Lecture 07. Neighboring Groups Pt. II & Lec. 8. Solvation
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00:00
KalisalzeChemische ReaktionFunktionelle GruppeLactoseVancomycinChemische ReaktionKohlenstofffaserAcetateAzokupplungChlorideDoppelbindungFunktionelle GruppeSenf <Lebensmittel>StickstoffatomTellerseparatorEinsames ElektronenpaarMolekülstrukturComputeranimationVorlesung/Konferenz
00:59
HomocysteinFunktionelle GruppeChemische ReaktionVerbrennungAzokupplungDoppelbindungSetzen <Verfahrenstechnik>Systemische Therapie <Pharmakologie>OktanzahlBicycloheptaneCarbokationVorlesung/Konferenz
01:35
SchwelteerAminosalicylsäure <para->HomocysteinDiatomics-in-molecules-MethodeAuxineOktanzahlChemische StrukturCarbokationCyclopropanDoppelbindungFunktionelle GruppeHydrocarboxylierungKohlenstoff-14IonenbindungStickstoffatomElektronische ZigaretteSymptomatologieAzokupplungGummi arabicumTrichlormethinVorlesung/Konferenz
02:58
ZigarreLactoseIonenbindungChemische StrukturAzokupplungChemischer ProzessHydrocarboxylierungVulkanisationProteinfaltungPropionaldehydFülle <Speise>CyclopropanFunktionelle GruppeMesomerieOktanzahlVorlesung/Konferenz
03:54
BiskalcitratumKohlenstofffaserCobaltoxideMesomerieSekretSubstrat <Chemie>Fülle <Speise>Chemische ReaktionFunktionelle GruppeKatalaseHomocysteinVorlesung/Konferenz
04:59
Wasserwelle <Haarbehandlung>BiskalcitratumMagnetometerKohlenstofffaserKohlenstoff-14Chemische ReaktionOrganisches LösungsmittelAromatizitätBenzoesäureIsotopenmarkierungAmeisensäureOrdnungszahlElektronische ZigaretteSubstituentVorlesung/Konferenz
06:00
WursthülleEthylbenzolNitroverbindungenBenzoesäureFunktionelle GruppeIsotopenmarkierungSubstrat <Chemie>AromatizitätMethoxygruppeBenzolringVorlesung/Konferenz
06:54
BenzolringKettenlänge <Makromolekül>SeitenketteChemische StrukturOrganische ChemieAromatizitätCobaltoxideFunktionelle GruppeMesomerieSubstitutionsreaktionSetzen <Verfahrenstechnik>Systemische Therapie <Pharmakologie>Einsames ElektronenpaarOktanzahlBukett <Wein>AusgangsgesteinElektron <Legierung>AllmendeCarbanionMethoxygruppeVorlesung/Konferenz
08:06
Substrat <Chemie>StickstoffatomEpoxidharzSubstitutionsreaktionChemische StrukturAromatizitätSystemische Therapie <Pharmakologie>Elektron <Legierung>Funktionelle GruppeIridiumRingspannungVorlesung/Konferenz
08:56
MagnetometerKörnigkeitVinylverbindungenCyclopropanHydrocarboxylierungChemische StrukturKohlenstofffaserIsotopieeffektMesomerieMethoxygruppeSetzen <Verfahrenstechnik>IonenbindungZusatzstoffAllmendeFunktionelle GruppeIsotopenmarkierungVorlesung/Konferenz
09:56
BiskalcitratumAuxineIonenbindungChemische ReaktionChemische StrukturMolekülEssigsäureSetzen <Verfahrenstechnik>OktanzahlKonformationsisomerieElektron <Legierung>WasserstoffbrückenbindungKohlenstofffaserKörnigkeitTransformation <Genetik>Vorlesung/Konferenz
11:50
VulkanisationOktanzahlKonformationsisomerieMolekülKohlenstofffaserIonenbindungSystemische Therapie <Pharmakologie>WasserstoffDecalinQuellgebietVorlesung/Konferenz
12:55
IonenbindungWasserstoffKohlenstoff-14Systemische Therapie <Pharmakologie>RingspannungSetzen <Verfahrenstechnik>DecalinTorsioVorlesung/Konferenz
14:00
KonformationsisomerieWasserstoffScherfestigkeitFunktionelle GruppeGeröllIonenbindungElektron <Legierung>BiosyntheseCyclische VerbindungenCarbokationKörnigkeitVorlesung/Konferenz
14:54
