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Lecture Comments (25)

1 answer

Last reply by: Professor Starkey
Mon Oct 20, 2014 11:45 PM

Post by Ahmad Alshammari on October 20, 2014

Let me tell you something Pro Starkey. I studied your lectures before the exam in hours. And I ended up with B+ in the exam. I wish I studied it in weeks before the exam, I am sure I would've got a hundred%!

Thank you very much!

1 answer

Last reply by: Professor Starkey
Tue Mar 18, 2014 9:37 PM

Post by saima khwaja on March 18, 2014

Why is MgBr and not MgCl? and is that one molecule or two separate?

2 answers

Last reply by: Nicholas Elias
Fri Oct 18, 2013 4:46 PM

Post by Nicholas Elias on October 18, 2013

Does branching also influence the boiling point of an alcohol like lets say we compare a 5 carbon branched alcohol to pentanol?

3 answers

Last reply by: Professor Starkey
Sun Oct 13, 2013 11:18 PM

Post by Serena Chanelian on October 9, 2013

Hi! The workup after the ketone/aldehyde is exposed to a Grignard Reagent is H20 or H30+ to protonate the alkoxide and generate an alcohol. Would using methanol CH3OH as the workup work as well since the pH of water and methanol are very similar? Thank you!

1 answer

Last reply by: Professor Starkey
Tue Aug 13, 2013 11:32 AM

Post by Briana Kallias on August 11, 2013

In the last slide where we have to provide the reagents for the first problem, would it be possible to, step 1: react it with NaBH4 in Ch3OH to create the OH group, step 2: react with OH- to remove one hydrogen and create a primary carbocation, and step 3: react with LiCH3 to add the new CH3 group to where the carbocation was located?

1 answer

Last reply by: Professor Starkey
Sun Sep 23, 2012 11:05 PM

Post by Nigel Hessing on September 22, 2012

Hello, at 24:50 you said that allylic and benzylic reactions favours SN2, but I thought that they favoured SN1 because they form a stable carbocation.. I thought because the Sn2 is a concerted mechanism the transition state is not as important as the carbocation? Can you please clarify?

1 answer

Last reply by: Professor Starkey
Fri Apr 27, 2012 1:01 AM

Post by Rachel Paquette on April 26, 2012

at 42:00 min in you are talking about proton transfer form the H-OCH2CH3 to the cyclopentane, however, every time I try this problem on my own I want to reaction the entire ethanol group and then deprotonate the H. Does this not occur because the ethanol is not needed as a nucleophile but instead the cylopentane is acting as the nucleophile and just needs an electrophile?

1 answer

Last reply by: Professor Starkey
Tue Dec 13, 2011 8:35 PM

Post by Matt Minken on December 11, 2011

For the last slide in the transform problem, could you have used the organolithium CH3Li? thanks

2 answers

Last reply by: Professor Starkey
Sat Nov 5, 2011 4:35 PM

Post by Thomas Notto on October 27, 2011

In the above lecture you wrote "-OCH3MgBr".... Shouldn't that be -OCH3MgCl... since you started with MgCl... Just wondering where the "Br" came from in the explained reaction.

0 answers

Post by christopher aime on April 30, 2011

agreed

1 answer

Last reply by: Professor Starkey
Sat Jul 30, 2011 12:20 AM

Post by Dalila Talbi on April 19, 2011

Good morning,
I like Professor Starkey's videos. Is there a way I can have a print out of her notes shown on the video? it will help me a lot.
Thanks
D

Alcohols, Part I

Draw the product formed from this reaction:
Draw the product formed from this reaction:
Draw the product formed from this reaction:
Draw the product formed from this reaction:
Draw the products formed for the first and second reaction:
Draw the product formed from this reaction:

*These practice questions are only helpful when you work on them offline on a piece of paper and then use the solution steps function to check your answer.

Answer

Alcohols, Part I

Lecture Slides are screen-captured images of important points in the lecture. Students can download and print out these lecture slide images to do practice problems as well as take notes while watching the lecture.

  • Intro 0:00
  • Alcohols 0:11
    • Attributes of Alcohols
    • Boiling Points
  • Water Solubility 5:00
    • Water Solubility (Like Dissolves Like)
  • Acidity of Alcohols 9:39
    • Comparison of Alcohols Acidity
  • Preparation of Alkoxides 13:03
    • Using Strong Base Like Sodium Hydride
    • Using Redox Reaction
  • Preparation of Alkoxides 17:41
    • Using K°
    • Phenols Are More Acidic Than Other Alcohols
  • Synthesis of Alcohols, ROH 21:43
    • Synthesis of Alcohols from Alkyl Halides, RX (SN2 or SN1)
  • Synthesis of Alcohols, ROH 25:08
    • Unlikely on 2° RX (E2 Favored)
    • Impossible on 3° RX (E2) and Phenyl/Vinyl RX (N/R)
  • Synthesis of Alcohols, ROH 26:26
    • SN1 with H₂O 'Solvolysis' or 'Hydrolysis'
    • Carbocation Can Rearrange
  • Synthesis of Alcohols, ROH 30:08
    • Synthesis of Alcohols From Alkenes: Hydration
    • Synthesis of Alcohols From Alkenes: Oxidation/Diol
  • Synthesis of Alcohols, ROH 33:14
    • Synthesis of Alcohols From Ketones and Aldehydes
  • Organometallic Reagents: Preparation 37:03
    • Grignard (RMgX)
    • Organolithium (Rli)
  • Organometallic Reagents: Reactions 41:45
    • Reactions of Organometallic Reagents
  • Organometallic Reagents: Reactions as Strong Nu: 46:40
    • Example 1: Reactions as Strong Nu:
    • Example 2: Reactions as Strong Nu:
  • Hydride Nu: 50:52
    • Hydride Nu:
  • Examples 53:34
    • Predict 1
    • Predict 2
  • Examples 56:43
    • Transform
    • Provide Starting Material

Transcription: Alcohols, Part I

Hi and welcome back to Educator.0000

Next we are going to be talking about alcohols; we are going to do two different parts.0002

