Zn(BH4)2/Al2O3: A new synthetic method for the efficient and convenient reduction of organic carbonyl compounds to their corresponding alcohols

Article abstract of DOI:10.2298/JSC120111044S

Zn(BH₄)₂ (0.5-2 mmol) in the presence of Al ₂O₃ (1 mmol) reduces a variety of organic carbonyl compounds such as aldehydes, ketones, acyloins, α-diketones and α,β-unsaturated carbonyl compounds to their corresponding alcohols. The reduction reactions were realized in THF at room temperature affording high to excellent yields of the products. The chemoselective reduction of aldehydes over ketones was successfully accomplished with this reducing system. In addition, regioselectivity and exclusive 1,2-reduction of conjugated carbonyl compounds to their corresponding allylic alcohols in high to excellent yields was successfully accomplished.

Full text of DOI:10.2298/JSC120111044S

J. Serb. Chem. Soc. 78 (1) 1–13 (2013)
JSCS–4391
UDC 547.447:66.094.2+546.47’273’11+
546.62’214+542.913:547.43
Original scientific paper
Zn(BH4)2/Al2O3: A new synthetic method for the efficient
and convenient reduction of organic carbonyl compounds
to their corresponding alcohols
*
DAVOOD SETAMDIDEH , BEHROOZ KHEZRI and MEHDI RAHMATOLLAHZADEH
Department of Chemistry, Faculty of Sciences, Mahabad Branch,
Islamic Azad University, Mahabad, 59135-443, Iran
(Received 11 January 2012)
Abstract: Zn(BH4)2 (0.5–2 mmol) in the presence of Al2O3 (1 mmol) reduces a
variety of organic carbonyl compounds such as aldehydes, ketones, acyloins, α-
diketones and α,β-unsaturated carbonyl compounds to their corresponding
alcohols. The reduction reactions were realized in THF at room temperature af-
fording high to excellent yields of the products. The chemoselective reduction
of aldehydes over ketones was successfully accomplished with this reducing
system. In addition, regioselectivity and exclusive 1,2-reduction of conjugated
carbonyl compounds to their corresponding allylic alcohols in high to excellent
yields was successfully accomplished.
Keywords: Zn(BH4)2; Al2O3; reduction; carbonyl compounds; chemoselective;
regioselectivity.
INTRODUCTION
It is well known that sodium borohydride reduces organic carbonyl com-
pounds to their corresponding alcohols using enormously different reducing sys-
1
tems. In order to control the reducing power of the reagent, hundreds of substi-
tuted borohydrides have been introduced in the chemical literature and many are
2a–c
2d
3a
now commercially available, e.g., Li(BH ),
K(BH ),
Ca(BH ) ,
4
4
4 2
3b–d
4
5a,b
Cu(BH ) ,
Ti(BH ) , Zr(BH ) ,
LiBH , Ca(BH ) and Zn(BH ) are the
4 2
4 3
4 4
4 4 2 4 2
modified borohydride agents that have better solubility in aprotic solvents, so
their uses and applications are of interest in organic synthesis. Among these
2+
reagents, zinc borohydride is unique because: a) Zn is a soft Lewis acid in
2+
+
+
comparison to Ca , Li and Na , which are hard acids and b) better coordination
2+
ability of Zn , which imparts selectivity in hydride transfer reactions. In
addition, reduction of aldehydes and ketones with NaBH impregnated on neutral
4
*Corresponding author. E-mail: davood.setamdideh@gmail.com
doi: 10.2298/JSC120111044S
1
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2
SETAMDIDEH, KHEZRI and RAHMATOLLAHZADEH
Al O under microwave irradiation has been reported. Although the reported
2
3
method is fast for the reduction of aldehydes, in the case of ketones, the need for
large amounts of NaBH (eightfold) and the moderate yields of the products are
4
5c–d
major limitations.