Tau-ProteinAluminiumbronzeBarytVerstümmelungPrimärelementIonenbindungElektron <Legierung>WerkstoffkundeOrbitalOrganspendePipetteÜbergangszustandAtomorbitalFunktionelle GruppeEinsames ElektronenpaarVorlesung/Konferenz
15:56
AzokupplungIonenbindungVorlesung/Konferenz
16:57
VancomycinChemische ReaktionChloroformKohlenstofffaserAtomabstandBromideÜbergangszustandOktanzahlReaktionsgeschwindigkeitBromAmeisensäureIonenbindungIsobutylgruppeVorlesung/Konferenz
17:56
SchwelteerMilAdenosylmethioninChemische ReaktionAmeisensäureOktanzahlChloroformOberflächenbehandlungGesundheitsstörungSonnenschutzmittelPolymorphismusGasphaseCHARGE-AssoziationVorlesung/Konferenz
19:03
SonnenschutzmittelHyperpolarisierungCHARGE-AssoziationOrganisches LösungsmittelVorlesung/Konferenz
19:48
CholinesteraseinhibitorVSEPR-ModellChemische ReaktionChromatographieDimethylsulfoxidEtherOrganisches LösungsmittelKohlenstofffaserMethylenchloridEthanAcetonitrilAllmendeChlorFunktionelle GruppeHexaneSetzen <Verfahrenstechnik>DiethyletherExtraktIonenbindungDipol <1,3->HyperpolarisierungKompressionsmodulForosaminKörpertemperaturMethanolKlinisches ExperimentMolekulardynamikVorlesung/Konferenz
22:07
EntzündungBiskalcitratumKaugummiChemische ReaktionWasserSonnenschutzmittelHyperpolarisierungVorlesung/Konferenz
23:07
SonnenschutzmittelWasserstoffbrückenbindungBromideFließgrenzeÜbergangszustandAmeisensäureFunktionelle GruppeEinsames ElektronenpaarIsobutylgruppeVorlesung/Konferenz
24:06
WasserstoffbrückenbindungMolekülWasserstoffBromBromideFarbenindustrieÜbergangszustandAmeisensäurePotenz <Homöopathie>AlterungFunktionelle GruppeVorlesung/Konferenz
25:01
GlykosaminoglykaneZearalenonEn-SyntheseOrganisches LösungsmittelChemische ReaktionSäureWasserstoffbrückenbindungElektrolytische DissoziationAllmendeAtomorbitalFluorideNeutralisation <Chemie>ÜbergangszustandVulkanisationWursthülleOktanzahlPotenz <Homöopathie>QuellgebietCHARGE-AssoziationBortrifluoridHyperpolarisierungVorlesung/Konferenz
26:55
ÜbergangszustandWursthülleDiamantEisenWasserstoffbrückenbindungOrganisches LösungsmittelMethanisierungSetzen <Verfahrenstechnik>MethylenchloridIonenbindungVorlesung/Konferenz
27:52
LinkerTetrahydrocannabinoleOrganisches LösungsmittelHyperpolarisierungAtomChemische ReaktionChemische StrukturLithiumMolekülWasserMethylenchloridKaliumKoordinative BindungLithiumbromidNatriumCHARGE-AssoziationKaliumcarbonatGangschwarmElektron <Legierung>Vorlesung/Konferenz
29:03
IonenbindungCHARGE-AssoziationKoordinative BindungChemische ReaktionLithiumLithiumorganische VerbindungenFaserplatteLigand <Biochemie>Organische ChemieLithiumsalzeElektron <Legierung>Vorlesung/Konferenz
29:56
ChlorkohlenwasserstoffeChemische ReaktionOrganische ChemieChlorideEsterThionylchloridEinsames ElektronenpaarAlkohole <tertiär->SulfurSulfiteChloretheneHydroxylgruppeWursthülleVorlesung/Konferenz
30:53
ChlorideChemische ReaktionMolekülOxidschichtSeleniteFunktionelle GruppeSulfideWursthülleChlorkohlenwasserstoffeDioxaneGrignard-ReaktionOxoniumVorlesung/Konferenz
32:15
GenortTetrahydrocannabinoleVOC <Ökologische Chemie>MolekülOrganisches LösungsmittelChlorideDioxaneChemische ReaktionChemischer ProzessVersetzung <Kristallographie>BenzolringFülle <Speise>Alkohole <tertiär->SulfiteAllmendeVorlesung/Konferenz
33:34
PharmazieChemischer ProzessFleischerChemieanlageOrganisches LösungsmittelSonnenschutzmittelÜbergangszustandReaktivitätInitiator <Chemie>Konkrement <Innere Medizin>OktanzahlStockfischAlkoholische LösungElektronische ZigaretteChemische HärteVorlesung/KonferenzBesprechung/Interview
