Chem 216 S11 Notes - Dr.

Masato Koreeda Date: May 10, 2011

Topic: _Experiment 4__ page 1 of 3.

Experiment 4: NaBH
4
Reduction of an Unknown Aromatic Ketone
[See: Eges book, Section 14.4, pp 545-549]

Two commonly used hydride-based reducing agents:

Na
+
B
-
H
H
H
H
- mild reducing agent
- relatively stable reagent (against moisture, air)
electronegativity values:
H 2.1; B 2.0; Al 1.5
|!e.n.| for B-H: 0.1
|!e.n.| for Al-H: 0.6
1. Sodium borohydride (NaBH
4
)
Li
+
Al
-
H
H
H
H
- powerful reducing agent
- reacts violently with water, ROH to produce H
2
gas
- Reactions with LiAhH are usually carried out in a polar aprotic solvent such as anhydrous tatrahydrofuran
(THF) and anhydrous (diethyl) ether (CH
3
CH
2
OCH
2
CH
3
)
2. Lithium aluminum hydride (LiAlH
4
)
more polarized, more on the H a stronger H donor
O
O
THF
(diethyl) ether
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.


In addition, the difference in the coordination power of Na
+
and Li
+
(stronger) on the carbonyl oxygen
further contributes to make the reactivity of LiAlH
4
stronger.
Reduction with LiAlH
4
requires an aqueous (usually acidic) workup.

Carboxylates/esters vs ketones/aldehydes


ease of reduction
C R O
O
carboxylate
C R O
O
ester
R' C R
O
ketone
C R H
O
aldehyde
NaBH
4
reduces
LiAlH
4
reduces
(carboxylic acid)
*
*
C R O
O
H
Al H
H
H
H
C R O
O
Al
H
H
H
Li
Li
+
H
2
H
3
O
+
-workup
RCH
2
OH
C=O C more electrophilic
R'

Chem 216 S11 Notes - Dr. Masato Koreeda Date: May 10, 2011
Topic: _Experiment 4__ page 2 of 3.

NaBH
4
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.


O
O
H
3
CO
O
H
3
CO
O
H
3
CO
OH OH
NaBH
4
H
3
COH
room temp.
+
cis-isomer trans-isomer
O
O
H
3
CO HO HO
OH OH
1. LiAlH
4
/ether
+
cis-isomer trans-isomer
2. H
3
O
+
-workup
0 C
For example, with NaBH
4
:
In contrast, with LiAlH
4
:


An intramolecular reaction involving a ketone/aldehyde C=O and an ester C=O during NaBH
4

reduction reaction is often observed:

O
O
OCH
3
NaBH
4
O
O
O
O
OH
O
OCH
3
C
2
H
5
OH
room temp.
+ +
NaBH
4
OH
O
OCH
3
O
OCH
3
O
O
OCH
3
O
O
OCH
3
O
O
O
+
OCH
3
cis
trans
-O
reacts faster with
the nearby ester C=O
than protonation by the
solvent
intramol.
reaction
O
OCH
3
O
O
O
+
OCH
3
attack to the ester C=O C
protonation from the solvent C
2
H
5
OH
These reaction rates are comparable.


Chem 216 S11 Notes - Dr. Masato Koreeda Date: May 11, 2011
Topic: _Experiment 4__ page 3 of 3.

Mechanism of NaBH
4
reduction [see: Eges, p. 546].


O
! -
!+
H B H
H
H
Na
H
O Na
in
C
2
H
5
OH
H OC
2
H
5
(solvent)
+ BH
3
H
OH
+ Na OC
2
H
5


BH
3
becomes B(OC
2
H
5
)
3
by reacting with ethanol, then, when heated with water, becomes B(OH)
3
.


The mechanism of the NaBH
4
reduction in a protic solvent such as ethanol, methanol, and water is
known to be quite complex since NaBH
4
reacts with the solvent,

e.g., NaBH
4
+ C
2
H
5
OH ! NaBH
3
(OC
2
H
5
) + H
2

Because of this, usually at least one mol. equivalents of NaBH
4
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 NaBH
3
(OC
2
H
5
) and NaBH
2
(OC
2
H
5
)
2
reduce ketones/aldehydes much faster than the
original NaBH
4
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.