Carbonyls, Nucleophilic Reactions and Leaving Groups

Question 1

General properties of Carbonyls include…

Answer 1

• 120 degree bond angles - TRIGONAL PLANAR
• susceptible to nucleophilic attack
• Pi bond breaks as weakest of 2 bonds
• alpha hydrogen weakly acidic

Question 2

Examples of Nucleophilic addition

Answer 2

• cyanohydrin formation
• Hemiacetal formation
• Hydride transfer

Question 3

Biological example of nucleophilic addition

Answer 3

formation of HCN poison from cyanohydrin

Question 4

Nu- vs Nu neutral

Answer 4

NU- is more potent

Question 5

Hydride transfer reaction requires which enzyme?

Answer 5

• lactate dehydrogenase

Question 6

In nucleophilic substitution…

Answer 6

• conjugate acids of good LG have low pKa’s

Question 7

2 types of hemiacetal formation

Answer 7

• acid catalysed

- base catalysed

Question 8

The lower the pKa in a leaving group…

Answer 8

the better the leaving group it is (more stable)

Question 9

Examples of Nucleophilic substitution reactions…

Answer 9

• peptide synthesis

- general nucleophilic substitution with a carbonyl

Question 10

Examples of Nucleophilic substitution with loss of carbonyl Oxygen

Answer 10

• acetal formation

- imine formation (Schiff base)

Question 11

Imine formation is…

Answer 11

• 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.

Question 12

An acetal has…

Answer 12

steric clashes

Question 13

Example of Substitution at the alpha carbon

Answer 13

• enol formation (acid and base catalysed)

- aldol reactions (formation of C-C bond) aldehyde with alcohol

Question 14

Example of aldol reaction in Citric acid cycle

Answer 14

Oxaloacetate to Citrate using citrate synthetase

Question 15

Esters can’t form readily but what can

Answer 15

Thiols

Question 16

‘Explain how a pair of enantiomers can be generated from this reaction’

Answer 16

• can attack from either side of planar face

Question 17

Cyanahydrin formation

Answer 17

• NaCN and H3O+
• CN- attacks Alpha carbon of carbonyl
• Neg Oxygen then attacks H of H3O+ arrow to oxygen
• Forms Cyanahydrin

Question 18

Hemiacetal formation (acid catalysed)

Answer 18

• 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+

Question 19

Base Catalysed Hemiacetal formation

Answer 19

• 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-

Question 20

Hydride Transfer uses

Answer 20

• Lactate Dehydrogenase

- H attacks pyruvate due to resonance in ring with N

Question 21

Nucleophilic substitution

Answer 21

• 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

Question 22

Acetal formation

Answer 22

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

Question 23

Imine formation

Answer 23

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

Question 24

Enol Acid

Answer 24

H3O+ used

Question 25

Enol Base

Answer 25

OH- used

Question 26

Aldol

Answer 26

H3o+ and H2O