Carboxylic Acids: Crash Course Organic Chemistry #30

Summary

This Crash Course Organic Chemistry episode explores carboxylic acids, detailing their role in everyday smells like feet and vomit, and their importance in organic synthesis. Deboki Chakravarti explains how carboxylic acids can be synthesized from alcohols or aldehydes and their conversion into useful compounds like esters and acid chlorides. The video also touches on the historical discovery and synthesis of penicillin, highlighting its significance in medicine.

Takeaways

• 🧫 Carboxylic acids are responsible for unpleasant smells such as those from feet, underarms, vomit, and goats.
• 🦠 Bacteria play a role in producing carboxylic acids like isovaleric acid in feet and malodorous molecules in underarms.
• 🍫 Butyric acid, which causes the smell of vomit, is also found in rancid butter and is used in some foods to add flavor.
• 🥨 Some carboxylic acids like caproic, caprylic, and capric acids are associated with the smell of goats and are found in their milk.
• 🧪 Carboxylic acids can be synthesized from alcohols or aldehydes through oxidation or from Grignard reagents and carbon dioxide.
• 🔍 Carboxylic acids are named based on the longest carbon chain and suffix '-oic acid', with examples like ethanoic and propanoic acid.
• 📚 Carboxylic acids are the highest priority in naming compounds, taking precedence over other functional groups like ketones.
• ⚗️ Carboxylic acids are weak acids, partially ionizing in water to form a hydrogen ion and a carboxylate ion.
• 🔥 They have high boiling points due to intermolecular hydrogen bonding and are liquids at room temperature if they have fewer than ten carbons.
• 🧪 Shorter-chain carboxylic acids can form water-soluble salts when reacted with sodium or potassium hydroxide.
• 🌸 Carboxylic acids can be converted into pleasant-smelling esters through Fischer Esterification, a reaction used in perfumes.
• 💊 Acid chlorides, derived from carboxylic acids, are important in organic chemistry and were used in the synthesis of penicillin, the first mass-produced antibiotic.

Q & A

What is the connection between the smells of feet, underarms, vomit, and goats?

The connection is carboxylic acids. The smell of feet is partly due to isovaleric acid, underarms due to malodorous molecules including carboxylic acids, vomit due to butyric acid, and goats due to caproic, caprylic, and capric acids.

How is butyric acid related to the smell of vomit and cheese?

Butyric acid is produced by bacteria in our gut and causes the stench of vomit. It is also found in rancid butter and is a key part of the aroma of parmesan cheese.

Why might we want to work with carboxylic acids despite their unpleasant smells?

We can make nice-smelling compounds using carboxylic acids as a starting point and convert them into other useful compounds for organic synthesis.

How can we make a carboxylic acid?

We can make carboxylic acids by oxidizing alcohols or aldehydes with chromic acid or another suitable oxidizing agent, or by reacting Grignard reagents with carbon dioxide.

What is the systematic naming convention for carboxylic acids?

The naming convention involves looking at the structure, using the number of carbons in the longest chain, and adding the suffix '-oic acid'.

Why do carboxylic acids have high boiling points?

Carboxylic acids have high boiling points due to the formation of intermolecular hydrogen bonds between two acid molecules or an acid and water.

How can carboxylic acids be converted into water-soluble salts?

Shorter-chain carboxylic acids can be reacted with sodium or potassium hydroxide to form water-soluble salts.

What is the issue with using nucleophiles in reactions involving carboxylic acids?

Most basic nucleophiles tend to deprotonate carboxylic acids instead of attacking the carbonyl carbon.

How is Fischer Esterification used to convert carboxylic acids into pleasant-smelling esters?

Fischer Esterification is an acid-catalyzed reaction of a carboxylic acid with an alcohol to form an ester, which often has a pleasant smell.

What is the significance of acid chlorides in organic chemistry?

Acid chlorides, along with other carboxylic acid derivatives, are involved in many useful reactions in organic chemistry, including the synthesis of the first mass-produced antibiotic, penicillin.

How did the discovery of penicillin happen?

The microbiologist Alexander Fleming discovered penicillin when he noticed that a fungus had contaminated one of his petri dishes and killed the bacteria present.

What was the breakthrough that made mass production of penicillin possible?

Mary Hunt discovered a fungus, Penicillium chrysogenum, on a spoiled cantaloupe melon that produced 200 times more penicillin than the fungus Fleming found, enabling mass production.

