Other Reactions of
Ketones and Aldehydes
Relative Reactivity of Carboxylic Acid Derivatives
Relative Reactivity of Carbonyl-containing
Compounds
Formation of hydrates (gem-diols) from
aldehydes and ketones
Mechanism of acid-catalyzed hydration of a
ketone
Formation of Acetals and Ketals
Formation of hemiketals and ketals from
ketones
The equilibrium can be driven to the right by removal of water from the
reaction (through a Dean-Stark trap, or addition of a drying agent)
Hemiacetal
Full ketals and acetals are quite stable (including stability to strong base), but
hemiketals and hemiacetals are in equilibrium with the aldehyde and ketone, with the
C=O group usually favored, except in the case of cyclic hemiacetals, like carbohydrates,
which exist primarily as cyclic hemiacetals as shown above. Note that the sixmembered ring size is favored.
The equilibrium between the open and closed (glucopyranose) form of glucose
results in epimerization of the anomeric carbon (the aldehyde carbonyl carbon in
the open chain form)
Notice that there are two C=O’s, but only the aldehyde (and not the carbamate)
carbonyl is affected by these reaction conditions.
Note the use of a diol to facilitate transformation to the FULL acetal, through
formation of a five-membered ring.
Note that only the ketone carbonyl is converted to the
ketal (since ketones are more reactive than amides).
This (ketalization) reaction is
reversible under acidic
conditions (and upon the
addition of water)
Use (of ketal) to ‘protect’ the ketone
during reduction of the esters
Note that the ketal is formed in step 1, the reduction is performed in step 2, and the
ketal is converted back to the ketone in step 3, above.
Formation of Oximes and
Hydrazones from Aldehydes
and Ketones
Compared with other imines (C=N), oximes and hydrazones are more stable,
due to resonance from the adjacent heteroatom through the C=N.
Mechanism of oxime formation
Hydroxylamine
(usually added as hydroxylamine
hydrochloride)
Oxime
(frequently solid)
Use of hydrazine (H2N-NH2) leads to formation of the
corresponding hydrazone.
Formation of Imines
Imines form rapidly from aldehydes and primary amines, but are not stable to
hydrolysis (back to the aldehyde and amine), and are rarely isolable.
Combination of Imine Formation
with Hydride (NaBH3CN) Reduction
of Intermediate Imine, to Produce
Amine
(Reductive Amination)
Mechanism of Reductive Amination
Procedure
Notice that it is the N-protonated iminium ion which is reduced by the hydride
reagent. To do this requires a hydride reagent which is stable under slightly acidic
conditions. The two most commonly used reagents are:
sodium cyanoborohydride, NaBH3CN, and
sodium triacetoxyborohydride, NaBH(OAc) 3