Hydrosilanes are not always reducing agents for carbonyl compounds but can also induce dehydration: A ruthenium-catalyzed conversion of primary amides to nitriles

Article abstract of DOI:10.1002/ejoc.200800523

A practical procedure for production of nitriles is offered by the triruthenium carbonyl cluster catalyzed dehydration of primary carboxamides with hydrosilanes under neutral conditions. This is the first example that a transition-metal-catalyzed activation of Si-H bonds does not lead to the reduction of carbonyl compounds but to dehydration. Possible mechanisms for the dehydration is discussed on the basis of NMR spectroscopic detection of intermediary species. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800523

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200800523
Hydrosilanes Are Not Always Reducing Agents for Carbonyl Compounds but
Can Also Induce Dehydration: A Ruthenium-Catalyzed Conversion of Primary
Amides to Nitriles
Shiori Hanada,[a] Yukihiro Motoyama,[b] and Hideo Nagashima*[b]
Keywords: Amides / Dehydration / Cyanides / Hydrosilanes / Ruthenium
A practical procedure for production of nitriles is offered by
the triruthenium carbonyl cluster catalyzed dehydration of
primary carboxamides with hydrosilanes under neutral con-
ditions. This is the first example that a transition-metal-cata-
lyzed activation of Si–H bonds does not lead to the reduction
of carbonyl compounds but to dehydration. Possible mecha-
nisms for the dehydration is discussed on the basis of NMR
spectroscopic detection of intermediary species.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
tions,[3b,3c] and a facile removal of both the silicone waste
and the metal residues is achieved.[3d] The reduction of less-
reactive secondary amides was also carried out by an ap-
propriate choice of hydrosilanes.[3e] Within this context, we
expected that primary amides would also reduce to the cor-
responding amines by an appropriate choice of hydrosilanes
and reaction conditions. To our astonishment, the reaction
that actually occurred was not the reduction of amides to
primary amines as expected, but a dehydration of amides to
nitriles as shown in Scheme 1. To the best of our knowledge,
this is the first example of a transition-metal-catalyzed acti-
vation of Si–H bonds that does not lead to the reduction
of carbonyl compounds but to dehydration.
Introduction
For hydrosilylation reactions, it is well known that the
Si–H bond in hydrosilanes is added across an unsaturated
bond with the aid of transition-metal catalysts.[1] Applica-
tion of hydrosilylation to the reduction of C=O and C=N
functional groups has been actively studied in organic syn-
thesis, as the process has advantages over conventional hy-
dride reductions; hydrosilanes are easy to handle and envi-
ronmentally problematic waste is not formed. Furthermore,
possibilities in catalyst design can lead to high reactivity
and high selectivity of the reduction processes.[2] We have
reported the triruthenium carbonyl cluster, (µ3,η2,η3,η5-
acenaphthylene)Ru3(CO)7 (1), to be one of the most reac-
tive catalysts for the catalytic reduction of aldehydes,
ketones, and carboxylic acid derivatives with hydrosilanes
(Figure 1).[3]
Scheme 1. Reactions of primary amides with hydrosilanes.
Figure 1. (µ3,η2,η3,η5-Acenaphthylene)Ru3(CO)7 (1).
Results and Discussion
When p-toluamide (2a) was treated with hydrosilanes
listed in Table 1 in the presence of a catalytic amount of 1
at room temperature, hydrogen gas evolved, which lead to
the dehydrogenative silylation of 2a to give silylated amides
(vide infra). Aqueous workup of the reaction mixture re-
sulted in hydrolysis of the silylated amides to give complete
recovery of 2a. In contrast, dehydration of 2a proceeded
smoothly at higher temperatures to give p-tolunitrile (3a).