On the other hand, zinc tetrahydroborate, Zn(BH ) , as a
4 2
non-conventional hydride transfer agent, has been reported to effect very
efficient chemo-, regio- and stereoselective reductions. This potential reducing
agent is neutral and can be used in a range of aprotic solvents, such as ether, THF
and DMF. In spite of this, zinc tetrahydroborate has been used less than regular
reducing agents in laboratories for the reduction of organic compounds, probably
because of its non-availability as a commercial reagent, being freshly prepared in
solution, and the problem of controlling its reducing power. To overcome these
limitations, stable modifications of Zn(BH ) in the form of tertiary amino or
4 2
phosphinoligand complexes, such as [Zn(BH ) (dabco)] (dabco: 1,4-diazabicyclo
4 2
2,6
7
8
10
[2.2.2.] octane,
[Zn(BH ) (pyz)] (pyz: pirazin), [Zn(BH ) (Ph P) ],
[Zn(BH ) (bpy)] (bpy: bipyrdine), [Zn(BH ) (py)] (py: pyridine),
[Zn(BH ) –XP ] (XP4: crosslinked 4-polyvinylpiridine), [Zn(BH ) (nmi)]
(nmi: N-methylimidazole) and [Zn(BH ) (nic)] (nic: nicotine)
4 2
n
4 2
3
1–2
9
4 2
4 2
11
12a
4 2
4
4 2
12b
have been
4 2
made and used for the reduction of organic compounds. The challenge in che-
mistry to develop efficient processes, reaction media and conditions are some of
the most important issues in the scientific community in this matter. In this con-
12
text and in continuation of previous studies with modified reducing systems,
herein, Zn(BH ) /Al O is introduced as a new combination reducing system for
4 2
2 3
the efficient and convenient reduction of carbonyl compounds to their corres-
ponding alcohols.
RESULTS AND DISCUSSION
Ranu et al. reported Zn(BH ) to be a reducing agent capable of reducing
4 2
13a–c
some organic carbonyl compounds.
To investigate the influence of alumina
on the rate of reduction and the lack of systematic information on the reduction
of carbonyl compounds with zinc borohydride in the presence of alumina without
using any other agent directed the focus of the present study to an investigation
of the influence of alumina as a moderator catalyst on this transformation. The
preliminary experiments showed that the reduction of benzaldehyde (1 mmol) as
a model compound with Zn(BH ) (1 mmol) in THF or CH CN was not com-
4 2
3
pleted after 1 h at room temperature. However, when this reaction was performed
in the presence of neutral alumina (1 mmol), the rate of reduction was dramatically
accelerated and the reaction was completed within 1 min (Scheme 1).
These results prompted an investigation of the optimum reaction conditions
to examine the influence of alumina as a catalyst. For the selection of the appro-
priate solvent(s) and amount of catalyst in such reductions, a set of experiments
was performed on the reduction of benzaldehyde and acetophenone as model
compounds, the results of which are given in Tables I and II, respectively.
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REDUCTION OF ORGANIC CARBONYL COMPOUNDS
3
Zn(BH4)2 (1 mmol)
CH2OH
CHO
CH3CN (3 mL) or THF (3 mL), rt, 2 h, 70-75%
Zn(BH4)2/Al2O3(1/1 mmol)
THF (3 mL) or CH3CN (3 mL), rt, 1 min, 94%
Scheme 1. Comparison of the reduction of benzaldehyde by Zn(BH4)2 in the presence and
absence of neutral alumina.
TABLE I. Optimization reaction conditions for reduction of benzaldehyde with the Zn(BH4)2,
neutral Al2O3 system at room temperature
Entry
Molar ratioa
(1/0.5/0)
(1/1/0)
Solvent (3 mL)
Time, h
Conversionb, %
1
2
3
4
5
6
7
a
THF
THF
CH3CN
THF
1
2
2
<100 c
<100 c
<100 c
100
100
100
(1/1/0)
(1/0.5/1) d
(1/0.5/2)
(1/0.5/1) d
(1/1/1)
0.08
1.5
0.08
0.016
THF
CH3CN
THF
100
b
Molar ratio benzaldehyde/Zn(BH ) /Al O ; completion of the reaction was monitored by TLC (eluent, CCl ,
4 2
2
3
4
c
Et O: 5/2); the yields of isolated pure products were 50 % for entry 1, 75 % for entry 2 and 70 % for entry 3;
2
d
the reduction reactions were performed in the presence of acidic, basic or neutral alumina and the same results
were obtained
TABLE II. Optimization reaction conditions for the reduction of acetophenone with the
Zn(BH4)2, neutral Al2O3 system at room temperature
Entry
Molar ratioa
Solvent (3 mL)
Time, h
Conversionb, %
1
2
3
4
5
a
(1/1/0)
(1/1/1)d
(1/1/2)
(1/2/1)d
(1/2/2)
THF
THF
THF
THF
THF
b
1
1
1
0.8
1.2
<100c
100
<100c
100
100
Molar ratio acetophenone/Zn(BH ) /Al O ; completion of the reaction was monitored by TLC (eluent, CCl ,
4 2
2
3
4
c
d
Et O: 5/2), the yield of isolated pure products were 60 % for entry 1 and 80 % for entry 3; the reduction
2
reactions were performed in the presence of acidic, basic or neutral alumina and the same results were obtained
The results showed that the reduction of benzaldehyde at room temperature
with 0.5 molar amount of Zn(BH ) in the presence of 1 molar amount of neutral
4 2
Al O was very efficient (Table I, entries 4 and 6). In addition, it is noteworthy
2
3
that the reduction reactions were performed in the presence of acidic and basic
Lalumina and the same results were obtained. Then these optimal conditions
were applied for the reduction of structurally different aliphatic and aromatic
aldehydes with neutral alumina. All the reactions were performed with 0.5 mol
Zn(BH ) per mol aldehyde at room temperature and the corresponding primary
4 2
alcohols were obtained in high to excellent yields (83–97 %), as could be seen in
Table III.