The first part is going to be discussing the structure of alcohols and the synthesis of alcohols; in other words, how do you prepare them.0006

An alcohol is an organic molecule that contains an OH functional group.0013

Because oxygen is so electronegative, it pulls a lot of electron density toward itself, especially away from this tiny little hydrogen.0018

What we end up with is a huge partial minus and partial plus on these two atoms; so the OH group is a very, very polar functional group.0025

That is going to define a lot of its physical properties; they can undergo hydrogen bonding with each other.0034

In other words, one molecule of an alcohol, partial minus, partial plus, can interact with another molecule of alcohol, partial minus, partial plus.0041

There is such a strong attraction between the oxygen on one and the hydrogen on the other that we actually draw a dashed line connecting them.0056

We call that a hydrogen bond; it is easy for the protons to be transferred from one structure to the other.0064

It results in a very strong association, a very strong association, a very strong affinity for one molecule of an alcohol to another molecule of an alcohol.0073

The physical property effects we see on that is we see an increased boiling point.0080

Because if these are very strongly attracted to one another, it is going to difficult to tear them apart from one another and put them in the vapor phase.0084

We also see an increased water solubility because very much like water, like dissolves like; water is polar; water can hydrogen bond; so a very strong affinity between alcohols and water.0091

Another feature that we are going to be seeing is that the OH group is acidic; in other words, it can be deprotonated.0102

It can act as an acid; it can donate an H+ very easily; we will see reactions of alcohol with a wide variety of bases as well.0111

Let's take a look at some sample boiling points; these boiling points are listed in degrees C so that we can observe the effects on boiling point by various functional groups.0122

If we take a look at a molecule like pentane, completely nonpolar molecule; all it has are carbon-carbon bonds and carbon-hydrogen bonds; all very nonpolar.0137

We compare that to an ether, let's say, where we have an oxygen in here; which now makes it--we have some polar bonds; so there is a small dipole moment here; this is polar molecule.0149

But you don't see a huge difference in boiling points; these are about the same molecular weight; not a huge difference, they are essentially the same.0165

The polarity isn't having... this small amount of polarity is not having a big difference in the boiling point.0174

But instead, if you have an OH group for that oxygen, rather than just an oxygen with carbons on either sides, now look at the huge jump we get in boiling point difference.0179

Even ethanol is now a smaller molecule, yet it has over twice the boiling point; this effect here is because of hydrogen bonding.0190

Those ethanol molecules are very strongly attracted to one another; it is difficult to take them apart, put them in the vapor phase; we have to put more energy into it; that increases the boiling point.0202

When we compare ethanol to butanol, how do we explain that difference in boiling points?--they both have the OH; so they have the same polarity, same hydrogen bonding capability.0213

But now we see the trend where as you increase the molecular weight, you increase the boiling point; so all other things being equal, a larger molecule is going to have a higher boiling point.0225

Then finally I put this molecule on here; this is called ethylene glycol; he is an example of a diol with two OH groups.0235

In fact, I just noticed a typo with my structure here, excuse me; ethylene glycol has just two carbons and two OHs.0242

Notice this boiling point--197; so lots of hydrogen bonding in the case of ethylene glycol because it has two OH groups; a very big network of hydrogen bonding there.0251

That high boiling point is very useful to us; we use ethylene glycol as a component of antifreeze; it is good in that capacity because it is very hard to boil.0267

Antifreeze is th coolant that goes through your car and cools down the engine; it needs to be high boiling because it is going to get very hot.0279

We don't want it to just boil away; you can't just fill your radiator with water because the boiling point is too low.0285

We can see here a clear trend that the presence of an OH group or multiple OH groups is going to have an increase in the boiling point of those molecules.0290

When we take a look at water solubility, we describe water solubility in terms of grams per 100 milliliters of water.0302

If I had a 100mL sample of water, how much of this material could I dissolve in there?0313

If we take again a look at something like pentane, this liquid is completely immiscible with water; they form two separate layers; there is no solubility.0318

Once again, it is because this is a completely nonpolar molecule; it has no affinity for water; in fact, you can describe this as being hydrophobic.0327

Something that is nonpolar is hydrophobic--it fears water; there is nothing about it that is similar to water.0339

Remember, with solubility, we are always talking about like dissolves like; the more similar a molecule is to water, the more it has in common with it, the better the solubility.0345

For example, if you put in an ether, now you have a little bit of polarity; we have a big jump in water solubility.0360

This does have appreciable water solubility; that is because it can accept hydrogen bonds from water.0369

In other words, this oxygen can be attracted to a water molecule and form some hydrogen bonding there; it can be a hydrogen bond acceptor from water.0382

Even though this ether can't hydrogen bond with itself, if you just had a sample of ether, it can undergo hydrogen bonding with water; that increases its water solubility.0392

This is diethyl ether; because it has some water solubility, that is why whenever we use ether in a reaction work up and we are doing an extractive work up.0403

The ether layer is wet with dissolved water and it must be dried.0414

Any extractive work up that you do, where you partition your reaction components between an organic layer and an aqueous layer in a sep funnel for example.0427

If you are using ether, some water will always dissolve into the ether layer and the ether going into the water layer.0437

Part of any work up procedure is going to be taking that ether layer and drying it somehow.0446

Removing that water by using a drying agent like calcium chloride or magnesium sulfate and getting rid of that water.0450

By looking at the structure, we can see the polarity and the hydrogen bonding capability; that would explain why it does have some water solubility.0457

It is also going to be something that is very relevant to us in the laboratory.0466

But then when we move to a molecule with an OH, you might think now there must be a huge jump in water solubility because now we can now both donate and accept hydrogen bonding, a lot more interaction.0470

But when we look at these two molecules, they both have four carbons; but this has a really long carbon chain that is nonpolar.0480

We end up getting this balance, this tradeoff, between this nonpolar part and this polar part, this hydrophilic part and this hydrophobic part.0488

You can see that actually these have very similar water solubilities, not very different at all.0496

However, if you shorten up that nonpolar chain and you look at something like this--this is ethanol; it is completely miscible with water.0502

