Carbonyl chemistry- O/S Nucleophiles with aldehydes and ketones

Question 1

What are the two main ways a nucleophile attacks a carbonyl

Answer 1

1. Nucleophilic addition

2. Nucleophilic substitution

Question 2

What is another method of addition to carbonyls

Answer 2

1. Addition using an oxygen nucleophile
2. Results in the loss of carbonyl oxygen
3. Specific to aldehydes and ketones

Question 3

What happens if you add OHCH2CH2OH to an aldehyde with h+

Answer 3

1. Forms an acetyl + H2O
2. The carbonyl oxygen is lost and forms the O in H2O
3. Oxygens in acetyl come from the OHCH2CH2OH

Question 4

How is it known that the carbonyl oxygen forms the H2O

Answer 4

1. Used oxygen 18 on the carbonyl and saw that it was O18 in the H2O product and normal O in the acetyl

Question 5

What is formed when you add water to an aldehyde/ketone

Answer 5

1. A hydrate
2. Two alcohol groups attached to the R groups
3. Reversible reaction

Question 6

Why is it difficult to isolate hemi-acetal

Answer 6

1. Add alcohol to aldehyde/ketone produces a hemi-actetla
2. Most work-ups require water but adding water shifts the equilibrium back towards the aldehyde/ketone
3. Entropy- negative- 2 starting materials= 1 product
4. So equilibrium is on the left as DG>0

Question 7

How are acetals formed

Answer 7

1. Adding alcohol to aldehyde/ketone first forms hemiacetal and then adding more forms acetal
2. Acetal can be isolated
3. But still has entropy issues.

Question 8

What is a hemi-acetal

Answer 8

1. RC(OH)OR

Question 9

How can a hemiacetal be formed

Answer 9

1. Form very slowly in presence of alcohol- not a great nucleophile
2. Rate of formation is increased by either acid or base

Question 10

Why does adding an acid speed up the rate of hemiacetal formation

Answer 10

1. The aldehyde/ketone forms an oxonium ion

2. This is much more electrophilic as carbonyl carbon has more electron density pulled away from it

Question 11

Why does adding a base speed up the rate of hemiacetal formation

Answer 11

1. OH- deprotonates the alcohol so it becomes a much better nucleophile

Question 12

Why do ring structures form from a aldehyde/ketone with alcohol group on other end

Answer 12

1. DH is slightly -ve
2. DS is neutral
3. DG <0, so equilibrium lies to right

Question 13

How can an acetal be formed

Answer 13

1. Formed very slowly in presence of alcohol
2. Rate of formation increased by acid only
3. Add heat and pTSA (acid)

Question 14

What is pTSA

Answer 14

1. Common organic acid

2. Nice crystalline powder to work with as dry

Question 15

What is a problem with acetal formation and how is it solved

Answer 15

1. Water is produced which can reverse the reaction
2. Excess of ethanol pushes equilibrium to the right and swamps out water produced
3. Remove the H2O from reaction by MgSO4, using a molecular sieve, using Dean Stark reagent

Question 16

What is the more stable alcohol reactant

Answer 16

1. Diol more stable than monomeric alcohol

2. As cyclic acetyl are more stable than non-cyclic

Question 17

How can acetals be hydrolysed

Answer 17

1. Reverse of formation

2. Acid and add water back in

Question 18

What can acetals be used for

Answer 18

1. They are protecting groups

2. Protect carbonyl carbon from attack- especially for aldehydes and ketones

Question 19

What can sulfur nucleophiles be used for

Answer 19

1. Useful in synthesis
2. Can protect carbonyl groups- diathiane formation
3. Form using acid, Toluene and Dean Stark- same as acetals formation

Question 20

How can you remove the sulfur protecting group to reform the carbonyl

Answer 20

1. Need Acid + Water + HgCl2 = carbonyl back

2. Or add raney-Ni + H2 = reduced so no Oxygen after

Question 21

What is the Baeyer Viliger reaction

Answer 21

1. Converts a ketone to an ester

Question 22

How can you convert a ketone to an ester

Answer 22

1. Using peracids

2. Forms an oxonium ion intermediate and then forms an ester

Question 23

Describe properties of peracids

Answer 23

1. Nucleophilic atom- OH

2. Carrying good leaving group o-c(=o)-R