Turk J Chem

23 (1999) , 123 126.

UB

ITAK
Transition Metal Compound Mediated Reduction of
-Amino Acids to 1,2-Amino Alcohols with NaBH
4
in
Water
Ayhan S. DEM

IR,

Idris M. AKHMEDOV,

O. SESENO

GLU
Middle East Technical University, Faculty of Arts and Science, Department of Chemistry,
06531, Ankara-TURKEY
Received 03.08.1998
A new ecient and cost-eective method for the preparation of 1,2-amino alcohols is described.
The reactions of amino acids with NaBH4 in the presence of NiCl 2 or MoO3 in water give 1,2-amino
alcohols in high yield. When optically pure amino acids were used, optically pure 1,2-amino alcohols
were obtained.
Introduction
The chiral 1,2-amino alcohols are important compounds, because a large number of natural products contain
the amino alcohol functionality and many amino alcohol derivatives have chemotherapeutic properties. They
also have applications especially as chiral auxiliaries for dierent asymmetric synthesis reactions
1
. 1,2-
Amino alcohols can be prepared from readily available amino acids. Reduction of amino acids to form amino
alcohols has been reported recently. One approach uses a sodium borohydride-sulfuric acid system
2
, while
another employs NaBH
4
-iodine
3
. Other reagents have also been used for the reduction of amino acids, such
as lithium aluminum hydride
4
, borane-methyl sulde in the presence of boron triuoride etherate
5
, and
lithium borohydride in the presence of trimethylsilyl chloride
6
.
Sodium borohydride is a mild reducing agent with high selectivity. The combination of sodium
borohydride with cobalt, nickel, iridium, osmium, copper, platinum, titanium, and rhodium halides has been
employed to reduce functional groups, which are inert to sodium borohydride alone
7
.
Experimental
General method for the preparation of 1,2-amino alcohols:
To a mixture of -amino acid (30 mmol) and transition metal compound (45 mmol, 1.5 equivalent) in
water (100 mL) NaBH
4
(300 mmol, 10 equivalent) (exothermic reaction, reux condenser is necessary) was
carefully added at room temperature (evt. cooling). An alternative procedure is the addition of transition
metal compound to the mixture of amino acid and NaBH
4
in water. This method sometimes gave a better
yield. The resulting dark mixture was stirred at ambient temperature for 6-10 h (checked by TLC; Silical
123
Transition Metal Compound Mediated Reduction of -Amino..., A. S. DEM

IR,

I. M. AKHMEDOV,
Gel, EtOAc:Hexane:MeOH 1:1:1). The residue was treated with aqueous KOH (20%, 20 mL) and extracted
several times with dichloromethane. The aqueous layer was saturated with NaCl and extracted again with
dichloromethane. The combined organic layers were washed with water and again with brine, before being
dried over MgSO
4
. After ltration and evaporation of solvent, the 1,2-amino alcohols were obtained as an
oil or solid. Further purication was achieved by distillation under vacuum or by recrystallization.
Results and Discussion
*
O
OH
1
R
NH
2
NaBH
4
, MoO
3
or
NiCl
2
, Water
*
OH
2
R
NH
2
Scheme 1
We have previously reported that treatment of hydroxyiminophosphonates with sodium borohydride
in the presence of MoO
3
or NiCl
2
aorded the aminophosphonic acids in good yield
8
. In this study we
would like to report the selective reduction of -amino acids with the same transition metal compounds.
As shown in Scheme 1, the reduction of -amino acids with sodium borohydride in the presence of
NiCl
2
or MoO
3
at ambient temperature in water gave the corresponding 1,2-amino alcohols in high yield.
The reduction is carried out by adding NiCl
2
or MoO
3
to the mixture of NaBH
4
and amino acid in water.
This reaction step is exothermic and sometimes cooling is necessary. The same reaction can also be achieved
by adding NaBH
4
to the solution of amino acid containing one of the above transition metal compounds.
Dierent amino acids were used for this reduction with dierent functional groups and corresponding 1,2-
amino alcohols were obtained (Table). As expected, the optical purity of 1,2-amino alcohols, determined
from the optical rotation values, were the same as the starting material. By all reduction reactions NaBH
4
was used in excess, and the ratio for the best yield was: substrate/ NiCl
2
or MoO
3
/ NaBH
4
1/1.5/10.
Decreasing the amount of NaBH
4
decreased the yield of the reaction rapidly.
The reaction of NaBH
4
with NiCl
2
and MoO
3
is exothermic and deposits a black granular precipitate,
which is referred as metal boride in the literature
7,9
. This precipitate was collected by ltration. After the
excess borohydride has hydrolyzed, the water was decanted and black granules were washed with absolute
ethanol. The reduction of amino acids in the presence of NaBH
4
was also attempted with this solid material
instead of NiCl
2
and MoO
3
, but no reaction took place. The same black granulas were also used for the
hydrogenation of amino acids in a Parr hydrogenation apparatus but this experiment also gave no product.
After all of these experimental observations, we think that the mechanism involves the transition metal
assisted hydride reduction, while the corresponding borides are formed.
124
Transition Metal Compound Mediated Reduction of -Amino..., A. S. DEM

IR,

I. M. AKHMEDOV,
Table 1. Reduction of Amino Acids with NaBH4 /NiCl 2 and NaBH4 /MoO3 in water
a
Amino Acid Amino alcohol Yield (%)
b
mp (bp/mm Hg)
2,10
MoO
3
NiCl
2
L-Proline 78 81 74-76

C/2
L-Valine 73 78 (100-102

C/25)
L-Phenylalanine 82 83 92-94

C
L-Alanine 73 77 (172-174

C)
DL-Phenylglycine 83 81 74-77

C
L-tert.Leucine 77 76 (102-104

C/18)
DL-Methionine 71 78 (134-138

C/8)
a) The spectroscopic data of the amino alcohols are in agreement with the published data
2,10
. b) The
reaction was monitored by TLC until no more starting material was present. This was consistent with 100%
conversion of reactant to the product. Lower experimental yields were due to the loss of some material
during the isolation process.
It can be concluded that the NaBH
4
-MoO
3
and NiCl
2
system provides a useful and simple synthetic
route under mild conditions for the preparation of 1,2-amino alcohols from -amino acids. Large scale
preparation is also possible.
Acknowledgements
We thank Middle East Technical University (AFP-1997), Turkish State Planning Organization (DPT-1996),
and the Scientic and Technical Research Council of Turkey for their nancial support.
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