34:43
AtomorbitalVorlesung/Konferenz
Transkript: Englisch(automatisch erzeugt)
00:15
Okay, we are going to continue with lecture seven today and finish it up. And we're also including in that lecture eight,
00:22
which is really just a couple of things for me to say about solvation. So when you look online for the notes for these lectures, I combine them together. There is no longer a link to separate notes for lecture eight. Okay, so we were talking about neighboring group participation in ionization reactions. And we had mentioned things like mustards
00:41
where nitrogen lone pairs can assist in the ionization of leaving groups like chloride. We had talked about acetate groups bending over with lone pairs on carbonyls, making five-membered rings when they participate in the ionization. And so instead of talking about lone pairs, I want to shift over and talk about double bonds and when they can help groups to ionize away.
01:02
And I want to urge you to look for homoallyl groups when you look at ionization reactions. And here's an example of that. Let's take a look at the rates for SN1 ionization, the loss of this to give a carbocation for these two types of norbornyl systems. They look very similar. The only difference is that this one has a double bond here
01:22
at this position. And when you look at the relative rates for SN1 ionization to make a carbocation, when you have that double bond over there at the 2, 3 position of the norbornyl system, the rate is, the relative rate, it looks a lot faster.
01:44
Why is there this huge difference in rate for the ionization of this tosyloxy group over here? Obviously, it has to do with the double bond. And this is purely an example of something akin to neighboring group participation. It's sort of related to what we had over there with that nitrogen mustard,
02:01
except now this involves a double bond. Let me go ahead and draw out some explicit participation. I'll draw a little bit of arrow pushing to see what would happen if I did use that double bond to help push out the leaving group. What would we see happening here? I'll try to draw some of those structures that you would get. And I hope you'll immediately see what's going on here
02:20
to be something you're already familiar with. Now, you can't tell from my arrow pushing which bond I'm forming, which carbon atom I'm forming a bond to. You can't tell whether I'm forming a bond to here or here. So, arbitrarily, I'm going to make the carbocation end up at this position.
02:41
And why is that a special carbocation? It's got that amazing cyclopropyl carbonyl setup right here. These bonds in this three-membered ring are strained. They're donating in to that carbocation. So, it's a great carbocation that you form that's stabilized in low energy.
03:01
Or conversely, this pi bond is indeed helping to push out that leaving group. And it buys you 100 billion fold in rate acceleration. And of course, there's another resonance structure I could draw that would put the three-membered ring bond to here and leave the carbocation on top. So, this is nothing more than forming a cyclopropyl carbonyl cation.
03:30
It's just that we didn't have a cyclopropane in our starting material. So, maybe you didn't see that. When you look at the problem set that I just assigned you, all over the place, I have these tricks embedded in here.
