Core 3: Organic Carbonyls

Question 1

Why is the attack of nucleophiles on carbonyls favourable?

Answer 1

The σ bond formed is stronger than the π bond broken.

Question 2

Draw the mechanism for forming an enolate ion. In what conditions does this occur?

Answer 2

In basic conditions.

Question 3

What kind of arrows are used for nucleophilic addition using charged and neutral nucleophiles?

Answer 3

Straight arrows for charged, reversable arrows for neutral.

Question 4

How can rates of attack on carbonyls by nucleophiles be increased?

Answer 4

Using an acid catalyst to protonate the oxygen.

Question 5

When will a nucleophilic substitution reaction occur in preference to an addition? What carbonyls does this occur for?

Answer 5

When a good leaving group is present. This is common for carboxylic acid derivatives: acyl chlorides, acid anhydrides, esters and amides. Does not occur for aldehydes and ketones.

Question 6

Draw the mechanism for forming an enol. In what conditions does this occur?

Answer 6

In acidic conditions.

Question 7

Why are aldehydes more reactive than ketones?

Answer 7

Sterically: nucleophiles are less hindered as the carbon is less crowded and this also makes the transition state lower in energy.

Electroniclly: the ketone carbon is less electrophilic due to the +I effect of an acyl group.

Question 8

What should be considered when choosing a source of hydride?

Answer 8

NaBH₄ is a weaker source than LiAlH₄. It can be used in water and will only reduce aldehydes and ketones. LiAlH₄ reacts violently with water and will reduce the other carbonyls.

An excess is used so for every 2 H^- ions required 1 mole of hydride is used.

Question 9

How are alcohols oxdised?

Answer 9

Doing Jones oxidation with CrO₃ and H⁺.

Question 10

How are cyanide ions delivered to a reaction?

Answer 10

A small amount NaCN is added with HCN. When the CN^- ions are used up from NaCN, the negatively charged oxygen will remove the H from HCN and form a new CN^- ion.

Question 11

What arrows are used for the nucleophilic addition of cyanide?

Answer 11

Reversable arrows.

Question 12

Where do you draw the arrow from when using organometalics?

Answer 12

From the centre of the R-M bond.

Question 13

What is the structures and names of the four most common organometallics?

Answer 13

Organolithiums R-Li

Grignard reagents R-MgX

Reformatsky reagent EtO₂C-CH₂-ZnBr

Alkynylsodium reagents RC≡C^-Na⁺

Question 14

What are the arrows used for the addtion of organometallics to carbonyls?

Answer 14

Straight arrows.

Question 15

How can alkenes be formed from aldehydes and ketones?

Answer 15

Via the Wittig reaction.

Question 16

Draw a mechanism for water adding to aldehydes or ketones uncatalysed, with acid and with base. What is the name of the product?

Answer 16

A hydrate.

Question 17

How do you form acetals? Draw the mechanism.

Answer 17

Alcohol is added to an aldehyde or ketone with an acid catalyst, this reacts to form a hemiacetal. This then eliminates its OH group with an acid catalyst which then reacts with another equivalent of alcohol to form the acetal. This is done with MgSO₄ as water is produced and every step is an equlibrium.

Question 18

What is the main use of acetals and what reagent is key? How can this use be manipulated?

Answer 18

They can be used as protecting groups when targeting less reactive carbonyls. Ethan-1,2-diol is added to the carbonyl to form a cyclic acetal which is resistant to attack. Removing water forms the acetal which is done with mag.sulfate. Hence to remove the protecting group, water is added.

Question 19

How can thiols be used with carbonyls?

Answer 19

They can be added to form thioacetals. The key use is using ethan-1,2-dithiol to form the cyclic thioacetal. Then Raney nickel and H₂ are introduced to form an alkane from a carbonyl. This is called the Mozingo reduction.

Question 20

How do primary amines react with carbonyls? How does the pH have to be controlled? Draw a mechanism.

Answer 20

They add to form an imine. The pH has to be controlled as an acid catalyst is required but too acidic would protonate the amine and remove its nucleophilic effects.

Question 21

What is formed from the reagents, aldehyde/ketone, NH₄Cl and NaCN?

Answer 21

The NH₄Cl and NaCN form NH₃, HCN and NaCl. The iminium ion forms from the NH₃ with HCN acting as a acid. The CN^- ion then attacks nucleophilically to form an α-amino nitrile which can react on to form an α-amino acid.

Question 22

Draw the mechanism for esterification using a suitble catalyst.

Answer 22

Question 23

Name the products of the reaction of acyl chloride with each reactant.

1. H₂O
2. ROH
3. Organometallics and H⁺
4. 2NH₃
5. Reducing agent

Answer 23

1. Carboxylic acid and HCl
2. Ester and HCl
3. Tertiary alcohol
4. Primary amide and NH₄Cl
5. Primary alcohol

Question 24

Under what conditions do enols and enolates form?

Answer 24

Enols form in acidic conditions, enolates form in basic conditions.

Question 25

How can enols be stabilised?

Answer 25

Conjugation and intramolecular hydrogen bonding.

Question 26

Draw a mechanism for the reaction of enols with bromine as a given electrophile.

What effect does the product have on further reactions?

Answer 26

The bromine has a -I effect on the oxygen, reducing its basicity and decreasing the rate of futher reactions.

Question 27

Describe the steps of the iodoform reaction.

Answer 27

A base removes an α-hydrogen, this reacts with the enolate ion formed via electrophilic addition. This occurs until all 3 α-carbon bonds are to iodine. This is now a good leaving group and will undergo substitution with OH^- and take a hydrogen from the carboxylic acid formed. All steps apart from the nucleophilic attack of the double bond are reversible.

Question 28

What is the aldol condensation?

Answer 28

When an α substitution occurs with another carbonyl as the electrophile. If the starting reagent is an aldehyde, the product is called a β-hydroxy-aldehyde, also know as an aldol.

Question 29

For the aldol condensation, how does the carbonyl change the rate of reaction?

Answer 29

For an aldehyde, the equlibrium lies in favour of the aldol product, the ketone favours the reactants.

Question 30

How are enones formed?

Answer 30

When an aldol (or ketone equivalent) is heated with acid or base, water will eliminate and the enone will form.

Via the acid route a water leaving group is formed after the aldol is in its enol form.

Via the base route an α-hydrogen is removed and -OH^- is eliminated.

Question 31

How can cross aldol reactions be controlled?

Answer 31

1. Using one carbonyl unable to form the enolate ion - no α-hydrogens.
2. The carbonyl unable to form the enolate is more reactive to nucleophiles.
3. The carbonyl acting as a nucleophile is slowly added to the reaction.

Question 32

How is the reaction to form a β-keto ester different to the aldol reaction?

Answer 32

The electrophilic equivalent undergos a substitution instead of the addition with the OR group being removed. This then removes the α-hydrogen which requires a work-up to be added.