Reduction of nitrobenzene derivatives using sodium borohydride and transition metal sulfides

Article abstract of DOI:10.1016/j.tetlet.2014.08.068

Reported here is the reduction of aromatic nitro compounds using sodium borohydride and transition metal sulfides as catalysts. The reaction conditions were optimized using the reduction of nitrobenzene as a model reaction. The catalysts studied were iron sulfide (Fe₃S₄), copper sulfide (CuS), zinc sulfide (ZnS), cobalt sulfide (Co₃S₄), and nickel sulfide (NiS). The reduction was monitored using gas chromatography. Quantitative conversions were achieved using Co₃S₄ and NiS, representing a ten-fold increase in reactivity compared to the non-catalyzed reaction. Fe₃S₄ and ZnS had no apparent effect on the reduction of nitrobenzene while the reduction using CuS showed a marginal increase. The reduction method was applied to several aryl-nitro derivatives containing either electron-withdrawing or electron-donating groups. Halogen containing aryl-nitro compounds were reduced without dehalogenation. The reduction had no effect on other functional groups such as carboxylic acids, esters, amides, or alkenes, indicating that the reduction is highly chemoselective.

Full text of DOI:10.1016/j.tetlet.2014.08.068

Tetrahedron Letters 55 (2014) 5468–5470
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reduction of nitrobenzene derivatives using sodium borohydride
and transition metal sulfides
Samuel Piña Jr. a, Diana M. Cedillo a, Carlos Tamez b, Nezhueyotl Izquierdo a, Jason G. Parsons a,
Jose J. Gutierrez a,
⇑
a Department of Chemistry, The University of Texas-Pan American, United States
b Environmental Science and Engineering, The University of Texas at El Paso, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Reported here is the reduction of aromatic nitro compounds using sodium borohydride and transition
metal sulfides as catalysts. The reaction conditions were optimized using the reduction of nitrobenzene
as a model reaction. The catalysts studied were iron sulfide (Fe3S4), copper sulfide (CuS), zinc sulfide
(ZnS), cobalt sulfide (Co3S4), and nickel sulfide (NiS). The reduction was monitored using gas chromatog-
raphy. Quantitative conversions were achieved using Co3S4 and NiS, representing a ten-fold increase in
reactivity compared to the non-catalyzed reaction. Fe3S4 and ZnS had no apparent effect on the reduction
of nitrobenzene while the reduction using CuS showed a marginal increase. The reduction method was
applied to several aryl-nitro derivatives containing either electron-withdrawing or electron-donating
groups. Halogen containing aryl-nitro compounds were reduced without dehalogenation. The reduction
had no effect on other functional groups such as carboxylic acids, esters, amides, or alkenes, indicating
that the reduction is highly chemoselective.
Received 20 May 2014
Revised 14 August 2014
Accepted 18 August 2014
Available online 23 August 2014
Keywords:
Heterogenous catalysis
Metal sulfides
Reduction
Chemoselective
Sodium borohydride
Published by Elsevier Ltd.
The reduction of nitroaromatic compounds to their correspond-
ing aryl amines is an important reaction for the synthesis of
various pharmaceuticals, dyes, and other industrially related
compounds.1 Additionally, diazotization of these aryl amines can
easily yield important aromatic derivatives.2
Traditionally, nitroaromatic compounds are reduced using iron
and hydrochloric acid3 or via catalytic hydrogenation.4 Some
drawbacks, however, include the use of corrosive reagents and
risks associated with highly flammable molecular hydrogen.
NaBH4, a mild reducing agent, does not reduce nitroaromatic
compounds under normal conditions. However, several NaBH4
catalytic systems have been developed for the reduction of
nitroaromatic compounds. Accordingly, NaBH4/Raney nickel,1
NaBH4/CuSO4,5 NaBH4/Ni2B,6 NaBH4/CoCl2,7 NaBH4/Ni(OAc)2Á4H2O,8
and NaBH4/SnCl2Á2H2O9 have been proven successful in the
reduction of nitroaromatic compounds.
