A ferrous center as reaction site for hydration of a nitrile group into a carboxamide in mild conditions

Article abstract of DOI:10.1021/ja710560g

Mild conversion of the nitrile substituent into an amide functional group is observed upon coordination of CNTPA [CNTPA = (6-cyano 2-pyridylmethyl)bis(2-pyridylmethyle)amine] to FeCl₂ followed by reaction with water. The crystal structure of CNTPAFeCl₂ is reported and reveals that the nitrile group does not coordinate but is activated in the vicinity of the ferrous center. Upon treatment with water under anaerobic conditions, CNTPAFeCl₂ converts into H₂NCOTPAFeCl₂, [H₂NCOTPA = (6-carboxamido 2-pyridylmethyl)bis(2-pyridylmethyle)amine], the X-ray crystal structure of which is reported. The new ligand H₂NCOTPA can easily be obtained upon decomplexation. Copyright

Full text of DOI:10.1021/ja710560g

Published on Web 01/31/2008
A Ferrous Center as Reaction Site for Hydration of a Nitrile Group into a
Carboxamide in Mild Conditions
§
§
|
§
Nasser K. Thallaj, Juliette Przybilla, Richard Welter, and Dominique Mandon*
Laboratoire de Chimie Biomim e´ tique des M e´ taux de Transition and Laboratoire DECOMET, Institut de Chimie,
UMR CNRS nï. 7177-LC 3, UniVersit e´ Louis Pasteur, 4 rue Blaise Pascal, B.P. 1032,
F-67070 Strasbourg cedex, France
Received November 28, 2007; E-mail: mandon@chimie.u-strasbg.fr
The mild and efficient hydration of nitriles in ecological-friendly
conditions, a challenging research area, still far from being achieved
by synthetic chemists,1 is known in biological systems: Nature
has designed the so-called nitrile hydratases (NHases), which are
metal-containing proteins that are key players in the process of
-7
8,9
assimilation of nitriles upon conversion to amides. The presence
(III)
(III)
of Co
or Fe
ions centers is essential to the activity of the
enzyme, and a generally accepted hypothesis involves the interaction
of the substrate and reagent with the metal site.10-14 The detailed
mechanism of the reaction, however, is far from being completely
understood, especially the question as to whether water molecule
or the nitrile, or both, coordinates to the metal in order to be
activated.
Figure 1. ORTEP drawing of L1FeCl2. Selected bond lengths (Å) and
angles (deg): Fe-N3 2.202(4); Fe-N1 2.215(4); Fe-N2 2.266(4); Fe-
N4 2.312(4); Fe-Cl1 2.3496(15); Fe-Cl2 2.4324(15); N3-Fe-Cl2 166.97-
In our efforts to develop electron-deficient iron complexes with
tripodal tetraamine ligands,1
5-17
we synthesized the cyanide-R-
) (6-cyano 2-pyridylmethyl)bis(2-
(
12); N1-Fe-N4 146.20(17); N2-Fe-Cl1 171.22(12); C18-C19-N5
78.8(6). The insert shows contacts between the iron center and C19,
equatorial chloride Cl and the nitrile substituant, and tilting of the C C N
5
substituted tripod CNTPA, L
1
1
pyridylmethyle)amine, and report that under anaerobic and wet
conditions, the dichloroferrous complex L FeCl converts to L
FeCl , with L ) H NCOTPA, (6-carboxamido 2-pyridylmethyl)-
bis(2-pyridylmethyl)amine. Decomplexation of L
free L
ligand, that has incorporated 18O when H
1
18 19
2
-
segment.
1
2
2
2
2
2
FeCl
2
affords the
18O is used. This
2
2
reaction represents to our knowledge the first example of the
hydration of a nitrile carried out by a ferrous (Fe( ) center to yield
the corresponding carboxamide. We also demonstrate that the nitrile
group does not need to be coordinated to react with water.
II)
The preparation of L
1
and L
1 2
FeCl follows straightforward
procedures.1
8,15
L FeCl is a red thermally stable and moderately
1 2
(II)
oxygen-sensitive compound displaying an Fe )> ligand MLCT
3
2
transition at λ ) 389 nm (ꢀ ) 1.96 × 10 mmol‚cm ) in its UV-
vis spectrum in line with a tetradentate coordination mode of the
ligand.1 Both its H NMR (well resolved paramagnetically shifted
5,19
1
Figure 2. ORTEP drawing of the [L2FeCl]+ cation. Selected bond lengths
(Å) and angles (deg): Fe-N2 2.1339(16); Fe-O1 2.1443(16); Fe-N4
2.1913(18); Fe-N5 2.2195(19); Fe-N3 2.2430(18); Fe-Cl1 2.3328(6);
O1-C1 1.259(3); N1-C1 1.329(3); N2-Fe-Cl1 173.00(5); N5-Fe-N4
-1
2
signals) and the molecular conductivity data (Λ ) 13.8 S‚mol ‚cm
-
3
15
at 10 M) support a pseudo-octahedral geometry in solution. IR
-
1
1 2
spectroscopy shows νCN at 2238 cm . Single crystals of L FeCl
1
51.37(7); N3-Fe-O1 150.97(6); N1-C1-O1 121.9(2).
could be obtained. As expected from solution studies, the ligand
coordinates in a tetradentate fashion around the metal, and the two
chloride ions complete the coordination sphere. The ORTEP
diagram is displayed in Figure 1.
Contacts between the nitrile group and the iron and equatorial
