Facile synthesis of nitriles via manganese oxide promoted oxidative dehydrosulfurization of primary thioamides

Article abstract of DOI:10.1039/c2cc36635e

In the presence of manganese oxides, dehydrosulfurization of various kinds of primary thioamides including aromatic, heterocyclic, and aliphatic ones efficiently proceeded to give the corresponding nitriles in high yields. The observed catalysis was truly heterogeneous, and manganese oxides could be reused.

Full text of DOI:10.1039/c2cc36635e

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COMMUNICATION
Facile synthesis of nitriles via manganese oxide promoted oxidative
dehydrosulfurization of primary thioamidesw
Kazuya Yamaguchi, Kazuhisa Yajima and Noritaka Mizuno*
Received 12th September 2012, Accepted 1st October 2012
DOI: 10.1039/c2cc36635e
In the presence of manganese oxides, dehydrosulfurization of
various kinds of primary thioamides including aromatic, hetero-
cyclic, and aliphatic ones efficiently proceeded to give the
corresponding nitriles in high yields. The observed catalysis
was truly heterogeneous, and manganese oxides could be reused.
thioamides including aromatic, heterocyclic, and aliphatic
ones could be converted into the corresponding nitriles in
high yields under very mild conditions.
ð1Þ
Nitriles have widely been utilized in production of pharmaceuticals,
1
agricultural chemicals, and fine chemicals. Classically, nitriles have
Initially, 28 kinds of (metal) oxides (except for expensive
platinum group metal oxides, Table S1, ESIw) were examined
for the dehydrosulfurization of thiobenzamide (1a) to benzo-
nitrile (2a) in chloroform at 30 1C.z Among oxides examined,
been synthesized by non-green procedures using hazardous
1
inorganic and organic cyanides. Instead of these antiquated
procedures, several efficient catalytic procedures for nitrile synthesis
2
from methylarenes (ammoxidation), alcohols (ammoxidation),
3
amorphous MnO showed the highest performance for the
2
4
and amides (dehydration) have been developed until now though
dehydrosulfurization; 98% yield of 2a was obtained in only
these systems have several shortcomings such as harsh reaction
2–4
15 min (Fig. S1, ESIw). Amounts of amorphous MnO could
2
conditions (typically Z130 1C) and/or limited substrate scope.
be reduced; even when the dehydrosulfurization of 1a was
carried out using a reduced amount of amorphous MnO2
(9 mg, 41 mol% with respect to 1a), 87% yield of 2a was
obtained in 1 h (at 100 1C in toluene). Other oxides gave much
lower yields of 2a (r10% yields, Fig. S1, ESIw). The activities
of a series of manganese oxides (amorphous MnO , a-MnO ,
In order to expand possible choices of nitrile synthesis, the
development of efficient catalytic procedures from a variety of
starting materials is a very important subject.
Thioamides have attracted considerable attention in organic
synthesis as versatile synthons due to their unique reactivity and
5
wide availability. For example, various important chemicals
2
2
b-MnO , and d-MnO ) for the dehydrosulfurization of 1a
2
2
6
7
including nitriles, amides, amidines, and sulfur-containing
8
increased with an increase in their specific surface areas
5a
heterocycles (e.g., thiazoles, thiazolins, and thiazolinons)
(Table 1), and the reaction rates were approximately proportional
have been synthesized from thioamides in the presence of
stoichiometric reagents and/or transition metal catalysts. With
regard to synthesis of nitriles via dehydrosulfurization of
to their specific surface areas (Fig. S2, ESIw). While KMnO was
converted into amorphous MnO during the dehydrosulfurization
2
4
under the conditions described in Table 1, 2a was obtained in 97%
yield. Probably, 1a and/or the hydrogen sulfide formed would act
6a,b
6c
primary thioamides, metal carboxylates,
butyltin oxide,
6d–f
6d–f
organotelluroxides,
organotellurinic acids,
6h
selenoxides, diphosphorus tetraiodide, and organic halides/
organo-
as reductant(s) for KMnO , and the dehydrosulfurization was
4
6f,g
likely promoted by the in situ generated MnO . MnSO ꢀH O and
2
4
2
6i
inorganic bases have generally been utilized in stoichiometric
Table 1 Dehydrosulfurization of thiobenzamide (1a) to benzonitrile
(2a) by various manganese oxides and salts
amounts because these reagents are irreversibly converted into
5b,6
the corresponding sulfides.
a
Thus, to date there have been no
reports on efficient ‘‘catalytic’’ dehydrosulfurization of primary
thioamides, as far as we know.
