Carbonyl chemistry- reduction

Question 1

What allows one carbonyl to react over another

Answer 1

1. Difference in reactivity

2. Chemoselectivity

Question 2

Would NaOH react more readily with ester or amide functional group in compound

Answer 2

1. Ester over amide

2. Ester is more reactive as donates less back into the carbon so the carbon is more electrophilic

Question 3

What are metal hydrides

Answer 3

1. One of the most common reducing agents
2. Source of ‘H’ nucleophile
3. Have different reactivities
4. The more reactive the less selective it is

Question 4

Order LiAlH4, LiBH4 and NaBH4 by reactivity

Answer 4

1. LiAlH4 is most reactive as it has a lewis acidic carbanion and a nucleophilic anion
2. Then LiBH4
3. Then NaBH4

Question 5

What are Lewis acid hydrides

Answer 5

1. Charge neutral lewis acids
2. Only source of H when they form Lewis acid-base complex
3. Useful for reduction of electron rich carbonyl derivatives

Question 6

Give two examples of lewis acid hydrides

Answer 6

1. DIBAL- forms a bridged dimer

2. BH3 (borane)- forms a bridged dimer

Question 7

What reducing reagents react with Aldehydes

Answer 7

1. LiAlH4- readily reacts
2. LiBH4- readily reacts
3. NaBH4- readily reacts
4. BH3- slowly reacts

Question 8

What reducing reagents react with ketones

Answer 8

1. LiAlH4- readily reacts
2. LiBH4- readily reacts
3. NaBH4- readily reacts
4. BH3- slowly reacts

Question 9

What reducing reagents react with esters

Answer 9

1. LiAlH4- readily reacts
2. LiBH4- readily reacts
3. NaBH4- slowly reacts
4. BH3- slowly reacts

Question 10

What reducing reagents react with amides

Answer 10

1. LiAlH4- readily reacts
2. LiBH4- no reaction
3. NaBH4- no reaction
4. BH3- readily reacts

Question 11

What reducing reagents react with carboxylic acids

Answer 11

1. LiAlH4- slowly reacts
2. LiBH4- no reaction
3. NaBH4- no reaction
4. BH3- readily reacts

Question 12

Describe the reactivity of LiAlH4

Answer 12

1. Reacts with everything
2. Best with higher reactivity carbonyls
3. Slow reaction with carboxylic acids

Question 13

Describe reactivity of LiBH4

Answer 13

1. Reacts with the most reactive carbonyls

2. Doesn’t react at all with amides or carboxylic acids

Question 14

Describe reactivity of NaBH4

Answer 14

1. Reacts with most reactive carbonyls
2. Slow react with esters
3. Doesn’t react with amides or carboxylic acids

Question 15

Describe reactivity of BH3

Answer 15

1. Reacts best with less reactive carbonyls

2. Slow reactions with esters, ketones and aldehydes

Question 16

What is BH3 useful for

Answer 16

1. Good at reducing less electron rich in presence of more reactive carbonyls

Question 17

How are aldehydes and ketones reduced to primary and secondary alcohols

Answer 17

1. Nucleophilic addition
2. One hydrogen equivalent
3. Secondary alcohol produced contains a stereogenic centre

Question 18

How are esters, amides and carboxylic acids reduced

Answer 18

1. Nucleophilic substitution first
2. Then nucleophilic addition
3. 2 hydrogen equivalents

Question 19

How can aldehydes and ketones be reduced to alkanes

Answer 19

1. Clemmensen reaction

2. Wolff-Kishner reaction

Question 20

Describe the clemmensen reaction

Answer 20

1. Zn(Hg) and concentrated HCl- very harsh conditions

2. Very harsh conditions

Question 21

Describe the Wolff- Kishner reaction

Answer 21

1. N2H4.H2O (>10 eq)
2. KOH (>5 eq)
3. > 180 degrees
4. Very harsh conditions

Question 22

What can cyanide be used for

Answer 22

1. Generate a new c-c bond and cyanohydrin functionality

2. It is a carbon based nucleophile

Question 23

Describe how cyanide can be used to convert an aldehyde or ketone

Answer 23

1. Reaction is reversible
2. Add NaCN, H2O and HCl to aldehyde or ketone
3. Produces a alcohol with a CN group

Question 24

Why is the conversion of an aldehyde/ketone using cyanide reversible

Answer 24

1. The CN group is a good leaving group

2. This means it is reversible

Question 25

What is formed if you add acid and water to a nitrile

Answer 25

1. A carboxylic acid is produced | 2. Need to be around 100 degrees

Question 26

How can a nitrile undergo functional group interconversion to become a carboxylic acid