Table 1 shows the yield of 3a when 2a (0.5 mmol) was
treated with hydrosilanes (Si–H: 1.25 mmol) in dimethoxy-
ethane (DME) in the presence of 1 (2.5 mol-% to 2a) at
Perhaps, the reduction of tertiary amides is the most use-
ful example to show the utility of complex 1. The reaction
proceeds at ambient temperature under neutral condi-
[a] Graduate School of Engineering Sciences, Kyushu University,
Kasuga, Fukuoka 816-8580, Japan
[b] Institute for Materials Chemistry and Engineering, Kyushu
University,
Kasuga, Fukuoka 816-8580, Japan
Fax: +81-92-583-7819
E-mail: nagasima@cm.kyushu-u.ac.jp
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2008, 4097–4100
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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S. Hanada, Y. Motoyama, H. Nagashima
SHORT COMMUNICATION
70 °C for 7 h. Several trialkylhydrosilanes and hydrosilox- aromatic and aliphatic amides generally occurred at 70–
anes can be used for the present dehydration, and hydride 80 °C to give the desired nitriles as a single product. The
reduction of the CϵN group formed is not observed under yield of the nitriles as determined by NMR spectroscopy
these conditions. However, the yield of nitrile 3a is sensitive was found to be over 95% after 12–24 h. After purification
to the structure of the organosilane used (Entries 1–8). of the crude product, dehydration of the para-substituted
Among the hydrosilanes we have examined, a bifunctional benzamide derivatives 2a–2c proceeded smoothly to give
organosilane, 1,2-bis(dimethylsilyl)ethane (BDMSE),[4] pro- the corresponding benzonitriles 3a–3c in 88–90% isolated
vided the best results, as listed in Table 1. After 7 h, the yields (Entries 1–3). The electron-withdrawing chloro sub-
conversion of 2a reached ca. 60%, where 3a was formed as stituent retards the reaction, and a twofold amount of 1
a single product in 61% yield (Entry 8). A longer reaction was needed for effective conversion of the amide 2d (Entry
time (12 h) resulted in complete conversion of the amide 2a 4). In the reactions of o-toluamide (2e) and α- and β-naph-
to afford the nitrile 3a in 90% isolated yield (Entry 9). In thamides (2f and 2g, respectively), the yield of the product
our previous papers, we reported that reduction of amides was found to improve at slightly higher temperatures
with poly(methylhydrosiloxane) (PMHS) by catalyst 1 re- (80 °C, Entries 5–7). Neither reduction of a carbon–bro-
sulted in gelation of PMHS, and all of the ruthenium spe- mine bond nor elimination of hydrogen bromide occurred
cies are soaked up.[3d] The reaction of 2a with PMHS in the in the reaction of 6-bromohexanamide (2j) to give the de-
presence of 1 led to a vigorous evolution of gas, and the sired 6-bromohexanenitrile 3j in 95% isolated yield (Entry
silicone gel containing ruthenium was obtained within 10). The present system was also effective for the dehy-
10 min. However, the corresponding nitriles were isolated dration of amides containing a tri-substituted alkenyl moi-
only in 10% yield (Entry 6). Presumably, 2a was bonded
with the silicone gel by either Si–O or Si–N bonds (vide
Table 2. Dehydration of various primary amides with BDMSE cat-
infra). Although with a lower catalytic activity, other ruthe-
nium carbonyl complexes, Ru3(CO)12 and [RuCl2(CO)3]2,
also catalyzed the dehydration reaction under similar condi-
tions (Entries 10 and 11). In contrast, 3a was not formed
when either other ruthenium complexes {(η5-C5H5)RuCl-
(PPh3)2, [(η6-C6Me6)RuCl2]2, and [(η6-C6Me6)RuCl-
(MeCN)2](PF6)} or other late transition metals such as
Co2(CO)8, RhH(CO)(PPh3)3, and IrCl(CO)(PPh3)2 were
used as the catalyst (see Supporting Information).
alyzed by triruthenium carbonyl cluster 1.[a]
Table 1. Dehydration of p-toluamide 2a by various silanes and ru-
thenium complexes.[a]
Entry
Catalyst
Silane
Yield [%][b]
1
2
3
4
5
6
7
8
1
Et3SiH
Ͻ2
Ͻ2
46
36
10
10
Ͻ2
1
(EtO)2MeSiH
(nOctyl)Me2SiH
Me3SiOSiMe2H
HMe2SiOSiMe2H
PMHS
1
1
1
1
1
1,2-(HMe2Si)2C6H4
1
HMe2Si(CH2)2SiMe2H 61
HMe2Si(CH2)2SiMe2H Ͼ95 (90)[d]
HMe2Si(CH2)2SiMe2H 51
HMe2Si(CH2)2SiMe2H 19
9[c]
10
11
1
Ru3(CO)12
[RuCl2(CO)3]2
[a] Reaction conditions: 2a (0.5 mmol), ruthenium complex 1
(2.5 mol-% to 2a), DME (0.25 mL), hydrosilanes (Si–H:
1.25 mmol), 70 °C, 7 h, under nitrogen atmosphere. [b] Determined
by 1H NMR spectroscopy analysis with dibenzyl ether as an in-
ternal standard. [c] For 12 h. [d] The yield in parentheses was the
isolated yield by silica gel chromatography.
