Conversion of alkanenitriles to amidines and carboxylic acids
mediated by a cobalt(II)–ketoxime system
Maximilian N. Kopylovich,
a
Vadim Yu. Kukushkin,*
b
M. Fátima C. Guedes da Silva,
a,c
Matti Haukka,
d
João J. R. Fraústo da Silva
a
and Armando J. L. Pombeiro*
a
a
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Av. Rovisco Pais,
1049–001 Lisbon, Portugal. E-mail: pombeiro@ist.utl.pt
b
Department of Chemistry, St.Petersburg State University, 198904 Stary Petergof,
Russian Federation. E-mail: kukushkin@VK2100.spb.edu
c
Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisbon,
Portugal. E-mail: fatima.guedes@ ist.utl.pt
d
Department of Chemistry, P.O. Box 111, FIN-80101, Joensuu, Finland.
E-mail: Matti.Haukka@Joensuu.Fi
Received (in Cambridge, UK) 9th February 2001, Accepted 17th May 2001
First published as an Advance Article on the web 15th June 2001
The conversion of sterically unhindered organonitriles RCN (R = Me, Et, n-Pr, n-Bu) into the corresponding
amidines RC(
NH)NH
2
, isolated as the nitrate salts, and carboxylic acids RCO
2
H proceeds in the appropriate
nitrile as solvent in the presence of Co(NO
3
)
2
6H
2
O or the cobalt() complex trans-[Co(MeCN)
2
(H
2
O)
4
](NO
3
)
2
and a ketoxime R'
2
C
NOH (R'
2
= Me
2
or C
5
H
10
) but does not proceed at all with either the cobalt compound or the
ketoxime taken alone. The amidinium nitrates were characterized by C, H, N elemental analyses, FAB
+
-MS, IR,
1
H
and
13
C{
1
H} NMR spectroscopies and the structures of RC(
NH
2
)NH
2
+
NO
3
-
(R = Et, n-Pr, n-Bu) were determined
by X-ray crystallography, while the carboxylic acids were identified by GC and
1
H and
13
C{
1
H} NMR spectroscopies.
The reaction proceeds differently with sterically hindered organonitriles, e.g. i-PrCN and t-BuCN, and—instead of
amidinium salts—ammonium nitrate and the appropriate carboxylic acids were identified. The structure of trans-
[Co(MeCN)
2
(H
2
O)
4
](NO
3
)
2
, which is anticipated to be an intermediate in the reaction of Co(NO
3
)
2
6H
2
O, was
determined by X-ray diffractometry.
Introduction
It is well-known that the development of efficient methods for
the formation of the C–N amide linkage is of paramount
importance due to the high synthetic utility of amides, their
numerous industrial applications and their pharmacological
significance.
1,2
As far as amidines RC(
NH)NR'R are con-
cerned, their direct synthesis from RCN and R'RNH can only
be achieved when the nitrile bears a strong electron-acceptor
group R, e.g. CCl
3
.
3
A general, although more time-consuming,
method for preparation of amidines is based on the Pinner
reaction and involves the reaction between RCN and R'OH (or
R'SH, the so-called Thio-Pinner reaction
2,4
) in a non-aqueous
solvent containing substantial amounts of HX (X = Cl, Br) fol-
lowed by the interaction of the imino ester salt RC(OR')
NHHX thus formed with ammonia, primary or secondary
amines.
1,5,6
It was also established that unactivated organo-
nitriles RCN, i.e. with electron-donor groups, can still be
activated towards the coupling with amines by application of
Lewis acids such as FeCl
3
, AlCl
3
, ZnCl
2
7
or MeAl(Cl)NR'R.
8–10
Other metal-based systems, e.g. Ln(SO
3
CF
3
)
3
(Ln =
lanthanide)
11,12
or CuCl,
13
have also proved to be useful in the
generation of amidines from nitriles and primary or secondary
amines. In fact, lanthanide() triflates catalyze the reaction of
nitriles (NCR) with primary amines (R'NH
2
) and diamines
[H
2
N(CH
2
)
n
NH
2
, n = 2–4] to form N,N '-disubstituted amidines
RC(
NR')NHR' (R = Me, Et, Ph; R' = alkyl, Ph) and cyclic
amines, respectively, with loss of NH
3
.
12
More recently a facile
synthesis of amidines involving the intermolecular reductive
coupling of nitriles with organic nitro or aza compounds
induced by SmI
2
,
14
TiCl
4
/Sm
15,16
or TiCl
4
/Zn
16
has been
reported.
As an extension of our previous work on platinum-,
17,18
rhodium-
19
and rhenium-mediated
20
organonitrile–oxime
couplings giving iminoacylated oximes
17–20
or Δ
4
-1,2,4-
oxadiazolines
18
we have focused our attention on 3d metals and
attempted to promote the nitrile–oxime coupling using the
cobalt() ion. In contrast to our expectations, we observed,
instead of the iminoacylation reaction, an intriguing conver-
sion of an alkanenitrile to amidine and carboxylic acid and
these results are reported herein.
Results and discussion
We recently reported an unusual metal-mediated coupling
between nitriles bound to a metal center and oximes
HON
CR'
2
which gave addition products with either mono-
dentate [M]–HN
C(R)ON
CR'
2
[M = Pt(),
17
Re()
20
] or
bidentate [M]–NH
C(R)–O–N
CR'
2
[M = Rh()
19
] imino-
acylated ligands depending on the metal center. Being inter-
ested in extending our research into nitrile–oxime couplings
to other metal systems we investigated the reactions with 3d
metals and, in particular, we studied nitrile and oxime reactions
mediated by the cobalt() ion. In the latter case, however, the
reaction took a different route and we observed, instead of the
iminoacylation, the facile conversion of an alkanenitrile, RCN,
to the appropriate amidine, RC(
NH)NH
2
, and carboxylic
acid, RC(
O)OH. The amidines were isolated in a good yield as
their nitrate salts.
Isolation and identification of amidinium salts
The conversion of RCN (R = Me, Et, n-Pr, n-Bu) proceeds at
50 °C for 8 h in the appropriate nitrile as solvent in the presence
of Co(NO
3
)
2
6H
2
O and a ketoxime R'
2
C
NOH (R'
2
= Me
2
or
C
5
H
10
), but does not proceed at all with either the cobalt salt or
the ketoxime taken alone. With a view to achieving better
reaction conditions, separation of amidinium salts and yield
1
PERKIN
DOI: 10.1039/b101337h J. Chem. Soc., Perkin Trans. 1, 2001, 1569–1573 1569
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