Reaction of Aldehydes and ketones

Summary

The video script covers the process of adding nucleophiles to carbonyl compounds, specifically focusing on aldehydes and ketones. It explains the formation of a tetrahedral intermediate and discusses reduction reactions using lithium aluminum hydride and sodium borohydride. Additionally, the script delves into the use of Grignard reagents and organolithium compounds to form alcohols from carbonyl compounds, providing detailed examples and explanations of primary, secondary, and tertiary alcohol formations.

Takeaways

• 🧪 Nucleophiles are attracted to the partially positive carbon in carbonyl groups, leading to the formation of a tetrahedral intermediate.
• 🔍 The tetrahedral intermediate is formed when a nucleophile attacks the carbonyl group, but it requires breaking the double bond and redistributing electrons.
• ⚔️ No good leaving groups are present in the initial tetrahedral intermediate, so a proton from water or acid is picked up by the oxygen to form an alcohol.
• 🛠️ Lithium aluminum hydride (LiAlH4) is a strong reducing agent used to reduce ketones and aldehydes to alcohols, but it requires careful handling to avoid water contamination.
• 💧 The 'quenching' process involves adding water at the end of the reaction with LiAlH4 to provide the hydrogen for the alcohol formation.
• 🌱 Sodium borohydride is a milder reducing agent than LiAlH4 and can be used in an alcoholic solvent, with the alcohol providing the hydrogen for the reduction.
• 📉 The reducing power of sodium borohydride is selective, only reducing ketones and aldehydes, unlike LiAlH4 which is a more general reducing agent.
• 🔗 The reduction of aldehydes by LiAlH4 results in primary alcohols, while ketones are reduced to secondary alcohols.
• 🌿 Grignard reagents or organolithium compounds, which contain a nucleophilic carbon, can also attack carbonyl groups to form tetrahedral intermediates and eventually alcohols.
• 🔄 The final product of the reaction with Grignard reagents depends on the type of carbonyl compound: aldehydes form primary alcohols, ketones form tertiary alcohols.
• 📚 The script provides examples of how different reducing agents and nucleophiles interact with carbonyl compounds, resulting in various types of alcohols.

Q & A

What is the role of nucleophiles in reactions involving carbonyl groups?

Nucleophiles are attracted to the partially positive carbon in carbonyl groups (aldehydes or ketones). They attack the carbonyl carbon, leading to the formation of a tetrahedral intermediate. This process is crucial in various reactions such as reductions and the formation of alcohols.

Why does the carbon in the carbonyl group have a partial positive charge?

The carbon in the carbonyl group has a partial positive charge due to the electronegativity of the oxygen atom, which pulls electron density away from the carbon, making it more electrophilic and thus more susceptible to nucleophilic attack.

What happens when a nucleophile attacks a carbonyl carbon?

When a nucleophile attacks a carbonyl carbon, the double bond is broken, and the electrons are given to the oxygen atom, resulting in a tetrahedral intermediate. This intermediate is key in further reaction steps, such as the formation of alcohols.

What is the tetrahedral intermediate and why is it significant?

The tetrahedral intermediate is a reaction product formed when a nucleophile attacks a carbonyl carbon, leading to a four-coordinate carbon. It is significant because it represents a key step in many carbonyl reactions, and its properties determine the subsequent reaction pathways.

How does the presence of good leaving groups affect the tetrahedral intermediate?

If the tetrahedral intermediate has good leaving groups, it can undergo further reactions such as elimination to form new products. However, in the context of the script, the intermediate formed does not have good leaving groups, leading to the formation of an alcohol.

What is the purpose of adding water or acid to the tetrahedral intermediate?

Adding water or acid to the tetrahedral intermediate allows the oxygen to pick up a proton, which is crucial for the formation of alcohols. This step is part of the workup or quenching process in many carbonyl reactions.

What are lithium aluminum hydride and sodium borohydride, and how do they differ in their reducing abilities?

Lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are both reducing agents used in organic chemistry. LiAlH4 is a very strong reducing agent capable of reducing aldehydes, ketones, and even some esters, while NaBH4 is a milder reducing agent typically used for aldehydes and ketones, making it a selective reducer.

Why is lithium aluminum hydride considered a strong reducing agent?

Lithium aluminum hydride is considered a strong reducing agent because it can donate hydride ions (H-) effectively, reducing various functional groups such as carbonyls to alcohols. Its strong reducing power also requires careful handling to avoid unwanted side reactions.

