Organic Chemistry - Synthesis of Aldehydes and Ketones

Summary

This chemistry lesson delves into the synthesis of ketones and aldehydes from various molecular structures, including primary alcohols, secondary alcohols, alkenes, benzene rings, alkynes, carboxylic acids, nitriles, and esters. It highlights the importance of selecting appropriate reagents and conditions to achieve the desired products, such as using mild oxidizing agents like PCC or DMP for primary alcohols, and the Gattermann-Koch reaction for benzene rings. The script also touches on ozonolysis for alkenes and the reduction of nitriles and esters to form aldehydes, offering a comprehensive guide to organic synthesis techniques.

Takeaways

• 🧪 The lecture discusses the synthesis of ketones and aldehydes from various organic molecules using specific reagents.
• 🍾 Primary alcohols can be oxidized to aldehydes using mild oxidizing agents like PCC, DMSO, or DMP to avoid over-oxidation to carboxylic acids.
• 🔍 To convert an aldehyde to a ketone, a two-step process involving a Grignard reagent (RMgX) and subsequent oxidation is described.
• ⚗️ Secondary alcohols can be directly oxidized to ketones using either mild or strong oxidizing agents, with caution to avoid over-oxidation to carboxylic acids.
• 🔬 Ozonolysis, involving ozone and DMSO, is a method to cleave alkenes to yield ketones and formaldehyde, a special type of aldehyde.
• 🏵 The Friedel-Crafts acylation is a technique to introduce a ketone group onto a benzene ring using acyl chloride and aluminum chloride as a catalyst.
• 🌐 Gattermann-Koch synthesis is an alternative method for creating an aldehyde on a benzene ring using carbon monoxide, hydrochloric acid, and a catalyst under high pressure.
• 🌊 Adding mercury ion, sulfuric acid, and water to an alkyne can result in the formation of an enol, which readily tautomerizes to a ketone through Markovnikov addition.
• 🛠 To create an aldehyde from a carboxylic acid, one can first convert it to an acid chloride and then reduce it using a mild reducing agent like lithium tri-tert-butoxyaluminum hydride.
• 🍾 The Grenald reaction is used to convert nitriles to ketones by adding a Grignard reagent followed by an acid to hydrolyze the intermediate imine.
• 🧴 DIBAL-H (Diisobutyl aluminum hydride) is a reagent that can be used to reduce esters to aldehydes in a one-step process.

Q & A

What is the primary goal of the video script?

The primary goal of the video script is to cover the synthesis of ketones and aldehydes from various types of molecules using appropriate reagents.

Why can't a primary alcohol be directly converted into a ketone?

A primary alcohol cannot be directly converted into a ketone because oxidation of a primary alcohol typically leads to an aldehyde or a carboxylic acid, not a ketone.

What is a mild oxidizing agent that can be used to convert a primary alcohol into an aldehyde?

Mild oxidizing agents such as PCC (Pyridinium Chlorochromate), DMSO (Dimethyl Sulfoxide), or DMP (Dess-Martin Periodinane) can be used to convert a primary alcohol into an aldehyde.

What is the process of converting an aldehyde to a ketone, as described in the script?

The process involves reacting the aldehyde with a Grignard reagent (RMgX), followed by the addition of an acid to remove the magnesium ion, and then re-oxidizing the intermediate to form the ketone.

How can a secondary alcohol be converted into a ketone?

A secondary alcohol can be converted into a ketone using either mild reagents like PCC or strong oxidizing agents like mercuric acid (Hg(OAc)2), provided that the alcohol is on a secondary carbon.

What is ozonolysis and how is it used to synthesize ketones and aldehydes from alkenes?

Ozonolysis is a reaction where ozone (O3) is added to an alkene in the presence of DMSO (Dimethyl Sulfoxide). This cleaves the double bond in the alkene, replacing the bonds with oxygen to form a ketone and an aldehyde, specifically formaldehyde in some cases.