Now it is a polar enough water molecule; it has this hydrogen bonding capability; it is soluble in all proportions.0513

You can never have too much ethanol so that it separates out as a separate layer from water.0521

This is the alcohol; we are studying alcohols in this unit; we have heard of alcohols before in our day to day lives.0527

One of the alcohols is one that humans can drink without getting too sick; that is grain alcohol; this is the actual alcohol structure.0534

As an organic chemist, our definition of alcohols extend to anything containing an OH group.0544

But in our everyday lives, this is the alcohol that is referred to as alcohol that is drinkable; it is the two carbon chain called ethanol.0550

Of course, the alcoholic beverages that are out there are aqueous solutions with some alcohol in there; the proof tells you what percentage of alcohol is in there; the rest of it is just water.0560

This is something that we might already have seen some evidence for; that ethanol is in fact miscible with water.0572

Let's talk about the other physical property, the other reactivity or feature of an alcohol; that is the fact that it is acidic; it can be deprotonated.0582

We have... let's compare an alcohol OH to an amine NH and see if maybe we can explain why an OH is pretty acidic.0591

If fact, if you look at their pKa numbers, this has a pKa of about 16; that is a very low number, really easy to deprotonate an alcohol; where an amine has a pKa of about 40.0599

Let's just do this comparison as a review of things that affect acidity and basicity and see if we can explain that and understand why alcohols are so easily deprotonated.0610

As usual, we are going to want to consider the conjugate base of each of these to decide why they have such a big difference in pKa.0621

In other words, let's let methanol be an acid and get deprotonated; instead of having an OH, we will have an O-; that is the conjugate base of methanol.0629

The conjugate base of methyl amine has an NH with a minus; we remove an H+ from each; now we compare the two; we have an O- versus an N-.0643

Which of those is more stable?--we look for a difference in the stability of the conjugate bases to explain differences in acidity.0658

We know that oxygen is more electronegative than nitrogen; let's start by stating our facts; oxygen is more electronegative than nitrogen.0666

If you have a negative charge, would that prefer to be on the more electronegative atom or the less electronegative atom?0682

It prefers on the more electronegative; oxygen better handles the negative charge because it is more electronegative and O- is better than N-.0688

That means CH3O- is the more stable and therefore less reactive; if you are more stable, you are less reactive and therefore weaker conjugate base.0703

Whichever conjugate base is more stable, that makes it less reactive; that makes it the weaker conjugate base; and the weaker conjugate base has the stronger parent acid.0721

That can be our last comment; CH3O- has the stronger parent acid; is that what our pKa data tells us?0730

Sure, again pKa of 16; that is a difference of twenty-four units; that is kajillions times more acidic having a hydrogen on an oxygen compared to a hydrogen on something like a nitrogen.0741

It is because oxygen is so electronegative; if you think about the periodic table, we all know that fluorine is the most electronegative atom.0753

Oxygen right next door is the second most electronegative atom in the periodic table.0761

Oxygen, that means it is really good at pulling electron density toward itself; it is very, very happy having a negative charge on itself.0767

That means it is pretty reasonable to deprotonate an OH and convert it to an O- because oxygen doesn't mind having a negative charge.0775

If we wanted to deprotonate an OH to give an RO---these are called alkoxides because we have an alkyl group and an O-.0785

Just like hydroxide is HO-, alkoxide is RO-; how would we prepare an alkoxide if we wanted to?0797

What we would have to do is we would start with the alcohol and we would completely deprotonate it; we want to remove 100% of the H+ from all the OH containing molecules.0804

There is going to be two strategies we can have for this; one option is we can use a very strong base like sodium hydride.0816

Again when I say strong base, what do you think as sometimes a strong base?--you think hydroxide, NaOH; NaOH is not going to do it.0822

Think about it; you can't use an O- to create another O- and be able to do so in an equilibrium that is going to be heavily favored in one direction or the other.0830

This would simply set up an equilibrium with water and the alkoxide; we don't want an equilibrium; we want a one way street.0841

Rather than using NaOH, the base we are going to be using is sodium hydride; that is NaH; that is Na+ and H-; H- is called hydride.0850

This is a very effective base; we just said the alcohol can act as an acid; what happens when you react these two?0863

The base is going to grab that proton, leave the two electrons behind on the oxygen; it is going to give us an O-; it is going to form methoxide here.0871

If we use sodium hydride, we are going to get the sodium salt; this forms sodium methoxide; just a little vocabulary in there on how we are going to name our alkoxides if we have them.0883

What is the other product in this case?--we use sodium hydride as a base; we have an H-; it is combining with an H+.0896

Our other product is hydrogen; what do you know about hydrogen?--it is a gas; it is going to bubble away.0903

Tell me how does this reverse reaction look?--if you wanted to consider whether or not it is going to be going forwards or backwards.0910

Because our hydrogen gas, one of our products, is leaving, the reverse reaction becomes impossible; there is no reverse reaction.0918

That is what makes sodium hydride something that is ideal for making alkoxide; 100% of the alcohol will be converted to an alkoxide.0926

Another possibility is to use a redox reaction to do this, pretty much the same transformation.0938

But instead of using sodium hydride, we are going to use sodium metal; this is sodium zero (Na0) or sodium dot(Na·).0944

This is a metal; it has a single electron in its valence shell that makes it a very good reducing agent.0950

We have seen sodium metal as a reducing agent for alkynes, doing the dissolving metal reduction to a trans alkene.0956

If we were to react with an alcohol instead, what happens is we end up forming two equivalents of sodium methoxide and hydrogen gas.0963

We actually get the exact same products out that we did in this acid-base reaction; but this mechanism is more complicated.0974

It is not a simple proton transfer; it is an electron transfer; we call those redox reactions.0980

We look at this reaction carefully; we see that we are starting with sodium metal and we end up with Na+; that is the oxidation that is occurring.0986

In other words, sodium is releasing that electron, donating it to someone else, getting oxidized itself and causing a reduction in the hydrogen of the methanol.0994

