Dehydration of primary amides to nitriles catalyzed by [CNC]-pincer hydrido cobalt(III) complexes

Article abstract of DOI:10.1016/j.catcom.2018.12.002

The dehydration reactions from primary amides to nitriles were catalyzed by the [CNC]-pincer hydrido cobalt(III) complexes [(ortho-F₄C₆–CH[dbnd]N–C₁₀H₆)Co(III)(H)(PMe₃)₂] (1), [(2,5-F₂C₆H₂–CH[dbnd]N–C₁₀H₆)Co(III)(H)(PMe₃)₂] (2) and [(2,4,5-F₃C₆H–CH[dbnd]N–C₁₀H₆)Co(III)(H)(PMe₃)₂] (3) as catalysts with (EtO)₃SiH as an efficient reducing agent. These hydrido cobalt(III) complexes as catalysts are suitable for many substrates and have good functional group tolerance. Among the three cobalt hydrides, complex 2 is the best catalyst. This is the first hydrido cobalt complex-catalyzed dehydration of primary amides to nitriles.

Full text of DOI:10.1016/j.catcom.2018.12.002

CatalysisCommunications120(2019)72–75
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Catalysis Communications
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Short communication
Dehydration of primary amides to nitriles catalyzed by [CNC]-pincer
hydrido cobalt(III) complexes
⁎
Shishuai Rena, Yangyang Wanga,b, Fei Yanga, Hongjian Suna, Xiaoyan Lia,
a School of Chemistry and Chemical Engineering, Key Laboratory of Special Functional Aggregated Materials, Ministry of Education, Shandong University, Shanda Nanlu
27, 250199 Jinan, PR China
b College of Chemistry and Chemical Engineering, Northwest Normal University, 730070 Lanzhou, PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
Dehydration
Amide
The dehydration reactions from primary amides to nitriles were catalyzed by the [CNC]-pincer hydrido cobalt
(III) complexes [(ortho-F4C6eCH]NeC10H6)Co(III)(H)(PMe3)2] (1), [(2,5-F2C6H2eCH]NeC10H6)Co(III)(H)
(PMe3)2] (2) and [(2,4,5-F3C6HeCH]NeC10H6)Co(III)(H)(PMe3)2] (3) as catalysts with (EtO)3SiH as an effi-
cient reducing agent. These hydrido cobalt(III) complexes as catalysts are suitable for many substrates and have
good functional group tolerance. Among the three cobalt hydrides, complex 2 is the best catalyst. This is the first
hydrido cobalt complex-catalyzed dehydration of primary amides to nitriles.
Nitrile
Cobalt hydride
1. Introduction
the dehydration of primary amides into nitriles in the presence of H2O-
MeCN [13]. In 2005, Marazzi described a mild method to convert pri-
Since the first transition metal carbonyl hydrides HCo(CO)4 and
H2Fe(CO)4 were reported by Hieber in 1931 [1], more and more hy-
drido metal complexes have been synthesized and reported. Chemists
have found the wide applications of hydrido metal complexes in or-
ganic synthesis, pharmaceutical, perfume and agrochemical industries
[2]. Especially, hydrido metal complexes as catalysts have been applied
in the reduction of unsaturated substrates by hydrogenation, hydrogen-
transfer, and hydrosilylation reactions and so on [3].
mary amides to nitriles in good yields using PdCl2 as a catalyst and
acetonitrile as a dehydrating agent [14]. In addition, other examples for
dehydration of amides have been studied using metal complexes as
catalysts, such as U [15], V [16], Ru [17], Cu [18] and etc., with silanes
as dehydrating agents. Among them, several examples of iron catalysts
using silanes as dehydrating agents have been published [19–22]. In
2011, Inoue group illustrated the zinc catalyst for the dehydration of
primary amides by using N-methyl-N-(trimethylsilyl)trifluoroacetamide
(MSTFA) as the dehydrating reagent [23]. In 2017, Li group reported
the ZnBr2-catalyzed dehydration of primary amides to nitriles using
propylphosphonic anhydride as the promoter and poly-
methylhydrosiloxane (PMHS) as the dehydrating reagent [24]. Buch-
wald group studied a copper-hydride-catalyzed dehydration of primary
amides using hydrosilanes [25]. In 2016, our group reported the de-
hydration of primary amides to nitriles using the hydrido thiophenolato
iron(II) complexes as catalysts and (EtO)3SiH as an efficient reducing
agent in moderate to very good yields [26]. We also explored the hy-
drido silyl iron complex (o-Ph2PC6H4SiMe2)Fe(H)(PMe3)3 in the re-
duction of primary amides using (EtO)3SiH as the dehydrating agent
and proposed the catalytic pathway [27].
