Facile copper-mediated activation of the N-H bond and the oxidative cleavage of the C2-C3 bond in 1H-2-phenyl-3-hydroxy-4-oxoquinoline

Article abstract of DOI:10.1039/b315919a

The reaction of 1H-2-phenyl-3-hydroxy-4-oxoquinoline (PhquinH₂; 1) with metallic copper leads to Cu^II(PhquinH)₂ while in the presence of PPh₃ to Cu¹₂Cu ^II(Phquin)²(PPh₃)₄. In the presence of tmeda and O₂ ring cleavage occurs to give Cu^II(tmeda) (PhquinH)(N-baa). Both reactions represent a mild N-H activation and an oxidative C-C bond scission.

Full text of DOI:10.1039/b315919a

Facile copper-mediated activation of the N–H bond and the oxidative
cleavage of the C2–C3 bond in 1H-2-phenyl-3-hydroxy-4-oxoquinoline
Miklós Czaun,a Gábor Speier*ab and László Párkányic
a Department of Organic Chemistry, University of Veszprém, 8201 Veszprém, Hungary.
E-mail: speier@almos.vein.hu; Fax: +36 88 427 492; Tel: +36 88 422 022/4657
b Research Group for Petrochemistry, Hungarian Academy of Sciences, 8201 Veszprém, Hungary
c
Hungarian Academy of Sciences, Chemical Research Center, Institute of Chemistry, H-1051 Budapest,
Hungary
Received (in Cambridge, UK) 5th December 2003, Accepted 2nd March 2004
First published as an Advance Article on the web 18th March 2004
The reaction of 1H-2-phenyl-3-hydroxy-4-oxoquinoline
(PhquinH2; 1) with metallic copper leads to CuII(PhquinH)2
while in the presence of PPh3 to CuI2CuII(Phquin)2(PPh3)4. In
the presence of tmeda and O2 ring cleavage occurs to give
CuII(tmeda)(PhquinH)(N-baa). Both reactions represent a mild
N–H activation and an oxidative C–C bond scission.
presence of N,N,NA,NA-tetramethylethylenediamine (tmeda) in
DMF at 60 °C dioxygen is present even in a very small
concentration, complex 5 is formed in 41% yield. During the
reaction the C2–C3 bond in the 1H-2-phenyl-3-hydroxy-4-ox-
oquinoline is cleaved, both oxygen atoms of O2 are incorporated
into 1, based on 18O2 experiments, and CO is released to give the
mixed ligand copper(II) complex 5 (Fig. 3, Scheme 2). The CO
content was determined by GC–MS (81–89%) and volumetric
measurements (equimolar amount of O2 consumed and CO
released). After acidic hydrolysis of 5 and methylation of the
1H-2-Phenyl-3-hydroxy-4-oxoquinoline (1) is isoelectronic with
flavonol (2) and both compounds are degraded by microorganisms
by the use of molecular oxygen. In both cases the C2–C3 bond in
the heterocyclic ring is cleaved by the dioxygenases 1H-3-hydroxy-
4-oxoquinaldine 2,4-dioxygenase (1)1 and quercetin 2,3-dioxyge-
nase (2)2 with concomitant release of carbon monoxide (Scheme 1).
The latter contains copper(II) ions at its active site, while that
metabolizing 1 does not have any metallic cofactor.3 In the course
of model studies of quercetinase numerous copper complexes of
flavonol have been prepared and characterized.4 In all cases the
flavonolate ligand coordinates to the copper ion as a bidentate