[a] Reaction conditions: primary amide (2a–2k: 1.0 mmol), ruthe-
nium complex 1 (16.3 mg, 2.5 mol-%), DME (0.5 mL), 1,2-bis(di-
methylsilyl)ethane (246 µL, 1.25 mmol, Si–H: 2.5 equiv. to 2), un-
der nitrogen atmosphere. [b] Determined by 1H NMR spectroscopy
analysis. The yield in parentheses was the isolated yield by silica
gel chromatography. [c] 5.0 mol-% of 1 was used. [d] The lower
yield was caused by substantial loss of the product in the purifica-
Table 2 shows the results obtained for the dehydration of
various primary carboxamides (2a–2k) with BDMSE (Si–
H: 2.5 equiv. to the amide). In the presence of 2.5–5 mol-
% of the triruthenium carbonyl cluster 1, the reactions of tion process.
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Eur. J. Org. Chem. 2008, 4097–4100

A Ruthenium-Catalyzed Conversion of Primary Amides to Nitriles
ety, e.g. the reaction of citronellamide 2k at 80 °C for 20 h
gave citronellyl nitrile 3k as a single product. Hydro-
silylation towards the C=C bond did not occur (Entry 11).
In contrast, reduction of the C=C bond, presumably
through 1,4-hydrosilylation of the α,β-unsaturated nitriles
formed, is a major side reaction in the reaction of α,β-un-
saturated carboxamides.[5] Trans-cinnamamide was con-
verted mainly to dihydrocinnamonitrile, which was ob-
tained in ca. 50% yield.
Scheme 3. Thermal decomposition of bis(trimethylsilyl)amide de-
rivatives.
An intriguing feature of this new reaction is the role of
hydrosilanes as dehydrating reagents; hydrosilanes usually
act as reducing reagents in this particular catalytic reaction.
In fact, the present catalytic system is effective for the re-
duction of tertiary and secondary amides.[3] A clue towards
understanding the mechanism is the reaction of N–H
groups of primary amides with hydrosilanes to give H2,
which facilely takes place in the presence of 1. A plausible
mechanism is shown in Scheme 2. The reaction of a pri-
mary amide with two equivalents of an Si–H group gives
an equilibrium mixture, bis(silyl)amide A and N,O-bis-
(silyl)imidate B.[6] It is known that the bis(silyl)imidate B
facilely eliminates a siloxane molecule to form the corre-
sponding nitrile under thermal conditions (200–250 °C).[7]
Conclusions
The present reaction, which presents the effective use of
hydrosilanes as dehydrating reagents under catalysis by 1,
provides an important new aspect in organic chemistry. It
is known that halosilanes and alkoxysilanes are useful in
dehydration reactions in organic synthesis because of the
strong affinity of Si and O.[11] However, an intramolecular
esterification reported by Mukaiyama is the only prece-
dence for an organohydrosilanes behaving as dehydrating
reagents, in which a substrate containing two acidic protons
and an oxygen atom reacts with a hydrosilane with the aid
of a rhodium catalyst and a strong Lewis acid, which leads
to the elimination of a siloxane. Synthesis of nitriles by de-
hydration of primary amides conventionally requires
strongly acidic and vigorously reactive reagents[12] such as
phosphorus pentoxide,[12c] titanium tetrachloride,[12d] or
thionyl chloride.[12e] Although several dehydrating reagents
that can be used under milder conditions have been devised
recently,[13] only a few reactions occur under neutral condi-
tions.[14] They all have drawbacks. The present report
clearly demonstrates the utility of catalytic activation of hy-
drosilanes in the dehydration of primary amides to nitriles,
which leads to a new process that proceeds under neutral
conditions and does not give intractable waste. Further in-
vestigation on transition-metal catalysis inducing dehy-
dration with hydrosilanes is underway.