How does sodium borohydride reduce carbonyl compounds?

Sodium borohydride reduces carbonyl compounds by donating a hydride ion to the carbonyl carbon, forming a tetrahedral intermediate. The subsequent addition of water or acid leads to the protonation of the oxygen, resulting in the formation of an alcohol.

What is the difference between the reduction of aldehydes and ketones by lithium aluminum hydride?

Lithium aluminum hydride reduces aldehydes to primary alcohols and ketones to secondary alcohols. This is because the reduction involves the addition of a hydride ion and a proton to the carbonyl carbon, leading to different products depending on the initial carbonyl compound.

How do Grignard reagents and organolithium compounds react with carbonyl compounds?

Grignard reagents (RMgX) and organolithium compounds (RLi) are nucleophilic and can attack the carbonyl carbon, forming a tetrahedral intermediate. The reaction typically results in the formation of alcohols, with the nature of the alcohol depending on the carbonyl compound (e.g., aldehydes form primary alcohols, ketones form tertiary alcohols).

Outlines

00:00

🧪 Nucleophiles and Carbonyl Reduction Reactions

This paragraph discusses the fundamental concepts of nucleophilic addition to carbonyl groups, which are electrophilic due to the partial positive charge on the carbon atom. The process involves the formation of a tetrahedral intermediate when a nucleophile attacks the carbonyl carbon. The intermediate is characterized by the presence of a negatively charged oxygen atom, which, in the absence of good leaving groups, will pick up a proton from a water molecule or an acid to form an alcohol. The paragraph also introduces two reducing agents, lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4), which are used to reduce aldehydes and ketones to primary and secondary alcohols, respectively. The mechanism of these reductions is simplified to illustrate the transfer of hydride ions and protons from water to form the alcohol products.

05:04

🌿 Grignard and Organolithium Reagents in Carbonyl Reactions

The second paragraph delves into the use of Grignard reagents (RMgX) and organolithium reagents, which are nucleophilic carbons that can attack carbonyl groups. The reaction proceeds through the formation of a tetrahedral intermediate, which, upon protonation, yields alcohols. The type of alcohol produced depends on the type of carbonyl compound being reduced: aldehydes yield primary alcohols, while ketones yield tertiary alcohols. The paragraph provides examples of these reactions, including the reduction of formaldehyde to a primary alcohol using phenylmagnesium chloride and the reduction of a ketone to a tertiary alcohol using methyllithium. The summary emphasizes the role of the counter ion, typically magnesium, in the intermediate and the importance of the proton source in the final step of the reaction.

Keywords

💡Nucleophile

A nucleophile is a chemical species that donates an electron pair to form a chemical bond in reaction. In the context of the video, nucleophiles attack the partially positive carbon in a carbonyl group, leading to the formation of a tetrahedral intermediate.

💡Carbonyl

A carbonyl group consists of a carbon atom double-bonded to an oxygen atom (C=O). It is a key functional group in aldehydes and ketones, making the carbon atom electrophilic and susceptible to nucleophilic attack, as discussed in the video.

💡Tetrahedral Intermediate

A tetrahedral intermediate is a transient structure formed during the nucleophilic attack on a carbonyl group, where the carbon atom becomes sp3 hybridized and bonded to four groups. This intermediate is central to the mechanisms described in the video.

💡Lithium Aluminum Hydride (LiAlH4)

LiAlH4 is a strong reducing agent used to reduce carbonyl compounds to alcohols. In the video, it is explained how LiAlH4 adds a hydride ion to the carbonyl carbon, forming a tetrahedral intermediate that is eventually protonated to yield an alcohol.

💡Sodium Borohydride (NaBH4)

NaBH4 is a milder reducing agent compared to LiAlH4, used specifically for reducing ketones and aldehydes to alcohols. The video explains that NaBH4 can be used in alcoholic solvents, simplifying the reaction process.

💡Grignard Reagent

A Grignard reagent consists of a carbon bonded to magnesium and is highly nucleophilic. The video describes how Grignard reagents attack carbonyl groups, forming tetrahedral intermediates that are protonated to yield alcohols.

💡Reduction

Reduction refers to the gain of electrons or hydrogen by a molecule. The video covers the reduction of carbonyl compounds to alcohols using LiAlH4 and NaBH4, highlighting the importance of controlling reaction conditions to achieve desired products.

💡Electrophile

An electrophile is a species that accepts an electron pair. In the video, the carbonyl carbon acts as an electrophile due to its partial positive charge, making it the target for nucleophilic attack.