Outlines

00:00

🧪 Carboxylic Acids: Smelly Beginnings

The paragraph introduces the concept of carboxylic acids by relating them to everyday smells such as feet, underarms, vomit, and goats. It explains how these smells are due to the presence of carboxylic acids like isovaleric acid, malodorous molecules from bacteria, butyric acid, and others. The paragraph also mentions that despite their unpleasant smells, carboxylic acids can be used to create pleasant-smelling compounds and are important in organic synthesis. The video then delves into the chemistry of carboxylic acids, explaining how they can be synthesized from alcohols or aldehydes through oxidation, or from Grignard reagents and carbon dioxide. It covers the naming conventions for carboxylic acids, their acidic properties, and how they behave in water due to their weak acidic nature. The paragraph concludes by discussing the reactions of carboxylic acids, including their conversion to salts with bases and their tendency to form hydrogen bonds, which contribute to their high boiling points.

05:00

🔬 Esterification and Acid Chlorides

This paragraph focuses on the transformation of carboxylic acids into other functional groups, specifically esters and acid chlorides. It describes Fischer Esterification, an acid-catalyzed reaction between a carboxylic acid and an alcohol to form an ester, which are often associated with pleasant smells like flowers and fruits. The paragraph details the mechanism of esterification, including the role of the acid catalyst and the reversible nature of the reaction. It also discusses how removing water, a product of the reaction, can push the equilibrium forward to increase ester yield. The paragraph then addresses the challenge of nucleophiles deprotonating carboxylic acids and explains how converting carboxylic acids to acid chlorides can overcome this issue. The conversion process using phosphorus pentachloride is outlined, highlighting the formation of a stable double bond as a key step. The paragraph concludes with a historical account of the discovery and development of penicillin, an important carboxylic acid used in medicine, and its synthesis from a mold found on a spoiled cantaloupe by Mary Hunt.

10:03

📚 Organic Chemistry of Penicillin

The final paragraph provides a preview of upcoming topics in the series, focusing on the organic chemistry involved in the synthesis of penicillin. It mentions the discovery of different types of penicillin, such as penicillin F and G, and the work of Dr. John C. Sheehan in synthesizing penicillin V from scratch. The paragraph outlines the educational journey that will unfold, including the exploration of how penicillin kills bacteria and the various reactions involved in its synthesis. It also encourages viewers to support Crash Course on Patreon to help keep the educational content free and accessible.

Keywords

💡Carboxylic Acids

Carboxylic acids are organic compounds that contain a carboxyl group (-COOH). They are characterized by an acidic hydrogen atom that can be ionized in water to form a carboxylate ion and a hydrogen ion. In the video, carboxylic acids are introduced as the compounds responsible for the unpleasant smells of feet, underarms, and vomit. They are also mentioned as key components in the production of rancid butter and parmesan cheese, showing their dual role in both negative and positive olfactory experiences.

💡Isovaleric Acid

Isovaleric acid is a specific type of carboxylic acid with a five-carbon chain. It is produced by bacteria on foot skin and contributes to the smell of feet. The video uses isovaleric acid as an example to illustrate how bacteria can produce carboxylic acids that have distinct and sometimes unpleasant odors.

💡Malodorous Molecules

Malodorous molecules are those that have an unpleasant or foul smell. The video discusses how bacteria can convert odorless underarm secretions into malodorous molecules, including carboxylic acids, which are then responsible for body odor.

💡Butyric Acid

Butyric acid is a carboxylic acid with a four-carbon chain. It is responsible for the smell of vomit and is also found in rancid butter and parmesan cheese. The video uses butyric acid to demonstrate how a single compound can have different associations, from the unpleasant smell of vomit to the desirable flavor in certain foods.

💡Caproic Acid

Caproic acid, along with caprylic and capric acids, are carboxylic acids named after the Latin word for goats due to their presence in goat's milk and contributing to its distinct smell. These acids are used in the video to show how carboxylic acids can be associated with both natural and synthetic flavors.

💡Organic Synthesis

Organic synthesis refers to the construction of organic compounds from simpler precursors through chemical reactions. The video mentions that carboxylic acids can be used as starting materials to create pleasant-smelling compounds, highlighting their utility in organic synthesis.

💡Grignard Reagents

Grignard reagents are organometallic compounds used in organic synthesis to form new carbon-carbon bonds. The video explains that reacting a Grignard reagent with carbon dioxide can produce a carboxylic acid, demonstrating the versatility of these reagents in organic chemistry.

💡Fischer Esterification

Fischer Esterification is an acid-catalyzed reaction between a carboxylic acid and an alcohol to form an ester. The video describes this process as a way to convert carboxylic acids into pleasant-smelling esters, which are often found in perfumes and are key to the fragrances of flowers and fruits.