What is Friedel-Crafts acylation and how is it used to create a ketone on a benzene ring?

Friedel-Crafts acylation is a reaction where an acyl chloride (RCOCl) is added to a benzene ring in the presence of a catalyst like aluminum chloride (AlCl3). This results in the formation of a ketone on the benzene ring.

How can an alkyne be converted into a ketone or an aldehyde?

An alkyne can be converted into a ketone by adding a mercury ion (Hg2+) and sulfuric acid (H2SO4), which leads to the formation of an enol intermediate that tautomerizes to a ketone. For an aldehyde, anti-Markovnikov addition using diisobutylaluminum hydride (DIBAL-H) followed by oxidation with hydrogen peroxide and sodium hydroxide (NaOH) is used.

What is the process of converting a carboxylic acid into a ketone or an aldehyde?

A carboxylic acid can be converted into a ketone by adding two equivalents of an alkyl group connected to lithium (RLi). To form an aldehyde, the carboxylic acid is first converted into an acid chloride using thionyl chloride (SOCl2), and then reduced using lithium tri-tert-butoxyaluminum hydride (LiAl(OtBu)3H).

How can a nitrile be converted into a ketone or an aldehyde?

A nitrile can be converted into a ketone by adding a Grignard reagent (RMgX) and then acidifying to hydrolyze the intermediate imine. To form an aldehyde, diisobutylaluminum hydride (DIBAL-H) is used to reduce the nitrile directly.

What is the role of diisobutyl aluminum hydride (DIBAL-H) in the synthesis of aldehydes?

Diisobutyl aluminum hydride (DIBAL-H) is used as a reducing agent to convert esters and acid chlorides into aldehydes by selectively reducing the carbonyl group.

Outlines

00:00

🧪 Synthesis of Ketones and Aldehydes from Alcohols

This paragraph discusses the conversion of primary and secondary alcohols into ketones and aldehydes using various reagents. Primary alcohols can be oxidized to aldehydes using mild oxidants such as PCC, DMSO, or DMP. To form a ketone from an aldehyde, a two-step process involving Grignard reagent and re-oxidation with mild reagents or mercuric acid is described. The situation is reversed for secondary alcohols, which can be directly oxidized to ketones using either mild or strong oxidizing agents, with caution advised to avoid over-oxidation to carboxylic acids.

05:02

🌟 Organic Reactions with Alkenes and Benzene Rings

The paragraph covers the synthesis of ketones and aldehydes from alkenes and benzene rings. Ozonolysis is presented as a method to cleave double bonds in alkenes, yielding ketones and formaldehyde, a special type of aldehyde. For benzene rings, Friedel-Crafts acylation is introduced to attach an acyl group, resulting in ketones. An alternative method for synthesizing aldehydes on benzene rings, the Gattermann-Koch synthesis, is also discussed, involving carbon monoxide, hydrochloric acid, and a catalyst under high pressure.

10:02

🔍 Advanced Synthesis Techniques for Alkynes and Carboxylic Acids

This section delves into the synthesis of ketones and aldehydes from alkynes and carboxylic acids. For alkynes, a method involving mercury ion, sulfuric acid, and water is described, which leads to the formation of an enol and subsequently a ketone. Anti-Markovnikov addition is also discussed, using a different set of reagents to achieve the desired aldehyde. Carboxylic acids can be converted to ketones through the addition of organolithium compounds, while a more complex process involving acid chloride and a specific reducing agent is required to synthesize aldehydes from carboxylic acids.

🛠️ Nitrile and Ester Transformations to Ketones and Aldehydes

The final paragraph addresses the synthesis of ketones and aldehydes from nitriles and esters. Nitriles can be converted to ketones through a Grignard reaction and to aldehydes using diisobutyl aluminum hydride. For esters, while there is no direct method to create a ketone, an aldehyde can be synthesized using the same reducing agent as for nitriles. The paragraph concludes with a note on the importance of understanding the mechanisms behind these synthetic processes.

