Structure of 2-[(phenyl)-(3,5-dimethyl-pyrazol-1-yl)-methyl]-malonic acid diethyl ester

Article abstract of DOI:10.1007/s10870-010-9743-5

The titled new functionalized ligand of type 2-[(phenyl)-(3,5-dimethyl- pyrazol-1-yl)-methyl]-malonic acid diethyl ester (4) is prepared in good yield through condensation of 3,5-dimethyl-pyrazole, with 2-arylidene-malonic acid diethyl esters 3. The struc

Full text of DOI:10.1007/s10870-010-9743-5

J Chem Crystallogr (2010) 40:812–815
DOI 10.1007/s10870-010-9743-5
ORIGINAL PAPER
Structure of 2-[(Phenyl)-(3,5-Dimethyl-Pyrazol-1-yl)-Methyl]-
Malonic Acid Diethyl Ester
•
I. Meskini L. Toupet M. Daoudi
•
•
•
•
•
A. Kerbal M. Akkurt Z. H. Chohan
T. Ben Hadda
Received: 9 November 2009 / Accepted: 12 February 2010 / Published online: 9 March 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The titled new functionalized ligand of type
2-[(phenyl)-(3,5-dimethyl-pyrazol-1-yl)-methyl]-malonic acid
diethyl ester (4) is prepared in good yield through conden-
sation of 3,5-dimethyl-pyrazole, with 2-arylidene-malonic
acid diethyl esters 3. The structure of 4 was determined by
spectral (IR, 1H and 13C NMR), elemental analyses and X-ray
diffraction data. The title compound (4) crystallizes in the
monoclinic space group P21/a, with a = 7.9253 (2), b =
Keywords Polydentate N,O,O-ligand ꢀ
b-Amino dicarbonyl compound ꢀ Malonate ꢀ
Michael reaction ꢀ Aqueous medium
Introduction
The rational design of new HIV-1 Integrase (H–I) inhibitors,
one validated target for chemotherapeutic intervention [1],
is fundamentally based on intermolecular coordination
between H–I/chemical inhibitor/metals (Mg?2 and Mn?2
,
˚
17.1299 (5), c = 13.4522 (4) A, b = 90.220 (2)°, V =
3
1,826.25 (9) A , Z = 4 and with Rint = 0.021. The molecular
˚
conformation shows two possible pockets ready to coordinate
two metal atoms. The crystal structure of (4) is stabilized by
inter-molecular C–H_O and C–H_N hydrogen bonding.
co-factors of the enzyme), leading in the formation of
bimetallic complexes [2, 3]. Thereby, several bimetallic
metal complexes, in many cases exploring the known-well
polydentate ligands, appear in this scenario as the most
promising concept to employ in either enzyme/drug inter-
action or electron transfer process, in the last case involving
the biological oxygen transfer [4–6]. Another exciting
example of application for such polydentate ligand involves
the synergic water activation, that occurs via the so-called
‘‘remote metallic atoms’’. Such organometallic compounds
are structurally deemed to promote or block the H–I activity
[7]. These explanations above detailed clearly demonstrate
that polydentate ligands are of special interest in the bio-
organometallic chemistry field [8]. Looking for the design
of new bimetallic coordinating ligands to further explore in
the building of intermolecular system involving H–I/inhib-
itor/metal complexation, we have targeted to study the
crystallographic structure of polydendate malonate O,N,O-
ligand (4).
L. Toupet (&)
Institut de Physique—IPR—UMR CNRS 6251,
´
Universite de Rennes 1, Rennes, France
e-mail: loic.toupet@univ-rennes1.fr
I. Meskini ꢀ M. Daoudi ꢀ A. Kerbal
´
Laboratoire de Chimie Organique, Universite Sidi
`
Mohammed Ben Abdellah, Fes, Morocco
M. Akkurt (&)
Department of Physics, F.A.S, Erciyes University,
38039 Kayseri, Turkey
e-mail: akkurt@erciyes.edu.tr
Z. H. Chohan
Department of Chemistry, Bahauddin Zakariya University,
Multan, Pakistan
To prepare such polydentate ligands, aza-Michael reac-
tions appear to be key-step to lead the b-amino esters. In fact,
this kind of reaction has been largely employed to generate
structurally diverse b-amino dicarbonyl compounds, where
the undoubtedly importance of this aza-Michael step it is
T. B. Hadda (&)
Laboratoire de Chimie des Materiaux,
´
Universite Mohammed Premir, 60000 Oujda, Morocco
´
e-mail: taibi.ben.hadda@gmail.com
123