ligand through its 3-hydroxy and 4-carbonyl groups. Since 1 has a
nitrogen atom in position 1 of the heterocyclic ring it can also act as
a binding site to metal ions. Here we wish to show that 1H-
2-phenyl-3-hydroxy-4-oxoquinoline coordinates to copper(II) in a
similar fashion to flavonol. Furthermore metallic copper induces
N–H activation in 1 and if dioxygen is present a facile oxidative
cleavage of the C2–C3 bond can be observed which resembles the
enzymatic reaction.
Fig. 1 The molecular structure of 3 with selected bond distances (Å) and
angles (°): Cu(1)–O(1) 1.9067(13), Cu(1)–O(2) 1.9307(13), O(1)–C(1)
1.319(2), O(2)–C(10) 1.291(2), C(1)–C(10) 1.425(2), O(1)–Cu(1)–O(2)
85.74(6), O(1)–Cu(1)–O(2_2) 94. 26(6).†
Metallic copper reacts with 1H-2-phenyl-3-hydroxy-4-oxoqui-
noline (1) in DMF at 50 °C to give complex 3 in 33% yield and
probably H2 as found also in the similar reaction of Cu0 with 2 in
the presence of 2,2A-bipyridine.5 The complex contains a Cu(II
)
centre with mB = 1.97 and EPR parameters of g = 2.128 and A =
71.8 G. It has a square planar geometry around the copper(II) ion
and one Cu–O distance is somewhat longer and the other shorter
than those in the corresponding bis(flavonolato)copper(II) com-
plex5 (Fig. 1). If the reaction is carried out in the presence of
triphenylphosphine the trinuclear copper complex 4 is formed in
good yield (30%). 4 contains a copper(II) ion in a square planar
Fig. 2 The molecular structure of 4 with selected bond distances (Å) and
angles (°): Cu(2)–O(1) 1.9177(13), Cu(2)–O(2) 1.9286(14), Cu(1)–N(1)
2.0175(14), Cu(1)–P(1) 2.2791(7), Cu(1)–P(2) 2.2558(6), O(1)–Cu(2)–
O(2) 93.70(6), N(1)–Cu(1)–P(1) 117.76(5), N(1)–Cu(1)–P(2) 121.46(5),
P(2)–Cu(1)–P(1) 119.09(2).†
coordination. It is paramagnetic with mB
= 1.64 and EPR
parameters of g = 2.116 and A = 71.1 G. The other two copper(
I)
ions coordinate to the nitrogen atoms of the heterocycles. It
represents a smooth activation of the N–H bond as found in a few
cases with other metal complexes too.7 The Cu(
I) ions are
tricoordinated and the geometry around the copper(
I) ions is planar
(Fig. 2). The bond lengths of the coordinated heterocycle indicate
electron delocalization with longer CNN and C–O bond distances as
in the uncoordinated compound.8 When during the reaction of
metallic copper and 1H-2-phenyl-3-hydroxy-4-oxoquinoline in the
Fig. 3 The molecular structure of 5 with selected bond distances (Å) and
angles (°): Cu(1)–O(1) 1.9250(19), Cu(1)–O(2) 1.955(2), Cu(1)–N(1)
2.049(3), Cu(1)–N(2) 2.033(3), C(7)–O(1) 1.323(3), C(8)–O(2) 1.290(4),
C(8)–C(7) 1.418(4), O(1)–Cu(1)–O(2) 85.21(9), O(1)–Cu(1)–N(2)
170.78(10), O(2)–Cu(1)–N(2) 92.81(12), O(1)–Cu(1)–N(1) 92.82(10),
O(2)–Cu(1)–N(1) 167.02(10), N(2)–Cu(1)–N(1) 87.09(11).†
Scheme 1
1004
C h e m . C o m m u n . , 2 0 0 4 , 1 0 0 4 – 1 0 0 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