Nitriles are important intermediates in organic synthesis and in-
dustrial chemistry [4,5]. Moreover, nitriles as raw materials can be
easily converted to other functional group such as carboxylic acids,
amides, aldehydes, ketones, esters, heterocycles etc. [6,7]. Dehydration
of primary amides is one of the most common methods for the synthesis
of nitriles [8,9]. Traditionally, the dehydration reaction has been rea-
lized by base or Lewis acid as a dehydrating agent [8,10]. Recently, a
catalytic transformation from amides to nitriles has been developed and
the catalytic process is heterogeneous in early work. Over alumina,
lamp black, pumice, or silica improved yields of nitriles could be ob-
tained [9]. In 2009, Beller's group reported the dehydration of amide
using tetrabutylammonium fluoride (TBAF) as a catalyst and silanes as
dehydrating agents [11]. Yamamoto group disclosed rhenium(VII) oxo
complexes as a practical dehydration catalyst for dehydration of pri-
mary amides to the corresponding nitriles through azeotropic reflux
[12]. In 2007, Pasha group reported the use of ZnCl2 as a catalyst for
From the above literature review, we know that on the one hand
there are few reports on the transition metal hydrides as catalysts for
this process; on the other hand, the example of hydrido cobalt com-
plexes as catalysts has not been studied. In 2018, our group reported the
⁎ Corresponding author.
E-mail address: xli63@sdu.edu.cn (X. Li).
https://doi.org/10.1016/j.catcom.2018.12.002
Received 18 July 2018; Received in revised form 5 December 2018; Accepted 6 December 2018
Availableonline07December2018
1566-7367/©2018ElsevierB.V.Allrightsreserved.

S. Ren et al.
CatalysisCommunications120(2019)72–75
Fig. 1. Cobalt(III) hydrido complexes 1–3.
synthesis of [CNC]-pincer hydrido cobalt(III) complexes, [(ortho-F4C6-
CH=N-C10H6)Co(III)(H)(PMe3)2] (1), [(2,5-F2C6H2-CH=N-C10H6)Co
(III)(H)(PMe3)2] (2) and [(2,4,5-F3C6H-CH=N-C10H6)Co(III)(H)
(PMe3)2] (3) (Fig. 1), from reactions of polyfluorinated aryl imines with
CoMe(PMe3)4 via selective C–H/C–F bond activation. We explored that
the hydrido cobalt(III) complexes 1–3 as catalysts, (EtO)3SiH as redu-
cing agent for reduction of aldehydes and ketones [28]. Therefore, we
report in this paper the dehydration of primary amides to nitriles cat-
alyzed by [CNC]-pincer hydrido cobalt(III) complexes, (1), (2) and (3)
(Fig. 1) as catalysts using (EtO)3SiH as an efficient reducing agent.
catalyst is necessary for this reaction. However, the conversion was
91% when the reaction time was extended to 36 h (entry 4, Table 1).
The conversion was low when reaction time was 12 h or 18 h (entries
5–6, Table 1). Among complexes 1–3, complex 2 has the highest ac-
tivity for amide dehydration (entries 2, 7 and 8, Table 1). Our group has
reported that the complex [(C6H4eCH]NeC10H6)Co(III)(H)(PMe3)2]
(4) has a high catalytic activity in hydrosilylation of aldehydes and
ketones [30]. When we used complex 4 to catalyze the dehydration of
primary amides, only 48% conversion was detected (entry 9, Table 1).
