Pi Bonds as Electrophiles (Ketones + Aldehydes) Flashcards
what makes carbonyl groups such excelled electrophiles?
the resonance form has an incomplete octet
describe the geometry of ketone and aldehyde groups
- C and O are sp2 hybridised
- trigonal planar geometry
- pi bond is perpendicular to the plane of the carbonyl
draw and describe the two main steps of nucleophilic additions to electrophilic aldehydes and ketones
- nucleophilic attack
- protonation to give an alcohol
what is the angle of attack of the nucleophile to the carbon?
the angle of attack is 105’ to the plane of the carbon (sp2; trigonal planar), converting it to an alkoxide ion (sp3, tetrahedral)
what are the two ways in which a nucleophile can attack an electrophile? how does this impact the stereochemistry of the products?
- 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
which is more reactive - aldehydes or ketones? why?
aldehydes are slightly more reactive than ketones towards nucleophilic attack due to steric and electronic effects
steric effects that differentiate aldehyde and ketone reactivity
- 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
electronic effects that differentiate aldehyde and ketone reactivity
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
does nucleophilic addition to an aldehyde or a ketone have a greater activation energy (ΔG‡)?
ketones
what are the three main nucleophile types?
carbon: R-MgBr, R-Li, R-≡C:(-), :≡C(-):
hydrogen (hydride): H(-) in NaBH4, LiAlH4
oxygen: H2O/HO(-), ROH/RO(-)
what are organometallic compounds?
a large family of compounds in which carbon is bonded to an electropositive metal
what are Grignard reagents?
an important class of organometallic compounds that contains a carbon atom bonded to a magnesium atom
eg H3C(-) (+)MgBr
what gives Grignard reagents their properties?
highly polarised C-Mg bond causes the carbon to behave as a carbanion (negatively charged carbon)
how are Grignard reagents made?
slide 13
state 3 varieties of organohalides that can be used to make Grignard reagents
- alkyl halides
- allyl halides
- aryl halides
why is diethyl ether important in the synthesis of Grignard reagents?
it helps to stabilise the very reactive Grignard reagent by acting as a lewis base
two ways in which Grignard reagents react
- act as very strong bases and will react with any acidic hydrogens (eg OH, NH, SH) including water and alcohols
- act as excellent nucleophiles with carbonyls
Grignard reagents can only be prepared using starting materials and solvents that DO NOT contain —-
acidic hydrogens
draw a mechanism for the reaction of a Grignard reagent with an alcohol
draw a mechanism for the reaction of a Grignard reagent with an aldehyde or a ketone
give an example of a class of compounds other than Grignard reagents that can also react with carbonyls by nucleophilic addition
organolithiums (mechanism on slide 17)
define a hydride
a nucleophilic hydrogen - a hydrogen atom with increased electron density
draw sodium borohydride (NaBH4)
draw lithium aluminium hydride (LiAlH4)
which is a better nucleophile between NaBH4 and LiAlH4 and why?
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
what solvent is used with NaBH4? why?
alcohol solvent - NaBH4 is a mild hydride source and reactions usually use alcohol solvents
what solvent is used with LiAlH4 and why?
LiAlH4 is a strong hydride source and reactions are run in parotid solvents like Et2O since the hydride reacts violently with water and alcohols
draw the mechanism for carbonyl reduction reactions using hydride nucleophiles
how does water react with aldehydes or ketones?
water can react with aldehydes and ketones to form gem-diols (or hydrates) in a reversible reaction
define geminal (=gem)
atoms or functional groups attached to the same atom
what does the equilibrium of the reaction between water and aldehydes depend on?
the reactivity of the carbonyl - hydrates of aldehydes are typically favoured and ketones hydrates are less favourable
define a catalyst
a substance that increases the rate of a reaction but is not consumed
what are two ways to increase hydration rates?
- base-catalysed hydration (hydroxide is a better nucleophile than water)
- acid-catalysed hydration (decreased electron density of carbonyl makes protonated carbonyl is a better electrophile than water)
how do alcohols react with aldehydes and ketones?
simple alcohols react in a similar manner as water with aldehydes and ketones to form hemiacetals and hemiketals in a reversible reaction
draw a hemiacetal
draw a hemiketal
draw the mechanism for acid-catalysed hemiacetal formation (forward reaction)
draw the mechanism for acid-catalysed hemiacetal formation (reverse reaction)
are intramolecular reactions to form acyclic hemiacetals favoured in the presence of water?
no
are intramolecular reactions to form cyclic hemiacetals favoured?
yes, due to the smaller entropy cost
define anomeric carbons
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
when simple sugars cyclise to form hemiacetals, they form:
anomie’s, which are cyclic monosaccharides differing in configuration at the Homeric carbon
glycosidic bond
links sugar units (bond at the anomeric carbon)
look at how anomie’s form from a acyclic sugar