That started out with a +1 oxidation state; but when it is in its elemental form, it is hydrogen gas; it has a 0 oxidation state... 0 oxidation number.1005

We went from a +1 to a 0; that is a reduction; in oxidation... where there is reduction, the gain electrons.1018

This mechanism is not one we are going to study; but it is more of a predict-the-product or providing the reagents.1025

The other thing, like all redox reactions, this reversible reaction is impossible; redox reactions always go to transferring the electron to give the more stable species.1033

What is great about both of these is that they are both irreversible; if we need to form an alkoxide, you have two good choices, sodium hydride or sodium metal.1045

Those are two great reagents that we can count on; sodium metal works; but sodium, lithium, potassium, those are all group 1A; those would all work to do this oxidation.1058

As you move down in the periodic table, your atoms are getting bigger and bigger and bigger; that electron is being held even further and further from the nucleus.1073

That makes it a lot more reactive; so something like potassium, which is bigger, is going to be more reactive.1081

That is useful for certain alcohols like this t-butyl alcohol; this is a weaker acid than something like ethanol or methanol; why is that?1087

Because these alkyl groups, this tertiary alcohol, this is a tertiary alcohol; those are in general weaker acids and less willing to give up a proton than a primary or secondary.1104

Because these alkyl groups are all electron donating; that is not a good thing if you want to be forming and O- here; that would be destabilized by those alkyl groups donating electron density.1117

This would be a very very very slow reaction if we use sodium metal or even lithium metal; but if you use potassium metal, that is going to be strong enough to do this redox reaction.1128

Same idea, our products are going to be an O-K+; we are going to get the alkoxide; the other product here is this H+ that we have--is going to come off as hydrogen gas.1141

When we balance our redox reaction, you see we are using two equivalents of the alcohol and two equivalents of the potassium; so we will get two equivalents of this guy.1158

This is called potassium t-butoxide... t-butoxide or tBuOK; we have seen this before as a nice strong bulky base that we have used.1165

The reason that we usually see this as the potassium salt is because that is the one that is commercially available; that is the one that is typically made.1179

That is how we typically make it--is by using potassium metal to do this redox reaction.1186

One other example of an alcohol, when we are talking about acidity, let's talk a second about phenols; a phenol is a very special alcohol; it is when we have the OH group on a benzene ring.1193

These are significantly more acidic than other alcohols; an ordinary alcohol has a pKa of something like 16 or 18 or somewhere in that range; phenol has a pKa of about 10.1203

Again eight zeros; that is tens of millions of times more acidic; in that case, this NaOH is okay; this is a weaker base--is okay.1214

You don't need to use sodium hydride; you don't need to use sodium metal; you can but you don't have to.1230

Typically we try and use the least reactive base we can because that is going to be easier to handle and maybe cheaper or a simpler reaction to run; so weaker base is okay.1236

When we do the deprotonation here, now we are using hydroxide to do our deprotonation; the products then are going to be sodium phenoxide--is what we call it when we have a pheynl O-.1253

Sodium phenoxide and water as our other product; water has a pKa of about 16 which would not be good if we were trying to deprotonate something with a very similar pKa.1265

But because this is so much more acidic, it is a million times more acidic, we know the equilibrium lies in the direction of the weaker acid-base pair.1275

In this case, the equilibrium would be very much favored in the forward direction.1285

In fact hydroxide is very effective and is suitable for deprotonating a phenoxide and essentially completely converting it to the anion, to the O-, the alkoxide.1290

How would we make an alcohol group?--where does an OH come from in a structure?--there is a few different strategies we can have for this.1306

One way of installing that OH group is by doing some kind substitution reaction.1314

In other words, if I had a leaving group on the carbon chain, I could replace that leaving group with an OH; then my resulting product would be an alcohol.1319

We have a few different substitution mechanisms; we have Sn1 mechanism; we have Sn2 mechanism; let's take a look at both of those.1327

If we wanted to do an Sn2, remember Sn2 is backside attack; we need a strong nucleophile to come in and attack and kick off the leaving group in a single step.1335

The nucleophile I would use here would be hydroxide, very strong nucleophile; it is great at doing the Sn2; the problem is that it is also a very strong base.1344

We have a competition going on between the Sn2 that it would do if it was a nucleophile or an E2 is another thing it could do as a base--it could go after a proton.1358

The way we decided between Sn2 and E2, this competition, is we considered steric hindrance knowing that the backside attack can't have any steric hindrance.1371

When would the Sn2 mechanism be reasonable for alcohol synthesis?--only when our carbon chain has very little if any steric hindrance.1381

If we have a methyl halide or if we have a primary halide, those would be best; maybe it is allylic or benzylic; that would also help support the Sn2 mechanism.1392

For example, if you had ethyl bromide and you treat him with sodium hydroxide, because this is a primary RX, a primary alkyl halide, this is our electrophile.1403

The hydroxide is our nucleophile; no problem attacking the carbon, kicking off the leaving group; this would be a great Sn2.1416

This would be a great Sn2; this would be a reasonable way to make an alcohol; we just made an alcohol by using hydroxide as our nucleophile.1426

This one is a little trickier because we have... if you look at this carbon, it is now secondary; it has some steric hindrance.1438

But because it is allylic, this is something that makes the Sn2 not so bad; that is something that would make this possible.1445

The reason Sn2 is okay here is because the π bond stabilizes the transition state of the Sn2; we have p orbitals here.1459

We form a p orbital as the nucleophile is kicking out the leaving group; that helps make the Sn2 a faster reaction; it competes better.1473

This is another case where, even though it is secondary, you would probably get as your major product the substitution product.1483

But that is a rare case--if it is benzylic meaning it is next to a benzene ring or allylic meaning it is next to a double bond.1493

Otherwise if you are a secondary alkyl halide, you are a secondary leaving group, there is enough steric hindrance where Sn2 is not going to be favorable.1500

For example, if we just have plain old cyclopentyl bromide and we try to do hydroxide, there is enough sterics here that, instead of doing the Sn2, the E2 is faster.1510

Meaning it acts as a base; it attacks the β hydrogen--that is what bases do; forms a π bond, kicks out the leaving group.1522