💡Acid Chlorides

Acid chlorides are reactive derivatives of carboxylic acids where the hydroxyl group is replaced by a chlorine atom. The video explains that acid chlorides can be formed using phosphorus pentachloride, and they are important in organic chemistry for their reactivity in forming new compounds, such as in the synthesis of penicillin.

💡Decarboxylation

Decarboxylation is a chemical reaction where a carboxylic acid loses its carboxyl group as carbon dioxide, often resulting in the formation of an alkene. The video mentions decarboxylation as a way to remove the carboxylic acid group from a molecule, which can be useful in certain synthetic pathways.

💡Penicillin

Penicillin is a group of antibiotics derived from Penicillium fungi and is one of the first mass-produced antibiotics. The video discusses the historical discovery of penicillin by Alexander Fleming and its subsequent development into a widely used medication. It also mentions the role of organic chemistry in the synthesis of different types of penicillin.

Highlights

Carboxylic acids are responsible for unpleasant smells like feet, underarms, vomit, and goats.

Isovaleric acid, produced by bacteria on foot skin, contributes to foot odor.

Bacteria convert underarm secretions into malodorous carboxylic acids.

Butyric acid causes the stench of vomit and is found in rancid butter and parmesan cheese.

Butyric acid is added to some American milk chocolate for a tangy flavor.

Caproic, caprylic, and capric acids, named after goats, contribute to the goaty smell.

Carboxylic acids can be used to create pleasant-smelling compounds and are useful in organic synthesis.

Carboxylic acids are made by oxidizing alcohols or aldehydes, or from Grignard reagents.

Carboxylic acids are named based on the longest carbon chain and suffix '-oic acid'.

Ethanoic acid, found in vinegar, is commonly known as acetic acid.

Carboxylic acids are weak acids with properties influenced by the -COOH group.

Carboxylic acids form intermolecular hydrogen bonds, leading to high boiling points.

Short-chain carboxylic acids form water-soluble salts when reacted with sodium or potassium hydroxide.

Carboxylic acids can be reduced back to alcohols using lithium aluminum hydride.

Decarboxylation is the process of removing the carboxylic acid group by heating.

Fischer Esterification converts carboxylic acids into esters, which are used in perfumes.

Esters are formed through an acid-catalyzed reaction involving a series of nucleophilic attacks and proton transfers.

Acid chlorides are formed by reacting carboxylic acids with phosphorus pentachloride.

Acid chlorides are important in organic chemistry and were used in the synthesis of penicillin.

The discovery of penicillin was accidental, and its development involved many scientists and breakthroughs.

Mary Hunt's discovery of a moldy cantaloupe led to the mass production of penicillin.

Penicillin is a family of compounds with different potencies and methods of administration.

The synthesis of penicillin V by Dr. John C. Sheehan was a significant achievement in organic chemistry.

Transcripts

You can review content from Crash Course Organic Chemistry with the Crash Course App,

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Hi!

I’m Deboki Chakravarti and welcome to Crash Course Organic Chemistry!

What’s the connection between the smells of feet, underarms, vomit and... goats?

Carboxylic acids.

The smell of feet is partly due to the presence of isovaleric acid,

which is produced by the bacteria living on your foot skin.

Bacteria also turn odorless underarm secretions, such as amino acids, into malodorous molecules,

which include carboxylic acids.

The stench of vomit is caused by butyric acid, produced by bacteria in our gut.

Butyric acid is also found in rancid butter (that's where its name comes from),

and it's a key part of the aroma of parmesan cheese.

It's also added to some brands of American milk chocolate to give a ‘tangy’ flavor.

Yes, I basically just said that puke-flavored chocolate exists,

and now it's going to haunt me forever.

And three carboxylic acids take their common names from the Latin word for goats:

caproic acid, caprylic acid and capric acid.

Found in small amounts in goats’ milk, and produced in larger amounts as the milk ages,

they contribute to that goaty stench.

Given these awful smells, you might wonder why we’d want to work with carboxylic acids at all.

But we can actually make some pretty nice-smelling compounds using carboxylic acids as a starting point,

and we can convert them into other useful compounds for organic synthesis.

[Theme Music]

Let’s kick off by reminding ourselves how we can make a carboxylic acid.

For example, we can oxidize alcohols or aldehydes with chromic acid or another suitable oxidizing agent.

We can also make them from Grignard reagents.