Scheme 2. Possible reaction mechanism.
Formation of A and B was actually confirmed by 1H and
29Si NMR spectroscopy analysis of the reaction mixture. In
the reaction of 2a with BDMSE (Si–H: 2.2 equiv. to 2a) in
the presence of 1 (2.5 mol-%) in [D6]benzene at 70 °C, the
N–H protons of amide 2a were completely consumed
within 1 h, and the 29Si NMR spectrum of the reaction mix-
ture showed four signals at δ = 10.1, 14.0, 15.7, and
23.9 ppm. These signals are the same as those for the bis-
silylated compounds prepared from p-toluoyl chloride and
lithium 2,4-bis(dimethylsilyl)-1-azacyclopentane according
to the literature methods[8] and support the presence of
both N,N- and O,N-silylated species.[9] As the reaction pro-
Experimental Section
General Remarks: H, 13C, and 29Si NMR spectra were measured
on JEOL GSX-270 (270 MHz) and ECA 600 (600 MHz) spectrom-
eters. Chemical shifts for H NMR spectroscopy are expressed in
1
1
parts per million downfield from tetramethylsilane as an internal
standard (δ = 0 ppm) in CDCl3, unless otherwise noted. Chemical
shifts for 13C NMR spectroscopy are expressed in parts per million
in CDCl3 as an internal standard (δ = 77.1 ppm), unless otherwise
noted. Chemical shifts for 29Si NMR spectroscopy are expressed in
parts per million downfield from tetramethylsilane as an external
standard. IR spectra were measured on a JASCO FT/IR-4200 spec-
trometer. Analytical thin-layer chromatography (TLC) was per-
formed on glass plates precoated with silica gel (Merck, Kieselgel
60 F254, layer thickness 0.25 mm). Visualization was accomplished
by UV light (254 nm), iodine, and phosphomolybdic acid.
1
gressed, H resonances from p-tolunitrile and a 29Si signal
at δ = 8.59 ppm from 2,5-bis(dimethylsilyl)-1-oxacyclopen-
tane arise. The 29Si signal at δ = 8.59 ppm slowly diminished
to give many peaks at 8–10 ppm, which suggest that ring-
opening polymerization of 2,5-bis(dimethylsilyl)-1-oxacy-
clopentane occurs.[10] We observed that the catalysis by 1
accelerates the reaction. Thermal decomposition of a mix-
ture of A and B, which were prepared from p-toluoyl chlo-
ride and LiN(TMS)2,[8] in DME at 70 °C for 6 h gave p-
tolunitrile 3a in only 27%. In contrast, the yield is increased
(µ3,η2,η3,η5-Acenaphthylene)Ru3(CO)7 (1)[3c] and 1,2-(HMe2Si)2-
[4a]
C6H4
were prepared by methods reported previously. Ru3-
and [RuCl2(CO)3]2
[15]
[16]
(CO)12
were prepared by the literature
methods.
Synthesis of 1,2-Bis(dimethylsilyl)ethane (BDMSE):[17] To a suspen-
to 55% in the presence of ruthenium complex 1 (Scheme 3). sion of lithium aluminum hydride (3 g, large excess) in tetraglyme
Eur. J. Org. Chem. 2008, 4097–4100
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4099

S. Hanada, Y. Motoyama, H. Nagashima
SHORT COMMUNICATION
Iura, T. Maki, H. Nagashima, J. Org. Chem. 2002, 67, 4985–
4988; c) Y. Motoyama, C. Itonaga, T. Ishida, M. Takasaki, H.
Nagashima, Org. Synth. 2005, 82, 188–195; d) Y. Motoyama,
K. Mitsui, T. Ishida, H. Nagashima, J. Am. Chem. Soc. 2005,
127, 13150–13151; e) S. Hanada, T. Ishida, Y. Motoyama, H.
Nagashima, J. Org. Chem. 2007, 72, 7551–7559.
(30 mL) was slowly added 1,2-bis(chlorodimethylsilyl)ethane (10 g,
23.2 mmol) at 0 °C; the mixture was then stirred at 50 °C for 3 h.