03:41
Because I'm counting on the fact that you're not good at seeing this. And so, your job is to try to see that stuff. This is like Sudoku, except instead of paying money to buy a Sudoku puzzle, I'm giving you free puzzles to work on. And you should be paying me money.
04:06
For, why don't I use? Well, this is a reaction. We're breaking the tosyloxy group. So, that's no longer, why don't I? Oh, there's another resonance structure.
04:21
Why didn't, I just don't have the time. You can draw another resonance structure where this is bonded over here. This one? Oh, no, because this oxygen is no longer bonded to that carbon. This is the cation that results from the ionization. Okay, so what's another secret way that I've hidden this stuff in your problems?
04:49
I'm going to ask you to compare the fates of two different and related substrates. This is not benzyl. We would refer to this as homo-benzyl. Homo means you've got one extra carbon atom.
05:02
So, instead of having allyl, if you have homo-allyl, that means you have one extra carbon. This is not benzyl. This is homo-benzyl. There's an extra carbon atom in there. So, let's try to imagine an SN1 ionization in the presence of formic acid as your solvent. That's your nucleophile and your solvent. We call that solvolysis. And so, let's imagine if we do a displacement reaction.
05:24
And what we're going to do is we're going to imagine what would happen if I put a C13 label right at that position. Right there at the benzylic position if I had a C13 label, carbon 13. What I'll show you is that the end products here depend
05:42
on the substituent on this aromatic ring.
06:00
Really, you get the same kind of phenethyl substituted product in both cases. But you don't know that anything interesting has happened here until you do that C13 labeling experiment. If I label these with a C13 at the benzylic position, the nitro group shows you that it's still there at the benzylic position. Didn't move anywhere. Nothing special. But when I look at the substrate
06:22
that has the methoxy group there, what I find is that that label is now scrambled. It's 50% C13 label here and 50% C13 labeling up there. And so what's going on with this? Let me just be clear that that's a C13 label at that position. How can you get 50% scrambling at that position?
06:42
Let's try to draw this out. I'm going to draw the substrate in this. I'm going to try to imagine what we would see if I looked at that edge on. So I'll try to draw this sort of three dimensionally. And so here's a picture of that aromatic benzene ring. If we were to stand on the side of that and view that edge on. And I'll draw that side chain substituent sticking off
07:03
of here with the tosylate leaving group. So there's that benzene ring side on. And if I look at the methoxy substituted system, I should be reminded that there's a resonance structure that I can draw in which I engage the lone pairs
07:20
on the oxygen atom. So the lone pairs are nucleophilic. We know that. So let's draw a resonance structure of this. I'll take these electrons right here and I'll donate them into the aromatic ring. And I think you've probably done a lot of these types of resonance structures in order to explain the rates of electrophilic aromatic substitution, why you favor ortho pair substitution.
07:40
Those are common concepts from sophomore organic chemistry. So when I draw the resonance structure for this, hopefully it'll be totally clear why we're seeing this scrambling effect. So now when I draw that resonance structure, what I can see is that there's a, in that resonance structure there's a carbanion located here
08:01
at the position para to the methoxy group. So here's the resonance structure. And so you can see why for the methoxy substituted substrate but not for the nitro substituted substrate, you can expect this kind of participation like that.
08:21
In other words, the aromatic ring, the electrons in the pi system of the aromatic ring can help to push out this leaving group. And so the intermediate that you generate has this structure that at first looks insane. And we call this particular ion, not an iridium ion,
08:44
we call this a phononium ion. It's a well-known kind of intermediate. This is called a phononium ion intermediate. There's 26 to 27 kilocalories per mole of ring strain in a three-membered ring.
09:00
But this is really just another cyclopropyl carbonyl. It's that same kind of cyclopropyl carbonyl. I can take that positive charge and roll it over here with a resonance structure and show that it's right next to those very nucleophilic cyclopropane bonds. And there's another resonance structure where it's located right here on the other side next to the cyclopropane bond. So that's a super stabilized kind of structure.
