as it gives us what we want. Oh, we protonated so I got to protonate that and then what do I do? We got to reduce that carboxylic acid
03:10
to an alcohol so we could use lithium aluminum hydride step one followed by H2O
03:24
to give us the product. So that's one step longer doesn't matter as long as you get the right product. Questions about that synthesis anybody? Yes, absolutely yeah
03:50
so you could do the same thing here so this could be rather than organolithium that could also be a grainer no problem with that. Alright so let's look at the third example this is devices synthesis of following compounds from compounds having four or fewer carbons. Alright so this one's a
04:05
little bit more complicated or complicated carbon skeletons here so so what's popping out at me immediately is that that carboxylic acid the CO2H group and I'm going to go retrosynthetically here and I know I can
04:24
make it the same strategy we just did here so make a grainerd and then we have CO2 and then we follow that by adding acid to make a carboxylic acid.
04:44
Okay and the grainerd I can make from corresponding alkyl halide and then I can make that a halide from the corresponding alcohol so we all of a
05:03
sudden in this chapter have gotten much more sophisticated in the things that we can synthesize when we were building carbon skeletons before it was all using deprotonated acetylene and that was a little easier to see this is a little harder to see. Alright so but we know we have a bunch of ways of making alcohols in this chapter certainly grainerd's a good way
05:23
of making alcohols we have to have four or fewer carbons so what I'm thinking is is that we can we have let's see one two three four I'm thinking if we break right here and then this is one two three four those are two four
05:45
carbon pieces so how am I going to make this bond right here I'm going to make this bond by you doing and making a grainerd and attacking an aldehyde so and again there's more than one way to do this but that is certainly a method that will work so going to make this using an aldehyde
06:05
so the alcohol side would be the aldehyde and then this side would just be a grainerd or a lithium let's just make it lithium here okay so that's what that would look like each each carbon is four pieces and the
06:26
corresponding alkyl halide and I'll just use bromine here all right everybody following that that retrosynthesis let's write out the
06:41
synthesis in the forward direction so that's sort of the thought process that goes that we have before we write out the synthesis in the forward direction on the exam we don't grade thought process because it's too
07:01
difficult to grade so you want to definitely want to write out the synthesis in the forward direction all right we could have made a grainerd also they're interchangeable for this reaction so there's our four carbon
07:23
aldehyde we follow that with water that gives us the alcohol we're looking for and then what we want to do there to turn that into we want to turn
07:41
that into a bromide what would we use PBR3-pyridine would not want to use HBR here because things are going to rearrange that's not what we want PBR3-pyridine we'll turn that into a halide and we can make a grainerd or
08:07
get a lithium-renate one we want to know we definitely want to make a grainerd here Mg ether because we're going to be using CO2 that makes the grainerd so this would be a reaction where I would call it open-ended and you have to write the the products from each step but pronation steps you
08:22
can include with the previous reagent so then we would have this CO2 not too many of these types they're very difficult to grade I usually have things in a box with an arrow and then you fill in each step okay questions anybody
08:41
on that synthesis so pretty sophisticated this is definitely what we want to do is we want to practice practice practice doing synthesis yes question you could start with the organolithium just whatever the directions say if it says only organic compounds then you would want to make
09:04
the organolithium compound okay just depends alright any other questions yes yes certainly and it should be H3O plus right actually I'm not going to
09:23
make a big deal about this yeah it should be H3O plus we already showed the water's not strong enough right that's more correct okay more questions yes okay yes you can use magnesium you don't have to use a
09:46
lithium reagent there you can make students tend to like Grignards better right you guys like Grignards better people use Grignards more often than anything else and that's perfectly fine okay so that is the end of chapter 20 we're going to start chapter 21 alright so this is all
10:25
about in this chapter we're going to talk about reversible reactions of type 1 carbonyls in the next chapter we're going to talk about reversible reactions of type 2 carbonyls okay and then we're going to
10:41