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SETAMDIDEH, KHEZRI and RAHMATOLLAHZADEH
TABLE III. Reduction of aldehydes (1 mmol) with the Zn(BH4)2 (0.5 mmol)/Al2O3 (1 mmol)
system in THF (3 mL) at room temperature; the reduction reactions were realized in the
presence of neutral alumina
Time Yielda
M.p. or B.p., °C
Found Reported14
Entry
Substrate
Product
h
%
1
2
3
4
Benzaldehyde
4-Chlorobenzaldehyde 4-Chlorobenzyl alcohol 0.08
3-Chlorobenzaldehyde 3-Chlorobenzyl alcohol 0.08
2,4-Dichlorobenzaldehyde 2,4-Dichlorobenzyl
alcohol
Benzyl alcohol
0.08
94 203–204
205
70–72
237
92
96
90
71–73
238
56–58
0.08
55–58
5
6
4-Methylbenzaldehyde 4-Methylbenzyl alcohol 0.1
93
93
60–62
258
59–61
259
4-Methoxybenzaldehyde
4-Methoxybenzyl
alcohol
0.1
7
8
9
10
11
4-Hydroxybenzaldehyde 4-Hydroxybenzyl alcohol 0.1
2-Hydroxybenzaldehyde 2-Hydroxybenzyl alcohol 0.1
97 119–122 118–122
92
94
94
84–85
31–33
92–94
83–85
30–32
92–94
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
4-Hydroxy-3-methoxy
benzaldehyde
Furfural
1-Naphthaldehyde
3-Nitrobenzyl alcohol 0.08
4-Nitrobenzyl alcohol 0.08
4-Hydroxy-3-
methoxybenzyl alcohol
Furfuryl alcohol
0.1
97 114–115 113–115
12
13
14
0.1
0.1
88 169–170
90 61–62
170
61–63
1-Naphthylmethanol
2,6-Dimethylhept-5-enal 2,6-Dimethylhept-5-en- 0.08
1-ol
90 225–227 225–226
15
Heptanal
1-Heptanol
0.08
83 177 176
a
Yields refer to isolated pure products
Next, attention was turned to the reduction of ketones using this reducing
system. The low reactivities of ketones relative to those of aldehydes led to the
reduction reactions being performed under different conditions, i.e., the reduc-
tions were performed with 1 molar amounts of Zn(BH ) at room temperature in
4 2
the presence of 1 molar amounts of neutral Al O in THF (Table II, entry 2). The
2
3
utility of this reducing system was further explored with the reduction of
structurally different aliphatic and aromatic ketones using 1 mol Zn(BH ) in the
4 2
presence of 1 mol neutral Al O per mol ketone in THF at room temperature.
2
3
Such reductions were also efficient and the corresponding secondary alcohols
were obtained in high to excellent yields (87–98 %) (Table IV).
The synthetic applications of vicinal diols are well known and their prepa-
rations from the reduction of acyloins or α-diketones have attracted a great deal
of attention. Reduction of α-diketones usually gives a mixture of α-hydroxy
15
ketones and vicinal diols. Selective reduction of α-diketones to acyloins or
16
vicinal diols can be undertaken with some chemical or biochemical reagents.