So the E2 elimination competes with the Sn2 anytime our nucleophile can be a strong base; because we are using hydroxide in this case, for sure that competition is going to be there.1532

E2 is favored in that case; of course, if it is tertiary, there is no chance of having the Sn2; so that is favored as well.1546

Remember if you have a phenyl or a vinyl alkyl halide, we can't do our Sn2 mechanism there because he is on an sp2 hybridized carbon.1553

A leaving group on an sp2 hybridized carbon is not what we have for backside attack; for backside attack, we need a tetrahedral carbon; we need an sp3 hybridized carbon.1564

It is a reaction of alkyl halides, not vinyl halides, not aryl halides; this would be no reaction.1573

Sn2 is one option for doing a substitution synthesizing an alcohol; we could also do an Sn1 reaction with water as our nucleophile.1581

This is a weaker nucleophile; water is not going to come and attack and do a one-step mechanism; but we can get a substitution via an Sn1 mechanism where we have a carbocation involved.1593

We call this reaction solvolysis because it is reacting with the solvent or more specifically hydrolysis since it is reacting with water.1605

What we need in this mechanism is... because we are forming a carbocation, this is going to be a reasonable option only if a favorable carbocation could be formed.1614

For example, if you have an allylic leaving group or benzylic or tertiary, those are all excellent carbocations; those would all be decent Sn1 mechanisms.1626

For example, we have this benzylic carbon with a leaving group; water is a weak nucleophile; that is why we are deciding that it cannot be the Sn2; it has to be the Sn1.1636

What mechanism is that?--what does that mean?--that means because there is no one here to attack, the leaving group just leaves on its own to give a carbocation to this electrophile.1650

We have water react as a nucleophile to an OH2; then we can deprotonate to get rid of that O+.1664

You could use the Br- here to tidy up; you might see that is sometimes; but really water, because we are doing hydrolysis, water is our solvent.1682

Water we have a lot of--that is probably going to be our best base here; we are going to get the alcohol.1689

Tell me about the stereochemistry here; what is the stereochemistry of this C-O bond?1697

Because the carbocation is planar, when water attacks, it can attack from the top face, it can attack from the bottom face.1705

Both of those are going to be equally likely; what we are going to get is a mixture of having the OH as a wedge and an OH as a dash.1711

So Sn1 is not a good situation with a chiral center unless it is okay to have a racemic mixture; then Sn1 is good.1720

But if you want stereocontrol then you need to find something like an Sn2 where you can do that backside attack; here we would get racemic mixture.1729

The other thing to keep in mind with water and trying to do an Sn1 mechanism is that, because you have a carbocation in your mechanism, it can rearrange.1741

If it is not one of these very very stable carbocations like in this case, we would get a positive charge here.1749

We might think that we could, when we do hydrolysis, we might get an OH in this position.1760

But in fact we don't because we are right next to a more substituted carbon; if the carbocation could somehow get over there, then it would be a more stable carbocation.1767

That in fact is the major product we get with rearrangement; we get this substituted product; we always have to keep that in mind.1780

Anytime we want to invoke a mechanism involving the carbocation, we have to make sure that, if there is a possibility of rearrangement, we account for that and that needs to be the product that we are expecting.1790

This is a good mechanism for you to try; see if you can do that complete Sn1 mechanism involving the carbocation rearrangement.1801

Another reaction we have seen in the past that gives an alcohol product is starting with an alkene starting material.1810

If you add water across an alkene double bond, you will end up with an alcohol product.1819

For hydration, remember we saw three different methods for adding water across a π bond.1825

If we used either H3O+ or this one, oxymercuration-reduction or oxymercuration-demercuration; this was the case where we broke the π bond; we add an H and an OH.1831

Where did hydrogen go?--both of these follow Markovnikov's rule; meaning the carbon with the hydrogen over here gets the hydrogen.1844

This last method, hydroboration-oxidation, this two-step method does the opposite regiochemistry.1858

We break the π bond; we add an H to the more substituted carbon, an OH to the less substituted carbon; we add the hydrogen to the carbon without the hydrogens; we have our CH3 there.1864

Our regiochemistry is different here; how about the stereochemistry?--is there anything we knew about the stereochemistry here with the hydroboration?1880

Do you remember that mechanism--hydroboration?--both the hydrogen and boron are added at the same time which means we have to add to the same face.1889

So another result of this is also we get syn addition; that means we need to show the H and the OH coming from the same face.1896

For example, they could be both wedges which forces this methyl group to be a dash; of course, it can come from the opposite face; it can come underneath.1903

Then we would get the enantiomer in which the H and the OH are the dashes and the methyl group is the wedge.1912

When we take a look at these products, we see that this is an alcohol product that we get; so another way that we can maybe put in an OH group on a carbon chain is to start with a double bond.1920

Then we could put the OH maybe on one carbon or the other depending on the reaction conditions we use, the reagents we use.1934

We could also do an oxidation reaction of an alkene; that would give a diol; for example, KMnO4 or if we use OsO4.1942

This was one of the several oxidations we studied for alkenes; this is the one that broke a π bond and did a dihydroxylation and added two OH groups.1951

It added them to the same face; again we would show some stereochemistry here; OH up, OH up; which then forces this methyl group down.1962

We call that syn dihydroxylation; if the it came from the bottom face, that would be the enantiomer.1973

This makes a special kind of alcohol; this makes a diol where we have two OH groups, one right next to each other.1980

If we have that special kind of target molecule, we can consider doing a dihydroxylation of an alkene.1988

Another great way to make an alcohol is to start from a ketone or an aldehyde; in other words, if I had a carbonyl on my carbon chain, that could get converted to an alcohol group.1996

The way we do this is we react it with a nucleophile of some kind because an aldehyde or a ketone... we are going to be studying these later.2009

We will see that these are electrophiles; they are electrophiles because this carbon-oxygen bond of course is polar because oxygen is electronegative.2018

It is also very polar because this has resonance; that has a resonance form with an O- and a C+.2026