Reacting the Grignard reagent with carbon dioxide gives a carboxylate salt,

which can be protonated with acid to give a carboxylic acid.

We can get a more specific name for any carboxylic acid by looking at its structure,

using the number of carbons in the longest chain and adding the suffix '-oic acid.'

A carboxylic acid with two carbons is ethanoic acid,

a carboxylic acid with three carbons is propanoic acid, and so on.

So in the previous reaction, we made 2-methylpropanoic acid.

When it comes to naming compounds,

carboxylic acids have the highest priority among carbon-containing functional groups.

So, say we have a molecule containing both a ketone and a carboxylic acid group,

the carboxylic acid forms the base name,

we assign the carboxylic acid carbon the number 1,

and the ketone gets a prefix.

An example of this is 4-oxopentanoic acid, also known as levulinic acid,

a compound used as a starting point for the synthesis of some pharmaceuticals and industrial chemicals.

This compound, like many we've mentioned, has a systematic IUPAC name and a common name.

Like how ethanoic acid, the acid in vinegar, has the common name acetic acid.

And as you’d expect from all these names, carboxylic acids are acidic.

If they have... oh about 4 carbons or fewer, they can dissolve in water.

The hydrogen in the -COOH part of the structure will be partially ionized,

forming a hydrogen ion and leaving behind a carboxylate ion.

Specifically, carboxylic acids are weak acids,

because they don’t release hydrogen ions into solution as much as a strong acid like hydrochloric acid does.

The -COOH part of these structures allows intermolecular hydrogen bonds to form between two acid molecules,

or an acid and water.

So carboxylic acids have high boiling points,

and all of those with fewer than ten carbons in a straight chain are liquids at room temperature.

We can react shorter-chain carboxylic acids with sodium or potassium hydroxide to form water-soluble salts too.

The hydroxide ion grabs the proton from the carboxylic acid group,

forming water and leaving a carboxylate ion behind.

In fact, even weak bases like ammonia can pull off a hydrogen ion and form a carboxylate ion.

As we know from earlier episodes, both hydroxide ions and ammonia are good nucleophiles –

which actually highlights an issue that can come up in the lab.

Most basic nucleophiles tend to deprotonate carboxylic acids!

So, unlike aldehydes and ketones, we can’t just use a nucleophile to add groups to the carbonyl carbon here.

We’ll have to get a little more creative with our chemistry.

Before we tackle that problem, though, let’s look at some of the other reactions carboxylic acids can undergo.

If we want to get back to an alcohol from a carboxylic acid,

we can use a reducing agent such as lithium aluminum hydride.

This is a powerful reducing agent, so after the reaction,

we add a proton source VERY carefully to react any unreacted lithium aluminum hydride and give our alcohol a proton back.

Another way to remove the carboxylic acid group has a very straightforward name: decarboxylation.

This involves heating the carboxylic acid, and replaces the carboxylic acid group with a hydrogen atom.

So if we heat the heck out of almost any carboxylic acid, we can get it to decarboxylate.

And this reaction happens really easily when you heat compounds that have a carbonyl group one carbon away from the carboxylic acid group.

However, sometimes you don't want to get rid of the carboxylic acid group entirely,

so there are also reactions to convert it into other functional groups.

In fact, we can freshen up some of those bad-smells by converting carboxylic acids into pleasant-smelling esters by Fischer Esterification.

This is an acid-catalyzed reaction of a carboxylic acid with an alcohol to form an ester.

Esters are often key parts of the smells of flowers and fruits, and are commonly used in perfumes.

Fischer Esterification can also be classified as a type of condensation reaction,

because the two reactants kick out a water molecule when they combine.

To get more specific, first, the carbonyl oxygen grabs a proton from the acid catalyst.

Next, the lone pair on the alcohol oxygen acts as a nucleophile,

attacking the carbonyl carbon.

Another alcohol molecule swoops in,

deprotonating the hydrogen from the oxonium ion in that one-two punch of attack-then-deprotonation we’re getting familiar with.

The OH group on the carboxylic acid finds a hydrogen ion from the acid catalyst,

which makes water, a good leaving group!

With a little help from the neighboring oxygen atom in the molecule, the water leaves.

And finally, another alcohol molecule from solution grabs the extra hydrogen on the carbonyl oxygen,

giving us an ester as our final product.

All of these steps are reversible, so the product isn’t formed super efficiently.

But never fear, le Chatlier is here!

We have the power to adjust the equilibrium of chemical reactions.

Specifically, if we remove one of the products along the way, we can push the reaction forward.

In a lab, removing the water as it forms using a special piece of equipment increases our yield of the ester.

