The first coordination compound with 5-methylisoxazole-3-carboxylate: Synthesis and structural characterization of [Cu(L2)(H2O)] ... H2O

Article abstract of DOI:10.1007/s10870-009-9563-7

The title compound, aquabis(5-methylisoazole-3-carboxylato-O,N)copper(II) monohydrate, [Cu(L₂)(H₂O)] ... H₂O is synthesized and characterized by X-ray diffraction, elementary analysis, and IR. The ligand coordinates to the

Full text of DOI:10.1007/s10870-009-9563-7

J Chem Crystallogr (2009) 39:766–771
DOI 10.1007/s10870-009-9563-7
ORIGINAL PAPER
The First Coordination Compound with 5-methylisoxazole-3-
carboxylate: Synthesis and Structural Characterization of
[Cu(L2)(H2O)] Á H2O
Torben Birk Æ Høgni Weihe
Received: 6 May 2008 / Accepted: 23 March 2009 / Published online: 5 April 2009
Ó Springer Science+Business Media, LLC 2009
Abstract The title compound, aquabis(5-methylisoazole-
3-carboxylato-O,N)copper(II) monohydrate, [Cu(L2)
As an interesting curiosity, 5-methylisoxazole-3-car-
boxylic acid (Scheme 1) can be synthesized in a one-pot
high-yield synthesis by reaction of 2,5-hexanedione with
hot nitric acid. This method was first described by A.
Angeli in 1891 [3]. In historical context, the acid occupies
an important part in connection with establishment of the
monoamine hypothesis for the pathology of depression. In
connection with the search for alternative anti tuberculosis
drugs after the discovery of pyridine-4-carbohydrazide
(isoniazid) in the early 1950s, the hydrazide of 5-methy-
lisoxazole-3-carboxylic acid and derivates were synthe-
sized [4]. In spite of the fact that anti tuberculosis
properties were absent, the benzyl hydrazide derivate
(isocarboxazid) was found to exhibit effective suppression
of depression [5]. Simultaneously, it was found that the
compound was a potent inhibitor of the monoamine oxi-
dase enzyme. As a result of these two observations the
monoamine hypothesis was introduced, explaining
the connection between the general emotional mood and
the concentration of neuron transmitter, e.g., serotonin,
noradrenalin [6].
(H2O)] Á H2O is synthesized and characterized by X-ray
diffraction, elementary analysis, and IR. The ligand coor-
dinates to the copper center in a bidentate O,N fashion
through the carboxylic acid moiety and the heteroaromatic
nitrogen atom. The complex crystallizes in the triclinic
˚
space group P1 with unit cell parameters a = 8.4080(12)A,
ꢀ
˚
b = 8.810(3), c = 10.318(2)A, a = 110.08(3)°, b = 104.81(2)°,
3
˚
c = 103.149(16)°, V = 650.9(3)A , Z = 2. In addition, the
synthesis of the free acid 5-methylisoazole-3-carboxylic
acid and pyridine containing complex bis(5-methylisoa-
zole-3-carboxylato)bispyridinecopper(II) monohydrate is
described.
Keywords Aquabis(5-methylisoazole-3-carboxylato-
O,N)copper(II) monohydrate Á Crystal structure Á
Synthesis
Introduction
Besides its application in medical chemistry, 5-methy-
lisoxazole-3-carboxylic acid has potential application from
a coordination chemistry point of view because of its
ability of acting as a multidentate ligand due to the content
of carboxylic acid moiety and the isoxazolic nitrogen atom.
Hitherto, no coordination compounds with this acid are
known. However, a limited number of transition metal
complexes with isoxazole derivates have been structurally
characterized.
The isoxazole system finds wide applications in organic
chemistry, due to its versatile chemical properties as being
stable but, depending on experimental conditions and
substitution pattern also easily cleavable [1]. Classically,
the isoxazole system is synthesized by 1,3-dipolar cyclo-
addition of either hydroxylamine to a 1,3-dicarbonyl
compound, or a nitrile oxide to an acetylene [2].
