Ketones, aldehydes and COOH derivatives Flashcards
How could you form a cyanohydrin?
React an aldehyde or ketone with
1) NaCN (CN-)
2) HCN
This is a reversible reaction
When forming a cyanohydrin, when does equilibrium favour the ketone?
When the R groups are large
This is because they are closer together in the cyanohydrin which leads to more steric strain
Why is LiAlH4 a stronger reducing agent than NaBH4?
The AlH bonds are more polar and so therefore the hydrogens are more partially negative
How could you form a primary alcohol?
By reduction of an aldehyde
The reducing reagent can be NaBH4 or LiAlH4 (H-)
Then perform acid workup (H+)
How could you form a secondary alcohol?
By reduction of a ketone.
The reducing agent can be NaBH4 or LiAlH4.
Then use an acid workup (H+)
Why are tertiary alcohols not easily oxidised?
This is because a C-C bond would need to be broken
What is jones oxidation?
Using the reagents CrO3 and H+ to oxidise carbonyls
How could you form an aldehyde?
By oxidation of a primary alcohol
The reducing agent can be CrO3/H+, KMnO4 or Na2CrO7.
Distill or use milder oxidation to isolate aldehyde from further oxidation to carboxylic acid.
Orange to green
How could you form a ketone?
By oxidation of a secondary alcohol
The reducing agent can be CrO3/H+, KMnO4 or Na2CrO7.
Orange to green
What is an organometallic?
This is a compound that contains an organic group bonded to a metal R-M
If the C-M bond is covalent or ionic depends on the structure of the R group and the electro positivity of the metal
How would you prepare a Grignard reagent?
R-MgX 1) React R-X with Mg 2) Conditions are a: -dry diethyl ether solvent (Need anhydrous conditions as GR reacts with water) -under an atmosphere of N2 gas (GR react with oxygen) -GR add R groups to compounds
What forms when you react a Grignard reagent with water?
An alkane is formed and a salt of HO- +MgX
How can you form a primary alcohol from a Grignard reagent?
React with methanal and do acid workup
See mechanism
Apart from reduction, how else can you form a secondary alcohol?
React an aldehyde with a Grignard reagent (R-MgX)
1) use acid workup and water
Byproduct is HOMgX
How could you form a tertiary alcohol?
React a ketone with a Grignard reagent (R-MgX)
1) use acid workup and water
Byproduct is HOMgX
What is the Wittig reaction?
Aldehydes and ketones react with phosphonium glides (R2C=PPh3) to form alkenes.
Byproduct is Ph3P=O
In a wittig reaction, what determines whether an E or Z alkene is formed?
Whether an E or Z alkene is formed selectively depends on the nature of the R group on the carbon atom if the phoshphonium ylide
How could you form a hydrate? (2 OH groups)
Water adds reversibly to aldehydes and ketones to form hydrates.
Rate can be increased by reacting with OH- to make carbonyl a stronger nucleophile or with H+ to make it a stronger electrophile.
- then reacts with water
- OH and H are reformed
When forming a hydrate what determines the position of equilibrium?
The stability of the carbonyl compound relative to the hydrate
Groups are closer together in the hydrate, so when R groups are large, the hydrate is destabilised relative to the carbonyl
How could you form an hemiacetal and an acetal
Alcohols add reversibly to aldehydes and ketones to form hemiacetals
1) H+ catalyst
2) alcohol
Then react with a second equivalent of alcohol to form a acetal
1) H+ catalyst
2) alcohol
-water is a leaving group
How could you ensure more acetal is produced?
Removing water from the reaction mixture forces the reaction to produce more acetal (as it is reversible) in an attempt to restore equilibrium
- anhydrous conditions- MgSO4
How can you reform the carbonyl from the acetal
Add water
How can you ensure a certain carbonyl group will react over another?
React with an acetal as it can act as a protecting group during the reaction.
The functional group can then be restored afterwards.
Carbonyl - H2O= acetal
Acetal +H2O = carbonyl
How could you form a thioacetal?
Thiols (RSH) add reversibly to aldehydes and ketones to form hemiacetals
1) H+ catalyst
2) thiol
Then react with a second equivalent of alcohol to form a acetal
1) H+ catalyst
2) thiol
-water is a leaving group
How could you prepare a cyclic thioacetal?
1) react an aldehyde or a ketone with an acid catalyst
2) react with ethane 1,2 dithiol
- water is a leaving group
What is the Mozingo reduction?
Thioacetals can be converted into alkanes by reaction with Raney Nickel (catalyst containing Ni) and hydrogen gas
What is the Clemmensen reduction?
Aldehydes and ketones can be converted into alkanes using Zn/Hg/HCl
How could you form an imine?
A primary amine adds reversibly to a to an aldehyde or a ketone to form an imine.
