Aldehydes and Ketones. Flashcards
What 2 steps are needed to turn a carboxylic acid into an aldehyde?
The carboxylic acid needs to be reduced to a primary alcohol.
The primary alcohol needs to be oxidised to an aldehyde.
What are 2 good reagents for the 2 steps of turning a carboxylic acid into an aldehyde?
Step 1: LiAlH4, dee, water.
Step 2: PCC, CH2Cl2.
What are the 2 steps of turning an aldehyde into a ketone?
Aldehyde to secondary alcohol.
Secondary alcohol to ketone.
What are the important factors of the cyanohydrin formation?
A new carbon-carbon bond is formed.
CN group can be converted to COOH and CH2NH2.
OH group can undergo functional group transformations.
What is a hemiacetal formation?
OH
I
R-C-H
I
O-RWhat is an acetal formation?
O-R
I
R-C-H
I
O-RWhat is a hemiketal formation?
OH
I
R-C-CH3
I
O-RWhat is a ketal formation?
O-R
I
R-C-CH3
I
O-RWhat is the Wittig reaction used for?
Conversion of aldehydes and ketones to alkenes.
What is the Baeyer Williger reaction used for?
The oxidation of ketones.
Ketones and aldehydes are what kind of group?
Carbonyl.
The carbonyl carbon has what hybridisation?
SP2.
In an aldehyde or a ketone what hybridisation is the oxygen?
SP2.
What are good reagents to turn a secondary alcohol into a ketone?
Chromic acid or KMnO4.
How can more complicated ketones be made?
Complicated ketones can be made by the oxidation of alcohols, which in turn can be made from reaction of a
Grignard and an aldehyde.
How are aldehydes made?
Aldehydes are made from the oxidation of primary alcohols. This oxidation needs to be done carefully to avoid over-oxidation to carboxylic acids.
What is ozonolysis?
Alkenes can be cleaved by ozone (followed by a mild reduction) to generate aldehydes and/or ketones.
What is an excellent method for the preparation of alkyl aryl ketones?
Friedal Crafts acylation.
What is dithiane?
Dithiane has relatively acidic hydrogens located between the two sulfur atoms.
How can the acidic hydrogens be removed from diathiane?
These can be removed by a
strong base.
How can dithiane anion can react with primary alkyl halides?
The dithiane anion can react as a nucleophile with primary alkyl halides, and this alkylation generates a thioacetal.
The hydrolysis of a thioacetal generates what?
The hydrolysis of a thioacetal generates an aldehyde.
How can the thioacetal can be turned to a ketone?
The thioacetal can be further deprotonated and reacted with another (different) alkyl halide to
generate a new thioacetal with two alkyl substituents. On hydrolysis, this thioacetal produces a ketone.
What is is a good route for the construction of unsymmetrical ketones?
The further hydrolysis of a thioacetal.
What reagents are very reactive towards carbonyl compounds?
Organolithium reagents.
Nitrile groups contain what compounds?
The cyano group (carbon nitrogen triple bond).
How do nucleophiles attack the nitrile group?
Since N is more electronegative than C, the triple bond is polarised toward the nitrogen, (similar to the C=O bond).
Therefore nucleophiles can attack the electrophilic carbon of the nitrile group.
How do Grignard reagents attack the nitrile group?
Grignard (or organolithium) reagents attack the nitrile to generate the magnesium (or lithium) salt of an imine.
Acid hydrolysis generates the imine, and under these acidic conditions, the imine is hydrolyzed to a ketone.
What are carboxylic acids often converted into in order to make it easier to reduce them into an aldehyde?
An acid chloride.
What will reduce acid chlorides to aldehydes?
Although strong reducing agents like LiAlH4 still reduce acid chlorides all the way to primary alcohols, milder
reducing agents like lithium aluminum tri(t
butoxy) hydride can selectively reduce acid chlorides to aldehydes.
Do acid chlorides react with Grignard (and organolithium) reagents
Yes.
What do we react an acid chloride with in order to form a ketone?
Lithium dialkylcuprate (R2-Cu-Li).
How is the lithium dialkyl cuprate produced?
The lithium dialkyl cuprate is produced by the reaction of two equivalents of the organolithium reagent with
copper (I) iodide.
2 R-Li + CuI = R2CuLi + LiI
What is the most common reaction of aldehydes and ketones?