As a result, the carbonyl carbon is very... remember this is called a carbonyl; I am going to be using that word a lot; that means the C-O double bond; it is a good word to know.2032

A carbonyl has the following polarity--a partial positive on the carbonyl carbon, partial negative on the carbonyl oxygen; that makes this carbonyl carbon a very good electrophile.2044

If you were to react it with a nucleophile, what happens is it attacks the carbon and it breaks this π bond and puts those electrons up onto the oxygen; we get some kind of intermediate like this.2056

If we were to then treat this with H3O+, some kind of workup procedure, at the end of the reaction, we are going to provide it with some kind of acid, some kind of proton source.2074

What will happen is we can protonate that O- with our work up and convert it to an OH group.2086

When we have a nucleophile adding into a carbonyl, the product we get has a nucleophile now connected to the carbonyl carbon and an OH group where the carbonyl oxygen used to be, the C-O double used to be.2097

Our product here is an alcohol; so this is another very good way to synthesize an alcohol and to come up with an OH as part of our final structure.2111

What nucleophile do we have available to us?--there is several we can look at; one nucleophile we have already seen is this acetylide ion.2126

He would be a very good nucleophile; we saw him doing Sn2s with alkyl halides; but he would also like to add into a carbonyl; he would be good at that.2133

But there is some other nucleophiles that we will be studying this unit that we have not yet seen.2142

This one is called a Grignard; it has an R group; that means some kind of carbon chain with a magnesium and a halide.2148

Anhydride, an example of that is something like LiAlH4; we are going to look at these new reagents and learn something more about their reactivities and what they do.2155

Here we see a C-; I can see how that is going to be a good nucleophile; but what about RMgX?--how do we get a nucleophile out of that?2167

This magnesium has a +2; the chloride, if you think about their oxidation state, the chloride has a -1.2176

That gives the alkyl group, this carbon group, the character of being a carbanion, being an R-.2185

We are going to be looking at things like this Grignard reagent as a source of R-; that would be a very good nucleophile.2193

Anhydride, as given as an example with this reagent, anhydride means we have an H with a lone pair and a negative charge; that would also be a very good nucleophile.2201

We are going to be adding maybe an alkyne group here or an R group here or a hydrogen here to be this final group in the position of where the carbonyl used to be.2212

Let's talk about this RMgX; it is an example of what is known as an organometallic reagent; it is called that because it has both an organic part and a metal.2226

M just represents some sort of metal; an R group is usually some organic component, some carbon chain; these are called organometallic reagents.2236

We are going to two examples of them; one is called RMgX; it has the formula of RMgX; one is RLi.2247

The first thing that we will do is we will talk about how to prepare them; where do they come from?--they are going to be prepared from an alkyl halide, a carbon chain with a halogen on it.2253

For example, if we were to take methyl bromide or bromomethane and react it with magnesium metal.2264

Here you are literally taking shavings of magnesium metal, magnesium turnings, tossing them into your reactions, stirring that reaction, heating it.2270

You will see your magnesium metal dissolve as it reacts; what it does is it inserts itself into the carbon-bromine bond; this is not a mechanism that we are going to worry about.2279

But we want to know what the product looks like; that is where we insert a magnesium into the carbon-bromine bond.2290

The other product here is going to be some salts; we are going to lose the bromide; we are going to make magnesium; that is not too important.2297

What we just said about this guy... he is called a Grignard reagent by the way, named after the chemist who developed the reagent; it has the general formula of RMgX.2308

This R in this case is just a methyl group; we will we see it could be just about anything.2322

The X is very often a bromide; but it also can be a chloride or a iodide; you can have another halogen there as well.2326

As we just mentioned, since the magnesium has a +2 and the bromine has a -1 as their oxidation state and the Grignard is a neutral molecule, that means the carbon has a -1 oxidation state.2334

These are not ionic compounds; you can think of this as having a combined partial +1 and this has a partial -1.2350

If you want to think of it as a partial charge rather than a full ionic charge, either one of those ways to consider it would be good.2359

Because it is a carbon with a negative charge, that means he would be a very good nucleophile; what is interesting is we just came from methyl bromide.2371

What kind of reactivity does methyl bromide have?--here we have a -1 for the bromine; we had a partial positive for this carbon.2378

We went from an electrophilic carbon, and then by attaching a metal to it, we turn it into a nucleophilic carbon.2388

That is what organometallic reagents looks like and that is how they behave--is that any carbon bearing a metal has negative charge character, anionic character.2395

The Grignard is one option; we get that when we react an alkyl halide with a magnesium metal.2404

If we did lithium metal instead, what happens is we do a halogen metal exchange; where we used to have the halogen, we now have a lithium.2409

If we consider the nature of this methyl group, this carbon, what kind of charge do you associate with a lithium?--what is the oxidation state of a lithium?2420

+1; we could say partial +1 if you would like; which again makes this carbon partial -1; this is another example of a nucleophile; all organometallic reagents are going to be nucleophilic.2429

Unfortunately he doesn't have a cool name like the Grignard; this is just called an organolithium... an organolithium reagent.2442

It has this general formula of some kind of carbon group with a lithium attached; we call those organolithiums.2451

What is great about these Grignard reagents, organolithium reagents, and organometallics in general is this R group that you are having the metal attached.2459

The R can be almost anything you can imagine; it can be an alkyl group just like we saw here; here we have a methyl; here we have a carbon chain.2468

You could attach a metal to a random sp3 hybridized carbon group; but you can also have aryl Grignards or aryl lithiums, phenyl lithiums, for example.2475

You can have a metal attached to an sp2 hybridized carbon; or vinyl, you could have it part of a double bond.2484

So huge variety in the types of carbon groups that can be attached to a metal and therefore be nucleophilic.2491

When it comes to synthesis, these organometallic reagents are really going to open up the door for us for making all sorts of interesting and new molecules.2498

Let's think about the reactions that an organometallic might undergo; we just learned how to make them; how do they behave?--what can they do?2506

One reaction that they have is that they are extremely strong bases; in other words, they can be protonated.2515

If we have this magnesium chloride on this carbon chain and we react it with an alcohol like this; we just learned how alcohols can be acidic.2522