💡Protonation

Protonation is the addition of a proton (H+) to a molecule. The video describes how the oxygen in the tetrahedral intermediate picks up a proton from water or an acid to form an alcohol.

💡Secondary Alcohol

A secondary alcohol has the hydroxyl group (-OH) attached to a carbon atom that is bonded to two other carbon atoms. The video explains how reduction of ketones or Grignard reagent reactions with aldehydes can produce secondary alcohols.

💡Primary Alcohol

A primary alcohol has the hydroxyl group (-OH) attached to a carbon atom that is bonded to only one other carbon atom. The video describes how the reduction of aldehydes with LiAlH4 or NaBH4 leads to the formation of primary alcohols.

💡Tertiary Alcohol

A tertiary alcohol has the hydroxyl group (-OH) attached to a carbon atom that is bonded to three other carbon atoms. In the video, tertiary alcohols are formed by the reaction of Grignard reagents or organolithium compounds with ketones.

Highlights

Introduction of nucleophiles to carbonyl compounds, such as aldehydes and ketones, and the formation of a tetrahedral intermediate.

Explanation of the electrophilic nature of the carbonyl carbon and its attraction to nucleophiles.

Mechanism of bond breaking and electron transfer to oxygen in the formation of a tetrahedral intermediate.

Identification of the tetrahedral intermediate as a common step in carbonyl reactions.

Discussion on the lack of good leaving groups in the intermediate, leading to the formation of an alcohol.

Introduction of lithium aluminum hydride as a strong reducing agent for carbonyl compounds.

Procedure for using lithium aluminum hydride, including the importance of excluding water.

Simplified mechanism of lithium aluminum hydride reducing carbonyls to alcohols.

Introduction of sodium borohydride as a selective reducing agent for ketones and aldehydes.

Differences in reactivity between lithium aluminum hydride and sodium borohydride.

Examples of carbonyl reduction to alcohols using both reducing agents.

Explanation of the addition of Grignard reagents or organolithium to carbonyls.

Formation of secondary, primary, and tertiary alcohols depending on the type of carbonyl attacked by Grignard reagents.

Use of phenylmagnesium chloride in the reaction with formaldehyde to produce a primary alcohol.

Demonstration of the reaction of methyllithium with a ketone to yield a tertiary alcohol.

Emphasis on the nucleophilic carbon in Grignard reagents and its role in attacking the carbonyl group.

Summary of the outcomes of attacking aldehydes and ketones with different reagents to form various alcohols.