The introduction of fluorine groups as EWG on the benzene ring makes
the polarity of the Co-H bond in complexes 1–3 greater. Therefore the
nucleophilic ability of the hydrido hydrogen atom of complexes 1–3 is
higher than that of complex 4 and the catalytic activity of complexes
1–3 is stronger than that of complex 4. In comparison with entry 2, the
conversion was only 42% at 40 °C (entry 13, Table 1). However, when
increasing the reaction temperature, the conversion did not increase
(entry 14, Table 1). On the contrary, when the temperature is too high,
the conversion has decreased significantly. We checked the thermal
stability of the complex 2 in solution by in situ IR and found that
complex 2 is stable at 80 °C in solution. Perhaps under catalytic con-
ditions the catalyst (complex 2) has a deactivation or decomposition in
the presence of other components at high temperature. In order to ex-
plore the effect of the amount of silane on the reaction, (EtO)3SiH in
different molar ratios was added to the reaction mixture (entries 10–12,
Table 1). It was found that 1:3 (substrate:silane) is the best ratio. The
type of solvents is an important factor that affects the amide dehydra-
tion. It is found that THF (entry 2, Table 1) was the best reaction
medium for this catalytic system in comparison with toluene, DMF,
DMSO, dioxane, and acetonitrile (entries 15–19, Table 1).
2. Experimental section
2.1. General procedures and materials
Standard vacuum techniques were used in manipulations of volatile
and air-sensitive materials. Solvents were dried by known procedures
and distilled under nitrogen before use. Infrared spectra
(4000–400 cm−1), as obtained from Nujol mull between KBr disks,
were recorded on a Bruker ALPHA FT-IR instrument. NMR spectra were
recorded using Bruker Avance 300 MHz spectrometer. GC–MS was re-
corded on a TRACE-DSQ instrument and GC was recorded on a Fuli
9790 instrument. Melting points were measured in capillaries sealed
under N2 and were uncorrected. All the amides were purchased and
used without further purification. The purity of the triethoxysilane used
is 95%, the other 5% is tetraethoxysilane. The silanes were purchased
from J&K Scientific. Fe(PMe3)4 [29] and complexes (1–3) [28] were
prepared according to literature procedures and their data of char-
acterization are listed in the Supporting Information.
Caution! (EtO)3 SiH 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 dis-
proportionation, the formation of an extremely pyrophoric gas (pos-
sibly SiH4) has led to several fires and explosions reported in the lit-
erature.
The types of silanes for the reaction were explored (Table S1 in the
SI). The conversion was 86% when using Et3SiH as reducing agent in
toluene (entry 2, Table S1 in the SI). All reactions performed in THF or
dioxane or acetonitrile showed low conversions (up to 56%, entries 1, 5
and 6, Table S1 in the SI). The reaction did not occur in DMSO or DMF
(entries 3 and 4, Table S1 in the SI). Ph3SiH as reducing agent per-
formed in low conversions for this system. The 58% conversion was
detected in acetonitrile (entry 6, Table S2 in the SI). The conversion was
0% in THF and 42% in toluene (entries 1 and 2, Table S2 in the SI).
Using Ph2SiH2 as reducing agent, the conversion was 52% in THF or
24% in toluene respectively (entries 1 and 2, Table S3 in the SI). No
conversion was detected in DMF, DMSO, dioxane or acetonitrile (en-
tries 4–5, Table S3 in the SI). PhSiH3 as reducing agent for this reaction
was in moderate conversion. The conversions in THF and toluene were
similar (entries 1 and 2, Table S4 in the SI). The conversion was only
54% using TMDS as reducing agent in toluene and 42% in acetonitrile
(entries 2 and 6, Table S5 in the SI). This reaction did not occur with
TMDS in other solvents (entries 1, 3, 4 and 5, Table S5 in the SI). When
using PMHS as reducing agent the conversion was 71% in toluene and
0% in THF (entries 1 and 2, Table S6 in the SI). The low conversions
were detected in DMF, DMSO, dioxane, acetonitrile respectively (en-
tries 3 and 6, Table S6 in the SI). Compared to these silanes, (EtO)3SiH
as reducing agent in THF has the good conversion of 90% (entry 2,
Table 1).