get to the more complicated carbonyl chemistry alright so I just give you some ideas of why ketones and aldehydes type 1 are important we have anybody recognize this compound here testosterone we got a bit of that in this room don't we and progesterone here so we have some
11:06
steroids here this is glucose open chain we'll talk about open chain and glucose that's coming up in our very last chapter this quarter your last chapter of ochem so that's the open chain form of
11:21
glucose so you see the aldehyde and aldehydes and ketones figure prominently in perfume manufacturers they use a lot of them smell really good this smells like pistachio this one smells like camphor we have maraschino cherries for the aldehyde we have cinnamaldehyde which smells like cinnamon we've got raspberry flavoring we got
11:42
vanilla which smells amazing we're going to use that in this quarter in my lab and it's the whole lab smells like vanilla it's nice oil of violets and then we have this compound here where the different enantiomers sell differently we have a spearmint for one of the enantiomers and caraway for the other enantiomers so the receptors in
12:01
our nose are chiral so these are going to smell differently nomenclature of aldehydes and ketones we're going to wait till next chapter to do our nomenclature so right now we're going to shelve that preparation of aldehydes and ketones those are the sections you want to review chapter 21 6A and B we just had that
12:25
right so we don't need to do that now physical properties of aldehydes and ketones we'll jump right ahead here so here's some compounds with similar molecular weight minus 6.9 do not need to memorize these numbers we're just talking about trends here
12:42
aldehyde similar molecular weight aldehyde 20 degrees centigrade 56 for the ketone that makes sense because it's got one more carbon so as we increase molecular weight we increase boiling point
13:01
and then here similar molecular weight but this one is 82.3 degrees centigrade why is that one so much higher boiling point? Hydrogen bonding yeah okay so this one here these are hydrogen bond acceptors only so that means that these guys
13:29
when you put them in water they can hydrogen bond with water but when they're by themselves which they are when you're doing boiling point there's no hydrogen bonding that can take place so hydrogen acceptors only can't hydrogen bond with itself
13:46
or other molecules of itself whereas this one right here hydrogen bond donor plus acceptor and so that one has the highest
14:04
boiling point because it can hydrogen bond with itself alright so that makes good sense percent solubility in water
14:21
zero percent for the alkene infinite for all of these guys dipole moment 0.5 for the alkene 2.7 I've seen different numbers for these the aldehyde and the ketone similar but they're not exactly the same I think this number's from your book I'm not sure
14:42
2.7 so similar similar dipole and then 1.7 for the alcohol so even though we have a smaller dipole the alcohol has a higher boiling point because of hydrogen bonding and solubility diminishes rapidly with added carbon
15:01
so if we just take and we add one more carbon onto acetaldehyde here we only go from infinite solubility to 20 percent solubility in water alright so that's all we're going to say about physical properties
15:22
reversible addition reactions of aldehydes and ketones that's the main subject of this chapter as we saw in chapter 20 we have strong nucleophiles organolithium, grignard hydride and sodium alkanides once they add to the carbonyl they're on for good they cannot come back off again so those are irreversible additions
15:41
with weaker nucleophiles so we have water, alcohols, primary and secondary means and cyanide ion the reaction is reversible so we're going to get different products here because of this we're going to start with we're going to go in this order we're going to start with water then we're going to talk about alcohols and then amines and then cyanide last for all of the reagents
16:02
that do reversible addition we will start with water hydration this is what the reaction looks like we'll just use acetaldehyde here acetaldehyde in the presence of water with a trace of acid or base
16:22
only trace is all you need and if you do that you get this is a new functional group for you this is called a hydrate
16:49
it's also called a geminal diol so geminal means that the two alcohols are on the same carbon but more commonly this is the hydrate is more common
17:06
so that's a new functional group that you need to know so it's a carbon that's attached to two hydroxyls yes no actually the arrow should not be the opposite direction so we actually favor the aldehyde aldehyde is more stable
17:22
so this is thermodynamic conditions and under thermodynamic conditions it's you favor the more stable species this is more stable so you only get like a little bit of this forming it's a very small amount okay so even you know if you think about it even you know that jar of acetone that you have to clean things in the lab
17:41