Keywords

💡Ketones

Ketones are organic compounds containing a carbonyl group (C=O) bonded to two carbon atoms. In the context of the video, the synthesis of ketones from various starting materials such as primary alcohols, secondary alcohols, and alkenes is discussed. The video mentions the use of mild oxidizing agents like PCC or DMP to prevent over-oxidation to carboxylic acids.

💡Aldehydes

Aldehydes are organic compounds with a carbonyl group (C=O) bonded to a hydrogen atom and a carbon atom. They are intermediates in the oxidation of primary alcohols, as mentioned in the script. The video discusses the use of mild oxidizing agents to convert primary alcohols to aldehydes without further oxidation to carboxylic acids.

💡Primary Alcohol

A primary alcohol is an alcohol in which the hydroxyl (-OH) group is attached to a primary carbon, which is bonded to two hydrogen atoms. The video explains that primary alcohols can be oxidized to aldehydes using mild oxidizing agents, but cannot be directly converted to ketones without additional steps.

💡Secondary Alcohol

A secondary alcohol is an alcohol where the hydroxyl (-OH) group is attached to a secondary carbon, which is bonded to one hydrogen atom and two carbon atoms. The video mentions that secondary alcohols can be oxidized to ketones using mild or strong oxidizing agents, such as mercuric acid.

💡Ozonolysis

Ozonolysis is a reaction where an alkene is cleaved by ozone (O3), typically in the presence of a solvent like DMSO, to form carbonyl compounds. The video describes how ozonolysis can be used to convert alkenes into a mixture of ketones and aldehydes, including formaldehyde.

💡Fields Craft Acylation

Friedel-Crafts acylation is a reaction where an acyl chloride reacts with a benzene ring in the presence of a Lewis acid catalyst, such as aluminum chloride, to form a ketone. The video explains this process as a method for introducing a ketone group onto a benzene ring.

💡Gattermann-Koch Synthesis

The Gattermann-Koch synthesis is a method for preparing aromatic aldehydes by reacting benzene with carbon monoxide and hydrochloric acid in the presence of a catalyst like aluminum chloride and copper chloride. The video mentions this as a way to create an aldehyde on a benzene ring.

💡Alkynes

Alkynes are hydrocarbons with a carbon-carbon triple bond (C≡C). The video discusses the conversion of alkynes to ketones and aldehydes through reactions involving mercury ions and sulfuric acid, or by using anti-Markovnikov addition with diisobutyl aluminum hydride.

💡Carboxylic Acid

A carboxylic acid is an organic compound containing a carboxyl group (-COOH). The video explains that carboxylic acids can be converted to ketones by adding two alkyl groups using organolithium reagents, and to aldehydes by first converting to an acid chloride and then using lithium tri-tert-butoxide aluminum hydride.

💡Nitriles

Nitriles are organic compounds containing a nitrile group (-CN). The video discusses the conversion of nitriles to ketones through the Grignard reaction and to aldehydes using diisobutyl aluminum hydride, illustrating the versatility of nitriles in organic synthesis.

💡Esters

Esters are organic compounds derived from acids and alcohols, containing a carbonyl group bonded to an oxygen atom of an alkyl group. The video mentions that esters can be converted to aldehydes using diisobutyl aluminum hydride, highlighting the role of esters in the synthesis of carbonyl compounds.

Highlights

Introduction to the synthesis of ketones and aldehydes from various molecules using appropriate reagents.

Primary alcohols can be oxidized to aldehydes using mild oxidizing agents like PCC, DMSO, or DMP.

Conversion of aldehydes to ketones through the Green Art reaction with Grignard reagents and acid.

Secondary alcohols can be directly oxidized to ketones using mild or strong oxidizing agents.

Ozonolysis is a method for converting alkenes into ketones and formaldehyde through the cleavage of double bonds.

Field's craft acylation is a technique for synthesizing ketones on a benzene ring using acyl chloride and aluminum chloride.