Purification by direct distillation from the resultant suspension un-
der reduced pressure (64 °C/90 Torr) gave 1,2-bis(dimethylsilyl)-
1
ethane (BDMSE) in 81% yield (5.5 g). Colorless liquid. H NMR
(270 MHz, CDCl3): δ = 0.07 (d, J = 3.6 Hz, 12 H), 0.53 (t, J =
[4] Rate enhancement by proximate dual Si–H groups is often seen
in transition-metal-catalyzed hydrosilylation reactions, see: a)
H. Nagashima, K. Tatebe, Y. Ishibashi, A. Nakaoka, J. Sakaki-
bara, K. Itoh, Organometallics 1995, 14, 2868–2879; b) S. Han-
ada, Y. Motoyama, H. Nagashima, Tetrahedron Lett. 2006, 47,
6173–6177, and ref.[3a]
[5] In the reaction of trans-cinnamonitrile with BDMSE, dihy-
drocinnamonitrile was obtained in ca. 60% yield by [1,4]-ad-
dition, followed by hydrolysis.
[6] a) K. Itoh, M. Katsuda, Y. Ishii, J. Chem. Soc. B 1970, 302–
304; b) B. Dejak, Z. Lasocki, J. Organomet. Chem. 1983, 246,
151–158; c) M. S. Samples, C. H. Yoder, J. Organomet. Chem.
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[7] a) C. Kruger, E. G. Rochow, U. Wannagat, Chem. Ber. 1963,
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3255; c) B. Rigo, C. Lespagnol, M. Pauly, Tetrahedron Lett.
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1.7 Hz, 4 H), 3.84 (t of sept., J = 1.7, 3.6 Hz, 2 H) ppm. 13C NMR
(67.8 MHz, CDCl3): δ = –4.7, 7.2 ppm. IR (neat): νSi–H
=
2116 cm–1.
Typical Dehydration Procedure: To a stirred solution of p-toluamide
(2a) (1.0 mmol) and (µ3,η2,η3,η5-acenaphthylene)Ru3(CO)7 (1)
(16.3 mg, 2.5 mol-%) in dimethoxyethane (0.5 mL) was slowly
added 1,2-bis(dimethylsilyl)ethane (246 µL, Si–H: 2.5 equiv. to 2a).
At this time, the evolution of hydrogen gas was observed. After the
mixture was stirred at 70 °C for 12 h, the cooled reaction mixture
was diluted with diethyl ether and quenched by the addition of
sodium hydrogen carbonate. After it was stirred at room tempera-
ture for 30 min, the resultant mixture was filtered through a pad
of Celite, and the filtrate was concentrated under reduced pressure.
Purification by silica gel column chromatography (hexane/ether =
20:1) gave p-tolunitrile (3a) in 90% yield. Colorless liquid. 1H
NMR (270 MHz, CDCl3): δ = 2.42 (s, 3 H), 7.27 (d, J = 8.2 Hz, 2
H), 7.54 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR (67.8 MHz, CDCl3):
[8] a) J. Pump, E. G. Rochow, Chem. Ber. 1964, 97, 627–635, and
ref. 6a.
[9] A. R. Bassindale, T. B. Posner, J. Organomet. Chem. 1979, 175,
273–284.
[10] K. Matsubara, J.-I. Terasawa, H. Nagashima, J. Organomet.
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δ = 21.9, 109.4, 119.2, 129.9, 132.1, 143.7 ppm. IR (neat): νCϵN
=
2222 cm–1.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization data of
both the primary amides and the nitriles formed are presented.
[11] a) H. Vorbrüggen, Silicon-Mediated Transformations of Func-
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[12] Reviews, see; a) D. T. Mowry, Chem. Rev. 1948, 42, 189–283;
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Acknowledgments
This work was partially supported by a Grant-in Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology, Japan. S. H. is thankful for a Research Fellowship
from the Japan Society for the Promotion of Science for Young
Scientists.
[13] a) C. Kuo, J. Zhu, J. Wu, C. Chu, C. Yao, K. Shia, Chem.
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Received: May 29, 2008
Published Online: July 14, 2008
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Eur. J. Org. Chem. 2008, 4097–4100