09:23
And so that's why it's in particular when you have this methoxy group here, you really can easily form that type of phononium ion which is really just a cyclopropyl carbonyl cation. And so now when your nucleophile comes in, of course, you have no way to control whether the nucleophile is attacking the labeled carbon or the unlabeled carbon
09:42
because these look pretty similar, those two carbons. There might be a slight isotope effect. It would also work for ortho. That wasn't on the problem set, was it?
10:02
Okay, so let's take a look at sigma bonds. I don't even know what through space, most molecules are mostly empty space.
10:21
Electrons are very small. So maybe everything is through space. What I want to pay attention to here is the effects of conformation in medium-sized rings. And this is the idea we want to consider, is well-aimed carbon-hydrogen bonds, ones that are poised.
10:43
I want to think about the ionization of tosylates in acetic acid. So acetic acid is the solvent and it's the nucleophile in this reaction. Of course, it's a boring transformation, but these kinds of experiments really inform us about chemical structure.
11:03
And what I want to look at is how the rates vary as we vary the ring size. If you change this ring size from three to four to five to six to seven, every kind of ring size in between, what you find is that for some ring sizes,
11:21
this becomes much faster. And so the question is, why should that be faster for those particular sizes of rings?
11:42
So 11-membered rings aren't quite as fast. Twelve-membered rings actually seem pretty normal, like more closer to a six-membered ring. What's special about these types of ring sizes? So in order to understand why you get this rate acceleration for these particular ring sizes, we need to draw out the conformations of these kinds of rings.
12:01
And it's closely related. The reasoning for this kind of rate of ionization is closely related for why it is so hard to cyclize to make eight, nine, and ten-membered rings.
12:26
So I'm going to start off by drawing what you would get if you had two chair rings fused to each other. We call this a decalin ring system. It's a ten-carbon, bicyclic ring system. When you have two chairs fused, that's called decalin.
12:41
And the first thing that I note here with decalin, I'll draw the hydrogens at the bridge head because it helps me to better see the conformation of this molecule. The first thing that I see is every, and this is why chairs are so great. Every single carbon-carbon bond has a staggered orientation. So if I draw a Newman projection for any one
13:00
of the bonds, looking down the axis of any one of these bonds, what I would see is perfect staggering between these bonds. That minimizes the amount of torsional strain in any system.
13:20
So this type of bicyclic system is perfect, but what happens if I don't have this carbon-carbon bond in the middle? What happens if I have ten carbon atoms and no bond in the middle? It will not be a comfortable situation. So if you want, you can just, well, I don't want to draw that bond in the middle. I'm simply going to draw, again, this decalin ring system.
13:43
But if I don't have a bond in the middle and I still have these hydrogens sticking straight up and straight down and everything else is perfectly staggered, the question is where am I going to put these hydrogen atoms, which now have to exist in the middle of that ring? The problem is they're trying to exist in the same locations in space.
14:02
This is the conformation that minimizes torsional strain. And so now if I want to replace this carbon-carbon bond with two H's, that's a problem. And it's exactly this that makes it very hard to synthesize ten-member grains through cyclization. We call those bumping interactions
14:21
between the two hydrogens. We call those trans-annular interactions. Trans-annular means across the ring. So they're bumping into each other. And so if you take one of these groups down here and you replace this with a tosyl group and you look
14:43
at the ionization of that group, the carbocation that exists in this ring actually ends up being stabilized by the electrons in the opposite CH bond. I mean, these are right in each other's faces and the electrons in the CH bond are reaching across the ring
15:01
and donating into the anti-bonding orbitals. They're there in the cation and they're there in the starting materials and they're there in the transition state, lowering the energy for ionization of the tosylate group. So having that extra electron density, and my drawing doesn't do it justice. You have to imagine this CH bond poised above the anti-bonding orbital ready to overlap.