Reduction of α-diketones to vicinal diols with modified hydroborate agents is
12,17
also a subject of interest
and this goal was easily achieved by Zn(BH ) (2
4 2
mol) in the presence of 1 mol neutral Al O in THF at room temperature. The
2
3
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REDUCTION OF ORGANIC CARBONYL COMPOUNDS
5
reduction reactions were performed efficiently in short reaction times (20–40
min) (92–95 %) (Table V). Under different conditions, attempts to reduce α-di-
ketones into acyloins were unsatisfactory and only vicinal diols were identified
as the sole products. In addition, reduction of acyloins to vicinal diols is also a
subject of interest in organic synthesis. The applications of non-hydridic reduc-
18
12,17
tants and modified hydroborate
have also been reported for such reduc-
tions. Using Zn(BH ) (1 mol) in the presence of neutral Al O (1 mol) in THF
4 2
2 3
also easily provided this transformation at room temperature. Acyloin com-
pounds were reduced to their corresponding vicinal diols in high to excellent
yields with this reducing system (90–94 %) (Table V, entries 2 and 4).
TABLE IV. Reduction of ketones (1 mmol) with the Zn(BH4)2 (1 mmol)/Al2O3 (1 mmol)
system in THF (3 mL) at room temperature; the reduction reactions were realized in the
presence of neutral alumina
Time Yielda
M.p. or B.p., °C
Found Reported14
Entry
Substrate
Product
h
%
1
2
3
Benzophenone
Acetophenone
4-Bromoacetophenone
Diphenylmethanol
1-Phenylethanol
1-(4-
3
1
1
96
93
98
65–67
203
37–38
65–67
204
36–37
Bromophenyl)ethanol
4
5
6
4-Methylacetophenone 1-(4-Methylphenyl)-
ethanol
3
4
93 219–221 218–220
4-Methoxybenzo-
phenone
(4-Methoxyphenyl)-
(phenyl)methanol
2,3-Dihydro-1H-in-
den-1-ol
90
95
68–69
52–55
67–69
50–54
2,3-Dihyro-1H-inden-
-1-one
1.5
7
8
9
9H-Fluoren-9-one
4-Phenylcyclohexanone 4-Phenylcyclohexanol
4-Phenyl-2-butanone 4-Phenylbutan-2-ol
9H-Fluoren-9-ol
1.6
1
0.8
93 153–154 153–154
87
58–60
58
90 131–132
132
a
Yields refer to isolated pure products
The chemoselective reduction of one functional group without affecting the
other one is a well-known strategy for the preparation of molecules with ever-
increasing complexity in organic synthesis.
This subject is of great interest and numerous modified hydroborate systems
6,8–10a–c,12,13b,17,19
have been reported for it.
Since under the defined conditions,
the reduction of aldehydes and ketones with Zn(BH ) in the presence of Al O
4 2
2 3
is dependent on the molar ratio of Zn(BH ) to Al O , it was thought that this
4 2
2 3
system could have a chemoselectivity towards the reduction of aldehydes over
ketones. This fact was demonstrated with the selective reduction of benzaldehyde
in the presence of acetophenone using 0.5 mol Zn(BH ) in the presence of 1 mol
4 2
neutral Al O at room temperature in THF (Table VI, entry 3) (Scheme 2).
2
3
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SETAMDIDEH, KHEZRI and RAHMATOLLAHZADEH
TABLE V. Reduction of acyloins and α-diketones with the Zn(BH4)2/Al2O3 (1 mmol) in THF
(3 mL) at room temperature; the reduction reactions were realized in the presence of neutral
alumina
Zn(BH4)2/ Time Yielda
M.p. or B.p., °C
Entry
1
Substrate
Benzylb
Product
Found Reported14
Substrate
h
%
1,2-Diphenyl-
ethane-1,2-diol
1,2-Diphenyl-
ethane-1,2-diol
2/1
0.33 95
0.33 90
0.58 92
–
–
–
–
–
–
2
3
Benzoinb
1/1
2/1
1,2-Bis(4-methoxyphe- 1,2-Bis(4-me-
nyl)ethane-1,2-dioneb thoxyphenyl)-
ethane-1,2-diol
4
2-Hydroxy-1,2-bis(4- 1,2-Bis(4-me-
1/1
2/1
0.5 94
–
–
-methoxyphenyl)-
thoxyphenyl)-
ethane-1,2-diol
1,3-Diphenyl-
ethanoneb
5
1,3-Diphenylpro-
pane-1,2-dione
0.67 95 63–64
63–64
propane-1,2-diol
a
c
Yields refer to isolated pure products; the pinacols were formed as dl-meso mixtures that were not separated
TABLE VI. Optimization of the reaction conditions for the competitive reduction of benz-
aldehyde (1 mmol) and acetophenone (1 mmol) with the Zn(BH4)2, Al2O3 system in THF
(3 mL) at room temperature; the reduction reactions were performed in the presence of neutral
alumina
Entry Molar ratioa Time, h Yield of benzyl alcoholb, % Yield of 1-phenylethanolb, %
1
1/1/0.5/0
1/1/0.5/0.5
1/1/0.5/1
1/1/1/1
1
1
0.08
1
50
79
97
94
96
30
6
0
30
51
2
3c
4
5
1/1/2/1
1
a
b
Molar ratio as benzaldehyde, acetophenone, Zn(BH ) , Al O ; yields refer to isolated pure products by PLC
4 2
2
3
c
(eluent, CCl , Et O: 5/2); GC analysis was also performed
4
2
Scheme 2. Competitive reduction of benzaldehyde and acetophenone with Zn(BH4)2/neutral
Al2O3 system in THF; the ratio in parentheses is in mmol.