that's got a little bit of hydrate in there you didn't realize but it does okay so you have to work really hard to get rid of excess acid or base you only need a trace so this is a reaction that happens to a very small extent to the right if you want to actually isolate hydrate you have to drive the equilibrium otherwise you won't be able to isolate very much
18:00
alright this is going to have a this has an acid and a base catalyzed mechanism so it's going to remind you of a reaction from chapter nine where we had an acid and a base catalyzed mechanism you remember that opening up epoxides
18:22
remember that I made a big deal about that mechanism I put it on the exam and the reason I made a big deal about is it kind of prepares you well for carbonyl chemistry so a lot of these reactions have an acid catalyzed and a base catalyzed mechanism and you need to know both and you want to avoid the common pitfalls
18:41
the same pitfalls that you have when you did the epoxide ring opening so when you have an acid catalyzed mechanism you protonate things with H3O plus you don't protonate things with water because if you protonate things with water you get hydroxide on it in a base catalyzed mechanism you protonate things with water to produce hydroxide
19:01
so you want to kind of keep your species separate in an acid catalyzed mechanism we don't want to be making negatively charged species and in a base catalyzed mechanism we don't want to make hydronium ion because it's not going to be present in an acid catalyzed mechanism so we'll do base first and so that is a trace of hydroxide so you only need a catalytic amount
19:28
and if you could remember what happened with hydroxide and an epoxide it just directly attacked the epoxide right we did not protonate first and it's going to be the same thing here
19:42
so hydroxide ion is going to attack hydroxide ion great nucleophile so it's going to attack hydroxide it's going to attack the carbonyl directly so great nucleophile
20:05
attacks carbonyl directly alright so the arrow is going to come from one of the lone pairs on oxygen we're going to attack the carbonyl carbon
20:20
kick electrons up onto oxygen reversible arrows here because that can come right back off again and a lot of the time it does come right back off again
20:42
if we want to actually isolate hydrate we have to drive the equilibrium so it looks like that and then we protonate here base catalyzed mechanism we protonate with water and when we do that that's good because now when we do that
21:01
we're regenerating our hydroxide catalyst right so to check that you haven't made a mistake it makes you that you make sure that you regenerate that hydroxide in this last step here
21:24
we have that and then we regenerate our hydroxide again and that can now go and attack another carbonyl so hydroxide attacks directly and then we protonate with water do you see why we wouldn't want to protonate with H3O plus here that's a very common mistake on exams
21:41
to protonate with H3O plus are we going to have H3O plus in a base catalyzed mechanism no so that's why you don't want to use that we want to actually regenerate our hydroxide so that's the base catalyzed you need to know the base you also need to know the acid catalyzed mechanism so for acid catalyzed trace of H3O plus present
22:05
for the acid catalyzed mechanism so if you can remember back to epoxides what do we do in the acid catalyzed mechanism we protonated the oxygen first right we're going to do the same thing here
22:26
so nice to be able to draw that parallel here we're not going to protonate with water because if we protonated with water we'd make hydroxide ion and we don't want hydroxide ion appearing in an acid catalyzed mechanism so we're going to protonate with H3O plus
22:43
so arrow comes from the lone pairs on oxygen we grab a proton and we push electrons onto oxygen
23:04
so it looks like that that's our first step and that's important first step because protonation makes the carbonyl more electrophilic we mentioned that now we're seeing it in use here
23:21
protonation makes the carbonyl more electrophilic we're going to talk about why in class today I mean in discussion this week more electrophilic so weak nucleophile water
23:44
water is our weak nucleophile can attack so in the base catalyzed mechanism the nucleophile attacks the carbonyl first in an acid catalyzed mechanism we protonate the oxygen first and then the weak nucleophile attacks in the second step
24:01
so in the base catalyzed we protonate in the second step in the acid we protonate in the first step so here's our weak nucleophile we know that water is a very weak nucleophile and so what we need to do is soup up the electrophilicity of that carbonyl so that our weak nucleophile can attack so it looks like that
24:26
so we have a reversible arrows all the way through here at any point we can reverse back again so this keeps going forward, backward, forward, backward it could go up two steps and back one step and then forward again or it could go up three steps and back three steps