1) amine adds to form hemiaminal
2) add an acid catalyst, water leaves to form the imine
Water is a byproduct so it’s a condensation reaction
Why is an acid catalyst needed to make an imine from a primary amine?
Amines are strong nucleophiles so they do not need an acid catalyst
Acid catalyst is need to convert hemiaminal into the imine
For the fastest rate pH of 4.5 needs to be maintained
Why does pH4.5 need to be maintained for imine formation?
If the pH is lower than 4.5 then the amine becomes protonated and RNH3+ cannot act as a nucleophile
If the pH is above 4.5 there is not enough H+ to protonate the OH group into the hemiaminal
What is the Strecker synthesis?
Protonated imines can react with a cyanide ion to make an alpha amino acid NH4Cl + NaCN = NH3+ HCN+ NaCl - NH3 is the nucleophile - CN- is the acid 1) NH3 2) CN- 3) H+ and water
How can you form an amine from an imine?
The C=N bond of imines can be reduced to for amines.
You use a H2/Ni catalyst.
Describe the mechanism of a nucleophile and ketone?
Forms a tertiary alcohol
Nucleophillic addition
See mechanism
Describe the mechanism of a nucleophile and ester?
Nucleophillic acyl substitution
Describe the mechanism of a nucleophile and a carboxylic acid?
Competitive deprotonation
First step is deprotonation of the alpha hydrogen
What are the best leaving groups?
The best leaving groups are neutral molecules or stable ions
A stable anion is one with a low pka value of the conjugate base
Describe the relative reactivity of carbonyls
The more positive the carbon atom, the more reactive it is
Acyl chloride>acid anhydride>ester>amide
Why is an acyl chloride the most reactive?
The +I effect is stronger than the +M effect
Why is an acid anhydride the second most reactive
The -I effect is larger than the +M effect
This is because the +M effect is weak because the lone pair on the oxygen is shared
Why is an ester the second least reactive?
This is because the +M effect is stronger then the -I effect
Why is an amide the least reactive?
This is because the +M effect is much stronger than the -I effect
What is the esterification reaction?
The reaction between a carboxylic acid and an alcohol produces an ester.
- requires an acid catalyst (2 react)
- all steps are reversible
- force reaction forward= excess of alcohol and dehydrating agent
- water is a byproduct
How do you form a carboxylic acid from an acyl chloride?
This is a hydrolysis reaction where water is the reagent.
HCl is the byproduct
How do you make an ester from an acyl chloride?
This is an alcoholysis reaction.
The reagent is an alcohol (ROH).
The byproduct is HCl
Often as base is added
How do you form a tertiary alcohol from an acyl chloride?
This is a reaction with an organometallic RMgX and then reaction with H+
This is a nucleophillic addition reaction
How do you form a primary amide from an acyl chloride?
This is an aminolysis
The reagent is 2NH3
One NH3 acts as a nucleophile and one acts as a base
The byproduct is an NH4Cl
How do you form a primary alcohol from an acyl chloride?
This is a reduction reaction with NaBH4 and then reaction with H+
This is a nucleophiliic addition reaction
How do you make an acyl chloride from a carboxylic acid?
The reagent is SOCl2
How do you make a carboxylic acid from an acid anhydride?
This is a hydrolysis reaction where water is the reagent.
2 carboxylic acids are made.
O=O-R is the leaving group
How do you make an ester and carboxylic acid from an acid anhydride?
This is an alcoholysis reaction and the reagent is an alcohol ROH
O=O-R is the leaving group
How do you form a primary alcohol from an acid anhydride?
This is a reduction reaction where LiAlH4 is the reagent. You then react it with H+.
2 primary alcohols are made
Why is pyradine useful?
Some bases can act as nucleophilic catalysts
Make species more electrophilic and pyradine is a better leaving group
How do you form a primary amide and a carboxylate ion from an acid anhydride?
This is an aminolysis reaction where 2NH3 are the reagents.
How do you form a carboxylic acid and an alcohol from an ester?
(Saponification)
This is an hydrolysis reaction with reagents H2O, H+ or OH- and then reacting with H+
This reaction is reversible
Basic conditions are used as it forces equilibrium forward
The deprotonation of COOH is irreversible
How can you form a primary amide and an alcohol from and ester?
This reaction is aminolysis and the reagent is NH3
How do you form a mixture of primary and tertiary alcohols from an ester?
This is a reduction mechanism.You use LiAlH4 not NaBH4 and then react with H+
OR
You can reduce with organometallics (RMgX) and then react with H+ and H2O in a nucleophillic addition reaction
How can you form a carboxylic acid and an alcohol from an ester?
Hydrolysis, H2O, H+ or H2O, OH- then H+
Why do amides only under go few nucleophilic acyl substitutions?
This is because the carbonyl carbon atom is not a good electrophile and so they are not very reactive
How do you form a primary amide and then amine from a carboxylic acid?