BET surface
Yield of
2a (%)
2
area (m g
ꢁ1
)
Entry
Oxide or salt
Herein, we demonstrate for the first time heterogeneously
catalyzed selective dehydrosulfurization of primary thioamides
to nitriles with simple manganese oxides [eqn (1)]. In the
1
2
3
4
5
6
7
8
Amorphous MnO
2
304
97
54
36
—
—
—
—
98
51
42
24
97
4
3
o1
a-MnO
b-MnO
2
2
d-MnO
2
presence of amorphous MnO , various kinds of primary
2
KMnO
4
MnSO
MnS
4
ꢀH O
2
Department of Applied Chemistry, School of Engineering,
The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656,
Japan. E-mail: tmizuno@mail.ecc.u-tokyo.ac.jp;
Fax: +81-3-5841-7220; Tel: +81-3-5841-7272
w Electronic supplementary information (ESI) available: Experimental
details, Tables S1 and S2, and Fig. S1–S4. See DOI: 10.1039/c2cc36635e
None
a
Reaction conditions: 1a (0.2 mmol), oxide or salt (50 mg), chloro-
form (3 mL), air (1 atm), 30 1C, 15 min. Yields were determined by GC
using naphthalene as an internal standard. See also Fig. S2, ESI.
This journal is c The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11247–11249 11247

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a
MnS were not effective for the dehydrosulfurization. Chloroform,
toluene, acetonitrile, and acetone were good solvents, giving 2a in
moderate to high yields (65–98% yields, Table S2, ESIw). On the
other hand, 1,4-dioxane and N,N-dimethylformamide (DMF)
were not effective for the present dehydrosulfurization (r21%
yields, Table S2, ESIw).
Table 2 Dehydrosulfurization of various nitriles
Time
(min) Product
Yield
(%)
Entry Substrate
1
1a 15
2a
2b
2c
2d
2e
98
82
86
90
92
To verify whether the observed catalysis is derived from
solid amorphous MnO
dehydrosulfurization of 1a to 2a was carried out under the
conditions described in Table 1, and MnO was removed from
2
or leached manganese species, the
b
2
1b 30
1c 45
1d 60
1e 15
1f 15
2
the reaction mixture by filtration at ca. 30% conversion of 1a.
When the reaction was again carried out with the filtrate, no
further production of 2a was observed (Fig. S3, ESIw). It was
confirmed by ICP-AES analysis that no manganese species
was detected in the filtrate. Thus, the above-mentioned results
show that the observed catalysis for the present dehydrosul-
3
c
4
9
furization is truly heterogeneous.
After the dehydrosulfurization of 1a was completed, amor-
5
6
7
2
phous MnO was easily retrieved from the reaction mixture by
simple filtration with >95% recovery. The retrieved MnO
2
could be reused for the dehydrosulfurization of 1a; for the fifth
reuse, 70% yield of 2a was still obtained, while the formation
rates of 2a were gradually decreased by repeating reuse
experiments (Fig. 1). The main reason for the deactivation
of amorphous MnO2 is probably a decrease in the specific
surface area during the transformation and/or the drying step
2f
86
1g 15
1h 30
1i 30
2g
2h
2i
86
83
97
2
ꢁ1
before reuse (after the fifth reuse: 153 m g , cf. fresh one:
2
ꢁ1
3
04 m g , Fig. S2, ESIw). When prolonging the reaction time
to 40 min (from 15 min), 2a was obtained in 98% yield even
d
8
for the sixth reuse (Fig. 1). The total turnover number based
on total amount of manganese species in amorphous MnO
reached up to 2.6 after the sixth reuse.