24:41
and it's just all every single step is reversible if we want to isolate a single product we definitely need to drive the equilibrium all right so now we've protonated the oxygen first
25:00
we have the weak nucleophile attack what's the last step? We have to have some sort of base come in and I don't want you to use B B, B minus generic base what is our actual base here? It's water not hydroxide
25:21
if we use water then we are regenerating our catalyst and we don't want to use water to protonate or we don't want to use hydroxide to protonate because this is an acid catalyzed mechanism we're not going to see hydroxide in here
25:50
need to know the mechanism and the forward and the reverse direction
26:05
and forward and reverse direction so we're doing the forward direction right now and then in discussion we're doing the reverse direction actually twice in this worksheet for this week
26:21
questions so far? Anybody? All right formation of hydrate is reversible as we kind of made a big point about with all these reversible arrows by the way when I'm grading mechanisms on the test I only grade curvy arrows so I only grade this part here I don't grade whether you have reversible or forward arrows
26:43
so you don't have to worry so much about it but I'm trying to show it here because all of those steps are definitely reversible factors that favor addition which is formation of the hydrate more stable the carbonyl the less favorable the addition that makes sense the more sterically hindered the carbonyl compound the less favored the addition
27:01
so we're doing an addition here and so it makes sense that the more reactive the carbonyl the more hydrate we're going to form and if we have a really unstable carbonyl then the hydrate actually can be favored in some instances so let's compare here
27:20
we have acetaldehyde versus ketone we've talked about this already we've talked about this one, let's do it again now we're seeing which one of these is more electrophilic all right so we know that methyl is an electron donating group
27:43
all right so that's going to donate a little electron density into that carbonyl making it a little bit less positive right
28:01
so one electron donating group makes carbon less positive over here we've got two of them so that's double the effect isn't it so two electron donating groups
28:27
make carbon even less positive less positive means more stable so that was our inductive effect
28:41
it's a very slight inductive effect with methyl but it's there nonetheless and then our second thing was resonance effect or steric effect so this one here aldehyde is less sterically hindered
29:01
this one is more sterically hindered so it's got two methyl groups more sterically hindered that means it's going to slow down the rate of the nucleophile attacking the carbonyl so more sterically hindered and so what we can see both of these effects actually work together this compound a ketone is less
29:23
subject to nucleophilic attack another way of saying that is that it's less electrophilic right two ways to say the same thing
29:45
so it's also it's more stable and since it's more stable the hydrate is less favored
30:05
so we can completely correlate the hydrate formation and the extent of hydrate formation with how stable the carbonyl is looking at this next example we have we both have both have aldehydes but as you can see when we put fluorines here
30:23
we have pretty dramatic effect here these fluorines are gonna pull electron density away there's three of them so they're already powerful on their own and now we have three of them so if we're comparing partial positive charge on the carbonyl carbon and which one of these guys is gonna be more electrophilic
30:47
first one or the second one second one by far so electron withdrawing fluorines
31:05
make the carbonyl carbon more positive therefore it's gonna be less stable therefore it's gonna be more electrophilic
31:20
all of these are interchangeable ways to say the same thing more electrophilic more subject to nucleophilic attack well more subject to nucleophilic attack
31:52
and if it's more subject to nucleophilic attack then the water's gonna wanna attack it and make a hydrate okay so that means that the hydrate's gonna be more favored
32:11
all right so all different ways to come to the conclusion that the hydrate's gonna be more favored let's do one more where we're comparing reactivity so very good possibility
32:24
that you're gonna have something where you're comparing a reactivity of carbonyl compounds we already talked about that all mixed and then we could have one where we have aldehydes and ketones with electron withdrawing groups things like that
32:44
all right so we have again we're doing the same thing we're comparing partial positive charge on the carbonyl carbon see which one has the most partial positive charge and what you can see here is that we do have resonant stabilization this is benzaldehyde and we do have resonant stabilization for benzaldehyde
