Carbonyls Flashcards
What undergoes nucleophilic addition reactions?
Aldehydes + ketones
What undergoes nucleophilic addition elimination reactions?
Carboxylic acid derivatives
What does elonate ions + reactions require?
Alpha hydrogen
What is the carbon in carbonyl?
Trigonal planar sp2
What is the O in carbonyl?
Trigonal planar sp2
Describe C-O?
Sigma bond between sp2 orbitals on C + O
Where do all sigma bonds lie?
In same plane - 120 degrees part
Describe C-O pi bond
Between parallel p orbitals on C + O
Compare C=O to C=C
C=O shorter, stronger + more polar than C=C in alkenes
What is Lipinski’s Rule of 5 for?
Orally absorbed drugs
What are Lipinski’s Rule of 5?
Molecular weight <500
logP <5
H-bond donors <5
H-bond acceptors <10
What happens to polar drugs that break Lipinski’s Rule of 5?
Poorly absorbed
How may carbonyl group intercact with binding sites?
H-bonding = carbonyl group H-bond acceptor
2 possible interactions (2 L.P on O)
Dipole-dipole interactions
Why does reduction aldehyde/ketone give alcohol?
Weakens H-bond interactions
Weakens dipole-dipole moment interactions
Is COOH a WA?
YES
Why is COOH a WA?
Transfer H+ to H2O to give H3O+ + carboxylate anions RCO2-
Why is there a greater acidity in carboxylic acids compared to alcohols?
Resonance stabilisation of carboxylate anion
Carboxylate ion = conjugate base of carboxylic acid
When are resonance structure possible?
When more than one valid Lewis structure can be written for a molecule
OR
When two or more adjacent π-orbitals in same place
What are resonance structures?
Imaginary representing location of e-
What must resonance structures have?
Same no. of e-
Valid Lewis dot structures
Position of all atoms same in all resonance structures
Does hybridisation change resonance structures?
NO
In alkoxide ion where is the negative charge?
Localised on O
In carboxylate ion where is the negative charge?
Delocalised over 2 equivalent O atoms, giving resonance stability
How do you purify COOH?
RCOOH Add dilute NaOH RCOONa Add HCl (aq) Add fresh ether RCOOH
What does the group bonded to acyl carbon determine?
Class of compound
Carbonyl group + OH?
Carboxylic acid
Carbonyl group + Cl?
Acid chloride
Carbonyl group + OC(O)R?
Acid anhydride
Carbonyl group + OR’?
Ester
Carbonyl group + NR2?
Amide
What is the reactivity for added group?
OH Cl OC(O)R DECREASING REACTIVITY OR' NR2
How can all added groups be converted back to parent carboxylic acid?
By acid/base hydrolysis
What are thioesters + acyl phosphates?
Biological COOH derivatives
Why is carbonyl group polar?
O more electronegative than C
Why is carbonyl carbon electrophilic?
Susceptible to nucleophilic attack
How can the reactivity of aldehydes, ketones, carboxylic acids, esters + amides be enhanced?
And why?
By protonation of carbonyl O
Carbonyl becomes more electrophilic
= carbonyl more susceptible to nucleophilic attack
What undergoes nucleophilic addition?
Aldehydes + ketones
For weak nucleophiles in nucleophilic addition what is required?
Carbonyl group requires activation = acid catalyst
What are aldehydes/ketones converted to in nucleophilic addition?
Alcohols
How is nucleophilic addition reversed in basic conditions?
Baes removes H+
Carbonyl formation with loss of leaving group
Nucleophile leaving group
How is nucleophilic addition reversed in acidic conditions?
Protonation of original nucleophilic species
Loss of leaving group + formation of protonated carbonyl
What can nucleophiles be?
Charged OR neutral
What are some negative nucleophiles?
OH- hydroxide H- hydride R3C- carbanion RO- alkoxide CN- cyanide
What are some neutral nucleophiles?
H2O water
ROH alcohol
NH3 ammonia
RNH2 amine
Can the nucleophile approach above or below C=O plane?
BOTH
What does aldehyde have?
Less steric crowding
What does ketone have?
More steric crowding
What happens in reactions at C=O?
e- pair moves from C=O to electronegative O
= tetrahedral alkoxide ion intermediate
= new bonds formed
= increased steric crowding
Why are aldehydes more reactive than ketones?
1 large substituent group bonded to C=O
Ketone = 2
Why are alkyl groups e- releasing?
Aldehyde has greater partial positive charge on carbonyl than ketone
Aldehyde carbon more electrophilic than ketone carbon
Which is more stable primary or secondary carbocation?
Secondary
What is more stable aldehyde or ketone?
Ketone
= More stabilisation of delta positive on C
How is a cyanohydrin formed?
HCN adds to aldehyde + ketone
What is HCN?
Toxic gas
Because HCN is toxic what happens?
HCN usually generated in situ
NaCN (excess) + acid
What is the equation for HCN?
HCN + H2O —-> CN- + H3O+
CN- + H3O+ —-> HCN + H2O
What is formed when cyanohydrin hydrolysis?
Carboxylic acid
What is formed when cyanohydrin reduction?
Amine
What aldehyde reduced to?
Primary alcohol
What ketone reduced to?
Secondary alcohol
What is source of hydride ion in reduction of aldehydes/ketones?
NaBH4 = sodium borohydride
OR
LiAlH4 = lithium aluminium hydride
How many moles of aldehyde/ketone can be reduced by 1 mole of NaBH4?
4