Gattinger-Koch synthesis is an alternative method for creating aldehydes on a benzene ring using carbon monoxide and hydrochloric acid under high pressure.

Alkynes can be converted to ketones through the addition of mercury ions, sulfuric acid, and water, resulting in an enol that tautomerizes to a ketone.

Anti-Markovnikov addition for alkynes involves the use of DIBAL-H and subsequent oxidation with hydrogen peroxide and sodium hydroxide to form aldehydes.

Carboxylic acids can be transformed into ketones by adding two alkyl groups using organolithium reagents.

Conversion of carboxylic acids to aldehydes involves creating an acid chloride and then reducing it with lithium tri-tert-butoxide aluminum hydride.

Nitriles can be converted to ketones through a Grenard reaction, forming an imine intermediate that hydrolyzes to a ketone.

Diisobutyl aluminum hydride (DIBAL-H) is a reagent used to convert nitriles to aldehydes.

Esters can be indirectly converted to ketones, but there is no direct method; aldehydes can be formed using DIBAL-H.

In the case of cyclic esters, DIBAL-H results in an aldehyde with an alcohol group due to the ring structure.

Emphasis on the importance of understanding the mechanisms for the practical applications of these synthetic methods.

Transcripts

hello and welcome back to organic

chemistry today we will be covering

synthesis of ketones and aldehydes we

will look at many different molecules

and try to convert them into ketones and

aldehydes

using the appropriate reagents we will

not be covering the mechanism so i

advise you to look at the mechanisms on

your own later

as for now let's start off with our

first molecule over here

here we have our primary interest is our

primary alcohol on this alkane

and what we want to do with this alcohol

is try to convert to either a ketone or

an aldehyde

now since it's a primary alcohol can we

change it into a ketone

well sadly no if we try to oxidize this

alcohol it'll either turn to an aldehyde

or a carboxylic acid and so to change it

into an aldehyde

we have to oxidize it now if you provide

too strong of an oxidizing agent you

just create a carboxylic acid

and so we don't want to do that we want

to have a mild oxidizing agent

and our possible reagents is either pcc

either dmso or we can use dmp

and we can use either of these they will

work just fine in creating an aldehyde

and our product would look something

like this

now if we really wanted that ketone what

we could do

is actually react this aldehyde with

step one a green art where r over here

represents any alkyl group

magnesium and x represents a halite then

we can add an acid in order to

remove the magnesium from the oxygen ion

that would have a negative charge on it

and then we can

re-oxidize it again and we can use

either

either of these mild reagents or we can

use something

like hg so4 and

h2 so4 and if you recognize what this is

this is a combination to create mercuric

acid and that will create

this ketone right here and r is the r

group that we added from the

greenhouse reagent so that is one way to

create a ketone

from primary alcohol however notice that

you are adding

extra alkyl groups to it in order to

perform this

now if we have a secondary alcohol the

situation flips

can we create a ketone from this well

yes we can and we can use either

our mild reagents or we can use a strong

reagent

and we can just use mercuric acid is one

and it's a real this is considered a

strong oxidizing agent

so be careful when using this make sure

that it is a secondary carbon or

secondary alcohol that we have over here

and that will make sure that it only

turns into ketone if you use mercuric

acid

on something like a primary alcohol

you'll just create a carboxylic acid

so over here we have our ketone

now can we change this into an aldehyde

well sadly we can't because this is a

secondary

carbon in order to have an aldehyde we

have to have a primary carbon and that's

it

now let's look at our next molecule

over here we have an alkene

now what can we do with an alkene well

there is one method

in order to create either ketone or an

aldehyde but that would only depend on

the substituents that we have over here

on one side of this alkene we have two

carbon bonds and the other side we have

hydrogens and that's it

and so what we could do is do something

called ozonolysis

and if we create if we add ozone along

with dmso

which is dimethyl sulfoxide what that

happens is it cleaves that middle bond

in between the two carbons and basically

replaces

the bonds that the carbon was missing

with an oxygen

and so we get a ketone over here

plus an aldehyde

and this is actually a special type of

an aldehyde an aldehyde with no carbon