33:17
so we can draw that resonant structure and we can keep going
33:21
here we can draw a bunch of resonant structures let's do one more this is starting to look like chapter 18 isn't it
33:58
all right so highly resonant stabilized right
34:07
so benzaldehyde highly resonant stabilized
34:25
more stable is less reactive so therefore less electrophilic
34:49
we could also say less subject to nucleophilic attack we could say all those things and then we can also conclude that the hydrate is gonna be less favored
35:04
all right so here's a chart here you do not need to memorize these numbers but you're definitely seeing some trends here now so remember this is the equilibrium constant here so if the equilibrium constant is greater than one that means the reaction is favored to the right which forms the hydrate
35:21
so here's hydrate over here and if the equilibrium constant is greater than one then the hydrate's favored so what do we see formaldehyde, hydrate's favored acetaldehyde we have about a one to one ratio here of this and this ketone 1.4 times 10 to the minus third so ketone is favored
35:42
are you seeing this all coming together here? three fluorines for acetaldehyde now it's gonna see we go all the way from here here's 1.06 with the three fluorines we make this more electrophilic and so we also get more hydrate okay
36:01
phenyl ring here that's not favored okay we just showed that that was less electrophilic more stable so less hydrate ketone here we actually can favor the hydrate when we put the three fluorines here and more fluorines the better right for making hydrate and then so you definitely see the trends here
36:21
okay so that's what we're talking about so don't want you to memorize those numbers but if I had a bunch of aldehydes and ketones there and I asked you to rank them or to tell me which one's gonna form the most hydrate which one's gonna form the least you'd be able to answer that question just based on understanding that chart okay
36:40
questions yes they do they do but they're still contributing structures it's not a major thing the proof is right here in how much hydrate you form right so we go from here that's 1.06 and now we go here and it's eight times 10 to the minus third
37:01
that's really the proof that that is playing a role over here was another question no? okay that's hydrate and we're gonna be able to make the same approximations when we're the same sort of statements when we talk about the addition of alcohols
37:25
to ketones and aldehydes all right and we're gonna have a base catalyzed reaction and an acid catalyzed reaction and the only difference here is that the base catalyzed you get a different product actually than you do the acid catalyzed
37:41
so this one's a little bit more difficult so here our nucleophile is alcohol, H-O-R so base catalyzed reaction is gonna look a lot like hydrate move it up just a little bit
38:01
yeah better oh this is off the top okay reversible arrows I'm not gonna show you
38:20
I'm not gonna show any particular direction CH3O minus is our catalyst trace a base that's a new functional group we have a carbon that's bonded to hydroxyl
38:41
and a methoxy group and that is called a hemiacetal so we have a bunch of new functional groups in this chapter here that's a hemiacetal a carbon that's bonded both to a hydroxyl and a methoxy group or an alkoxy group the mechanism is gonna completely remind you
39:00
of base catalyzed hydrate formation all right so our nucleophile is methoxide ion that's a good nucleophile right? we're not gonna protonate the carbonyl first we're gonna attack directly
39:22
so the arrow's gonna come from one of the lone pairs on oxygen we're gonna kick electrons up onto the carbonyl oxygen reversible steps so I'm having reversible arrows
39:46
so when we use the base catalyzed we attack the carbonyl first with the base and then we protonate second
40:03
and we wanna protonate with methanol so that we regenerate our methoxide catalyst we don't wanna protonate with acid that's a very common mistake to protonate with acid here and we don't have acid because this is a base catalyzed mechanism and a lot of students who aren't really very prepared for the exam will use a combination of acids and bases
40:22
in their mechanisms and you usually don't get any points when you do that so you wanna keep that straight there's our hemiacetal questions on the base catalyzed mechanism? Yes, it could
40:44
that's why the reaction's reversible okay so what happens here we have this attack kick electrons up onto oxygen and the electrons on oxygen come down and can kick off with oxygen that's why we have reversible arrows it's gonna keep going back and forth if you wanna isolate a hemiacetal
41:01
you have to drive the equilibrium because this wants to be here wants to be as a ketone unless it's one of those really activated ones that we talked about on the previous page all right acid catalyzed so what are we gonna do first?