Nucleophilic addition.
What usually happens in a nucleophilic addition reaction on an aldehyde or a ketone?
This is usually the addition of a nucleophile and a proton across the C=O double bond.
What happens when the nucleophile attacks the carbonyl group in a nucleophilic addition reaction?
As the nucleophile attacks the carbonyl group, the carbon atom changes from sp2
to sp3
The electrons of the pi bond are pushed out onto the oxygen, generating an alkoxide anion.
Protonation of this anion gives the final product.
To turn a hydride into a ketone what is used?
A strong nucleophile.
What happens to the carbonyl in acidic solution?
The carbonyl group is a weak base, and in acidic solution it can become protonated.
This makes the carbon very electrophilic (see resonance structures), and so it will react with poor nucleophiles.
The base catalysed addition reactions to carbonyl compounds result from what?
The base catalysed addition reactions to carbonyl compounds result from initial attack of a strong nucleophile, whereas the acid catalysed reactions begin with the protonation of the oxygen, followed by attack of the weaker
nucleophile.
Are aldehydes or ketones more reactive?
Aldehydes are more reactive than ketones.
Why are aldehydes more reactive than ketones?
Ketones have two alkyl substituents whereas aldehydes only have one.
Why do carbonyls undergo reactions with nucleophiles?
Carbonyl compounds undergo reaction with nucleophiles because of the polarisation of the C=O bond.
Why do ketones have their partial positive charge reduced more than aldehydes?
Alkyl groups are electron donating, and so ketones have their effective partial positive charge reduced more than
aldehydes (two alkyl substituents vs. one alkyl substituent).
Which carbon is the site that the nucleophile must approach for the reaction to occur?
The electrophilic carbon is the site that the nucleophile must approach for reaction to occur.
Why do ketones offer more steric resistance to nucleophilic attack?
In ketones the two alkyl substituents create more steric hindrance than the single substituent that aldehydes have.
What is the phosphorus stabilised anion called in the Wittig reaction?
The phosphorus stabilised anion is called an YLIDE, which is a molecule that is overall neutral, but exists as a
carbanion bound to a positively charged heteroatom.
How are phosphorus ylides produced?
Phosphorus ylides are produced from the reaction of triphenylphosphine and alkyl halides.
The wittig reaction is a good source of what?
This is a good general route to make new C=C double bonds starting from carbonyl compounds.
Alkenes.
How many steps are in a Wittig reaction?
2.
What are the 2 steps in a Wittig reaction?
This reaction starts with the nucleophilic attack of the Phosphorus on the alkyl halide. This generates an alkyl triphenylphosphonium salt. Treatment of this salt with a strong base removes a proton from the carbon bound to the phosphorus, and generates
the ylide.
The carbanionic character of the ylide makes it a very powerful nucleophile, and so it reacts rapidly with a
carbonyl group.
This produces an intermediate which has charge separation - a betaine.
Betaines are unusual since they have a negatively charged oxygen and a positively charged phosphorus.
Phosphorus and oxygen always form strong bonds, and these groups combine to generate a four membered ring - an oxaphosphetane ring. This 4 membered ring quickly collapses to generate an alkene and (very stable) triphenyl phosphine oxide.
What is the driving force of the Wittig reaction?
The elimination of Ph3P=O is the driving force of this reaction.
What is the strategy of the Wittig reaction?
By dividing a target molecule at the double bond, you can decide which of the two components should best come
from the carbonyl, and which from the ylide.
From what kind of alkyl halide does the ylide usually come from?
In general, the ylide should come from an unhindered alkyl halide since triphenyl phosphine is so bulky.
A primary one.
How does the hydration of ketones happen?
Hydration proceeds through the two classic nucleophilic addition mechanisms with water (in acid) or hydroxide (in
base) acting as the nucleophile.
In acidic conditions how does hydration of a ketone occur?
Acidic Conditions – Protonation followed by nucleophile attack.
In basic conditions how does hydration of a ketone occur?
Basic Conditions – Nucleophile attack followed by protonation
Are ketones or aldehydes more likely to form hydrates?
Aldehydes.
Why are aldehydes more likely to form hydrates?
Aldehydes are more likely to form hydrates since they have the larger partial positive charge on the carbonyl
carbon (larger charge = less stable = more reactive).