The usefulness of this chemoselectivity of the reduction was further exa-
mined with the reduction of benzaldehyde in the presence of other ketones. As
shown in Table VII, benzaldehyde was reduced exclusively, or nearly so.
Reduction of unsaturated carbonyl compounds with sodium borohydride,
one of the most widely utilized reducing agents, is highly solvent dependent and
20a,b
generally does not result in useful regioselectivity.
To control the reducing
potential and selectivity of NaBH into regioselective 1,2-reduction of conju-
4
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REDUCTION OF ORGANIC CARBONYL COMPOUNDS
7
gated enones, numerous hydroborate agents have been developed in the follow-
ing ways: a) by the replacement of hydride(s) with sterically bulky substituents or
electron-withdrawing/releasing groups in order to discriminate between the struc-
20c–f
tural and electronic environments of carbonyl groups;
b) combination with
20g–k,3a
20a
Lewis acids
and mixed solvent systems; c) use of transition metal hyd-
roborates and their new modifications; d) use of quaternary ammonium and
20l
19e–f,20m–n
phosphonium tetrahydroborates;
e) and finally immobilization on an
20o
anion exchange resin.
TABLE VII. Competitive reduction of benzaldehyde (1 mmol) in the presence of ketones
(1 mmol) to their corresponding alcohols with Zn(BH4)2 (0.5 mmol), neutral Al2O3 (1 mmol)
in THF (3 mL) at room temperature
Entry
Ketone
Time, h
Yield1a, %
Yield2b, %
1
2
3
Acetophenone
Benzophenone
9H-Fluoren-9-one
4-Phenylbutan-2-one
0.08
0.08
0.08
0.08
97
93
95
91
0
2
3
4
8
a
b
Yield1 of benzyl alcohol refers to isolated pure products by PLC (eluent, CCl , Et O: 5/2); yields of corres-
4
2
ponding alcohols for ketones refer to isolated pure products by PLC (eluent, CCl , Et O: 5/2)
4
2
The usefulness of the studied reducing system was further investigated with
the regioselective 1,2-reduction of α,β-unsaturated carbonyl compounds. Thus,
the reduction of cinnamaldehyde was examined. The reduction reaction occurred
with 0.5 mmol Zn(BH ) in the presence of 1 mmol neutral Al O in 5 min at
4 2
2 3
room temperature in THF with a perfect regioselectivity and the product
cinnamyl alcohol was obtained in high yield (Table VIII, entry 1). This procedure
was also applied for the reduction of citral at room temperature and geraniol was
obtained in 92 % yield (Table VIII, entry 2).
Furthermore, the reductions of conjugated enones with the studied reducing
system were investigated. The results showed that the procedure was also
regioselective and efficient, but the reduction reactions were performed using 1
molar amounts of Zn(BH ) in the presence of 1 molar amounts of neutral Al O
4 2
2 3
at room temperature in THF. Regioselective 1,2-reductions of benzylidene-
acetone and chalcone were successfully achieved, with high to excellent yields of
the corresponding allylic alcohols (Table VIII, entries 3 and 4).
In order to show the efficiency of the reducing system Zn(BH ) /Al O , the
4 2
2 3
results obtained in the present were compared with those of reported in the li-
21a
21b
9
terature for NaBH /MoCl ,
NaBH /Dowex1-x8,
[Zn(BH ) (bpy)],
4
5
4
4 2
10
8
20m
[Zn(BH ) (py)],
[Zn(BH ) (Ph P) ], Ph PMe(BH )
and [PhCH (dab-
2
4 2
4 2
3
2
3
4
19e
co)]BH
, as given in Table IX.
