Topic 11: Carbonyls: Reactions of Aldehydes and Ketones Flashcards
Orbitals involved in the addition reaction of carbonyls
LUMO on electrophilic carbonyl
HOMO on the nucleophile
pi* antibonding orbital of the C=O
HCl pKa
-8.0
H2O pKa
15.7
ROH pKa
15-18
CH4 pKa
48
How does pKa of nucleophile affect it’s ability to react with a carbonyl
The higher the pKa, the less stable the nucleophile so the equilibrium favours the products.
Equilibrium favours lower pKa
How to prepare an alkyl halide for an addition reaction
Treat with appropriate metals e.g. Li / Mg
in appropriate solvent e.g. tetrahydrofuran (THF) or diethyl ether
Sodium Borohydride (NaBH4) is a relatively mild, … agent. It only readily reacts with the…, e.g., …
Reduction of less electrophilic esters is comparatively slow. … can therefore be used as a … reducing agent with the solvent …
nucleophilic reducing
most electrophilic carbonyl functional groups
aldehydes and ketones.
NaBH4
chemoselective
EtOH or iPrOH
Lithium Aluminium hydroxide (LiAlH4) is a powerful … agent
Due to its high reactivity, LiAlH4 reduces even e.g., … Compared with NaBH4, it is a very … reducing agent:
LiAlH4 is a … reagent and must be used with care. It reacts violently with … Reactions are therefore normally performed in ethereal solvents e.g. …
nucleophilic reducing
weakly electrophilic carbonyl groups
esters, amides (to amines) and carboxylic acids
chemoselective
highly flammable
protic solvents
THF, Et2O
Diisobutylaluminium hydride (DIBAL-H) is a … agent. It displays a different reactivity profile to that shown by NaBH4 and LiAlH4 which are … agents;
Thus, whilst DIBAL-H readily reduces aldehydes and ketones, it also reacts readily with …
neutral, electrophilic reducing
nucleophilic anionic hydridic reducing
esters and tertiary amides
In its monomeric form, DIBAL-H adopts a … structure in which the aluminium centre is …The empty … on the aluminium centre renders it strongly Lewis acidic. In the presence of DIBAL-H, a carbonyl oxygen can function as a … .The formation of the resulting … complex has the effect of increasing the … of the carbonyl carbon and the … of the appended hydride substituent in the associated DIBALH unit. Intramolecular hydride transfer now effects …
trigonal planar
sp2-hybridised
p AO
Lewis base
Lewis acid–Lewis base
electrophilicity
nucleophilicity
reduction.
DIBAL-H is a particularly versatile … agent.
In the case of esters, the reaction … govern the outcome of the reaction.
Synthesis of Alcohols: Reduction of esters – use … temperatures (typically …) and using … equiv. DIBAL-H
Under these conditions, the initial … intermediate collapses to release an … which in the presence
of a … equivalent of DIBAL-H, undergoes further reduction to afford a … product after aqueous
work-up.
Synthesis of Aldehydes:
Reduction of esters – use … temperatures (…) and … equivalent of DIBALH.
Under these conditions, the initially formed … intermediate is often sufficiently … that further reaction is prevented until …
which allows the isolation of the …
reducing
stoichiometry and reaction conditions
‘high’
0 °C
2
tetrahedral
aldehyde
second
primary alcohol
low
–78 °C
1
tetrahedral
stable
aqueous work-up
aldehyde
The reversible addition of water to give the hydrate.
The mechanism is similar to other nucleophilic addition reactions. However, as water is a … the rate of reaction is slow.
2 ways of increasing the rate of reaction in a nucleophilic addition process:
Increase the …
Increase the …
In the case of the hydration reaction, the rate can be increased using both approaches by using … respectively. In the presence of water, aldehydes and ketones exist in … .The position of this depends on the … hydration is under … control, if the equilibrium lies on the left, then something must be … e.g. … leads to … as they are … so exert a … effect. Upon hydration, the carbonyl carbon goes from … The two substituents are therefore … leading to …
relatively poor nucleophile,
electrophilicity of the carbonyl group,
nucleophilicity of the nucleophile.
acid or base
equilibrium with their hydrates.
relative stabilities of the carbonyl group and the hydrate
thermodynamic
stabilising the carbonyl group and/or destabilising the hydrate
increased alkyl substitution increased stabilisation of the group
electron donating
+I
sp2-trigonal planar to sp3-tetrahedral
pushed closer together
increased steric repulsions and an increased destabilisation
HBr pKa
-9.0
