Efficient reductive dehydration of primary amides to nitriles catalyzed by hydrido thiophenolato iron(II) complexes under hydrosilation conditions

Article abstract of DOI:10.1016/j.catcom.2016.08.024

The reductive dehydration of amides to nitriles under hydrosilation conditions with hydrido thiophenolato iron(II) complexes [cis-Fe(H)(SAr)(PMe₃)₄] (1–4) as catalysts is reported using (EtO)₃SiH as an efficient reducing agent in the yields up to 93%. The merits of this catalytic system, the low catalyst loadings (2?mol%) and the amount of efficient reducing agent (EtO)₃SiH, make this method more attractive.

Full text of DOI:10.1016/j.catcom.2016.08.024

Catalysis Communications 86 (2016) 148–150
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Catalysis Communications
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Short communication
Efficient reductive dehydration of primary amides to nitriles catalyzed by
hydrido thiophenolato iron(II) complexes under
hydrosilation conditions
d
d
Benjing Xue a, Hongjian Sun a, Yan Wang b, Tingting Zheng a,c, Xiaoyan Li a, , Olaf Fuhr , Dieter Fenske
⁎
a
School of Chemistry and Chemical Engineering, Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University, Shanda Nanlu 27, 250199 Jinan, China
b
c
Marine College, Shandong University at Weihai, Weihai 264209, China
Department of Chemistry, Capital Normal University, 100037 Beijing, China
d
Institut für Nanotechnologie (INT) und Karlsruher Nano-Micro-Facility (KNMF), Karlsruher Institut für Technologie (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen,
Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 June 2016
Received in revised form 14 August 2016
Accepted 16 August 2016
Available online 20 August 2016
The reductive dehydration of amides to nitriles under hydrosilation conditions with hydrido thiophenolato
iron(II) complexes [cis-Fe(H)(SAr)(PMe3)4] (1–4) as catalysts is reported using (EtO)3SiH as an efficient reducing
agent in the yields up to 93%. The merits of this catalytic system, the low catalyst loadings (2 mol%) and the
amount of efficient reducing agent (EtO)3SiH, make this method more attractive.
© 2016 Elsevier B.V. All rights reserved.
Keywords:
Dehydration
Silane
Iron hydride
Amide
Nitrile
1. Introduction
methyl-N-(trimethylsilyl)trifluoroacetamide) as dehydration regent
for the first time [17]. Moreover, with MSTFA as dehydration regent,
Aromatic nitriles and derivatives are widely used in drugs, dyes, pig-
ments and chemical reagents [1]. Moreover, aromatic nitriles are very
important intermediates in synthetic chemistry. The nitrile group can
transform into other functional group, such as amine, carboxyl, alde-
hyde, ketone, and heterocycle, etc. [2].
Enthaler has studied copper and zinc as catalysts for dehydration of pri-
mary amides to nitriles [18,19]. Compared to above work, iron seems to
be more attractive because it's abundant and lowly toxic [20–22].
Nagashima and co-workers reported that iron complexes can act as
the catalysts for the reduction of tertiary carboxamides to their corre-
sponding amines, using hydrosilane as a reducing reagent [23–25]. For
a long time, Beller's group devoted into the catalytic synthesis of
benzonitriles [26]. In 2009, Beller reported the first iron-catalyzed dehy-
dration of primary amides to nitriles with (EtO)2MeSiH as a dehydrating
agent [27]. Then Enthaler presented the usefulness of an easy-to-adopt
dehydration system composed of FeCl2 and MSTFA for the dehydration
of primary amides [28]. The catalytic activity of Knölker-type iron com-
plexes had been demonstrated for the dehydration of primary
benzamides into benzonitriles using inexpensive PMHS as the
hydrosilane at 100 °C [29]. As far as we know, the literature about dehy-
dration of primary amides to nitriles by iron catalyst is very few. There-
fore, we carried out research work in this area.
The dehydration of primary amides is one of the most basic methods
in the synthesis of nitriles [3,4]. Traditionally, this transformation can be
conducted through some strongly acidic agents, such as SOCl2 [5], TiCl4
[6], P2O5 [7] and POCl3 [8]. For years, the reduction of amides has been
generally based on some precious metals, for example, Rh [9], Ru [10],
Ir [11] and Pt [12]. The development of novel catalyst is of great interest
for its valuable price as well as significant waste generation [13,14]. In
2009, Beller's group presented the first fluoride-catalyzed dehydration
reaction of primary amides to the corresponding nitriles [15]. Darcel
and his co-workers showed that a well-defined NHC iron complex can
be employed as an efficient catalyst for the reduction of amides by
hydrosilylation using phenylsilane [16]. In 2011, Enthaler established
an excellent method for the dehydration of primary amides to nitriles
in the presence of a straightforward uranium catalyst and MSTFA (N-
Herein we report four well-defined catalysts hydrido thiophenolato
iron(II) complexes [cis-Fe(H)(SAr)(PMe3)4] 1–4 (Fig. 1). They are capa-
ble of conducting the dehydration of amides to nitriles utilizing
(EtO)3SiH as an efficient reducing agent under hydrosilation conditions
in good yields with some functional group tolerance. According to
⁎
Corresponding author.
E-mail address: xli63@sdu.edu.cn (X. Li).
http://dx.doi.org/10.1016/j.catcom.2016.08.024
1566-7367/© 2016 Elsevier B.V. All rights reserved.