bonds at all is called formaldehyde it's

actually pretty unstable

but this oils analysis basically cleaves

that middle bond

and it makes sure that even if you have

only

one carbon bond or actually no carbon

bonds at all you will not get a

carboxylic acid you will simply just get

a ketone or an aldehyde it's a mild form

of alkene cleavage and this is one

this is one way you can get ketones and

aldehydes from double bonds

now let's look at a benzene if we have a

benzene ring

can we create a ketone aldehyde well yes

we can now how do we get

create a ketone one way to do this

is called uh fields craft acylation

and what we do is provide this benzene

with an acyl chloride with that or

acid chloride is something like say now

what this looks like

is you have our double a carbonyl group

connected to a chloride instead of an

uh a hot oxygen and a hydrogen

and then we have any r group which is

can be any alkyl group

and then if you add this with aluminum

chloride which will be our catalyst

what ends up creating what ends up

happening is we add

this acyl group onto the benzene and it

gets rid of that chloride and we just

get this product right here

and if you notice this is a ketone

now what if we wanted an aldehyde say

this r group that we wanted over here

would be a hydrogen how would we do that

well there's a different method we can't

just use

um an acyl chloride that looks like this

that's not right here this is extremely

unstable

this type of acyl chloride is not stable

enough for us to use and so we have to

use a different method

and what we do is use these following

regions we use carbon monoxide

we use hydrochloric acid and this is

under high pressure

then we have aluminum chloride and

we also have copper chloride

the carbon monoxide and hydrochloric

acid is what will create that

specific molecule i just showed you

that's pretty unstable and the aluminum

chloride and copper chloride will help

um catalyze this reaction and what we'll

just create

is this benzene ring with instead

of an r group we have a hydrogen

and so this is called the gattering

constant synthesis

and so this is one way of creating an

aldehyde on a benzene ring

now let's look at our next example over

here we have an

alkyne how do we create ketones and

aldehydes from an alkyne well

to create a ketone we can do something

where we add a mercury ion

we add sulfuric acid and we add some

water

and when you do that what this does is

it adds basically

an oh group to one of the carbons and

hydrogen to the other carbon and these

are the carbons containing that

alkyne and what this creates is this

transition state where we have something

called an enol which is basically

an alcohol group on a double bond

and this is extremely unstable so just

instantly total rises to some

to just a ketone and that's it now

notice that this is markovnikov addition

the hydrogen is being added to the

carbon that has the more hydrogens

and the alcohol group

is being added to the carbon that's more

substituted

now if we wanted to do it the other way

around what would end up happening is ha

if we wanted this double carbonyl group

to be on the edge

it would be the anti-markovnikov

addition and so to do that we have to do

something else our first step would be

to add

siamo or diasymal borohydride or boring

and then our second step would be to add

hydrogen peroxide and sodium hydroxide

naoh and this does the same process

where we get that transition state for

the enol but instead

the enol has the alcohol on the carbon

with the most amount of hydrogens the

less substituted one and this just

creates

our preferred aldehyde that we wanted to

look for

and so that's an alkyne and that's how

you can create either a ketone or

aldehyde notice that this is markovnikov

addition in the first step

the other one is anti-markovnikov now

for our second one we have a carboxylic

acid how do we change a carboxylic acid

into a ketone or an aldehyde well our

first step

to change it to a ketone would be to add

two alkyl groups connected

or two equivalences of an alkyl group

connected to a lithium

this is basically called an

organolithium where r over here

represents any alkyl group

and if we add this essentially

we have something that's very similar to

a greener

reaction but not quite and we get this

product right here it's a ketone and the

r group is connected

to that carbonyl now if we wanted

to do an aldehyde if we want to create

an aldehyde is that possible well

it is well actually not directly though

if we want to create an aldehyde we

cannot

simply just go straight to it but there

is something else that we know

we can change this carboxylic acid into

an acyl chloride or an acid chloride