4
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8
SETAMDIDEH, KHEZRI and RAHMATOLLAHZADEH
TABLE VIII. Reduction of conjugated carbonyl compounds with Zn(BH4)2, Al2O3 (1 mmol)
in THF (3 mL) at room temperature; the reduction reactions were performed in the presence
of neutral alumina
Zn(BH4)2/ Time Yielda
M.p. or B.p., °C
Found Reported14
Entry
1
Substrate
Product
Substrate
h
%
Cinnamaldehyde 3-Phenyl-2-propen-
-1-ol
0.5/1
0.08 96 33–34 33–35
2
Cis and trans Cis and trans-3,7-dime-
0.5/1
1/1
0.08 92
–
–
citral
thyl-2,6-octadien--1-olb
Benzylidene-
acetone
4-Phenyl-3-butene-
-2-ol
1
3
95 55–56 55–57
91 33–34 33–34
3
Chalcone
1,3-Diphenylprop-2-
1/1
4
-en-1-ol
a
b
Yields refer to isolated pure products; cis and trans geraniol were not separated
TABLE IX. Comparison of the reductions of aldehydes and ketones with Zn(BH4)2/Al2O3
system and with other reported reducing systems; I – Zn(BH4)2/Al2O3, II – NaBH4/MoCl5, III
– NaBH4/Dowex1-x8, IV – [Zn(BH4)2(bpy)], V – [Zn(BH4)2(py)], VI – [Zn(BH4)2(Ph3P)2],
VII – Ph3PMe(BH4), VIII – [PhCH2(dabco)]BH4
Molar ratio (reagent/substrate), time, h, yield, %
Entry Substrate
I
II21a
III21b
IV9
V10
VI8
–
VII20m VIII19e
1, Ima, 1, 0.25,
1
2
Benzal- 0.5, 0.08,0.5, 0.03, 1, 0.05, 0.25, 1, 0.5, 91
dehyde 94 96 96 0.02, 95
4-Methoxy- 0.5, 0.1, 1.5, 3, 99 1.5, 3, 0.35, 1, 1.3, 96 1, 0.17, 1, Im, 83 2, 0.8, 85
90
90
benzal-
dehyde
93
99
0.17, 99
89
3
4-Chloro- 0.5, 0.08, 1, 0.15, 1, 0.15, 0.25,
1, 0.2, 1, Im, 1, Im, 86 1, 0.23,
benzal-
dehyde
92
99
99
0.08, 98
99
88
90
4
5
Benzophe- 1, 3, 96 3, 3.2, 3, 3.2, 98 1, 0.75, 2, 4.3, 97
none 98 99
9H-Fluo- 1, 1.6, 93 2, 1.8, 2, 1.8, 1, 1.5, 2, 5.3, 2, 0.33, 1.6, 18,
–
–
2, 21.5,
90
–
ren-9-one
Benzoin 1, 0.33, 2, 0.17, 2, 0.17, 0.5, 0.08, 0.5, 0.5,
90 96 96 91 97
94
94
94
98
85
–
80
–
6
–
a
Immediately
EXPERIMENTAL
All substrates and reagents of the best available quality were purchased from commercial
1
sources and used without further purification. IR and H-NMR spectra were recorded on a
PerkinElmer FT-IR RXI and a 300 MHz Bruker spectrometers, respectively. Agilent 6890N
gas chromatograph equipped with a FID detector was used in this study. The products were
characterized by their 1H-NMR or IR spectra and comparison with authentic samples (melting
points or boiling points). The organic layers were dried over anhydrous sodium sulfate. All
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REDUCTION OF ORGANIC CARBONYL COMPOUNDS
9
yields refer to isolated pure products. TLC on silica gel 60 F254 aluminum sheets was applied
for purity determination of the substrates and products and to monitor the reactions.
A typical procedure for reduction of aldehydes with the Zn(BH4)2/Al2O3 system in THF
Zn(BH4)2 was prepared from ZnCl2 and NaBH4 according to an established procedure
from the literature.5 In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a
solution of benzaldehyde (0.106 g, 1 mmol) in THF (3 mL) was prepared. To this solution,
Zn(BH4)2 (0.048 g, 0.5 mmol) and then neutral Al2O3 (0.101 g, 1 mmol) were added and the
mixture was stirred at room temperature for 5 minutes. Completion of the reaction was
monitored by TLC (eluent, CCl4/Et2O: 5/2). Then, distilled water (1 mL) was added to the
reaction mixture and stirring was continued stirred for 5 min.. The mixture was extracted with
CH2Cl2 (3×6 mL) and dried over anhydrous Na2SO4. Evaporation of the solvent and a short
column chromatography of the resulting crude material over silica gel (0.015–0.040 mm, elu-
ent, CCl4/Et2O: 5/3) afforded the pure liquid benzyl alcohol (0.102 g, 94 %, Table III, entry 1).