(See Buchwald safety letter, Chemical & Engineering News (29 Mar
1993) Vol. 71, No. 13, pp. 2.)
2.2. General procedure for the dehydration of amides to nitriles
To a 25 mL Schlenk tube containing a solution of 2 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 procedures by Beller [19].
3. Results and discussion
In our initial trials, 4-chlorobenzamide was selected as a model
substrate to optimize the reaction conditions (Table 1). When 2% mol of
complexe 2 was used, 1 mmol of 4-chlorobenzamide and 3 mmol of
(EtO)3SiH reacted in THF at 60 °C. After 24 h, only 73% conversion was
detected (entry 1, Table 1). To our delight, a good conversion (90%)
was reached in the presence of 2 mol% of 2 (entry 2, Table 1). In
contrast, when no complex 2 was added to the reaction system, the
reaction could not proceed (entry 3, Table 1). This indicates that the
Based on the above analysis, the optimized conditions of the cata-
lytic reaction are summarized as follows: 2 mol% of hydrido cobalt
complex 2 as a catalyst, 3 equivalents of (EtO)3SiH, in THF at 60 °C for
24 h (entry 2, Table 1). The scope of the substrates was explored under
73

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CatalysisCommunications120(2019)72–75
Table 1
Exploration of conditions for amide dehydration.a
Entry
Catalyst
Loading (mol%)
Silane
Solvent
Temp. (°C)
Time (h)
Conv.b (%)
1
2
2
2
2
2
2
1
3
4
2
2
2
2
2
2
2
2
2
2
1
2
0
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
(EtO)3SiH
(EtO)3SiH
(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
60
60
60
60
60
60
60
60
60
60
60
60
40
80
60
60
60
60
60
24
24
24
36
12
18
24
24
24
24
24
24
24
24
24
24
24
24
24
73
90
0
2
THF
3
THF
4
THF
91
57
74
70
60
48
11
0
5
THF
6
THF
7
THF
8
THF
9
THF
10c
11d
12e
13
14
15
16
17
18
19
THF
THF
THF
33
42
60
83
50
61
59
68
THF
THF
Toluene
DMF
DMSO
Dioxane
CH3CN
a
b
c
d
e
Catalytic reaction conditions: amide (1.0 mmol), hydrosilane (3.0 mmol) and 1–3 (0.02 mmol) in 2 mL THF, T °C, t h.
Determined by GC with dodecane as the internal standard.
Hydrosilane (1.0 mmol).
Hydrosilane (2.0 mmol).
Hydrosilane (4.0 mmol).
Table 2
The reductive dehydration of amides to nitriles catalyzed by 1.a,b
aCatalytic reaction conditions: amide (1.0 mmol), (EtO)3SiH (3.0 mmol) and 2 (0.02 mmol) in 2 mL
THF, 60 °C, 24 h.
bIsolated Yield.
the optimized conditions. To our delight, the catalytic system with
hydrido cobalt(III) complex 2 as catalyst could be used for many amide
substrates (Table 2). These results indicate that the functional groups,
such as halides,heteroaromatic rings, nitro group and vinyl group, can
be tolerated under catalytic conditions except for carbonyl group. The
primary amides with the electron-withdrawing groups such as eF, eCl,
eI, eNO2 gave the respective nitriles in 81–92% yields. However, the o-
toluamide and the p-toluamide with the electron-donating group
showed a moderate result in 65% and 69% yield respectively while m-
toluamide gave rise to 84% yield. Pyridine amide could also be
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CatalysisCommunications120(2019)72–75
converted to corresponding nitrile in a moderate yield of 67%. When
the substrate contains both a C]C double bond and an amide group,
only the amide moiety is selectively reduced. For cinnamamide, the
yield of cinnamonitrile was 88%.
[3] M.A. Esteruelas, L.A. Oro, Chem. Rev. 98 (1998) 577–588.
[4] B.R. Pitta, O.W. Steward, F.F. Fleming, J. Org. Chem. 83 (2018) 2753–2762.
[5] G. Barker, M.R. Alshawish, M.C. Skilbeck, I. Coldham, Angew. Chem. Int. Ed. 52
(2013) 7700–7703.