H2O, H+ or H2O, OH- then H+ High temps and or concentrated acid or base = primary amide LiAlH4 then H+ = primary amine
What is a carbonyl alpha substitution reaction?
These reactions take place at the position next to the C=O group called the alpha position
They involve substitution of an alpha hydrogen by another group via either an enol (acidic condition) or an enolate ion (basic conditions) intermediate
What is keto- enol tautomerism?
The interconversion of the keto and enol form
This is catalysed by either an acid or base
What is the most stable structure isomer for carbonyl compounds?
The keto form which has C=O bond
The carbonyl compounds are in equilibrium with structural isomers called enols
Why is the keto form more stable than the enol form?
The keto form is more stable because the combined enthalpy of the C=O and C-H bonds is higher than the combined enthalpy for the H-O and C=C bonds in the enol form
This means equilibrium lies towards the keto form
How is the enol form stabilised?
Stabilised of the C=C bond is conjugated with a second pi bond or if the OH group is involved in intramolecular hydrogen bonding
The more substituted the C=C bond in the enol form, the more stable the enol
Why are carboxylic acids and derivatives less prone to enolisation?
This is because the C=O bond is normally stronger
The bond in an ester is stabilised by resonance with the OR group
Outline the reaction of enol with bromine
Enol as are nucleophiles and they react with electrophiles such as bromine in the presence of an acid catalyst
Bromine is introduced at alpha position of the ketone
Br is a weak base so water is more likely to act as a base in the final step
Why does further bromination not occur to the enol?
The Br group is a -I group
This reduces the basicity of the oxygen atom so it is less easily protonated
This reduces the rate of further bromination
Describe the acidity of an alpha hydrogen atom
Hydrogen atoms at the alpha position are more acidic than those in an alkene
What stabilises the enolate ion?
The -I effect and the -M effect of the C=O group stabilises the enolate ion, the major resonance form had the negative charge on the electronegative oxygen atom
Why are enolate ions stronger nucleophiles than enols?
This because they are negatively charged
Where do electrophiles react at?
They react at the carbon site rather then the oxygen to introduce a new substituents at the alpha position
What is the idodoform teaction
The reaction of a methyl ketone with iodine and excess hydroxide ion leads to the successive introduction of 3 idodine atoms at the alpha position via 3 enolate ion intermediates
What is used as a test for RCOCH3 ?
Formation of a yellow precipitate of ChI3 is used as a test for RCOCH3 in an unknown compound
What is a carbonyl- carbonyl condensation reaction?
In these reactions, two carbonyl molecules react together to form a single organic produce with a small molecule (water)
Link smaller starting materials by C-C bonds
What is the adol condensation?
This is a base catalysed dimerisation reaction for all aldehydes and ketones with an alpha hydrogen atom
What is the product of an adol reaction from an aldehyde?
It contains both an aldehyde and an alcohol group
What is the position of equilibrium for adol condensation?
Depends on the carbonyl compound
For an aldehyde it lies more towards the adol product
For the ketone it lies towards the ketone
How do you form a beta hydroxy-ketone?
An adol reaction of propanone
Outline the steps in an adol condensation reaction
1) two molecules of an aldehyde or ketone react in a rapid reversible adol reaction= beta hydroxy- ketone/alde
2) heated with acid or base catalyst to eliminate water (intermediate enol)
3) products are beta unsaturated carbonyls
What is a crossed adol reaction?
This involves the reaction of two different aldehydes or ketones
If the two aldehydes and ketones can form enolate ions equally well and can both act as an electrophile, then a reaction produces a mixture of all four possible products
How can a crossed adol reaction give a single product of high yield?
1) one of the carbonyls is unable to form an enolate ion (no alpha hydrogen)
2) the carbonyl unable to form the enolate is more reactive to the nucleophilic addition than the carbonalyl than can form the enolate
3) the carbonyl compound able to form the enolate is added slowly
What is the claisen condensation reaction?
Reaction of two molecules or an ester with one equivalent of base to form a beta keto ester
The enolate ester ion attacks a second molecule of the ester in a nucleophilic acyl substitution reaction
Which way is equilibrium pushed in the claisen condensation reaction?
The equilibrium is pushed towards the condensation product by removal of an acidic alpha hydrogen atom from the beta keto ester
One workup, the enolate ion is reprotonated to reform the beta keto ester
For a carbonyl with a leaving group, when is nucleophilic addition or substitution preferred ?
Depends on the leaving group
It X is a good leaving group, nucleophilic substitution
If X is not a good leaving group, nucleophilic addition
For a carbonyl with an alpha carbon, when is nucleophilic addition or alpha deprotonation preferred ?
Acting as a nucleophile or base?
With a nucleophile, it attacks the C=O on nucleophilic addition
With a base, it deprotonates the alpha position, alpha deprotonation