15:22
So you can see the effects of even sigma bonds helping to assist in pushing out leaving groups. Any kind of donation of filled orbitals into unfilled orbitals is a stabilizing interaction. Okay, so that's all we have to say
15:41
about neighboring group participation with lone pairs, with pi bonds, and ultimately if the positioning is just right even sigma bonds can have that kind of effect. Yes? No, I mean my confirmation doesn't do justice to this. I mean maybe if I put this other H going downward,
16:03
I mean again my drawing doesn't do, my drawing doesn't allow you to see which of these CH bonds is poised best above sigma star. Okay, so I had originally another lecture that had just a couple of things to it on solvation
16:21
and it's not really a full lecture. So you can consider this to be lecture eight, but we just have a few things to say about solvation.
17:17
So I want you to think about the SN1 transition state
17:20
for ionization of bromide from t-butyl bromide. In the transition state, the bond distance, the distance between bromine and carbon is getting longer. You're starting to build up more partial positive charge on this carbon, more partial negative charge on this carbon. And in particular, I want to look at the rates for this reaction as we change the solvent.
17:45
The relative rates actually, the rate constants. So we'll look initially at chloroform and then we'll compare that to formic acid and the rates of reaction in formic acid, which is a reasonably polar solvent. So if I assign a relative rate of one in chloroform
18:02
for this ionization reaction, it turns out that the rate in formic acid is substantially bigger. And I want you to remember this difference in rates. What if you could accelerate your PhD by a factor of 200,000, right? Or what if you had to wait over the weekend for your reaction to finish?
18:20
I'm basically giving you a recipe for how to make your reactions faster. There's something in here. Your reaction is you don't have to suffer with the reaction conditions you find in the literature. You can take basic concepts and apply them to how to make things faster. Why is this so much faster?
18:53
It has to do with this. Remember this Coulomb's Law or this variant of the Coulomb's Law where you say something about charge one times charge two divided
19:02
by the distance between the charge. Well, there's also another factor in there, either permittivity or dielectric constant or some version of that that has to do with the polarity of the solvent, the dielectric constant for the solvent. How good is the solvent at screening charges so the charges can't see each other?
19:22
It takes energy to pull a minus charge away from a plus charge. That's very, very energetically costly to take a plus and a minus and pull them apart. And if you could somehow decrease it so those charges couldn't see each other, then you'd make it easier to pull the charges apart. Let's go ahead and take a look at some dielectric constants for some various solvents.
19:44
I'm going to give you a table here. We're going to compare everything to the gas phase. What's the dielectric constant for the gas phase? It's not zero. It can't be zero because if it's zero,
20:02
you'd be dividing by zero. It's one. It's nothing can be lower than that. So if you think about non-polar solvents that are similar to the gas phase, hexane is a super non-polar solvent. Most things don't dissolve in hexanes but if more things dissolve in hexanes and you wanted a non-polar solvent, you might be inclined to use that.
20:21
There's other solvents that aren't quite as non-polar but are more commonly used. Ether, diethyl ether is a dielectric constant of only 4. THF is more polar than ether, tetrahydrofuran, but still it's sort of in this range where it's,
20:42
I wouldn't call that a non-polar solvent but it's not very polar. I would refer to hexanes and ether as non-polar. When somebody tells me non-polar solvent, those are the common types of solvents that you use for chromatography or for extractions that you would think of something as non-polar. THF is just slightly polar enough
21:01
where I wouldn't call it non-polar. Dichloromethane also has a dipole moment and it's a polar solvent. The 2 chlorine carbon bonds have dipoles associated with them and that's got about the same dielectric constant, bulk dielectric constant as THF. And now I'm going to show you a big jump to some common solvents.
21:21
I would refer to these as polar solvents, methanol, dimethyl formamide, acetonitrile, dimethyl sulfoxide. And they all have dielectric constants are
21:40
in this 30 to 40 range. So I'll give you the numbers here. 33 for methanol, 37 for DMF, the acetonitrile is 38. I never remember the exact numbers for these. But I remember that the DMSO is more polar than the rest of those as a group. I would consider all of these polar solvents
22:01
and DMSO the most polar among them. If I try to think about polar solvents to run my organic reactions in, DMSO is probably about the most polar solvent that I know of to run reactions in, except for one. There's one other solvent that I don't have on this list that is the most polar of all, water of course.