Pure isoxazole complexes are known in salts of FeII in
[Fe(isoxazole)6]2? which show spin-crossover magnetic
behavior, and [Fe3O(OAc)6(isoxazole)3][ClO4] [7]. Other
simply substituted isoxazolic ligands are represented by the
following coordination compounds:
T. Birk (&) Á H. Weihe
Department of Chemistry, University of Copenhagen,
Universitetsparken 5, 2100 Copenhagen Ø, Denmark
e-mail: Birk@kiku.dk
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J Chem Crystallogr (2009) 39:766–771
767
The light yellow solution is added to 200 g of crushed
ice, and placed in ice/water bath for ‘ h. The precipitated
crystals are separated by filtration and washed with ice
water (200 mL) and dried by air.
Calculated for H5C5N1O3: H 3.97%, C 47.25%; N
11.02%. Obtained: H 3.94%, C 47.45%; N 11.03%. Yield:
14.952 g (30% based on 2,5-hexanedione).
Scheme 1 Synthesis of 5-methylisoxazole-3-carboxylic acid
[Pt(5-methylisoxazole)2(Cl)2], [Pd(3,5-dimethyl-isoxaz-
ole)2(Cl2)], [Fe(3-amino-5-methylisoxazole)2(H2O)2][ClO]2,
[Zn(3-amino-5-methylisoxazole)2 Á (Cl2)] [8–11].
Synthesis of [Cu(L)2(H2O)] Á H2O
The isoxazole derivate of the antibacterial sulfanilamide,
sulfamethoxazole (5-methyl-3-isoxazolyl sulfanilamide),
has been the subject of some interest, due to the fact that
coordination to various transition metal ions increases the
pharmacological activity [12, 13]. Monodentate coordina-
tion of the isoxazole system is seen in [Zn(sulfameth-
oxazole)2(py)2(H2O)2] [14] and [Cu2(sulfamethoxazole)2
(l-CH3COO)4], bidentate coordination in [Hg(sulfameth-
oxazole)2] Á 2DMSO [12] and catenation in [Ni(sulfameth-
oxazole)2(H2O)2]? [15].
A solution of Cu(NO3)2 Á 3H2O (0,645 g) in water (20 mL) is
added to a solution of 5-methylisoxazole-3-carboxylic acid
(0,665 g; 5,23 mmol) and NaHCO3 (0,440 g; 5,24 mmol) in
water (10 mL). Slow evaporation resulted in large pillar
shaped blue crystals.
Table 1 Crystallographic—and structure refinement data for title
complex
Molecular formula
CCDC deposit no.
Molecular weight
T (K)
H12C10N2O8Cu1
CCDC 685636
352.76
In this work the synthesis and characterization of the
first coordination compound of 5-methylisoxazole-3-car-
boxylate is presented.
122(1)
Crystal system
Space group
Triclinic
P - 1
Experimental Section
˚
a (A)
8.4080 (12)
8.810 (3)
10.318 (2)
110.08 (3)
104.81 (2)
103.149 (16)
650.9 (3)
2
˚
b (A)
¨
Copper(II) nitrate-3-hydrate (Riedel-de-Haen), 2,5-hex-
˚
c (A)
anedione (Alfa Aesar, 97%), NaHCO3 and Pyridine (Lab-
Scan, HPLC) were all used as received.
a (°)
b (°)
c (°)
Elementary analyses of C, H and N were performed with
a CE Instruments Flash 112 series EA at the section for
microanalysis, University of Copenhagen by Birgitta
Kegel.
3
˚
V (A )
Z
Infrared spectra were recorded in the frequency range
400–4,000 cm-1 with a Perkin-Elmer 2000 FTIR spectro-
photometer by use of KBr technique.
F000
358
Dcal (mg m-3
Radiation type
l (mm-1
)
1.795
Mo Ka
The synthesis of 5-methylisoxazole-3-carboxylic acid is
described in [3] and as patents [4, 16]. The method
described herein follows the essence of the patent
literature.
