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Hi! I’m Deboki Chakravarti and welcome to Crash Course Organic Chemistry!
You might know aldehydes and ketones for their strong, often sweet, smells.
The ketone acetone, for example, is a common ingredient in nail polish remover.
And we met the fragrant aldehydes vanillin and cinnamaldehyde in Episode 2.
But these groups are also important in biochemistry and drug treatments.
There are ketone groups in sex hormones like progesterone and testosterone.
And then there’s cortisone, an anti-inflammatory medication, or dexamethasone,
a steroid that’s been used to treat arthritis, severe allergies, COVID-19, and sometimes cancer.
It's clear that aldehydes and ketones are important,
so it's not so surprising that organic chemists spend so much time trying to make them in more energy-efficient and non-polluting ways.
Let's get started...
[Theme Music]
Quite a bit of this episode is going to summarize chemistry we’ve covered before,
but with more detail.
If you’re diving in here – or even if it’s just been awhile since you watched them –
you may want to check out some of these episodes as a refresher.
We're gonna be dealing with a lot of carbonyls, a carbon attached to an oxygen with a double bond, like this:
The central carbon in this group is called the carbonyl carbon.
When it's at the end of a chain, attached to a carbon group and a hydrogen,
we're dealing with an aldehyde.
Or when the carbonyl carbon is attached to two carbon groups, it's a ketone.
To name an aldehyde, you just take the standard name for the carbon chain and pop an “al” (for aldehydes) on the end.
For example, these aldehydes are methanal and ethanal.
BUT these substances have been used by chemists for ages –
in fact, ethanal was first discovered nearly 250 years ago.
So they have these “old” common names that you have to learn if you want to talk the talk!
Thankfully, many of them are straightforward and just end in “aldehyde” –
like acetaldehyde and formaldehyde.
Other aldehydes go by their IUPAC names.
For example, (Z)-hex-3-enal smells of freshly cut grass and leaves, and is an attractant for lots of insects.
And even though 4-oxopentanal has both a ketone and an aldehyde,
the aldehyde takes priority in nomenclature and is designated position one.
We count along the carbon chain, and stick on the prefix oxo to indicate that the ketone is on carbon 4.
Which brings us to ketones, which all have “one” on the end,
so they're relatively easy to spot.
Some rely on IUPAC names, which are not as fun to say so we'll just put them on screen.
That's video magic!
And others have common names, such as acetone and acetophenone.
Now that we've practiced naming aldehydes and ketones, we can get into making them.
We've actually seen most of these methods already, so they'll hopefully sound familiar.
For example, in episode 24 we learned that primary alcohols can be oxidized to form aldehydes.
With a weaker oxidizing agent, such as pyridinium chlorochromate,
the reaction stops at the aldehyde.
Using strong oxidizing agents like chromic acid or even chromate salts is trickier, though.
Even though the reaction goes through an aldehyde intermediate, powerful oxidizing agents can produce carboxylic acids.
To get ketones, you can oxidize secondary alcohols with strong oxidizing agents like chromium (VI).
We don’t need to be so careful picking our reactants with secondary alcohols,
because they can only oxidize to the ketone.
These oxidation reactions are often heated.
But if you’ve ever forgotten about boiling water on the stove, you may have come back to a pot with little or no liquid left in it.
Just like pasta won’t soften in a waterless pot, we can’t let all the liquid solvent evaporate from our reaction.
Most reactions require solvent and the reactants can even burn up if we keep heating without solvent.
This is where a technique called reflux comes in,
which involves heating a chemical mixture while cooling any evaporated solvent so that it condenses back into the liquid.
That way, we don't lose anything even after heating for a long time!
No forgotten stovetop accidents here.
You can remember it like acid reflux,
that burning sensation when stomach acid bubbles up towards your throat and then rejoins your digestive juices.
The thing is, even though chromium (VI) is a useful oxidizing agent, it's unpleasant stuff.
Cancer, respiratory problems, kidney disease–you name it.
So we can use different oxidizing agents to make aldehydes and ketones too.
One option is ozone, O3, which is both higher-yielding and kinder to the environment.
The reaction is called ozonolysis, which we talked about in episode 17 with redox reactions.
In this reaction, we break the double bond of an alkene and form a carbonyl on each of the carbons involved.
For example, ozonolysis with 2-methyl-2-pentene, gives us both acetone and propanal.
If we start with a triple-bonded alkyne, we can also make our way to aldehydes and ketones.
We have hydroboration, which is anti-Markovnikov addition.
In episode 18, we showed BH3 for simplicity…
but BH3 doesn’t actually exist in that form.
There are more common, even bulkier reactants we can use to get really good anti-Markovnikov selectivity,
like borane-THF, a cool double ring structure called 9-BBN, and disiamylborane.
In hydroboration, we form the less substituted enol, thanks to the borane intermediate that forms from the bulky boron reagent.
On the other hand, oxymercuration is Markovnikov addition and gives us the more substituted alcohol.
But we're not done yet!
The enols that form from each of these reactions aren’t very stable,
and they exist in equilibrium with more stable carbonyl or “keto” forms.
This balance ultimately gives us aldehydes or ketones from these reactions.
We covered this mechanism in a lot of detail in episode 18, if you want to check back!