[6] V.Y. Kukushkin, A.J.L. Pombeiro, Chem. Rev. 102 (2002) 1771–1802.
[7] B. Gaspar, E.M. Carreira, Angew. Chem. Int. Ed. 46 (2007) 4519–4522.
[8] R.E. Kent, S.M. McElvain, Org. Synth. 25 (1945) 61–62.
[9] D.T. Mowry, Chem. Rev. 42 (1948) 189–283.
4. Conclusions
[10] I. Talbi, M.L. Efrit, S. Touil, ACS Omega 3 (2018) 5078–5082.
[11] S. Zhou, K. Junge, D. Addis, S. Das, M. Beller, Org. Lett. 11 (2009) 2461–2464.
[12] K. Ishihara, Y. Furuya, H. Yamamoto, Angew. Chem. Int. Ed. 41 (2002) 2983–2986.
[13] K. Manjula, M.A. Pasha, Synth. Commun. 37 (2007) 1545–1550.
[14] S.I. Maffioli, E. Marzorati, A. Marazzi, Org. Lett. 7 (2005) 5237–5239.
[15] S. Enthaler, Chem. Eur. J. 17 (2011) 9316–9319.
In summary, we report the first [CNC]-pincer hydrido cobalt-cata-
lyzed dehydration of the primary amides to nitriles. The well-defined
cobalt complexes showed high activity and good to excellent selectivity
for dehydration reduction of aromatic and aliphatic amides. The cata-
lytic system with hydrido cobalt catalyst has a wide scope of the sub-
strates.
[16] S. Sueoka, T. Mitsudome, T. Mizugaki, K. Jitsukawaa, K. Kaneda, Chem. Commun.
46 (2010) 8243–8245.
[17] S. Hanada, Y. Motoyama, H. Nagashima, Eur. J. Org. Chem. (2008) 4097–4100.
[18] S. Enthaler, M. Weidauer, Catal. Lett. 141 (2011) 1079–1085.
[19] S. Zhou, D. Addis, S. Das, K. Junge, M. Beller, Chem. Commun. (2009) 4883–4885.
[20] S. Elangovan, S.Q. Duque, V. Dorcet, T. Roisnel, L. Norel, C. Darcel, J.B. Sortais,
Organometallics 34 (2015) 4521–4528.
Acknowledgements
We gratefully acknowledge the support by NSF China No.
21572119/21272138.
[21] D. Bézier, G.T. Venkanna, J.B. Sortais, C. Darcel, ChemCatChem 3 (2011)
1747–1750.
[22] S. Enthaler, Eur. J. Org. Chem. (2011) 4760–4763.
[23] S. Enthaler, S. Inoue, Chem. Asian J. 7 (2012) 169–175.
[24] Y. Wang, L. Fu, H. Qi, S. Chen, Y. Li, Asian J. Org. Chem. 7 (2018) 367–370.
[25] R.Y. Liu, M. Bae, S.L. Buchwald, J. Am. Chem. Soc. 140 (2018) 1627–1631.
[26] B. Xue, H. Sun, Y. Wang, T. Zheng, X. Li, O. Fuhr, D. Fenske, Catal. Commun. 86
(2016) 148–150.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.catcom.2018.12.002.
[27] S. Ren, S. Xie, T. Zheng, Y. Wang, S. Xu, B. Xue, X. Li, H. Sun, O. Fuhrd, D. Fenske,
Dalton Trans. 47 (2018) 4352–4359.
[28] F. Yang, Y. Wang, F. Lu, S. Xie, X. Qi, H. Sun, X. Li, O. Fuhr, D. Fenske, New J.
Chem. 42 (2018) 15578–15586.
References
[29] H.-F. Klein, H.H. Karsch, Chem. Ber. 110 (1977) 2699–2711.
[30] H. Zhou, H. Sun, S. Zhang, X. Li, Organometallics 34 (2015) 1479–1486.
[1] W. Hieber, F. Leutert, Ber. Dtsch. Chem. Ges. 64 (1931) 2832–2839.
[2] A.J. Hoskin, D.W. Stephan, Coord. Chem. Rev. 233–234 (2002) 107–129.
75