)
1.72
Crystal size (mm)
Color, shape
0.6 9 0.16 9 0.15
Blue, Needle
2.6–25.0
0.565, 0.860
13,365
h range (°)
Absorb. correction Tmin, Tmax
No. measured reflections
No. independent reflections (Rint
No. reflections with I [ 2r(I)
Rint
Synthesis of 5-Methylisoxazole-3-Carboxylic Acid
)
2,291
Nitric acid (0.2 L; 5.2 M), placed in a conical flask
(1,000 mL) provided with a reflux condenser, is initially
heated to the boiling point. Then the heating source is
turned off and 2,5-hexanedione (45.751 g, 0.40 mol) is
added through the reflux condenser. At the beginning with a
speed of 2 drops/s until evolution of brown NO2 is observed
then with 1 drop/s. When steady reflux is obtained a gentle
heat is switch on. After addition of the 2,6-hexanedione
(*1 h) the heat is increased and the solution is boiled for at
least 1‘ h.
2,232
0.025
Number of ref. parameters
R[F2 [ 2 r(F2)]
wR(F2)
190
0.023
0.101
S (Goodness of fit)
(D/r)max
0.97
0.001
-3
)
˚
Dqmin, Dqmax (e A
0.52, -0.52
w = 1/[r2(F2o) ? (0.1P)2] where P = (Fo2 ? 2 F2c)/3
123

768
J Chem Crystallogr (2009) 39:766–771
X-ray Crystallographic Analysis
Calculated for H12C10N2O8Cu1: H 3.44%, C 34.14%; N
7.96%. Obtained: H 3.34%, C 33.91%; N 7.94%.
Single crystal data were obtained for the title compound at
122(1) K by use of a Nonius KappaCCD area-detector
diffractometer (graphite-monochromated Mo-Ka radia-
tion). The program COLLECT [17] was used for data
collection. Cell refinement was performed with EvalCCD
[18]. The structure was solved by direct methods with
SHELXS-97 and refined on F2 against all reflections with
SHELXL-97 [19]. Non-hydrogen atoms were refined
anisotropically; all hydrogen atoms were identified in a
difference Fourier map and subsequently introduced as a
riding model in the refinement.
Synthesis of [Cu(L)2(py)2] Á H2O
Same method as with [Cu(L)2(H2O)] Á H2O but with sub-
stitution of NaHCO3 with pyridine in excess.
Blue needle like crystals precipitates within 30 min.
Isolated by filtration washed with water and ethanol and
dried in air.
Calculated for H20C20N4O7Cu1: H 4.10%, C 48.83%; N
11.39%. Obtained: H 4.09%, C 49.07%; N 11.37%.
Crystallographic data and refinement data for the title
compound are given in Tables 1, 2 and 4.
Table 2 Fractional atomic coordinates and isotropic or equivalent
2
isotropic displacement parameters (A )
˚
Further information about the Crystallographic analysis
is deposited in the ‘‘Cambridge Crystallographic Data
Center’’ with registration number CCDC 685636. These
data can be obtained free of charge via www.ccdc.cam.
ac.uk/data_request/cif, by e-mailing data request@ccdc.