chloride are evidenced by dC18-Fe ) 3.54 Å, dC19-Cl1 ) 3.70 Å,
spectrum over 24-40 h, the Fe(II) )> ligand MLCT being shifted
3
2
to λ ) 396 nm (ꢀ ) 1.82 × 10 mmol‚cm ), with an isobestic
point at λ ) 412 nm. When the reaction temperature was lowered
to 0 °C, no change could be detected, even in the presence of more
added water.20 In H NMR, the formation of a new high-spin ferrous
species over 24 h was observed. An amido carbonyl group was
detected in IR with νCdO ) 1679 cm . The new L FeCl complex
2 2
could be obtained in a single-crystalline form. Its ORTEP diagram
is displayed on Figure 2.
Obviously, the nitrile substituent has been converted into an
amide group, with dC1O1 ) 1.258 Å and dC1N1 ) 1.329 Å. Unlike
1
and dN5-Cl1 ) 3.69 Å. The C18
C
19
N
5
segment is bent with
<
C C N ) 173.8°. This provides evidence for a repulsive
18 19 5
-
1
interaction between the equatorial chloride ligands and the CN
group, the latter being probably destabilized.
L
1
FeCl
2
is thermally stable in anaerobic solution for days. The
FeCl
addition of 100 equiv of degassed water to a solution of L
1
2
resulted in minor yet detectable changes in the UV-visible
1 2
in L FeCl , the substituted pyridyl arm lies trans to the chloride,
§
and the oxygen of the amide group coordinates to the iron center
trans to the tertiary amine of the tripod with dO1-Fe ) 2.14 Å. The
Laboratoire de Chimie Biomim e´ tique des M e´ taux de Transition.
Laboratoire DECOMET.
|
2414
9
J. AM. CHEM. SOC. 2008, 130, 2414-2415
10.1021/ja710560g CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
cm- . MS yielded the molecular ion at m/z ) 334.15 (L
1
+
Scheme 1. Proposed Mechanism for the Hydration of the Nitrile
Substituent upon Addition of Water to L1FeCl2
2
H ) and
a
+
3
56.14 (L
use of H
36.16 (L
2
Na ) as the main signal. As displayed in Scheme 2, the
1
8
18
2
O resulted in incorporation of O in L
2
with m/z )
1
8
+
18
+
3
2
[ O]H ) and 358.14 (L
2
[ O]Na ).
The involvement of a ferrous center in non-redox chemistry to
21,22
promote the conversion of functional groups is unusual.
To our
knowledge, the present communication is the first reported example
of hydration of a nitrile function by a ferrous complex. In addition,
we demonstrate that the smooth hydration reaction does not
necessarily require the nitrile to be coordinated, but activated in
the vicinity of a metal-coordinated water molecule. Enhanced Lewis
acidity at the metal center might also contribute to what could be
described as an anchimer effect, leading to nitrile hydration by a
simple “outer-sphere mechanism”.9 Comparative studies with
complexes of the same ligand with other transition metals are
currently under investigation in our laboratory.
,14
a
Crystal structures are provided for L1FeCl2, L2FeCl2.
Acknowledgment. We wish to thank Dr Remy Louis, head of
the Institut de Chimie in Strasbourg, for constant encouragements
and support, and the CNRS and ULP. The Conseil Scientifique de
l′ULP is acknowledged for specific support no. AO CS ULP 2006.
Scheme 2. Hydration of the Nitrile Substituent of L1 ) CNTPA
Leading to L2 ) H2NCOTPA, upon Temporary Complexation to
Iron Dichloride in Wet Conditions
a
Supporting Information Available: All synthetic details, including
the preparation and characterization of all compounds mentioned;
experimental details for the hydration reaction. For the two reported
structures, the crystallographic files in CIF format have been deposited.
This material is available free of charge via the Internet at http://
pubs.acs.org.
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(
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2
-
(
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(
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1
2
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(
(
(
4
Treatment of L
followed by acidification with CF
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organic phase under standard conditions with CH Cl afforded L
as a white solid together with variable amounts (however, never
1
FeCl
2
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2
3
CO H under inert atmosphere
2
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2
2
2
(
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1
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more than 20% based on NMR) of L
and 13C NMR, IR, and mass spectroscopy. In the 13C NMR, the
CN ) 117.3 ppm resonance was replaced by a new signal at δCO
167.0 ppm, and IR displayed a new absorption at νCO ) 1685
1 2
. L was characterized by H
δ
)
JA710560G
J. AM. CHEM. SOC.
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VOL. 130, NO. 8, 2008 2415