There are a few more options that we haven't learned yet, but here's a quick preview:
acid chlorides can react with organocopper compounds to give us ketones.
And using special, bulky reducing agents on esters can produce aldehydes.
Now, part of why we care about making aldehydes and ketones is because chemists can do so many things with them!
The carbon-oxygen double bond is polar, so we have a dipole.
In fact, because the oxygen is so electronegative, we actually end up with dipolar resonance
where, in one form, the oxygen atom has a negative charge while the carbonyl carbon has a positive one.
All of this means the carbonyl carbon is a prime target for nucleophilic attack –
specifically in addition reactions, because there’s no leaving group.
We end up with an sp3 carbon and electrons pushed onto a negatively charged oxygen,
which will tend to pick up a proton when we add some water at the end of the reaction and form an OH group.
A handy nucleophile we can add to the carbonyl group is a cyanide salt, C-N-minus.
This gives us a new functional group in the molecule that we can turn into other things,
like amines and carboxylic acids.
We’ll get to know these reactions much later in the series.
Of course, if you’ve ever read any Agatha Christie, you might know that sodium cyanide is one of the most rapidly acting poisons so…
double-check your risk assessment for this one!
A less scary reaction, from a health and safety point of view, is using an acetylide anion as our nucleophile.
The acetylide attacks the carbonyl carbon to ultimately form an alcohol with an alkyne functional group –
sometimes called a propargyl alcohol.
We can also choose hydride anions as our nucleophile.
And, yes, you heard me correctly!
A neutral hydrogen atom often loses its one electron to become H-plus,
but it can also gain an electron to have a pair and form H-minus.
Examples of hydride reagents are sodium borohydride and lithium aluminum hydride.
Let’s look at the mechanism of this reduction reaction using sodium borohydride.
Boron is an electropositive atom with only three valence electrons.
It doesn’t follow the octet rule, and tends to form neutral compounds with three covalent bonds.
But it will accept electrons into its empty p-orbital and form a borohydride anion, B-H-four-minus.
When a borohydride anion attacks the carbonyl group in an aldehyde or ketone,
both the electrons in that fourth B-H bond go with the hydrogen.
So this reaction results in neutral BH3 and an alcohol anion.
This alkoxide can then react with the water in the reaction to form an alcohol –
specifically a primary alcohol if we had an aldehyde, and a secondary alcohol if we had a ketone.
Notice the double bond in the molecule doesn’t react,
and the hydride anion only attacks at the electropositive carbonyl carbon.
And since aldehydes and ketones have trigonal planar molecular geometry,
the hydride can attack one side or the other, and we get a racemic mixture at a chiral carbon.
One last reagent that deserves a mention is the Wittig reagent, AKA phosphonium ylide.
It’s named after Georg Wittig, who won the Chemistry Nobel Prize for his work in 1979.
An ylide – and yes that's spelled y-l-i-d-e because English is annoying sometimes –
is a molecule with adjacent atoms that have opposite formal charges:
specifically a negatively charged carbanion attached to an atom with a positive charge.
In the Wittig reagent, the positively charged atom is phosphorus, in a compound known as a phosphorane.
This is another example of a resonance structure.
So when we react an aldehyde or a ketone via the Wittig reaction,
the mechanism begins when the nucleophilic carbanion of the ylide attacks the electropositive carbonyl carbon
– similar to these other reactions we've been doing!
This makes a zwitterion, a molecule containing atoms with positive and negative formal charges that are not adjacent –
so it's slightly different from an ylide.
In this case, the negatively charged oxygen of our zwitterion quickly reacts with the positively charged phosphorus to form a four-membered ring species called a 1,2-oxaphosphetane.
The 1,2 in the name tells us the oxygen and phosphorus are next to each other at the 1 and 2 positions of the four-membered ring.
The small ring is super unstable, while phosphorus-oxygen double bonds are very stable,
so the oxaphosphetane collapses to form an alkene and triphenylphosphine oxide.
This process is so fast, we often represent it as one step with two arrows.
And, by the way, this reaction only works with a primary ylide –
if we had two alkyl groups on the negatively charged carbon, the reactant is too chunky and the reaction doesn’t work.
The Wittig reaction is another carbon-carbon bond-making reaction, and chemists really love those!
Specifically, we form a Z-alkene as the major product – and the reason why is...
beyond the scope of this series.
So we won't get into it here.
If we can draw resonance structures for the carbanion in our Wittig reagent,
we have a molecule called a stabilized ylide.
This reagent with different resonance structures has slightly lower reactivity and gives us the E-alkene.
This mechanism is beyond the scope of our course too.
But, basically, since this reaction occurs more slowly,
we have time to form the more stable E-alkene as the major product –
as opposed to the sterically crowded Z-alkene favored by the Wittig reagent.
So aldehydes and ketones are really useful for organic chemists,
and there's a lot of information to keep straight!
In this episode we’ve learned that:
Aldehydes and ketones contain carbonyl groups, and the carbonyl carbon is very susceptible to nucleophilic attack.
We can make them by oxidizing alcohols.
We can reduce them to form alcohols.
And they allow us to extend the carbon chain by reactions with ylides.
In the next episode, we’ll look at organometallic chemistry –
the chemistry of molecules with carbon-metal bonds
Until then, thanks for watching this episode of Crash Course Organic Chemistry.
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