cam.ac.uk, or by contacting The Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax ?44(0)1223-336033.
x
y
z
U
iso*/Ueq
Cu1
C2
0.57051 (2)
-0.1201 (3)
0.22445 (2) 0.985583 (19) 0.00960 (16)
0.1491 (3)
0.1058
0.7312 (2)
0.7851
0.0178 (5)
0.021*
H2A -0.1850
H2B -0.1943
H2C -0.0866
0.0980
0.6260
0.021*
0.2748
0.7717
0.021*
O3
0.95094 (17) 0.22238 (17) 1.11658 (15) 0.0120 (3)
C4
0.0825 (3)
0.0101
-0.0278 (2)
-0.1207
0.2947 (3)
0.3288
0.6644 (2)
0.5708
0.0113 (4)
0.014*
H3C
H2O
O
H4
C5
1.2546 (3)
1.3116
1.2631 (2)
1.2007
0.0172 (4)
0.021*
N
O
N
O
H5A
H5B
H5C
O6
Cu
H2O
1.2274
0.1708
1.2340
0.021*
O
O
1.3335
0.3586
1.3672
0.021*
O
0.54232 (17) 0.00238 (17) 0.83433 (15) 0.0132 (3)
0.18074 (18) 0.21042 (17) 0.87527 (15) 0.0131 (3)
0.58406 (18) 0.42524 (19) 1.15433 (16) 0.0114 (3)
0.76662 (18) 0.63139 (18) 1.37812 (15) 0.0162 (3)
0.65374 (16) 0.38474 (15) 0.87452 (14) 0.0159 (3)
CH3
O7
O8
Fig. 1 Aquabis(5-methylisoazole-3-carboxylato-O,N)copper(II)mono-
hydrate
O9
O10
H10A 0.6150
0.5952
0.3174
0.4614
0.7796
0.8856
0.019*
0.019*
˚
Table 3 Selected bond lengths (A) and angles (°)
H10B
O11
N12
C14
N15
C16
C17
C18
C19
C20
C21
H21
O25
Bond
0.35531 (18) -0.20847 (18) 0.61434 (15) 0.0145 (3)
Cu1–O6
1.9553(16)
1.9662(17)
1.9847(19)
1.9840(17)
2.2064(13)
0.3153 (2)
0.8659 (2)
0.8111 (2)
1.0905 (2)
0.3938 (2)
0.0400 (3)
0.2583 (2)
0.7295 (2)
1.0431 (3)
1.1136
0.1447 (2)
0.4183 (2)
0.87141 (19) 0.0128 (4)
1.2445 (2) 0.0101 (4)
Cu1–O8
Cu1–N12
0.27919 (19) 1.12174 (17) 0.0103 (4)
Cu1–N15
0.3352 (2)
-0.0771 (2)
0.1011 (3)
0.0064 (2)
0.5016 (2)
0.4589 (3)
0.5527
1.2449 (2)
0.7264 (2)
0.7471 (2)
0.7480 (2)
1.2647 (2)
1.3283 (2)
1.4218
0.0121 (4)
0.0114 (4)
0.0126 (4)
0.0101 (4)
0.0107 (4)
0.0126 (4)
0.015*
Cu1–O10
Angles
O6–Cu1–O8
O6–Cu1–N12
O8–Cu1–N12
O6–Cu1–N15
O8–Cu1–N15
N12–Cu1–N15
O6–Cu1–O10
N12–Cu1–O10
170.44(5)
80.60(7)
97.84(7)
98.83(6)
80.84(7)
168.75(7)
97.41(6)
96.10(6)
0.53353 (19) -0.19086 (19) 0.41754 (16) 0.0226 (4)
H25A 0.6064
H25B 0.4828
-0.2493
-0.2211
0.4222
0.4610
0.027*
0.027*
* The isotropic displacement parameters
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J Chem Crystallogr (2009) 39:766–771
769
Fig. 2 The molecular structure
and atom labeling scheme of
aquabis(5-methylisoazole-3-
carboxylato-O,N)copper(II)
monohydrate. Displacement
ellipsoids are drawn at 50%
probability. H atoms with
arbitrary radii
O25
O10
O11
O6
C16
O3
C5
N15
C17
C19
C4
Cu1
C21
C14
N12
C18
C20
O7
O8
C2
O9
Results and Discussion
carboxylic oxygen ligator atoms and one axial water
ligand.
The molecular structure of the title compound [Cu(L)2
(H2O)] Á H2O is shown in Fig. 1. A selection of bond
distances and bond angles are given in Table 3.