The reduction of nitrobenzene was studied to screen the cata-
lysts. In a typical procedure, nitrobenzene (1 equiv) dissolved in
ethanol was treated with NaBH4 (3 equiv) in the presence of the
corresponding catalyst (10 mol %). The reactions were carried out
in a closed scintillation vial and sonicated for 60 min. The reaction
was also performed without catalyst for comparison. Figure 1
shows the GC plots for the reduction of nitrobenzene using
different catalysts.
The efficiency of each catalyst compared to the non-catalyzed
reaction is shown in Table 1.
As seen from Figure 1 and Table 1, the reduction of nitroben-
zene using NaBH4 occurred in 9% conversion in the absence of a
catalyst. No significant increase in the conversion was observed
with Fe3S4 or ZnS. It should be noted that copper sulfate has been
reported to catalyze the homogeneous reduction of aromatic nitro
compounds.5 However, we observed only marginal conversion
using CuS. Co3S4 and NiS, on the other hand, increased the conver-
sion by a factor of 10 compared with the non-catalyzed reaction.
After determining that only the cobalt and nickel sulfides
produced an effect in the conversion, we studied the effect of the
concentration of the catalyst. Table 2 summarizes the effect of
Co3S4 and NiS concentration on the reduction of nitrobenzene. The
reactions were carried out for 60 min using 3 equiv of sodium
borohydride with respect to the nitrobenzene. It was observed that
In this work we studied the effect of several transition metal
sulfides on the reduction of nitro-aromatic compounds using
NaBH4. The transition metal sulfides (Fe3S4, Co3S4, NiS, CuS, and
ZnS) were synthesized hydrothermally.10
⇑
Corresponding author.
E-mail address: jjgg@utpa.edu (J.J. Gutierrez).
http://dx.doi.org/10.1016/j.tetlet.2014.08.068
0040-4039/Published by Elsevier Ltd.

S. Piña Jr. et al. / Tetrahedron Letters 55 (2014) 5468–5470
5469
Table 2
Effect of catalyst concentrationa
Conversionb (%)
Co3S4
Mole (%)
NiS
75
92.6
96.3
99.1
97.6
1
2.5
5
10
20
85
92
99.9
99.9
98.7
a
Ethanol, rt, sonication; substrate/NaBH4 = 1:3, 1 h.
Monitored by gas chromatography.
b
Table 3
Effect of NaBH4 concentration
NaBH4 (equiv)
Conversion (%)
1
71
1.5
2
3
99.6
99.9
99.9
using a Millipore syringe filter to eliminate the catalyst from the
reaction mixture. This ensured that no further reaction was taking
place. It was observed that 83% conversion was obtained at 10 min
while quantitative conversions were achieved at 20 min.
Figure 1. GC plots for nitrobenzene reduction attempts: (a) No catalyst; (b) Fe3S4;
(c) Co3S4; (d) NiS; (e) CuS; (f) ZnS.
only 1 mol % Co3S4 caused significant increase in conversion (85%)
compared to the non-catalyzed reaction. The conversion increased
steadily up to 5 mol % and it remained relatively constant at
10 mol % and 20 mol %. The results suggest that 5 mol % of catalysts
is the optimum concentration since the load of catalyst is relatively
low while achieving excellent conversions. As it was the case with
Co3S4, the conversion increases steadily with the concentration of
NiS. However, the maximum conversion was achieved at 10 mol %
catalyst and it remained relatively constant at 20 mol %. It should
be noted that the results in Table 2 are from only one run at each cat-
alyst concentration. Multiple studies are necessary to determine if
catalyst saturation occurs at concentrations above 10 mol %.
Previous experiments demonstrated that using Co3S4 resulted
in higher conversions compared with NiS. Therefore, the effect of
the concentration of sodium borohydride on the Co3S4 catalyzed
reduction of nitrobenzene was investigated. The experiments were
conducted using 5 mol % Co3S4 with 60 min overall reaction time.