A typical procedure for reduction of ketones to alcohols with the Zn(BH4)2/Al2O3 system in THF
In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of
acetophenone (0.121 g, 1 mmol) in THF (3 mL) was prepared. To this solution, Zn(BH4)2
(0.095 g, 1 mmol) and then neutral Al2O3 (0.101 g, 1 mmol) were added. The resulting mix-
ture was stirred at room temperature for 60 min. The progress of the reaction was monitored
by TLC (eluent, CCl4/Et2O: 5/2). After completion of the reaction, distilled water (1 mL) was
added to the reaction mixture and then stirring was continued for an additional 5 min. The
mixture was extracted with CH2Cl2 (3×8 mL) and dried over anhydrous sodium sulfate. Eva-
poration of the solvent and short column chromatography of the resulting crude material over
above mentioned silica gel afforded pure crystals of 1-phenylethanol (0.11 g, 93 % yield,
Table IV, entry 2).
A typical procedure for reduction of α-diketones and acyloins with the Zn(BH4)2/Al2O3 system
in THF
In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of benzil
(0.21 g, 1 mmol) in THF (3 mL was prepared. To this solution, Zn(BH4)2 (0.190 g, 2 mmol)
and then neutral Al2O3 (0.101 g, 1 mmol) were added. The resulting mixture was stirred at
room temperature for 20 min. The progress of the reaction was monitored by TLC (eluent,
CCl4/Et2O: 5/2). After completion of the reaction, distilled water (1 mL) was added to the
reaction mixture and stirring was continued for an additional 5 min. The mixture was ex-
tracted with CH2Cl2 (3×10 mL) and dried over anhydrous sodium sulfate. Evaporation of the
solvent and short column chromatography of the resulting crude material over above
mentioned silica gel afforded pure crystals of 1,2-diphenylethane-1,2-diol (0.20 g, 95 % yield,
Table V, entry 1).
A typical procedure for the competitive reduction of aldehydes and ketones with the
Zn(BH4)2/Al2O3 system in THF (method A)
In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of benz-
aldehyde (0.106 g, 1 mmol) and acetophenone (0.120 g, 1 mmol) in THF (3 mL) was pre-
pared. To this solution, Zn(BH4)2 (0.048 g, 0.5 mmol) and then neutral Al2O3 (0.101 g, 1
mmol) were added and the mixture was stirred at room temperature. The progress of the
reaction was monitored by TLC. After 5 min, the reaction mixture was quenched by addition
of distilled water (1 mL) and this mixture was then stirred for an additional 5 min. The
mixture was extracted with CH2Cl2 (3×8 mL) and dried over anhydrous sodium sulfate. After
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10
SETAMDIDEH, KHEZRI and RAHMATOLLAHZADEH
the evaporation of solvent, the resulting crude products (0.223 g) were separated by plate layer
chromatoghraphy (PLC) over silica gel (60 F254 (0.063–0.200 mm), eluent, CCl4/Et2O: 5/2),
which afforded pure liquid benzyl alcohol as the sole product (0.106 g, 97 %) and aceto-
phenone (0.108 g, 89 %) as intact material (Table VI, entry 3).
A typical procedure for competitive reduction of aldehydes and ketones with Zn(BH4)2/Al2O3
system in THF (method B)
In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of
benzaldehyde (0.106 g, 1 mmol) and acetophenone (0.121 g, 1 mmol) in THF (3 mL) was
prepared. A sample of reaction mixture in THF is injected (0.1 μL) onto a HP5 30 m×25 μm
capillary column. The initial column temperature (100 °C) was held for 2 min, then increased
at 15 °C min-1 to 240 °C and held for 15 min. Benzaldehyde eluted first (7.28 min) followed
by acetophenone (10.29 min) with a relative response ratio of about 1:1 (Instrument para-
meters: injector temperature, 250 °C; detector temperature, 300 °C; flow rate (He), 45 mL
min-1, with He as the make-up gas). Then, to this solution, Zn(BH4)2 (0.048 g, 0.5 mmol) and
then neutral Al2O3 (0.101 g, 1 mmol) were added and the mixture was stirred at room tempe-
rature. The progress of the reaction was monitored by TLC. After 5 min, the reaction mixture
was quenched by the addition of distilled water (0.5 mL) and the stirring was continued for an
additional 5 min. and dried over anhydrous sodium sulfate. Again, a sample of reaction mix-
ture in THF is injected (0.1 μL) onto the GC column under the same conditions. Benzyl al-
cohol eluted first (9.71 min) followed by acetophenone (10.29 min) with a relative response
ratio of about 1:1. The reduction procedure afforded pure liquid benzyl alcohol as the sole
product and acetophenone as unreacted material.