Transcripts

alright first before we actually do

anything we're adding nucleophiles to

the carbonyl so we're gonna have a

carbonyl whether it's an aldehyde or a

ketone makes really no difference but

what happens is that the carbon of the

carbonyl is partial positive so it

attracts nucleophiles and when the

nucleophile attacks of course you cannot

have a 5 on that carbon so you need to

break the double bond and when you break

a bond you give the electrons to the

most electronegative element in this

case it's going to be the oxygen at the

top and you're going to now get a

nucleophile attached to a tetrahedral

carbon and at the very top I have an

oxygen then right now it's negative this

intermediate right here is the

intermediate that we arrive at anytime

we attack any carbonyl so we're going to

call it the tetrahedral intermediate and

when you get a tetrahedral intermediate

you check to see if you have good

leaving groups and this one doesn't

happen to have any good leaving groups

carbons this are 2 CH 3 s right here are

going to be bad leaving group and the

nucleophile that we just added we're

going to assume that it's also a bad

leaving group so things you don't have

any bad leaving groups in solution then

the oxygen is gonna pick up a proton

from water or from maybe hydronium if

you add a little bit of acid so it picks

up a proton and we end up with an

alcohol so that's what we're what we're

gonna see in this reactions when we

attack the carbonyl of the ketones and

the aldehydes the first reaction we're

gonna do is a reduction with lithium

aluminum hydride and lithium aluminum

hydride has four hydrates and it's a

very strong reducing agent when you

actually use lithium aluminum hydride

you have to keep water out of it so the

first step you just add the

I'm aluminum hydride in an ether solvent

and then at the very end of the reaction

you're gonna do what I like to call the

quenching people like to call workup but

we're going to be adding water and

that's where the hydrogen's on the

oxygen is going to come from so the

hydride is going to be a hydrogen that

has two electrons and a simplified

mechanism of course would be a hydride

attacking the carbonyl forming the

tetrahedral intermediate and if you form

the tetrahedral intermediate in this

particular case you would have two

carbons or maybe a carbon and a hydrogen

and we just added the hydride this is

the hydride from the lithium aluminum

hydride and then nothing can leave so

the next step would be when we add the

water at the very end the oxygen picks

up a proton from the water so this

hydrogen right here on the oxygen came

from the water this hydrogen came from

the lithium aluminum hydride now this is

a very simplified mechanism that doesn't

take into account what the aluminum or

the liam are doing but we also have a

second hydride reagent not as strong as

lithium aluminum hydride but quite

useful nonetheless it's sodium

borohydride we have seen it before in

3331 but now it's a much easier reducing

agent to use I don't need to have two

different steps and I don't need to have

syringes for this reaction sodium

borohydride can be used in an alcohol

and we see exactly the same thing the

hydride is going to be attached to the

carbon and this hydrogen right here came

from the alcohol

so whatever alcohol you're doing it's

gonna up you're using sorry it's going

to provide the hydrogen that goes on the

oxygen so we have two reducing agents

lithium aluminum hydride in

probably strong reducing agent sodium

borohydride is only good for ketones and

aldehydes so in that sense it's a

selectively reducing agent I have some

examples right here just to make sure

that we understand that lithium aluminum

hydride and sodium borohydride react

with carbonyls so I have a double bond

right here on the Left I am NOT going to

be touching the double bond it's going

to remain in place lithium aluminum

hydride can only reduce the ketone this

is a ketone so I reduce a ketone to a

secondary alcohol this is another ketone

I'm using sodium borohydride notice that

I still have an alcohol this one is

ethanol but all I'm gonna be doing is

reducing the carbonyl I'm not gonna

touch anything else in the molecule the

one at the bottom is an aldehyde and

notice that I have an alcohol on the

Left lithium aluminum hydride can only

reduce the carbonyl so it will take that

out of the hide to the primary alcohol

so aldehydes are reduced to primary

alcohols ketones are reduced to

secondary alcohols and we have two

examples of that all right this is one

of my favorite reactions it's the

addition of a green yard or an

organolithium if you have it to a

carbonyl and the green yard is a carbon

that's actually negatively charged and

it's basically a salt of magnesium so I

have two negative charges and I have my

magnesium in in the middle between them

but what's important again is that a

carbon that's attached to the magnesium

that's a nucleophilic carbon it has a

negative charge so it will attack the

carbonyl it will form a tetrahedral

intermediate and this tetrahedral

intermediate actually

shows that for every negative charge

there has to be a counter ion so the

magnesium is going to be next to the

negative oxygen there are no good

leaving groups in my tetrahedral

intermediate so the oxygen picks up a

proton from the acid at the end of the

reaction and I get in this particular

case I get a secondary alcohol anytime

you you attack an aldehyde with a

grignard you're gonna make a secondary

alcohol if you attack formaldehyde

that's gonna produce a primary alcohol

if you attack all the Heights secondary

alcohols and if you attack a ketone

you're gonna get a tertiary alcohol out

of that reaction all right let's do a

couple of problems in here let's attack

formaldehyde formaldehyde is your most

simple aldehyde and you can attack it

with green yards for organolithium so

I'm going to use phenol magnesium

chloride and again the carbon that's

attached to the magnesium this is a

nucleophilic carbon so it's going to

attack the carbon eel form a tetrahedral

intermediate and the tetrahedral

intermediate I have two hydrogen's

attached to it to the carbons and I just

attached a benzene ring to it it doesn't

have any good leaving groups it has two

hydrogen's terrible living groups and a

phenyl group you just came in let's not

kick it out so when you quench the

reaction when you're working it up with

water or maybe hydronium the oxygen is

going to pick up the hydrogen from the

water

and that's gonna give you your in this

case primary alcohol if you take an a a

ketone let's take two fentanyl and let's

use an organolithium for variety so we

are gonna use methyl lithium

so you add methyl lithium to it and then

you go ahead and you add water to the

reaction but the methyl is going to

attack the carbonyl form your

tetrahedral intermediate I just added a

second methyl so now I have two methyls

my oxygen is negative no good leaving

groups carbons are not leaving groups so

when I add the water that's when the

hydrogen picks up the the hydrogen right

there the oxygen picks up the hydrogen

and this one right here is a tertiary

alcohol so whenever I attack a ketone

I'm going to add a third carbon group to

the carbonyl and I get a tertiary

alcohol out of that reaction