This is an acid; this is a very strong base; we are going to get a proton transfer reaction to take place.2534

One way we can show this reacting, sometimes we just see the arrow coming from this carbon metal bond.2542

But I think an easier way to do the mechanism for these is wherever you had the metal attached, you treat that carbon as if it has a lone pair and a negative charge.2549

It doesn't really; it is not an ionic species; but that is a very helpful way to view it; it is a very helpful way to show mechanisms.2560

What we do is we will just put quotes around this species saying we don't really have this but it acts just like it; the quotes let us get away with that.2568

Now we can see this base; clearly it has a lone pair and a negative charge like other bases do; we can clearly see how we can do that proton transfer.2577

The base grabs the proton, leaves the electrons behind; the product we get is my cyclopentyl group--has been protonated; we have a proton in that position.2586

We also made some methoxide here; we deprotonated the alcohol and we protonated the Grignard in this case; what is the salt here?--this is going to be like an MgBr salt of the alkoxide.2598

Typically this is a side reaction; this is not a valuable reaction; this is something we are going to try to avoid.2617

What is very important to know is that Grignards will react with water; just like it will react with alcohol--has an acidic proton; water certainly has an acidic proton.2624

We must use very dry glassware, dry solvents; we can flame dry our glassware to get rid of any residual moisture that might be attached to it.2633

We will store our glassware in an oven to keep it super dry; then set up the reaction under argon or nitrogen, some inert atmosphere, so that it is nice and dry.2642

Our solvents, we will put some drying agents or we will freshly distill it so it is super dry.2654

Any bit of moisture in our reaction mixture or in our atmosphere has the potential of quenching our Grignard reaction, of reacting with a Grignard reagent and destroying it.2660

We are going to be very careful to do this kind of reaction in the appropriate conditions.2671

Of course when it comes to a solvent that we are using, we can't use a protic solvent like water or an alcohol because the Grignard cannot exist in those conditions.2677

Instead we need to use aprotic solvents; things like ethers, diethyl ether, THF stands for tetrahydrofuran--has this formula; some kind of ether is going to be used.2686

Again we should get used to these names of solvents because it is going to be very commonly part of your reaction conditions--is listing the solvent.2699

You don't want to worry too much about that when you see it or try to use it somehow as a reagent; it is just a solvent; all of our reactions have solvents associated with them.2707

There is one way we can make this a useful reaction; that is if we wanted to introduce a hydrogen into our structure or maybe even a deuterium.2718

Deuterium, which is what D stands for, is an isotope of hydrogen that has a neutron in here; it is H2.2733

It is so commonly used, instead of call it H2, we usually just use the letter D to represent deuterium.2743

Sometimes we want to include isotopic labels in a structure; this would be a way that we can do something like that.2750

For example, if we had a bromine here on our benzene ring and we reacted this with magnesium, that would insert a magnesium and turn this Br group into an MgBr group.2757

Then what would happen if we reacted this with D2O, deuterated water, instead of H2O?2769

We would expect that phenyl minus to protonate, deuterate in this case, add a D+; therefore you can get a deuterium installed in your structure; it can be a useful reaction.2774

But by in large, the reaction with alcohols and water just help us, guide us in our experimental conditions to make sure we avoid those so that the side reactions don't happen.2788

Where we are typically going to be using our organometallic reagents like a Grignard is as a strong nucleophile; this is where it is most useful; which means it reacts with an electrophile.2802

An electrophile like a carbonyl, not alkyl halides; we have seen those as electrophiles before; but these do not react with Grignards; we will see an example of that.2812

For example, let's say we had methyl lithium and cyclohexanone with some THF; what if we mixed all those together?2825

The methyl lithium, remember this is like having a CH3-; the lithium gives us a + charge; that means it is like we have a CH3---definitely a nucleophile.2833

I am going to put that in quotes to remind myself it is not really ionic; but it reacts kind of like that.2845

Is the carbonyl in this ketone, is the carbonyl an electrophile?--absolutely, this carbonyl carbon remember is always partially positive.2853

We will be seeing dozens of cases of that when we study carbonyls; what happens when you mix these two?2862

This is going to attack the carbonyl and break the π bond... I moved that up a little higher... going to attack the carbonyl carbon and break the π bond.2870

It doesn't matter if you show it coming from the right or left; but it is going to give me an O- where the carbonyl used to be.2882

Then after work up, step two is work up, I am going to protonate that O-; and I just synthesized what kind of functional group?--I just made an alcohol.2891

This would be a nice way to synthesize an alcohol; furthermore, notice what we just did here--because we had a carbon nucleophile and a carbon electrophile, we just made a new carbon-carbon bond.2909

Again that is unique in organic chemistry; that is a pretty special reaction to study; that is going to be extremely useful.2921

Grignards are extremely useful organolithiums for making alcohols and creating new carbon chains in the process.2928

Let's take a look at this example; we have methyl bromide; methyl bromide is definitely an electrophile because we have a carbon bearing a leaving group.2938

Phenyl magnesium bromide, what does that mean?--we have phenyl minus, put that in quotes.2947

It is just like having a phenyl ring with a lone pair and negative charge on one of the carbons, a strange looking species but that is how it behaves.2955

What would be very tempting here, what makes sense, is we can have this attack the carbon and kick off the leaving group; very tempting to do; however it does not happen.2965

That is just an exception that we really need to get used to seeing is that Grignards do not react with an alkyl halide.2980

Grignards... when I say Grignard, I mean Grignard organolithium; they are pretty much going to be used interchangeably for most of our reactions.2989

Grignards don't do Sn2s; they don't do Sn2 mechanisms; they are not there to react with an alkyl halide.2998

Remember how did you make this Grignard?--you started with the halide; we use alkyl halides or any kind of halide to prepare a Grignard.3008

That would not work at all if the Grignard, as it was being formed, started to react with the starting material.3018

They are compatible with each other; Grignards and organolithiums will not react with alkyl halides.3023

We are just going to have to try to keep that straight because it is really a reaction that is a logical one and one in fact that a lot of students make mistakes for in doing so.3028