The results are summarized in Table 3. As observed in Table 3,
using 1 mol equiv of NaBH4 resulted in 71% conversion. The results
suggest that at least 2 equiv of NaBH4 is needed to achieve quanti-
tative conversions.
The experiments described above demonstrated that quantita-
tive conversions in the reduction of nitrobenzene were possible
using Co3S4 and NiS. To demonstrate the scope of the newly devel-
oped method, the reduction of nitrobenzene derivatives containing
both electron withdrawing and electron donating groups was
investigated. The experiments were conducted using the optimum
conditions of 5 mol % of Co3S4 (which was demonstrated to be the
most efficient catalyst), 3 equiv of sodium borohydride, and the
reaction time was 60 min.11 Table 4 summarizes the results during
the reduction of several nitrobenzene derivatives. It should be
noted that the yields reported correspond to the isolated products.
As seen in Table 4, the newly developed system was employed
successfully in the reduction of nitrobenzene derivatives in moder-
ate (58%) to high (>90%) isolated yields. The isolated yield was
independent of the nature of the substituents. Thus, high yields
were observed for nitrobenzene containing electron withdrawing
groups (entries 2, 3, 4, and 8), and for nitrobenzene containing
electron donating groups (entries 5, 6, and 7). The seemingly low
Table 4
Reduction of nitrobenzene derivatives
After determining the optimum concentration of catalyst and
sodium borohydride, the effect of reaction time was investigated.
The experiments were conducted using 5 mol % of Co3S4 and
3 equiv of sodium borohydride. The reaction mixtures were filtered
Entry Substrate structure
Product structure
Isolated yield (%)
73
NO2
NH
2
1
F
NO
F
NH
2
2
3
4
5
6
7
81
91
86
58
93
90
Table 1
2
Reduction of nitrobenzenea
Cl
NO2
Cl
NH2
NO2
NH2
NaBH4
Br
H
NO
Br
H
NH
2
2
Ethanol
MxSy
N
NO2
NO2
N
NH2
NH2
2
2
MeO
MeO
Catalyst
Conversion (%)
—
9 ( 1.2)
9.3
99.9
96.3
11.2
10.9
H13C6O
NO
H13C6O
NH
Fe3S4
Co3S4
NiS
CuS
ZnS
2
2
NO2
NH2
HO
OH
8
84
HO
OH
a
Ethanol, rt, sonication; substrate/NaBH4/catalyst = 1:3:0.05, 1 h.

5470
S. Piña Jr. et al. / Tetrahedron Letters 55 (2014) 5468–5470
yield observed for entry 5 can be attributed to the high solubility of
the product in the solvents used during recrystallization.
also affords a mild and selective alternative for the effective
conversion of nitroaromatic compounds to their corresponding
aryl amines.
Products 1–6 are available commercially. Their physical proper-
ties and their IR and NMR spectra correspond to those for the
respective chemicals available from Sigma Aldrich Chemical Co
(see Supporting information). The 1H NMR and 13C NMR spectra
Acknowledgments
of p-hexyloxy-aniline (entry 7) correspond to the literature.12
A
This work was primarily supported by the National Science
Foundation under Award Number DMR-0934157, and by the
Welch Foundation Grant BG-0017.
new compound was obtained used the procedure reported here
(entry 8). The new compound, 2-amino-p-xylylene glycol, was
obtained as a white powder (mp = 130–132 °C). Its structure was
confirmed by its 1H NMR, 13C NMR, 13C DEPT-135, and FTIR spectra
(see Supporting information).
Supplementary data
It should also be noted that the newly developed reduction pro-
cedure did not result in dehalogenation as in the case of entries 2,
3, and 4. Thus, only reduction of the nitro group was observed
under the conditions studied. Furthermore, the NaBH4/metal sul-
fide system did not affect other functional groups like alkenes, car-
boxylic acids, esters, or amides, indicating the selectivity of the
reduction toward the nitro group.