Answer 26

1. Add acid (H2SO4), Water and 100 degrees | 2. Forms a carboxylic acid containing the same R group

Question 27

How can alkyl groups be added to carbonyls

Answer 27

1. Organometallic reactions | 2. Most common are either lithium or magnesium derived

Question 28

What are the properties of Li/Mg organometallics

Answer 28

1. Not ionic but covalent 2. Very strong nucleophiles 3. Very strong bases- pKa of conjugate acid >40 4. Therefore can deprotonate acid C-H bonds to form new organometallic reagents

Question 29

What is a grignard reagent

Answer 29

1. Organomagnesium compounds with the general formula RMgX | 2. X is a halide

Question 30

How is a Grignard reagent formed

Answer 30

1. Addition of magnesium to alkyl halides (I,Br,Cl) in etheric solvents (Et2O) 2. Addition to aryl halides (I,Br) in tetrahydrofuran (THF) 3. Involves insertion of magnesium into carbon-halogen bond (oxidative insertion)

Question 31

Why are the particular solvents used in formation of Grignard

Answer 31

1. Et2O used for alkyl halides- don't need high boiling solvent to keep heat in as not a lot of heat is needed 2. THF for aryl halides- holds heat in solution for aryl halides which need a higher heat

Question 32

How can you make organolithium reagents

Answer 32

1. Uses an oxidative insertion process 2. substitution of Lithium in alkyl halides (I,Br,Cl) in etheric solvents (Et2O) 3. Substitution of lithium in aryl halides (I,Br) in tetrahydrofuran (THF) 4. Replaces the halide completely 5. Also can use lithium halogen exchange as another method

Question 33

What do you need to be careful about when making Mg/Li organometallic reagents

Answer 33

1. Cannot have any acidic or carbonyl functional groups present 2. As the reagents are very basic and reactive 3. These need to be protected

Question 34

How are aldehydes and ketones reduced using organometallic reagents

Answer 34

1. Nucleophilic addition | 2. Form secondary and tertiary alcohols

Question 35

How is an ester reduced using an organometallic reagent

Answer 35

1. First reduction of OR group to form ketone by nucleophilic substitution 2. Then reduced further 3. 2 equivalents of reducing agent 4. Forms a tertiary alcohol

Question 36

How is an amide reduced using an organometallic reagent

Answer 36

1. First nucleophilic substitution to form aldehyde or ketone 2. Then react further 3. One reducing equivalent

Question 37

How is a carboxylic acid reduced using an organometallic reagent

Answer 37

1. It isn't

Question 38

What is a Wittig reaction

Answer 38

1. Use of phosphonium salts to convert aldehydes/ketones to alkenes 2. Utilises phosphorous ylide as the key reagent which is prepared in situ from phosphonium salt 3. Phosphonium salt is easily prepared from alkyl halide and phosphine - SN2 reaction

Question 39

How can the nature of the substituent on the ylid control E/Z geometry

Answer 39

1. R groups= H, OR, alkyl = Z-alkene | 2. R groups= alkyl = E-alkene

Question 40

Why does the difference in R-groups affect the stereochemistry

Answer 40

1. If R group= H, OR, alkyl, the phosphorous ylid is stabilised by delocalisation of -ve charge 2. If R group= alkyl only, the phosphorous ylid is unstabilised as the -ve charge can't be delocalised by conjugation

Question 41

What is a ylide

Answer 41

1. A ylide is a species which contains two oppositely charged atoms bonded directly to each other.