2
d
9
In contrast, stable crystalline a-MnO
without any loss of its performance; when the dehydrosulfur-
ization of 1a was carried out with the retrieved a-MnO , the
2
could be reused
d
1
0
1j 15
1k 20
1l 60
1m 15
2j
97
81
71
2
reaction rate and the final yield of 2a were almost the same as
those with fresh a-MnO (Fig. S4, ESIw).
2
11
2k
2l
Next, the scope of the present MnO -promoted dehydro-
2
sulfurization of primary thioamides was examined (Table 2).
The dehydrosulfurization of thiobenzamide derivatives
e
1
2
3
(
1a–1g), which contain electron-donating as well as electron-
withdrawing substituents, efficiently proceeded to give the
1
2m >99
a
Reaction conditions: substrate (0.2 mmol), amorphous MnO
50 mg), chloroform (3 mL), air (1 atm), 30 1C. Yields were determined
2
(
by GC using naphthalene as an internal standard. Acetone (3 mL).
b
c
d
Toluene/acetone (4 mL/2 mL). MnO
2
(100 mg), acetone (5 mL).
e
Substrate (0.1 mmol), MnO (25 mg). Boc = tert-butoxycarbonyl.
2
corresponding substituted benzonitrile derivatives in high
yields ( Z 82% yields). In the case of 1e, no dechlorination
proceeded. Notably, a phenolic thioamide of 1b was selectively
converted into the corresponding cyanophenol without any
side reactions. Heterocyclic thioamides (1h–1j) gave the
corresponding heterocyclic nitriles in high yields ( Z 83 yields).
Less reactive aliphatic thioamides (1k–1m) could also be
converted into the corresponding aliphatic nitriles ( Z 71%
yields). In the case of 1m, the dehydrosulfurization efficiently
Fig. 1 Reuse of amorphous MnO
2
.
Reaction conditions: 1a
(50 mg), chloroform (3 mL), air
1 atm), 30 1C, 15 min. For the sixth reuse experiment, the reaction
(0.2 mmol), amorphous MnO
2
(
time was prolonged to 40 min.
1
1248 Chem. Commun., 2012, 48, 11247–11249
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Notes and references
z A typical procedure for dehydrosulfurization: 1a (1.10 g, 8 mmol),
amorphous MnO (2 g), and chloroform (120 mL) were placed in a
2
Pyrex-glass reactor with a magnetic stir bar, and the reaction was
carried out at room temperature (ca. 25 1C) in 1 atm of air. After
3
2
0 min, MnO was separated by filtration and washed with chloroform
(>95% recovery). Evaporation of chloroform gave crude mixtures
containing 2a and elemental sulfur. Then, acetone was added to the
crude mixtures, followed by filtration to retrieve elemental sulfur
(
0.21 g, 83% yield). Evaporation of acetone afforded 0.73 g of 2a
(88% yield). The retrieved MnO was washed with deionized water
and dried at 150 1C prior to being used for the reuse experiment.
y In the presence of nitriles, elemental sulfur (S ) is soluble in chloro-
8
form but almost insoluble in acetone.
Scheme 1 Gram-scale dehydrosulfurization. Reaction conditions for
a: 1a (1.10 g), amorphous MnO (2 g), chloroform (120 mL), air
1 atm), room temp. (ca. 25 1C), 30 min. Reaction conditions for 1e: 1e
1.03 g), amorphous MnO (1.5 g), chloroform (90 mL), air (1 atm),
2
1
2
(
(
2
z The elemental analysis revealed that only a small amount of sulfur
species was detected in the retrieved amorphous MnO after the
dehydrosulfurization of 1a (below 1.1 wt%). It was confirmed by
room temp. (ca. 25 1C), 30 min. In the dehydrosulfurization of 1a and
e, elemental sulfur was also isolated in 83% (0.21 g) and 74% (0.19 g)
2
1
yields, respectively.