Speaking of tricky lab situations, how about that problem we mentioned earlier –

the issue of nucleophiles deprotonating carboxylic acids instead of attacking the carbonyl carbon?

To solve this problem, we can convert the carboxylic acid to a more reactive functional group:

an acid chloride, using either phosphorus pentachloride or thionyl chloride.

And let's just go with phosphorus pentachloride as our example.

The reaction starts when the lone pair of electrons on the carbonyl oxygen forms a bond with the phosphorus atom –

with a little help from the other oxygen in the molecule –

and kicks a chloride ion off of phosphorous pentachloride.

The chloride ion we kicked out in the previous step swoops back and attacks the carbonyl carbon.

Then, a very stable double bond forms between the phosphorus and this oxygen.

This double bond is a big part of why this reaction happens this way,

just like we saw in the Wittig reaction in Episode 28!

Specifically, with the formation of this bond, we lose chloride as a leaving group,

which pulls off the nearby hydrogen to reform our carbon-oxygen double bond.

This gives us the acid chloride, with hydrochloric acid and phosphorous oxychloride as the other products.

Acid chlorides, along with other carboxylic acid derivatives, are involved in many useful reactions in organic chemistry.

In fact, acid chlorides were used in the synthesis of the first mass-produced antibiotic:

penicillin, which is an important carboxylic acid in medicine.

Throughout the rest of the Crash Course Organic Chemistry series,

we’ll apply many of the reactions we learn to explore the chemical synthesis of penicillin.

But penicillin was an accidental discovery –

not a medicine dreamed up by humans.

And the story of this compound is much more complicated than just one scientist making a lucky discovery in 1928.

Let’s head to the Thought Bubble to learn more.

Returning to his lab after a summer holiday,

the microbiologist Alexander Fleming discovered that one of his petri dishes of bacteria had been unintentionally left out on a bench.

Spores of a fungus had blown into the lab and contaminated the dish,

and the temperatures had been perfect to encourage both the fungus and the bacteria to grow.

But wherever the fungus had grown, the bacteria were absent.

Fleming realized that the fungus made a chemical compound that killed the bacteria.

The fungus was from the genus Penicillium, so Fleming named this mysterious compound ‘penicillin'.

But, despite many attempts, he was unable to isolate it.

At Oxford University, a biochemist named Ernst Chain found Fleming’s publication on penicillin,

and suggested to his supervisor, Howard Florey, that they try to isolate it.

Penicillin was eventually isolated and purified in 1941.

That same year, penicillin was first used to treat an infection in a police officer.

It was later hailed as a wonder drug during World War II for its ability to combat infections in wounded troops.

But there was still a huge unsolved problem in the early 1940s:

the low yield of penicillin from the mold.

But in 1943, a bacteriologist named Mary Hunt made a breakthrough

while working at the US Department of Agriculture's Northern Regional Research Laboratory in Peoria, Illinois!

Nicknamed ‘Moldy Mary,’ she hunted down moldy fruits and vegetables to test for the presence of penicillin in the lab.

A spoiled cantalope melon had a fungus, Penicillium chrysogenum,

that produced 200 times more penicillin than the fungus that Fleming stumbled upon, making mass production possible!

Thanks, Thought Bubble!

Since Mary Hunt's cantalope discovery, we've learned a lot more –

like, the penicillins are actually a family of compounds,

with different potencies and ways to administer the medicine.

The penicillin that Fleming discovered and Chain and Florey isolated

(and even won a Nobel Prize for in 1945) was penicillin F.

The stuff that was produced from Hunt’s spoiled cantalope melon was penicillin G.

In later episodes, we’ll be looking at Dr. John C. Sheehan’s synthesis of penicillin V,

which is the first penicillin to be synthesized from scratch instead of extracted from a fungus.

This synthesis takes many steps.

So over the course of the series, we’ll fill out what we're calling our Mold Medicine Map,

and we'll discover how penicillin kills bacteria – all using organic chemistry!

In this episode, we:

Reviewed the reactions that form carboxylic acids

Recapped nomenclature and explained the properties of carboxylic acids

Reacted carboxylic acids to form salts,

and Formed esters and acid chlorides from carboxylic acids

In the next episode, we’ll start looking at how we can use carboxylic acid derivatives to get to other functional groups,

and see where some of these reactions fit into our synthesis of penicillin.

Until then, thanks for watching this episode of Crash Course Organic Chemistry.

If you want to help keep all Crash Course free for everybody, forever, you can join our community on Patreon.