22:21
And it's totally in a different class here. It's 78. So why don't you run more reactions like SN1 reactions in water? Well, most things aren't soluble in water. And of course water is reactive as well. It's a nucleophile and an electrophile. So that's why you don't use water more often.
22:40
Okay, so in other words, if you change from the gas phase to DMSO, you could expect things to be how much faster for an ionization reaction? Not 10 to the, just 50. If you go from 1 to 50, you can expect changes on the order of a factor of 50.
23:02
What's up with that? That's a lot bigger than 30 or a factor of 40 or even a factor of 78. There must be something else involved here that's related to solvent that's not just. This is an important part of why formic acid is faster. But this dielectric constant thing can't be the whole story.
23:23
So why else might that ionization be so much faster in formic acid?
23:49
I'm going to redraw that transition state where this T-butyl group is starting to become flat. And that bromide is walking away and starting to pick up its negative charge.
24:01
If you're in formic acid, formic acid is very powerful at hydrogen bonding. So let me draw one of the, and there's lone pairs on here. I'll draw some of them. Let's just imagine some of those hydrogen bonds. Let me draw it in a different color so it really gets emphasized. Here's a hydrogen bond. And if this is surrounded by formic acid molecules,
24:21
that can form very powerful hydrogen bonds to that bromide. In a way, it makes it a better leaving group. Importantly, those hydrogen bonds are stabilizing the transition state as this bromine is starting to walk away. As it's starting to walk away with its negative charge, those hydrogen bonds are already there assisting. They were there in the starting material.
24:41
They're there in the transition state. They're definitely there when the Br minus is floating all around on its own, hoping to stabilize the Br minus. So H bonds can stabilize the transition state. And what you have to imagine is not just one hydrogen bond, I won't draw the whole formic acid molecule here, but you can imagine this thing surrounded
25:01
by hydrogen bonds helping that to leave. So the effects of polar solvents are partially due to dielectric constant, but they're also due to very explicit effects that involve interactions between filled orbitals and unfilled orbitals like hydrogen bonds. Okay, so I want you to be cautious. Well, not overly cautious.
25:21
There's exceptions to this, this idea that polar solvents lead to rate accelerations. Of course, an SN2 reaction doesn't have this degree of reliance on dielectric. This is what I'm really talking about here is SN1 reactions to make carbocations.
25:52
Maybe I should just make this BF3 ethrate. So of course, you can distill. It always baffles me. It's a distillable liquid, but it's a common source
26:01
of boron trifluoride. You put it into your reaction and it dissociates to give you a very powerful Lewis acid. So there's a reversible dissociation of boron trifluoride ethrate. What's the effect of going to a, what's the effect of polarity on this reaction?
26:23
So up above what we said is that if you have a polar solvent that it screens these charges as they're starting to pull away. But in this case, you're not making ions. You start with an ion and you go to something that's neutral. And so here, polar solvents will decrease the rate of this ionization.
26:46
Polar solvents will decrease the rate of that ionization because the polar solvents will stabilize the starting materials and destabilize the more and more you go in the transition state towards those two products. So in most cases, ionization leads to ions, but here's a case
27:02
where you start with ions or something that's ionic and you go to something that's neutral. Okay, so let's look at some other explicit types of solvent effects like these formation
27:20
of these, formation of those hydrogen bonds.
27:51
So THF and dichloromethane have very similar dielectric constants, just as a judge of solvent polarity. But if you look at THF, it's totally different
28:11
from dichloromethane. Usually when you run reactions in dichloromethane and you add salts, potassium carbonate, sodium phosphate,
28:21
they're totally insoluble in dichloromethane. They just sort of spin around at the bottom of your reaction flask as this white solid that doesn't do anything. If you put lithium bromide in THF, it's totally soluble. It dissolves like it's dissolving in water. And you can't justify that based on dielectric constant. The reason why that's true is
28:41
because lithium is a second row atom and it wants eight electrons, just like every other second row atom. So as many solvent molecules as you can fit around there, you will find them attached to THF. I'm just drawing two molecules here attached to THF. If I want to match the charges, if I leave the charges off, those are dative bonds.
