Carbonyls Flashcards
Describe the structure of the carbonyl group ?
- c=o
- trigonal planar = 120
- sp² carbon and oxygen
Is a c=c or c=o stronger ?
- c=o is shorter and stronger
- more polar
How can carbonyl groups interact at binding sites, do they donate or accept H bond ?
- carbonyl group is a hydrogen bond acceptor
What happens during reactions at the carbonyl carbon?
- electron pair moves from C=O bond to the electronegative oxygen atom
- forming a tetrahedral alkoxide ion intermediate
- c goes from sp2 to sp3
Which has more steric crowding, aldehydes or ketones?
- ketones
- because attached to 2 alkyl groups whereas aldehydes are only attached to 1
What enhances the reactivity of aldehydes, ketones, carboxylic acids, esters, and amides?
- protonation of the carbonyl oxygen to becomes positively charged (O⁺-H)
- makes carbonyl carbon more electrophilic
- more susceptible to nucleophilic attack.
How does the carbonyl group react with weak nucleophiles?
- requires activation of carbonyl group
- by protonation of O to make (O⁺-H)
- also called acid catalysis
reaction of carboxylic acid with water ?
- RCOOH + H2O –> RCOO- +H3O+
- transfer a H+ to water
- forms H30+ which is a stronger acid
what kind of acids are carboxylic acids ?
- weak acids
Why are carboxylic acids more acidic than alcohols?
- resonance stabilization of the carboxylate anion (conjugate base)
- makes stronger acids compared to alcohols
- alcohols are neutral in water
What is the order of reactivity for carboxylic acid derivatives ?
- acyl chloride
- anhydride
- ester
- amide (least)
what happens to reactivity as the leaving group becomes more basic ?
- decreased reactivity as more basic
- eg. amide more basic so less reactive
What is the effect of resonance on reactivity of derivative ?
- more stable derivative is less reactive eg. amides
why is amide less reactive than carboxylic acid ?
- more basic
- more stable resonance structure so less reactive
reactions of Acyl chlorides ?
- react with H2O to get COOH
- react with ROH to get ester + HCl
- react with RNH2 to get amide
which is more reactive acid anhydride or acyl chloride ?
- acyl chloride
Why are aldehydes more reactive than ketones in nucleophilic addition reactions?
- only one large alkyl group = leading to less steric crowding
- so aldehyde carbon more elctrophilic (greater partial positive charge )
What happens when aldehydes are oxidized?
- forms carboxylic acid
What are anomers + example?
- stereoisomers specific to cyclyic sugars
- α-anomer: (OH) opposite the CH₂OH group, bottom
- β-anomer:(OH) is on the same side as the CH₂OH group, above
which anomer of glucose is more stable ?
- β-anomer
- more stable - lower in energy
What is keto-enol tautomerization?
- interconversion between keto and enol forms, - catalyzed by either acid or base
- involves resonance stabilization.
what is an acid anhydride ?
−C(=O)−O−C(=O)−
Draw the mechanism for the hydrolysis of acyl chlorides
Refer to tutorial sheet
Draw the reaction mechanism for acid-catalysed hydrolysis of esters ?
Refer to tutorial sheet
What happens during the hydrolysis of an acyl chloride ?
- reaction is nucleophilic acyl substitution
- ROCl + H20 —> RCOOH + HCl
- exothermic reaction
What happens during acid-catalysed hydrolysis of esters (5) ?
- nucleophilic substitution
- H20 is weak nucleophile, protonation of O -> O+ makes C more electrophilic so easier for nucleophile to attack
- requires acid catalyst eg. HCl, H2SO4 + heat
- products are a carboxylic acid + alcohol
- reversible reaction
What happens during base hydrolysis of esters (4) ?
- nucleophilic substitution
- requires strong base (NaOH, KOH) + heat
- reaction is irreversible
- products formed are carboxylate ion and alcohol
Why is base catalysed hydrolysis irreversible ?
- resonance stabilisation of the carboxylate ion lowers the energy + makes it more stable
- so unlikely to further react + form ester
How does protonation of oxygen in c=o make the carbon more electrophilic?
- (O → O⁺) increases its electron-withdrawing ability, pulling more electron density away from the carbon to stabilise it’s positive charge
- this creates a stronger partial positive charge on the carbon, making it more electrophilic and susceptible to nucleophilic attack.
How is nucleophilic addition reversed under basic conditions ?
- base removes proton
- carbonyl formation (reform double bond) with loss of leaving group
- nucleophile as leaving group
How is nucleophilic addition reversed in acidic conditions ?
- protonation of nucleophile
- loss of leaving group (nucleophile)
- protonation of O -> O+- H
- bond between O+ and H breaks
What is the pKa value for most aliphatic + aromatic carboxylic acids ?
- range 3-5
Why does the tetrahedral intermediate eliminatethe weakest base ?
- weak bases are more stable with a negative charge compared to strong bases
- so make good leaving groups in nucleophilic substitution
What is a thioester + are they more or less reactive than esters ?
- RC=O-SR’
- C-S bond weaker so easier to break + more susceptible to attack
- less resonance stabilisation in thioesters
What is a lactone + are they more or less reactive than open chain esters ?
- lactone is a cyclic ester
- more reactive than open chain esters due to ring strain which makes C more electrophilic
Why do nucleophile add to carbonyl compounds ?
- carbon is delta positive which attracts nucleophiles
What reagent’s are used for the reduction of aldehydes / ketones ?
- NaBH4 / LiAlH4
Why does the reaction not occur if the leaving group was -H or -R ?
- they are not stable anions
- anions needs to be stable for group to leave
Why do many drug compounds contain carbonyl groups?
- carbonyl groups can make hydrogen bonding interactions (and dipole interactions) with receptor binding sites in the body
- helping drug molecules to bind strongly.
Draw the mechanism of reduction of aldehydes and ketones
Refer to tutorial sheet
What is the hybridization of carbon in the carbonyl group, and how does it participate in bonding?
- has 3 sp2 orbitals
- one overlaps with O sp2 orbital to form sigma bond
- 2 other sp2 orbitals form sigma bond with R groups
- 1 unhybridised p orbital sideway overlaps with oxygens p orbital to form pi bond
What is the hybridization of oxygen in the carbonyl group, and how does it participate in bonding?
- forms one sigma (σ) bond with carbon using an sp² orbital.
- houses two lone pairs of electrons in the remaining two sp² orbitals.
- has one unhybridized p orbital that overlaps with the carbon’s p orbital to form the π bond.