B. Xue et al. / Catalysis Communications 86 (2016) 148–150
149
PMe3
Fe
PMe3
H
H
PMe3
PMe3
PMe3
Fe
PMe3
S
S
PMe3
PMe3
TMS
1
2
Me
PMe3
Fe
PMe3
Fe
H
H
PMe3
PMe3
PMe3
PMe3
MeO
S
S
PMe3
PMe3
4
3
Fig. 1. Thiophenolato hydrido iron(II) complexes 1–4.
literature [27–29], this study showed a convenient and efficient method
for dehydration of amides to nitriles.
of any catalyst or Fe(PMe3)4 (entry 1–2, Table 1). However, 1 mol% of
complex catalyzed the desired transformation and afforded
1
benzonitrile in 69% yield (entry 3, Table 1). To our delight, a good
yield (99%) was observed in the presence of 2 mol% of 1 (entry 5,
Table 1). At the given catalytic conditions, the reduction reaction was
completely finished within 24 h. The yield was lower when reaction
time was shorter than 24 h (entry 4, Table 1).
2. Experimental section
2.1. General procedures and materials
Standard vacuum techniques were used in the manipulations of vol-
atile and air-sensitive materials. Solvents were dried by known proce-
dures and distilled under nitrogen before use. Infrared spectra (4000–
400 cm−1), as obtained from Nujol mulls between KBr disks, were re-
corded on a Bruker ALPHA FT-IR instrument. NMR spectra were record-
ed using Bruker Avance 300 MHz spectrometers. GC-MS was recorded
on a TRACE-DSQ instrument and GC was recorded on a Fuli 9790 instru-
ment. Melting points were measured in capillaries sealed under N2 and
were uncorrected. Elemental analyses were carried out on an Elementar
Vario ELIII instrument. All the amides were purchased and used without
further purification. The purity of the triethoxysialne used is 95%, the
other 5% is tetraethoxysialne. The silanes were purchased from J&K Sci-
entific. Fe(PMe3)4 [30] and complexes (1–4) were prepared according
to literature procedures [31] and their data of characterization are listed
in supporting information.
Caution! (EtO)3SiH is flammable and highly toxic by inhalation and
may cause skin irritation and blindness. Even if during our studies on
the dehydration of amides, we used it without incident, triethoxysilane
should be used with precaution. Indeed, due to possible silane dispro-
portionation, the formation of an extremely pyrophoric gas (possibly
SiH4) has led to several fires and explosions reported in the literature.
(See Buchwald safety letter, Chemical & Engineering News (29 Mar
1993) Vol. 71, No. 13, pp. 2.)
Then we changed the hydrogen source to PMHS, Et3SiH, Ph3SiH,
Me2PhSiH, Ph2SiH2, PhSiH3, TMDS and Me(EtO)2SiH, no reaction was
observed (entries 6–13, Table 1). Comparing the results at different
temperatures, the yields were not ideal at the temperature 45 °C or
80 °C (entries 14–15, Table 1). The polar solvent seemed to be better
(entry 5, Table 1) than nonpolar solvent, such as toluene, diethyl
ether, pentane and isopropanol (entries 16–19, Table 1). The results
showed that THF was the best solvent among them with the yield of
99% for the catalytic reaction (entry 5, Table 1). Among four catalysts
Table 1
Exploration of the condition of catalytic reactions of benzamide with 1–4a.
Entry Catalyst
Loading Hydrogen
(mol%) source
Solvent
Temp. Time Conv.
(°C)
(h)
(%)b
1
2
3
4
5
6
7
8
Fe(PMe3)4
2
0
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
PMHS
Et3SiH
Ph3SiH
Me2PhSiH
Ph2SiH2
PhSiH3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
60
60
60
60
60
60
60
60
60
60
60
60
60
45
80
60
60
60
24
24
24
12
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
48
24
48
24
48
0
0
69
83
99
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
3
3
4
4
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
0
0
0
TMDS
Me(EtO)2SiH THF
2.2. General procedure for the dehydration of amides to nitriles
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
(EtO)3SiH
THF
THF
Toluene
Ether
Pentane
73
82
61
54
27
39
47
91
80
93
67
89
To a 25 ml Schlenk tube containing a solution of 1 in 2 ml of THF was
added amide (1.0 mmol) and (EtO)3SiH (0.50 g, 3.0 mmol). The reaction
mixture was stirred at 60 °C until there was no amide left (monitored by
TLC and GC-MS). The product was purified according to literature pro-
cedures by Beller [27].
Isopropanol 60
THF
THF
THF
THF
THF
THF
60
60
60
60
60
60
3. Results and discussion
In our initial investigation, benzamide was selected as a model sub-
strate. The reaction conditions had been optimized in the exploration of
the new reaction, such as solvent, temperature, silane, catalyst loading
and time (Eq. (1), Table 1). The reaction did not occur in the absence
a
Catalytic reaction conditions: amide (1.0 mmol), (EtO)3SiH (3.0 mmol) and 1 (0.02 mmol)
in 2 ml THF, T °C, t h.
b
Determined by GC analysis. n-Dodecane as internal standard (1.0 mmol).

