Carbonyls, Nucleophilic Reactions and Leaving Groups Flashcards
General properties of Carbonyls include…
- 120 degree bond angles - TRIGONAL PLANAR
- susceptible to nucleophilic attack
- Pi bond breaks as weakest of 2 bonds
- alpha hydrogen weakly acidic
Examples of Nucleophilic addition
- cyanohydrin formation
- Hemiacetal formation
- Hydride transfer
Biological example of nucleophilic addition
formation of HCN poison from cyanohydrin
Nu- vs Nu neutral
NU- is more potent
Hydride transfer reaction requires which enzyme?
- lactate dehydrogenase
In nucleophilic substitution…
- conjugate acids of good LG have low pKa’s
2 types of hemiacetal formation
- acid catalysed
- base catalysed
The lower the pKa in a leaving group…
the better the leaving group it is (more stable)
Examples of Nucleophilic substitution reactions…
- peptide synthesis
- general nucleophilic substitution with a carbonyl
Examples of Nucleophilic substitution with loss of carbonyl Oxygen
- acetal formation
- imine formation (Schiff base)
Imine formation is…
- dependent on pH
- two step synthesis A and B
- if too much acid around then step A blocked, therefore reaction slows down
- if too basic then step B blocked and wont happen.
An acetal has…
steric clashes
Example of Substitution at the alpha carbon
- enol formation (acid and base catalysed)
- aldol reactions (formation of C-C bond) aldehyde with alcohol
Example of aldol reaction in Citric acid cycle
Oxaloacetate to Citrate using citrate synthetase
Esters can’t form readily but what can
Thiols
‘Explain how a pair of enantiomers can be generated from this reaction’
- can attack from either side of planar face
Cyanahydrin formation
- NaCN and H3O+
- CN- attacks Alpha carbon of carbonyl
- Neg Oxygen then attacks H of H3O+ arrow to oxygen
- Forms Cyanahydrin
Hemiacetal formation (acid catalysed)
- H3O+
- Carbonyl Oxygen with R and H as groups attacks H3O+ gains hydrogen onto it
- Double bond attacks positive charge now on Oxygen
- ROH attacks alpha carbon now positive
- ROH attached onto hemiacetal has positive oxygen water attacks hydrogen bond attacks that positive oxygen
- forming hemiacetal and regeneration of H3O+
Base Catalysed Hemiacetal formation
- Nucleophile formation from reaction of RO-H + -OH –> RO- + H-OH
- RO- attacks alpha carbon, arrow jumps to oxygen
- neg charge now on oxygen jumps to H of water that then jumps
- Form Hemiacetal and OH-
Hydride Transfer uses
- Lactate Dehydrogenase
- H attacks pyruvate due to resonance in ring with N
Nucleophilic substitution
- Eto- attacks alpha carbon, arrow to oxygen
- depends on pka of groups which one is leaving group
- neg from oxygen goes to bond then leaving group leaves
Acetal formation
1) Form hemiacetal
2) H3o+ used, OH from hemiacetal attacks H arrow then to positive oxygen
3) Electrons on RO into bond, arrow then to +OH2
4) forms double bond O with R group attacked to O, double bond goes onto +O
5) forms water
6) HOR attacks positive charge on alpha carbon
7) water then attacks H on +OR, arrow then to O+ forms acetal
Imine formation
1) R-NH2 (electrons) attack alpha carbon group, arrow to oxygen
2) Neg oxygen attacks H of NH2 group which is now attached, bond into N+
3) H3O+ used
4) electrons on N attack its bond, resonate so that electrons from bond attack positive OH2 attached
5) dehydration occurs
6) water attacks H, bond into N+ (protonated imine) forms imine
Enol Acid
H3O+ used
Enol Base
OH- used
Aldol
H3o+ and H2O