if we have thymic chloride added to it

when is this happening is that we have

the carboxylic acid essentially but the

oh group is replaced with a chlorine

now this right here can actually be more

useful

in creating an aldehyde because since we

can't go to an aldehyde replace from a

carboxylic acid

what we can do here is change this into

either a ketone or an aldehyde

now if we want to create a ketone this

is just another way of creating ketones

from a carboxylic acid an

indirect way we can have

an r group over here and two of them

actually

connected to a copper and lithium and

this is called lithium

cuberate this is what that is and when

we add that we simply just create

this ketone right here in our group and

this looks exactly the same as if we

just added

two equivalences of an organolithium

it's just an indirect way

and if we want to create an aldehyde in

this situation it is possible

and to do so we have this reagent right

here and if you notice let me write it

out because it has a pretty long name

but i'll show you what's kind of

interesting about it

now notice how this is similar to

lithium aluminum hydride

but instead of having four hydrogens you

only have one hydrogen and you have this

group right here

now the name of this now changes to

lithium

triter butoxide aluminum hydride this is

the full name of it

and just a milder version of a lithium

aluminum hydride lithium

anhydride would be way too strong of a

reducing agent

and so it would just take it straight to

an alcohol and so this is a more milder

version

and this will give us our aldehyde

now notice this is useful on the acid

chloride because acid core it's a lot

more easy to reduce than a carboxylic

acid

and so this is your method in creating

an aldehyde from a carboxylic acid you

create an acid chloride

and then you change that to an aldehyde

now let's look at our next group

if we have a nitrile how do we create a

ketone

or an aldehyde well to create a ketone

what we do is we do a grenard reaction

we simply add

the green art reagent and then

afterwards we just add the acid

and then after that third and then

that's it

now remember how we had that primary

alcohol where when we changed the

aldehyde

after we changed the aldehyde we created

a ketone by doing the greenhouse

reaction

and our third step was oxidizing it one

more one

once more well in this scenario we don't

when we add that reynard reagent what

ends up happening is we create an imine

which is nitrogen with two bonds with a

double bond

and this acid will hydrolyze it and just

change it into a ketone

and so we just get this product right

here

and notice i label these carbons as a

and b these are the same carbons

a and b and so the carbon that used to

have a triple bond to a nitrogen now has

a double bond to an oxygen

now if we want to create an aldehyde

from this one way to do this

is by using this region right here let

me write it up first and then we'll say

what its name is

now this right here is called di

isobutyl aluminum hydride or

a shorter way to write it is this

double h or diacetyl aluminum hydride

and this essentially creates an aldehyde

of this nitrile

that looks just like this and our

carbons a and b are look right here

so that's what we can do with nitrile

it's pretty straightforward

now our next group that we're going to

look at is an ester can we create a

ketone or an aldehyde from ester

well if we wanted to create a ketone we

actually can

there's no direct way to do it there are

indirect methods like we had when we had

our primary alcohol

where we can simply create an aldehyde

and then create a ketone afterwards

now the first question is though can we

actually create an aldehyde

well we can if we want to create an

aldehyde we use the same reagent we just

covered a second ago

which is diisobutyl aluminum hydride

and this will essentially create this

aldehyde right here

where the group that existed

right here is now no longer attached

to our carbonyl group now say if we had

a ring

say for example we had some group like

this where we have

a carbonyl group like that if we end up

using

diisobutyl aluminum hydride

this would give us this product right

here we have our aldehyde obviously

and we have our carbons but then this

oxygen that we had over here

is no longer gone it's just an oh group

at this point so

it's not like this group is completely

gone if we have a ring

you realize that this is a connected

structure

and the oxygen oxygen that was and part

of

the ester group is now an alcohol

and so that is all for today make sure

you do cover

the mechanisms for all of these these

are really useful

but that is all for synthesis have a

great day