150
B. Xue et al. / Catalysis Communications 86 (2016) 148–150
Table 2
Under optimum conditions, the reduction of the carbonyl group was
easier than that of the amide group. When 1 equiv of (EtO)3SiH was
added into reaction system, only siloxane was detected by IR and GC-
MS and the amide group kept untouched. When 4 equiv of (EtO)3SiH
were added into the mixture, after hydrolysis, the β-hydroxy nitrile as
the final product was obtained in 85% yield. The result of catalytic reac-
tion seemed slightly poorer according to Beller's work [27].
The reductive dehydration of primary amides to nitriles catalyzed by 1.a,b
R—Cð¼ OÞNH2 þ ðEtOÞ SiH 1;2
→
mol%;THF R—CN
ð2Þ
3
Å
60C;24
h
Notably, the reduction of tertiary and secondary amides such as N,N-
dimethylbenzamide and N-phenylacetamide, respectively, couldn't
proceed under the optimum conditions.
4. Conclusions
In conclusion, a convenient and efficient reductive dehydration of
amides to nitriles has been developed employing hydrido thiophenolato
iron(II) complexes (1–4) as catalysts and (EtO)3SiH as an efficient re-
ducing agent under hydrosilation conditions.
aCatalytic reaction conditions: amide (1.0 mmol),
1 (0.02 mmol) in 2 ml THF, 60 °C, 24 h.
(EtO)3SiH (3.0 mmol) and
Acknowledgements
bIsolated yield.
We gratefully acknowledge the support by NSF China No. 21372143.
Appendix A. Supplementary data
cGC yield.
d(EtO)3SiH (4.0 mmol).
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.catcom.2016.08.024.
1–4, complex 1 seemed to be the best catalyst for the reductive dehy-
dration of amides to nitriles (entries 5, 20, 22 and 24, Table 1) because
a complete conversion needed a longer time with complex 2, 3 or 4 as
a catalyst.
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ð1Þ
The optimized catalytic reaction conditions can be summarized as
follows: benzamide (1.0 mmol), (EtO)3SiH (3.0 mmol), and 1
(0.02 mmol) in 2.0 ml of THF, 60 °C, 24 h. After the optimized conditions
were obtained, different substituted benzamides and aliphatic amides
were studied as substrates (Eq. (2), Table 2). Notably, the dehydration
of primary amides to nitriles by complexes 1–4 showed a wide scope
of substrates. The substrates with electron-donating group (methyl-,
methoxy-) or electron-withdrawing (halogen F, Cl, I or nitro) gave the
respective nitriles in 71–93% yield. No dehalogenation was observed
under our experimental conditions. Alkyl amide (phenylacetamide or
hexanamide) and heteroaromatic compound (pyridine carboxamide)
performed a moderate results (Table 2). Notably, the vinyl moiety of
acrylic amide could not be reduced under hydrosilation conditions as
acrylonitrile was selectively obtained in 88% GC-yield. The
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