The coordination polyhedron is described as a square
pyramid rather than a trigonal pyramid, due to the angles
between two equatorial ligands e.g., O6–Cu–N12:
80.60(7)° and O8–Cu–N12: 97.84(7)° and angels between
equatorial and apical ligands: O10–Cu–O6: 97.41(6)° and
O10–Cu–N12: 96.10(6)° Fig. 2. The square pyramid
geometry gives opportunity for yet another axial
The coordination polyhedron around the five coordi-
nated central CuII ion is formed by two equatorial
5-methylisoxazole-3-carboxylates in an O,N bidentate
fashion through the isoxazolic donor nitrogen and the
2
Table 4 Atomic displacement parameters (A )
˚
U11
U22
U33
U12
0.00279 (14)
U13
0.00006 (14)
U23
Cu1
C2
0.0063 (2)
0.0113 (10)
0.0080 (6)
0.0085 (9)
0.0123 (10)
0.0075 (7)
0.0081 (6)
0.0068 (7)
0.0133 (7)
0.0188 (7)
0.0146 (7)
0.0097 (8)
0.0076 (9)
0.0085 (8)
0.0086 (9)
0.0109 (9)
0.0086 (9)
0.0093 (9)
0.0103 (9)
0.0084 (9)
0.0251 (8)
0.0088 (2)
0.0177 (10)
0.0156 (7)
0.0109 (9)
0.0224 (10)
0.0123 (6)
0.0154 (7)
0.0111 (7)
0.0133 (7)
0.0144 (6)
0.0109 (7)
0.0125 (8)
0.0120 (9)
0.0107 (8)
0.0161 (9)
0.0119 (9)
0.0149 (10)
0.0116 (9)
0.0111 (9)
0.0132 (10)
0.0293 (8)
0.0083 (2)
0.0219 (11)
0.0144 (7)
0.0080 (9)
0.0229 (11)
0.0124 (7)
0.0142 (7)
0.0108 (7)
0.0133 (7)
0.0155 (7)
0.0107 (7)
0.0144 (9)
0.0111 (9)
0.0115 (8)
0.0101 (9)
0.0129 (10)
0.0125 (9)
0.0098 (9)
0.0106 (9)
0.0103 (9)
0.0193 (7)
-0.00063 (14)
0.0062 (9)
0.0066 (6)
0.0022 (8)
0.0127 (9)
-0.0001 (5)
0.0036 (5)
0.0005 (5)
-0.0021 (6)
0.0053 (5)
-0.0016 (6)
0.0016 (7)
0.0053 (7)
0.0028 (7)
0.0074 (7)
0.0057 (8)
0.0071 (8)
0.0053 (7)
0.0044 (8)
0.0045 (8)
0.0102 (6)
0.0065 (8)
0.0077 (5)
-0.0011 (8)
0.0105 (8)
0.0032 (5)
0.0072 (5)
0.0034 (5)
0.0054 (6)
0.0077 (5)
0.0030 (5)
0.0065 (7)
0.0037 (7)
0.0056 (6)
0.0017 (7)
0.0041 (7)
0.0011 (8)
0.0027 (7)
0.0040 (7)
-0.0004 (8)
0.0155 (7)
0.0041 (9)
0.0039 (5)
-0.0003 (8)
0.0073 (8)
-0.0001 (5)
0.0026 (5)
0.0000 (5)
0.0014 (6)
0.0076 (5)
0.0033 (5)
0.0050 (7)
0.0033 (7)
0.0039 (6)
0.0012 (7)
0.0060 (7)
0.0018 (7)
0.0036 (7)
0.0039 (7)
-0.0015 (7)
0.0121 (6)
O3
C4
C5
O6
O7
O8
O9
O10
O11
N12
C14
N15
C16
C17
C18
C19
C20
C21
O25
123

770
J Chem Crystallogr (2009) 39:766–771
equatorial CuII to ligand distances (average Cu–NIsoxazole
:
˚
1.9844 A and Cu–OCarboxylate: 1.9608 A) and also quite
˚
˚
long compared to equivalent distances 2.051(3) A and
˚
2.071(3) A in [Cu(sulfisoxazole)2(H2O)4] Á 2H2O [20].
This elongation interprets with a Jahn–Teller distortion in
the system (Table 4).
The bond distances between CuII and the carboxylate
˚
˚
oxygen (Cu–OCarboxylate: 1.9553(16) A and 1.9662(17) A)
match the copper acetate distances in the binuclear complexes
of the general type [Cu2(l-CH3COO)4(L)2]. For L : sulfa-
˚
˚
methoxazole (1.963(3)A–1.991(3)A) and 3-amino-5-methy-
˚
lisoxazole (1.959(4)A–1.974(4)A) [12], [21].
˚
The crystal packing of the title compound, Fig. 3, shows
a parallel packing of the individual molecular units.
Infrared spectra of the title compound and the free acid
are shown in Fig. 4. The infrared spectrum of 5-methyli-
soxazole-3-carboxylic acid consists of vibrations from the
3,5-disubstituted isoxazole ring by it self, the methyl group
and carboxylic acid moiety. Vibrations originating from the
3,5-disubstituted isoxazole ring were assigned by compar-
ison with the known fundamental IR vibrations for isox-
azole and 5-methylisoxazole [1].
