Download Carboxylates/esters vs ketones/aldehydes

Chem 216 S11 Notes - Dr. Masato Koreeda
Date: May 10, 2011
Topic: _Experiment 4__ page 1 of 3.
Experiment 4: NaBH4 Reduction of an Unknown Aromatic Ketone
[See: Ege’s book, Section 14.4, pp 545-549]
Two commonly used hydride-based reducing agents:
1. Sodium borohydride (NaBH4)
H
Na+ H B- H
H
electronegativity values:
H 2.1; B 2.0; Al 1.5
|Δe.n.| for B-H: 0.1
|Δe.n.| for Al-H: 0.6
- mild reducing agent
- relatively stable reagent (against moisture, air)
2. Lithium aluminum hydride (LiAlH4)
H
a stronger H donor
H Al- H more polarized, more on the H
H
In addition, the size differences between B and H and Al and H should make the dissociation of H- more effective for the Al-H
bond.
- powerful reducing agent
- reacts violently with water, ROH to produce H2 gas
- Reactions with LiAhH are usually carried out in a polar aprotic solvent such as anhydrous tatrahydrofuran
(THF) and anhydrous (diethyl) ether (CH3CH2OCH2CH3)
Li+
O
O
THF
(diethyl) ether
In addition, the difference in the coordination power of Na+ and Li+ (stronger) on the carbonyl oxygen
further contributes to make the reactivity of LiAlH4 stronger.
Reduction with LiAlH4 requires an aqueous (usually acidic) workup.
Carboxylates/esters vs ketones/aldehydes
ease of reduction
C=O C more electrophilic
R C O
O
R C O R'
O
R C R'
O
carboxylate
ester
ketone
(carboxylic
R C H
O
aldehyde
acid)*
NaBH4 reduces
LiAlH4 reduces
*
R C O H
O
Li
H
H Al H
H
H
R C O Al H
O
H
Li
+
H2
H3O+-workup
RCH2OH
Chem 216 S11 Notes - Dr. Masato Koreeda
Topic: _Experiment 4__ page 2 of 3.
Date: May 10, 2011
NaBH4 reduces ketone and aldehyde carbonyls to their corresponding alcohols
and reduces ester/lactone carbonyls extremely slowly at room temperatures
Therefore, selective reduction of a ketone/aldehyde in the presence of an ester/lactone group in the
same molecule is generally attainable.
For example, with NaBH4:
O
OH
NaBH4
H3CO
H3COH
room temp.
O
OH
+
H3CO
H3CO
cis-isomer
O
O
trans-isomer
In contrast, with LiAlH4:
1. LiAlH4/ether
0 °C
O
OH
2. H3O+ -workup
H3CO
OH
+
HO
O
HO
cis-isomer
trans-isomer
An intramolecular reaction involving a ketone/aldehyde C=O and an ester C=O during NaBH4
reduction reaction is often observed:
O
OCH3
NaBH4
O
C2H5OH
room temp.
O
OH
O
+
O
O
+
OCH3
O
NaBH4
-O
O
reacts faster with
the nearby ester C=O
than protonation by the
solvent
O
OCH3
O
OCH3
intramol.
reaction
O
O
+
OCH3
O
+
OCH3
O
cis
O
OCH3
O
O
O
OCH3
O
trans
attack to the ester C=O C
These reaction rates are comparable.
protonation from the solvent C2H5OH
OH
OCH3
O
Chem 216 S11 Notes - Dr. Masato Koreeda
Topic: _Experiment 4__ page 3 of 3.
Date: May 11, 2011
Mechanism of NaBH4 reduction [see: Ege’s, p. 546].
(solvent)
H OC2H5
δO
δ+
Na
H
H B H
H
in
C2H5OH
O
H
OH
Na
H
+ BH3
+ Na
OC2H5
BH3 becomes B(OC2H5)3 by reacting with ethanol, then, when heated with water, becomes B(OH)3.
The mechanism of the NaBH4 reduction in a protic solvent such as ethanol, methanol, and water is
known to be quite complex since NaBH4 reacts with the solvent,
e.g., NaBH4 + C2H5OH → NaBH3(OC2H5) + H2
Because of this, usually at least one mol. equivalents of NaBH4 are used for the reaction in a protic
solvent. What makes the kinetics of the reaction more complicated is the fact that these solvent reacted
reagents such as NaBH3(OC2H5) and NaBH2(OC2H5)2 reduce ketones/aldehydes much faster than the
original NaBH4 does.
Pre-lab Experiments: In Experiment 4, you need to go through a few pre-lab experiments (see p. 10 of
the lab manual) on your unknown aromatic ketone. After narrowing down to one or two possibilities
for the structure of your unknown aromatic ketone, obtain the information on the mp/bp and IR of your
expected REDUCTION product(s) (i.e., an alcohol, not your starting ketone) through the use of Reaxys
[https://www.reaxys.com/reaxys/secured/start.do;jsessionid=8DEDFF0EA14EB7ABC856F12631DBD
642]. The web address of the URL user guide of the Reaxys written by Dr. Ye Li is:
http://guides.lib.umich.edu/chem216
If your unknown ketone is likely to be
O
Draw the structure of its reduction product on the “structure editor” screen of the Reaxys program.
OH
The information you need to obtain is: bp or mp (the solvent used for recrystallization) and where to
find the IR data or spectrum of the reduction product. Please note that the Reaxys program does not
show you any IR data/spectra. It only gives you references to find such information.