The typical procedure for the regioselective 1,2-reduction of conjugated carbonyl compounds
with the Zn(BH4)2/Al2O3 system in THF
In a round-bottomed flask (10 mL) equipped with a magnetic stirrer, a solution of ben-
zylideneacetone (0.146 g, 1 mmol) in THF (3 mL) was prepared. To this solution, Zn(BH4)2
(0.0.95 g, 1 mmol) and then neutral Al2O3 (0.101 g, 1 mmol) were added. The resulting mix-
ture was stirred at room temperature. The progress of the reaction was monitored by TLC
(eluent, CCl4/Et2O: 5/2). After completion of the reaction within 60 min, distilled water (1
mL) was added to the reaction mixture and this mixture was then stirred for an additional 5
min. The mixture was extracted with CH2Cl2 (3×10 mL) and dried over anhydrous sodium
sulfate. Evaporation of the solvent and short column chromatography of the resulting crude
material over silica gel (eluent, CCl4/Et2O: 5/2) afforded pure liquid 4-phenyl-3-buten-2-ol
(0.140 g, 95 % yield, Table VIII, entry 3).
CONCLUSIONS
In this investigation, it was shown that the combination system of Zn(BH ) /
4 2
/Al O in THF reduces a variety of carbonyl compounds to their corresponding
2
3
alcohols in high to excellent yields. The reduction reactions were performed with
0.5–2 mmol Zn(BH ) in the presence of 1 mmol Al O in THF. Reduction of
4 2
2 3
acyloins and α-diketones by this reducing system also efficiently produced the
corresponding vicinal diols. In addition, the chemoselective reduction of alde-
hydes over ketones was successfully accomplished with this reducing system.
Regioselectivity of this system was also investigated with exclusive 1,2-reduction
of conjugated carbonyl compounds to their corresponding allylic alcohols in high
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REDUCTION OF ORGANIC CARBONYL COMPOUNDS
11
to excellent yields. All reductions were realized at room temperature. The high
efficiency of the reductions, short reaction times and easy work-up procedure
makes this combined reductant an attractive new protocol for the reduction of
carbonyl compounds and it could be a useful addition to the existing
methodologies.
Acknowledgments. The authors gratefully appreciate the financial support of this work by
the Research Council of the Islamic Azad University Branch of Mahabad, Iran. The assistance
of Mr. Avat Ali Poramjad and Mr. Chalak Azimi for running the FT-IR spectra is also
acknowledged.
И З В О Д
Zn(BH4)2/Al2O3: НОВ СИНТЕТИЧКИ ПОСТУПАК ЗА ЕФИКАСНУ РЕДУКЦИЈУ
ОРГАНСКИХ КАРБОНИЛНИХ ЈЕДИЊЕЊА ДО ОДГОВАРАЈУЋИХ АЛКОХОЛА
DAVOOD SETAMDIDEH, BEHROOZ KHEZRI и MEHDI RAHMATOLLAHZADEH
Department of Chemistry, Faculty of Sciences, Mahabad Branch, Islamic Azad University,
Mahabad, 59135-443, Iran
Zn(BH4)2 (0,5–2 mmol) у присуству Al2O3 (1 mmol) редукује различита карбонилна
једињења, као што су алдехиди, кетони, ацилоини, α-дикетони и α,β-незасићена карбо-
нилна једињења, до одговарајућих алкохола. Реакција се одвија у тетрахидрофурану као
растварачу, на собној температури, a принос производа је висок до одличан. Хемиосе-
лективна редукција алдехида у присуству кетона извршена је успешно. Осим тога,
постигнута је региоселективност и селективна 1,2-редукција конјугованих карбонилних
једињења до одговарајућих алилних алкохола у високом до одличном приносу.
(Примљенo 11. јануара 2012)
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