But we just need to remember that this is the one reaction Grignards don't do; they are going to react with carbonyls but not with alkyl halides.3040

The other nucleophile we will take a look at for synthesizing alcohols is the hydride nucleophile; hydride again means we have an H with a lone pair and a negative charge.3054

Typically for the reagents we are going to be seeing, especially when it is being nucleophilic... again we are going to put that in quotes.3067

Because these are not ionic species; the hydrogen minus is not floating around on its own; it is always going to be coordinated to a metal.3073

We are going to either use lithium aluminum hydride or sodium borohydride; you could see how similar these species are.3081

That aluminum is going to take one of the hydrogens and deliver it or the boron is going to deliver a hydrogen; but it is going to react as if it was an H-.3090

Let's see an example; if we start with a ketone or an aldehyde, we start with a carbonyl and we react it with lithium aluminum hydride.3100

This actually is often abbreviated LAH for lithium aluminum hydride; in step one, if we react this with LAH, that gives us a source of H-.3107

This is one of those cases where really saying the name of the reagent and thinking about the name of the reagent is going to help us predict the product.3119

The name of the reactive species is part of the name; it is lithium aluminum hydride--right there we see that we have H-; that means we have a nucleophile.3126

We need to look around for an electrophile; this carbonyl will be our electrophile; we attack the carbon and break the π bond; carbonyls do the same thing all the time.3135

We now have a hydrogen attached and an O-; just like with the Grignard, we are going to follow this up with a reaction to get rid of the O-.3151

We are going to do step two as some kind of aqueous work up; step two, we protonate; and our product is an alcohol.3163

This is described as a reduction reaction; we could describe this as a hydride reduction because we increase the number of C-H bonds while decreasing the number of C-O bonds.3182

Ketones and aldehydes can be reduced with a hydride reagent, either lithium aluminum hydride or sodium borohydride, to give as a result an alcohol product.3203

Let's see a few examples of this; we just saw one with lithium aluminum hydride; with LAH, we need a two-step process.3217

First we react with LAH; then we react with H3O+; we do a work up.3224

NaBH4 is less reactive; this is less reactive than LAH; so we don't need to do a stepwise approach; we can actually use as our solvent a protic solvent.3229

The NaBH4 is going to be donating our H-; the methanol here is going to be donating the H+ at the end.3244

It is going to available for, instead of a separate workup step; it is going to be our final protonation step.3253

What happens, same thing as LAH; we attack the carbonyl; let's see if we could just draw a product; we have our nucleophile added to the carbonyl carbon; what used to be the carbonyl is now an OH.3260

We have that same pattern each time whether it is a Grignard or a hydride; we add the hydrogen, we add the nucleophile to the carbonyl and our carbonyl is now an OH.3275

Let's try one more; how about if we took this ketone and we react it with hydride and alcohol; we expect to reduce the carbonyl from a ketone to an alcohol; we could do the mechanism for that.3286

What happens with this alcohol then if we treat it with H2SO4 and heat?--we saw that as a dehydration reaction.3306

This is a way to remove water from an alcohol and form an alkene, form a carbon-carbon double bond.3316

Let's think about the regiochemistry; is there more than one alkene that is possible?--where would the best one be?3324

We have our leaving group here; but our carbocation remember can go anywhere it wants because those can rearrange; so what would be the best location of the double bond in our final product?3331

I think we are going to want to go here so that the double bond is now conjugated with the double bonds that are already here in the benzene ring.3347

This is the major product; it is more stable than having the double bond in this position, in the vertical position, more stable because it is conjugated with the existing π bonds.3356

That means it has resonance; we can have delocalization of these π electrons; we have p orbital, p orbital, p orbital, p orbital; we have all these p orbitals are linked.3375

We can have resonance and delocalization of that alkene; that is going to be a more stable case because it is conjugated.3384

Remember Zaitsev's rule; Zaitsev's rule tells us that the more stable alkene is always going to be our major alkene.3393

Let's look at a few more examples; how about if we wanted to do this transformation?--here we have a one carbon chain; my carbonyl is now an OH and we have a new carbon here.3405

Let's draw this in as a methyl group, as a CH3, expand our line drawing; it looks like this is a new group that is here, that has been added.3422

If we wanted to react with this carbonyl carbon, we know that this is electrophilic; this is partially positive so it is electrophilic.3431

What we need to react with that carbon is we need a methyl that is a nucleophile; how can we make a methyl be nucleophilic?3441

I think all we need to do, if we had a lone pair and a negative charge, that would make it nucleophilic; how do we get to that reactivity and that species?3454

That is exactly what a Grignard reagent does; if we have CH3MgBr, that is nucleophilic; that would react with the carbonyl; we would do that as step one.3465

As step two, after the Grignard, we would need some kind of aqueous work up, H3O+ for example; that would protonate the O- to give an alcohol product.3478

More than doing just a simple reduction of the carbonyl, we also added in a new carbon group; this is how we could use our Grignard reagent.3490

Here is another example with an organometallic; where does this alkyl lithium come from?--how do we make an organometallic?3499

What will we make this, if we ask what starting materials do we need?--we are seeing the reaction conditions here; we have added in lithium metal; what did that lithium metal react with?3509

What did we need in that position?--we needed a halogen of some kind; we need an RX to go to an alkyl lithium or Grignard reagent too.3524

You can pick any halide you want--bromide, chloride, iodide; they would all do a good example.3537

The Grignard and the hydride reagents are new reactions, reaction with a carbonyl; those are new reagents that are very useful in forming the alcohol functional group.3545

That is useful; that is a new strategy for synthesizing alcohols; we can add that to our list of other reagents where we are doing more of a functional group in our conversion.3557

Going maybe from an alkyl halide to an alcohol or from an alkene to an alcohol by doing those sort of transformations as well.3568

The next part of the alcohol unit is going to look at reactions of alcohols; once we have an OH on a structure, what manipulations can we do to it?--what transformations can it undergo?3577

Thank for coming to Educator.com; I will see you again soon.3590