Pi Bonds as Electrophiles (Ketones + Aldehydes)

Question 1

what makes carbonyl groups such excelled electrophiles?

Answer 1

the resonance form has an incomplete octet

Question 2

describe the geometry of ketone and aldehyde groups

Answer 2

• C and O are sp2 hybridised
• trigonal planar geometry
• pi bond is perpendicular to the plane of the carbonyl

Question 3

draw and describe the two main steps of nucleophilic additions to electrophilic aldehydes and ketones

Answer 3

1. nucleophilic attack
2. protonation to give an alcohol

Question 4

what is the angle of attack of the nucleophile to the carbon?

Answer 4

the angle of attack is 105’ to the plane of the carbon (sp2; trigonal planar), converting it to an alkoxide ion (sp3, tetrahedral)

Question 5

what are the two ways in which a nucleophile can attack an electrophile? how does this impact the stereochemistry of the products?

Answer 5

• a nucleophile can attack from either face of the carbonyl carbon, either top or bottom lobe of the pi bond
• if the groups attached to the carbonyl are different, both chiral configurations of the alcohol, R and S, are produced
• this leads to a racemic mixture

Question 6

which is more reactive - aldehydes or ketones? why?

Answer 6

aldehydes are slightly more reactive than ketones towards nucleophilic attack due to steric and electronic effects

Question 7

steric effects that differentiate aldehyde and ketone reactivity

Answer 7

• aldehydes have only one substituent; the nucleophile is less hindered and more reactive
• ketones have two substituents; the nucleophile is more hindered and less reactive

Question 8

electronic effects that differentiate aldehyde and ketone reactivity

Answer 8

alkyl groups (C-based substituents) are electron donating groups, which stabilise the adjacent δ+ on the carbonyl atom
- aldehydes have one donating group so are less stable and more reactive
- ketones have two donating groups so are more stable and less reactive

Question 9

does nucleophilic addition to an aldehyde or a ketone have a greater activation energy (ΔG‡)?

Answer 9

ketones

Question 10

what are the three main nucleophile types?

Answer 10

carbon: R-MgBr, R-Li, R-≡C:(-), :≡C(-):
hydrogen (hydride): H(-) in NaBH4, LiAlH4
oxygen: H2O/HO(-), ROH/RO(-)

Question 11

what are organometallic compounds?

Answer 11

a large family of compounds in which carbon is bonded to an electropositive metal

Question 12

what are Grignard reagents?

Answer 12

an important class of organometallic compounds that contains a carbon atom bonded to a magnesium atom
eg H3C(-) (+)MgBr

Question 13

what gives Grignard reagents their properties?

Answer 13

highly polarised C-Mg bond causes the carbon to behave as a carbanion (negatively charged carbon)

Question 14

how are Grignard reagents made?

Answer 14

slide 13

Question 15

state 3 varieties of organohalides that can be used to make Grignard reagents

Answer 15

• alkyl halides
• allyl halides
• aryl halides

Question 16

why is diethyl ether important in the synthesis of Grignard reagents?

Answer 16

it helps to stabilise the very reactive Grignard reagent by acting as a lewis base

Question 17

two ways in which Grignard reagents react

Answer 17

1. act as very strong bases and will react with any acidic hydrogens (eg OH, NH, SH) including water and alcohols
2. act as excellent nucleophiles with carbonyls

Question 18

Grignard reagents can only be prepared using starting materials and solvents that DO NOT contain —-

Answer 18

acidic hydrogens

Question 19

draw a mechanism for the reaction of a Grignard reagent with an alcohol

Question 20

draw a mechanism for the reaction of a Grignard reagent with an aldehyde or a ketone

Question 21

give an example of a class of compounds other than Grignard reagents that can also react with carbonyls by nucleophilic addition

Answer 21

organolithiums (mechanism on slide 17)

Question 22

define a hydride

Answer 22

a nucleophilic hydrogen - a hydrogen atom with increased electron density

Question 23

draw sodium borohydride (NaBH4)

Question 24

draw lithium aluminium hydride (LiAlH4)

Question 25

which is a better nucleophile between NaBH4 and LiAlH4 and why?

Answer 25

LiAlH4 as the difference in electronegativity between aluminium and hydrogen is greater, leading to a greater δ- on the hydrogen, making it a better/more reactive nucleophile

Question 26

what solvent is used with NaBH4? why?

Answer 26

alcohol solvent - NaBH4 is a mild hydride source and reactions usually use alcohol solvents

Question 27

what solvent is used with LiAlH4 and why?

Answer 27

LiAlH4 is a strong hydride source and reactions are run in parotid solvents like Et2O since the hydride reacts violently with water and alcohols

Question 28

draw the mechanism for carbonyl reduction reactions using hydride nucleophiles

Question 29

how does water react with aldehydes or ketones?

Answer 29

water can react with aldehydes and ketones to form gem-diols (or hydrates) in a reversible reaction

Question 30

define geminal (=gem)

Answer 30

atoms or functional groups attached to the same atom

Question 31

what does the equilibrium of the reaction between water and aldehydes depend on?

Answer 31

the reactivity of the carbonyl - hydrates of aldehydes are typically favoured and ketones hydrates are less favourable

Question 32

define a catalyst

Answer 32

a substance that increases the rate of a reaction but is not consumed

Question 33

what are two ways to increase hydration rates?

Answer 33

1. base-catalysed hydration (hydroxide is a better nucleophile than water) 2. acid-catalysed hydration (decreased electron density of carbonyl makes protonated carbonyl is a better electrophile than water)

Question 34

how do alcohols react with aldehydes and ketones?

Answer 34

simple alcohols react in a similar manner as water with aldehydes and ketones to form hemiacetals and hemiketals in a reversible reaction

Question 35

draw a hemiacetal

Question 36

draw a hemiketal

Question 37

draw the mechanism for acid-catalysed hemiacetal formation (forward reaction)

Question 38

draw the mechanism for acid-catalysed hemiacetal formation (reverse reaction)

Question 39

are intramolecular reactions to form acyclic hemiacetals favoured in the presence of water?

Answer 39

no

Question 40

are intramolecular reactions to form cyclic hemiacetals favoured?

Answer 40

yes, due to the smaller entropy cost

Question 41

define anomeric carbons

Answer 41

the hemiacetal carbon of a cyclic sugar. this carbon was the carbonyl carbon of the aldehyde or ketones in the open chain form of the sugar

Question 42

when simple sugars cyclise to form hemiacetals, they form:

Answer 42

anomie's, which are cyclic monosaccharides differing in configuration at the Homeric carbon

Question 43

glycosidic bond

Answer 43

links sugar units (bond at the anomeric carbon)

Question 44

look at how anomie's form from a acyclic sugar