29:01
And if I want to have regular Lewis structure bonds, I have to put a minus 2 on there. Maybe that will make you uncomfortable. But if you want, you can just leave the bonds as dative bonds and don't put a charge. So lithium will happily take four ligands on it in order to reach that octet. When you look up crystal structures of lithium-containing ions, you generally see four bonds to lithium at least.
29:21
Or the important thing is you see eight electrons around lithium. So lithium wants those electrons. And we'll talk more about lithium and organolithium compounds and this desire to have extra bonds to lithium later.
29:48
Let me do this over on this other board here because I think I'm going to need a little more room. I want to look at two different SN2 reactions in order to take alcohols and convert them into alkyl chlorides.
30:09
So let's imagine taking this asymmetric alcohol. There's a stereogenic center in here that allows us to keep track of what's going on. And if you treat this with thionyl chloride, with SOCl2, you can replace the hydroxy group with chloride.
30:25
Ultimately, this kind of a reaction goes through a chlorosulfite ester. I'm not going to draw all the arrow pushing for that. I assume you've covered this at some point in your sophomore organic chemistry course. There's a lone pair on sulfur. It's not important for this reaction.
30:42
Okay, so you go through this chlorosulfite ester and then there's a chloride floating around that we've just displaced. And I'm going to draw it right here. And so when you use thionyl chloride on secondary alcohols, you generally get inversion of configuration. So what you get is the chloride that's got the opposite
31:02
configuration because it displaces the leading group with inversion. So this is just a simple SN2 reaction here. So you get inversion of configuration to get that final alkyl chloride.
31:21
And now you can use that to make a Grignard reagent or do whatever you're going to do with that. So now let me contrast this. Same starting material, same reagent.
31:43
For whatever reason, you decided to use dioxane for this reaction, you get a different result. It turns out that in this case the dioxane actually acts as a nucleophile that displaces the chlorosulfite
32:03
intermediate to give you an intermediate like this. Before the chloride can push out the chlorosulfite from the back, there's already a dioxane molecule waiting right there. And it displaces the chlorosulfite to give you this oxonium ion intermediate. So now when the chloride comes in, finally the chloride makes its way to the other side
32:22
of the molecule, it's like, oh, I got beat out by the dioxane solvent. Now the chlorosulfite comes in and when it displaces, still an SN2 reaction, now you end up with an overall retention of configuration because this process involved a double displacement.
32:41
You displace once in an SN2 reaction with a dioxane, you displace a second time with the chloride so the overall result is retention of configuration. Okay, so these, this is an effective solvent. It's not dielectric constant. Solvent is actually participating in the reaction and you have to look out for that in a lot of different reactions.
33:04
Benzene, if your stuff is soluble, then benzene. It depends on what your alcohol is soluble in. It'd be a common one. Well, or nowadays toluene because benzene is toxic.
33:33
Okay, so why are solvent effects great? Solvent effects are the reason why chemists will not suddenly all be out of jobs, right?
33:41
If it weren't for solvent effects, just about every transition state and every intermediate we could draw into a computer and hit the button and do ab initio calculations on, except for solvent effects. For solvents, you have to know how the solvents are going to participate and draw them specifically in in every conceivable configuration and nobody can do that.
34:01
So electronic structure calculations, every time you see somebody say, oh, I calculated this with a hard tree, Fox 631G star, B3 lip, LAN, LDZ, you know, something like that. When you see electronic structure calculations, they are virtually never taking solvent into account. And so these huge differences in reactivity
34:20
that you can see with solvent, factors of hundreds of thousands in rate, those will all be absent when you look at electronic structure calculations. Okay, so that's the end of, I guess, lecture 7 slash 8.
34:41
And that is the end of the material for the first exam. So when we come back on Monday, we're going to start talking about displacements in addition to sigma star orbitals, and that will not be on the exam that's on Wednesday. That's, this is where we end for exam 1 material. Okay, that's it. I'll see you guys. Enjoy your Friday.