41:21
Protonate the carbonyl first so for all the acid catalyzed mechanisms that we're gonna talk about we're gonna protonate the carbonyl first with acid and there's only one exception that we're gonna have in this chapter but in everything else we're gonna protonate the carbonyl first all right so let me just write out the reaction here
41:42
first and then we'll do the mechanism H3O plus or just protonated methanol so you can just add a trace of H2SO4 you'll make protonated methanol here
42:01
so that would be our catalyst we can form a hemiacetal but typically hemiacetals are difficult to isolate there are some exceptions and we'll talk about those coming up but this is the hemiacetal generally not isolable
42:38
it keeps going and we're gonna form
42:41
an actually a different product here so hemiacetal and then this is an acetal so hemihaffacetal so there's another new functional group
43:02
and we're not done we have a few more so this is an acetal so an acetal is a carbon that's attached to two alkoxy groups
43:20
I'm gonna show you the mechanism for this this is a mechanism that 99% of the time I put on midterms okay so very highly likely that you will have this mechanism on midterm one I'm not going to say for sure because I want a little bit of freedom here when I'm writing the test but most of the time I do all right so first we're going to form the hemiacetal
43:42
right here we have it right showing right here and then so I'm going to do that mechanism and then the second part we first we form this and then we go from the hemiacetal to the acetal all right so this is what it looks like here so as we said acid catalyzed mechanism most of the time 99% of the time
44:03
there's one exception in this chapter but most of the time we protonate the carbonyl first and this is just like what we did in chapter nine where we protonated the epoxide first same idea
44:25
notice the reversible arrows all these steps are reversible at any point in this mechanism we can just go back again it's an equilibrium process the product of this reaction is going to be an acetal it is not favored
44:41
is more stable to have a ketone than to have an acetal so we have to drive the equilibrium we'll talk about how you do that all right our nucleophile is methanol here and methanol is a weak nucleophile and so we protonate the carbonyl to make it more electrophilic so our weak nucleophile can attack
45:02
so weak nucleophile attack the carbonyl carbon we kick electrons up onto oxygen so so far it looks just like hydration all right so what do we need to do next
45:39
same thing we did with the epoxides right
45:42
we protonated the peroxide first the alcohol attacked and then we deprotonated the alcohol we're going to do the same thing here and once we do that we have the hemiacetal
46:12
so there's the hemiacetal again generally can't isolate that so it's going to keep going
46:20
and that's on the next page all right so I'm going to redraw the hemiacetal
46:44
all right so what we need to do here to go to an acetal this hydroxide ion needs to be replaced with a methoxy group so what's going to happen is is that this group is going to leave but it's not going to leave as hydroxide why not
47:00
hydroxide is not a good leaving number one and number two well I mean we had it in the hydrate but we're in acid-calase mechanism we don't want to be making hydroxide so we're going to protonate that first so depending on what you have here we can use hydronium ion if we add catalytic hydronium ion
47:21
or we can have the protonated alcohol which behaves just like hydronium ion right both of these have negative pKa so they're really strong acids okay so we're going to protonate the hydroxyl the hydroxyl is what's going to leave
47:41
so we're going to oh what happened I'll just use H3O plus here you can use either one of those species
48:03
yeah there's two ways to do the step after this I'm going to show you the way I do it I'm going to show you the way the book does it and you can do it either way it doesn't matter to me I like my way better of course but you don't have to do it my way okay so the way that I do it is that I have the electrons on this oxygen
48:26
come down and help kick off that leaving group so they kind of push that leaving group right off
48:52
and you get this species here which kind of looks like a protonated carbonyl and it behaves like a protonated carbonyl except that we have a methyl there instead of a hydrogen
49:01
the book shows it and we're going to keep going here we're going to run out of time here but the book shows it this way so let me show you the book shows this way and then we'll keep going we'll be able to finish this today but the book shows it this way for that step
49:21
so once you have this compound here with the protonated alcohol ready to go it has that group leave to make a carbocation
49:41
and a lot of students like this way better and that's perfectly fine and then they have these electrons come down to draw the resonance structure I want directly to the resonance structure I will accept both ways both ways are okay
50:07
both ways okay and then we will so that's this step right here that's this step and we will finish this mechanism next time