The method reported here compares favorably with other litera-
ture methods which use NaBH4 in the presence of cobalt or nickel
salts. For instance, when the system CoCl2/NaBH4 is used, the reac-
tions proceed in relatively low percent yields (35% to 50%), and
required high temperature (>200 °C).7 Furthermore, CoCl2 was used
in 200% mole ratio (i.e., 2 equiv relative to the substrate) while
quantitative conversions are obtained in the method reported here
using only 5 mol % of catalyst with respect to the substrate. Reduc-
tion of nitro derivatives using NaBH4/Ni(OAc)2Á4H2O (20 mol % with
respect to the substrate) proceeds in high yields (>90%) for the opti-
mized reaction. However, the reduction requires careful monitoring
of the amount of water in the reaction mixture. Accordingly, the
reduction proceeds in 10% yield in the absence of water and varies
between 60% and 92% depending on the amount of water added
to the solvent.8 An additional advantage of the method reported
here is that the use of heterogeneous catalysts allows for easy sep-
aration from the reaction mixture.
Supplementary data (detailed experimental procedures as well
as characterization data) associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
08.068.
References and notes
1. Pogorelic, I.; FilipanLitvic, M. J. Mol. Catal. A: Chem. 2007, 274, 202.
2. Colas, C.; Goeldner, M. Eur. J. Org. Chem. 1999, 1357.
3. Fox, B. A.; Threlfall, T. L. Org. Synth. 1964, 44, 34.
4. Hoogenraad, M.; Van Der Linden, J. B. Org. Process Res. Dev. 2004, 8, 469.
5. Yoo, S.; Lee, S. Synlett 1990, 419.
6. Nose, A.; Kudo, T. Chem. Pharm. Bull. 1988, 36, 1529.
7. Satoh, T.; Suzuki, S. Tetrahedron Lett. 1969, 10, 4555.
8. Setamdideh, D.; Khezri, B. Orient. J. Chem. 2011, 27, 991.
9. Satoh, T.; Mitsuo, N. Chem. Pharm. Bull. 1980, 29, 1445.
10. Metal sulfide catalysts were synthesized hydrothermally using Teflon lined
autoclaves placed inside stainless steel jackets. Fe3S4 was synthesized by
dissolving 30 mmol of FeCl3 and 60 mmol of thiourea in 20 mL of ethylene
glycol and 5 mL of H2O. The solution was then autoclaved at 180 °C for 1 h.
ZnS2 was synthesized by dissolving 2 mmol of Zn(NO3)2 and 12 mmol of Na2S
in 15 mL of H2O. The solution was then autoclaved at 140 °C for 1 h. Ni3S4,
Co3S4, and CuS2 were synthesized by dissolving 2 mmol of MCl2 and 12 mmol
Na2S in 15 mL of H2O. The solution was then autoclaved for 1 h at 140 °C. The
precipitate from each reaction was filtered, washed with water, followed by a
methanol wash, and then oven dried.
11. Typical reduction procedure: In a scintillation vial containing 8 mL reagent
alcohol, 2 mmol of the corresponding nitrobenzene derivative, 5 mol % of
Co3S4, and 0.227 g (6 mmol) of sodium borohydride were added. The vial was
capped and placed in the sonication bath for 1 h. The reaction mixture was
filtered using a Celite cake, washed with methanol, and the solvent evaporated
under reduced pressure. The residue was partitioned between water and ethyl
acetate. The layers were separated and the aqueous layer was back extracted
with ethyl acetate (2 Â 15 ml). The organic layers were combined, washed with
water, dried over MgSO4, and the solvent evaporated under reduced pressure.
The resulting product was dried under vacuum for 1 h.
In summary, quantitative conversions were achieved for the
reduction of nitrobenzene utilizing NaBH4/Co3S4 and NaBH4/NiS
systems. Reduction of various nitroaromatic compounds was suc-
cessfully carried out in moderate to high yields. The heterogenous
reduction system allows for simple filtration of transition metal
catalysts simplifying the work-up. The newly developed method
12. Huang, Y.; Tu, W.; Yuan, Y.; Fan, D. Tetrahedron 2014, 70, 1274.