C2–C3 bond in 1 and incorporation of two O-atoms into 3 and
concomitant CO release. Similar reactions of metallic copper with
acidic compounds leading to copper complexes in the presence of
O2 are well documented (e.g. copper bracelet).10 The oxygenation
of 3 resembles the enzyme reaction of 1 to give the cleavage
product as shown in Scheme 1.
Financial support by the Hungarian National Research Fund
(OTKA Nos. T030400 and T043414) is gratefully acknowledged.
Thanks to Drs A. Rockenbauer and L. Korecz (Budapest) for EPR
measurements.
Notes and references
†
Intensity data were measured on an Enraf-Nonius CAD4 diffractometer
at 293 K. The structures were solved by direct methods. The structures were
refined by full-matrix anisotropic least-squares on F2. The N–H hydrogen
atoms were located in difference maps (3,5), other hydrogen atoms were
added at idealized positions. All hydrogen atoms were included in structure
factor calculations but were not refined.
Crystal data. Compound 3: C36H34CuN4O6, Mw = 682.21, triclinic,
¯
space group P1, a = 9.340(2), b = 9.626(3), c = 10.522(1) Å, a =
101.86(1), b = 125.64(1), g = 107.73(2)°, V = 805.3(3) Å3, Z = 1, Dc
=
1.407 g cm23, m(Cu–Ka) = 1.396 cm21, 2904 reflections measured, 212
parameters refined on F2 using 2697 unique reflections to final indices
R[F2 > 3sF2)] = 0.043, wR = 0.115, w = 1/[s (Fo2) + (0.0787P)2
+
2
0.0874P], P
negative peaks were 0.505 and 20.767 e Å23
Compound 4: C54H46Cu1.5N2O3P2, Mw = 928.18, monoclinic, space
=
(Fo2+2Fc2)/3. The final residual Fourier positive and
.
group C2/c, a
= 40.058(4), b = 10.251(2), c = 27.769(4) Å, b =
125.64(1)°, V = 9267(2) Å3, Z = 8, Dc = 1.331 g cm23, m(Mo–Ka) =
0.809 cm21, 13945 reflections measured, 586 parameters refined on F2
using 13366 unique reflections to final indices R[F > 3sF)] = 0.038, wR =
0.083, w = 1/[s (Fo2) + (0.0526P)2], P = (Fo2+2Fc2)/3. The final residual
2
Fourier positive and negative peaks were 0.349 and 20.345 e Å23
.
Compound 5: C41H50CuN6O7, Mw = 802.41, monoclinic, space group
Pc, a = 10.033(3), b = 12.778(11), c = 17.681(15) Å, b = 117.36(6)°, V
= 2013(3) Å3, Z = 2, Dc = 1.21 g cm23, m(Cu–Ka) = 1.227 cm21, 5677
reflections measured, 504 parameters refined using 5190 unique reflections
2
2
to final indices R[F > 3sF)]
= 0.030, wR = 0.077, w = 1/[s (Fo )
Scheme 2
+(0.0536P) + 0.2737P], P = (Fo2+2Fc2)/3. The final residual Fourier
positive and negative peaks were 0.256 and 20.206 e Å23. CCDC
222925–222927. See http://www.rsc.org/suppdata/cc/b3/b315919a/ for
crystallographic data in .cif or other electronic format.
products MS data evidenced both labelled O-atoms in the
products,9 however some scrambling during the workup occurred.
Preliminary kinetic data show first order dependence of the reaction
rate on both 3 and O2. It is paramagnetic with mB = 1.91 and EPR
parameters of g = 2.129 and A = 55.9 G, and the geometry around
the Cu(II) centre is square pyramidal. The two N-atoms of tmeda
and the two O-atoms of the deprotonated 1 occupy basal
positions.
1 I. Bauer, N. Max, S. Fetzner and F. Lingens, Eur. J. Biochem., 1996,
240, 576.
2 T. Oka, F. J. Simpson and H. G. Krishnamurthy, Can. J. Microbiol.,
1977, 16, 493.
3 S. Fetzner, B. Tshisuaka, F. Lingens, R. Kappl and J. Hüttermann,
Angew. Chem. Int. Ed., 1998, 37, 576.
The results outlined show that copper metal probably deliberates
H2 from 1 to give 3 which in the presence of triphenylphosphine
reacts further with scission of the N–H bond to give the trinuclear
4 É. Balogh-Hergovich, J. Kaizer, J. Pap, G. Speier, G. Huttner and L.
Zsolnai, Eur. J. Inorg. Chem., 2002, 2287 and references therein.
5 I. Lippai, G. Speier, G. Huttner and L. Zsolnai, Chem. Commun., 1997,
741.
6 É. Balogh-Hergovich, G. Speier and G. Argay, J. Chem. Soc., Chem.
Commun., 1991, 551.
7 G. A. Ardizzoia, S. Brenna, G. LaMonica, A. Maspero, N. Maciocchi
and M. Moret, Inorg. Chem., 2002, 41, 610 and references therein.
8 M. Czaun, I. Ganszky, G. Speier and L. Párkányi, Z. Kristallogr. NCS,
2002, 257, 379 and unpublished results.
9 M. Czaun and G. Speier, Tetrahedron Lett., 2002, 43, 5961.
10 S. J. Beveridge and W. R. Walker, Aust. J. Chem., 1981, 33, 2331.
copper( )(II) compex 4. The driving force for these reactions are the
I
formation of the very stable chelate complexes 3 and 4. The
formation of the highly delocalized tridentate ligand in 4 may ease
the scission reaction of the N–H bond. 4 can not be considered as
a clear Cu( ) amido complex since the CNN bond length is longer
I
than that in the parent compound and the heterocycle is deloc-
alized.8 In the presence of tmeda and dioxygen 3 may be formed
first, which is oxygenated subsequently to 5 with cleavage of the
C h e m . C o m m u n . , 2 0 0 4 , 1 0 0 4 – 1 0 0 5
1005