XPS analysis that the average oxidation state of the sulfur species was
+4 (binding energy 2p3/2: 167.4 eV, e.g., SO and SO ). This sulfur
species could completely be removed by simple washing with deionized
water. In addition, the average oxidation of amorphous MnO was
2
preserved after the dehydrosulfurization of 1a.
2ꢁ
2
3
proceeded without deprotection of the tert-butoxycarbonyl
group.
In order to demonstrate practical usefulness of the present
dehydrosulfurization, the gram-scale transformations of 1a
1 (a) A. J. Fatiadi, in Preparation and synthetic applications of
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Wiley & Sons, Inc., Hodoken, New Jersey, 6th edn 2007.
(
1.10 g) and 1e (1.03 g) were carried out at room temperature
(
Scheme 1). These transformations also efficiently proceeded
without any decrease in the performance in comparison
with the small-scale transformations. After the reaction was
2
3
¨
¨
B. Lucke, K. V. Narayana, A. Martin and K. Jahnisch, Adv. Synth.
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2
completed, amorphous MnO was separated by filtration and
washed with chloroform. Evaporation of chloroform gave
0
crude mixtures containing nitriles and elemental sulfur (S ).y
Elemental sulfur is intrinsically insoluble, and the desired
nitriles are soluble in acetone. Thus, acetone was added to
the crude mixtures, followed by filtration to retrieve elemental sulfur
4
25–426, 85.
4
5
(a) K. Ishihara, Y. Furuya and H. Yamamoto, Angew. Chem.,
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´
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(
>99.99% purity by elemental analysis). Finally, evaporation of
acetone afforded 0.73 g of 2a (88% isolated yield) and 0.74 g of 2e
90% isolated yield). The purities of isolated 2a and 2e were >95%
by GC and NMR analyses).
(
(
In the previously reported dehydrosulfurization systems, the
reagents are irreversibly converted into the corresponding
6 (a) M. Avalos, R. Babiano, C. J. Dura
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n, J. L. Jimenez and
´ ´
2ꢁ
´
´
sulfides possibly by reaction with S species such as H
2
S,
2ꢁ 5b,6
. Thus, at least one equivalent (two equivalents
´
ꢁ
HS , and S
(
in some cases) of reagents is required in the previous systems,
6
and their repeated use is intrinsically impossible. In contrast, it
47, 4594; (d) T. Fukumoto, T. Matsuki, N. X. Hu, Y. Aso,
T. Otsubo and F. Ogura, Chem. Lett., 1990, 2269; (e) N. X. Hu,
Y. Aso, T. Otsubo and F. Ogura, Tetrahedron Lett., 1986, 27, 6099;
was confirmed by XPS analysis that no manganese sulfide was
(
f) N. X. Hu, Y. Aso, T. Otsubo and F. Ogura, Bull. Chem. Soc.
detected in the retrieved amorphous MnO after the dehydro-
2
Jpn., 1986, 59, 879; (g) N. X. Hu, Y. Aso, T. Otsubo and F. Ogura,
Chem. Lett., 1985, 603; (h) H. Suzuki, H. Tani and S. Takeuchi,
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sulfurization of 1a.z In addition, almost equimolar amounts of
elemental sulfur with respect to nitriles could be isolated, as
2
ꢁ
shown in Scheme 1. These results clearly indicate that S
(
j) S. Enthaler and S. Inoue, Chem.–Asian J., 2012, 7, 169.
0
species can be oxidized to S species in the presence of
7
(a) M. Nasr-Esfahani, M. Montazerozohori, M. Moghadam,
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U. T. Bhalerao, Tetrahedron, 1999, 48, 1953.
manganese oxides even under the present mild reaction
2ꢁ
conditions. It is known that the electron transfer from S
species to manganese oxides smoothly proceeds to form
0
10
oxidized sulfur species, e.g., S . The oxidizing ability of
manganese oxides would enable their catalytic and repeated
use for dehydrosulfurization (Fig. 1, Fig. S4, ESIw).
This work was supported in part by Grants-in-Aid for
Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
8 M. P. Foloppe, S. Rault and M. Robba, Tetrahedron Lett., 1992,
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9
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1
This journal is c The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 11247–11249 11249