Fig. 3 The crystal packing in aquabis(5-methylisoazole-3-carbox-
ylato-O,N)copper(II) monohydrat. Displacement ellipsoids are drawn
at 50% probability
coordination site. This is not seen in the title compound,
but could be found in the analogous pyridine complex
[Cu(L)2(py)2] Á H2O.
The O–H stretching vibration originating from the car-
boxylic acid group, dominates the spectrum with a broad
band at 3,200–2,600 cm-1. The C=O and C–O stretching
vibrations and the out-of-plan bending is seen at
The bond between CuII and the axial water ligand is
˚
quite elongated 2.2064(13) A in comparison to the
Fig. 4 IR spectra of 5-
methylisoxazole-3-carboxylic
acid and title complex. Bands
emphasized in the text are
indicated with an arrow
123

J Chem Crystallogr (2009) 39:766–771
771
1,708 cm-1, 1,269 cm-1 and 926 cm-1, respectively. By
coordination, the frequency of the C=O stretching is low-
7. Hibbs W, van Koningsbruggen PJ, Arif AM, Shum WW, Miller
JS (2003) Inorg Chem 42:5645. doi:10.1021/ic034226p
8. Horn E, Horiuchi A, Yamanaka M, Murakami M, Horiuchi CA
(2005) Z Kristallogr New Cryst Struct 220:239
ered to 1,656 cm-1
.
The methyl group at the isoxazole ring is seen in the
infrared spectra by its anti symmetric bending vibration
1,371 cm-1. The symmetric bending vibration of –CH3 at
1,446 cm-1 is overlapped with the C=C stretching vibra-
tion from the isoxazole ring.
9. Horiuchi A, Horn E, Ito K, Nakahodo T, Watabe M, Takahashi
TT, Houriuchi CA (2005) Z Kristallogr New Cryst Struct 220:27
10. Baran Y, Linert W (2001) J Chem Crystallogr 31:369. doi:
10.1023/A:1015651422973
11. Shen L, Li MC, Jin ZM, Hu ML, Xuan RC (2004) Acta Crys-
tallogr Sect E Struct Rep Online 60:m330. doi:10.1107/S160053
6804003939
12. de Lourenco L, Lang ES, Fenner H, Castellano EE (2005) Z
Anorg Allg Chem 631:745 and references therein. doi:10.1002/
zaac.200400443
The isoxazole ring system gives rice to a C4–H stretching
vibration at 3,139 cm-1, a C=N stretching vibration at
1,596 cm-1 and a C4–H out-of-plane bending vibration at
792 cm-1. By coordination, the bands are shifted to
3,120 cm-1, 1,583 cm-1 and 803 cm-1, respectively.
´
´
13. Kremer E, Facchin G, Esteves E, Albores P, Baran EJ, Ellena J,
Torre MH (2006) J Inorg Biochem 100:1167. doi:10.1016/j.jinorg
bio.2006.01.042
14. Garcia-Raso A, Fiol JJ, Rigo S, Lopez A, Molins E, Espinosa E,
Borras E, Alzuet G, Borras J, Castineiras (2000) Polyhedron
19:991. doi:10.1016/S0277-5387(00)00355-7
15. Torre MH, Calvo S, Pardo H, Mombru AW (2005) J Coord Chem
58:513. doi:10.1080/00958970500037516
Acknowledgments The authors are grateful to Mr. Flemming
Hansen (Centre of Crystallographic Studies, University of Copenha-
gen) for collection of the X-ray diffraction data.
16. Niemczyk HJ (2003) Patent US 6,518,254 B1 20,030,211
17. Nonius (1999) COLLECT. Nonius BV, Delft, The Netherlands
18. Duisenberg AJM, Kroon-Batenburg LMJ, Schreurs AMM (2003)
J Appl Cryst 36:220. doi:10.1107/S0021889802022628
19. Sheldrick GM (2008) Acta Crystallogr A 64:112. doi:10.1107/
S0108767307043930
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