J Chem Crystallogr (2010) 40:812–815
813
viewed by the large number of unconventional methodolo-
gies as well as the broadened of applications [9–11].
Table 1 Crystal data and structure refinement for 4
Empirical formula
C19H24N2O4
Formula weight
344.40
Temperature
110(2) K
Results and Discussion
Wavelength
0.71073 A
Monoclinic, P21/a
Crystal system, space group
Unit cell dimensions
Chemistry
˚
a = 7.9253 (2) A
a = 90°
b = 90.220 (2)°
c = 90°
The treatment of 2-(benzylidene)-malonic acid diethyl
esters (3) in the presence of 3,5-dimethyl-pyrazole, in an
aqueous medium at room temperature brings about highly
and efficient regioselective aza-Michael addition to pro-
duce the corresponding b-amino dicarbonyl compound 4
(Scheme 1) as it was previously published for analogue
compound [12].
˚
b = 17.1299 (5) A
˚
c = 13.4522 (4) A
3
˚
1826.25 (9) A
Volume
Z
4
Calculated density
F(000)
1.253 Mg/m3
736
0.09 mm-1
2.82–27.00°
-10 B h B 10, -21 B k B 21,
-17 B l B 16
Absorption coefficient
h range for data collection
Limiting indices
X-ray Structure Determination of O,N,O-ligand (4)
Suitable single crystal of malonate derivative 4 was
obtained by recrystallization from ethanol. A white-trans-
parent crystal of C19H24N2O4 having approximate dimen-
sions of 0.25 9 0.25 9 0.15 mm was mounted on a glass
fibre. All measurements were made in the x-scan technique
on a CCD Saphire 3 Xcalibur diffractometer (Oxford
Diffraction) with graphite monochromatized Mo Ka radi-
ation. The structure was solved by direct methods using the
program SIR-97 [13]. The non-hydrogen atoms were
refined anisotropically by the full-matrix least-square
techniques using the program SHELXL97 [14]. All the
hydrogen atoms bonded to C atoms were located geomet-
rically and treated using a riding model, with C–H = 0.95–
Reflections collected/unique
Completeness to h = 27.00
Absorption correction
24138/3827 [Rint = 0.021]
96.3%
None
Full-matrix least-squares on F2
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
3827/0/226
1.10
Final R indices [3,056 reflections
with I [ 2r(I)]
R indices (all data)
R1 = 0.048, wR2 = 0.150
R1 = 0.058, wR2 = 0.155
-3
˚
-0.52 and 0.58 e A
Largest diff. peak and hole
are essentially in the same plane, with maximum deviations
˚
1.00 A and Uiso(H) = 1.2 or 1.5Ueq(C). The details of the
˚
˚
of -0.037(2) A for C18 and 0.003(2) A for C19. The
pyrazole ring is not coplanar with the phenyl ring. There is
an interplanar angle of 62.01(9)° between them. The tor-
sion angles N1–C1–C2–C6, C9–C1–C2–C3, N1–C1–C2–
C3 and C9–C1–C2–C6 are -49.84(16), 65.30(17),
-168.37(12) and -176.17(13)°, respectively. In addition,
the torsion angles C15–N1–C1–C2 of 125.04(16)° and
C2–C1–C9–C10 of -117.66(16)° also confirm that the mol-
ecule has a non planar conformation. In the crystal structure,
there is no classic hydrogen bond found (Tables 3, 4).
crystal and experimental data were listed in Table 1.
Selected bond distances and bond angles are given in
Table 2. The molecular structure of the title O,N,O-ligand
is shown in Fig. 1. Packing and hydrogen bonding inter-
actions are illustrated in Figs. 2 and 3.
The values of the geometric parameters of the title
molecule are in normal. The molecule has not a planar
conformation (Fig. 2). Except the H-atoms, the pyrozole
ring and the C-atoms of the methyl groups connected to it
CH
CH
3
3
CH
CH
O
3
3
O
O
O
O
N
O
CH3
CH3
H
(i)
O
O
(ii)
O
O
O
N
+
O
O
CH
3
H C
3
2
3
1
4
Scheme 1 Conditions for reaction: (i) piperidine, CH3CO2H, EtOH/D; (ii) 3,5-dimethyl-pyrazole, H2O/R.T
123

814
J Chem Crystallogr (2010) 40:812–815
˚
Table 2 Bond lengths (A) and angles (°) for 4
O1–C3
1.192(2)
O4–C6
1.320(2)
O2–C3
1.326(2)
1.464(3)
1.203(2)
125.1(2)
124.1(2)
122.5(1)
125.3(2)
108.6(1)
112.7(1)
O4–C7
1.460(2)
1.354(2)
1.364(2)
119.7(1)
111.0(1)
108.7(1)
113.7(1)
107.9(1)
110.8(1)
O2–C4
N1–C15
O3–C6
N1–N2
O1–C3–C2
O1–C3–O2
O3–C6–C2
O3–C6–O4
N1–C1–C2
N1–C1–C9
N2–N1–C1
C1–C2–C3
C1–C2–C6
C2–C1–C9
C3–C2–C6
C2–C3–O2
Fig. 2 The packing and the C–H_O and C–H_O hydrogen bonding
interactions of the title ligand (4) viewed down a axis. Hydrogen
atoms not involved in hydrogen bonding have been omitted for clarity
Fig. 1 ORTEP view of the title compound with the atom numbering
scheme. Displacement ellipsoids for non-H atoms are drawn at the
50% probability level. Critical spatial distances [O1_O3 = 3.52,
˚
O3_N2 = 3.94 and O1_N2 = 5.06 A]
Experimental Section
Fig. 3 View of the packing and the hydrogen bonding interactions of
the title ligand (4) viewed down c axis. Hydrogen atoms not involved
in hydrogen bonding have been omitted for clarity
All materials and solvents used were of reagent grade as
received from commercial sources. The starting material
2-(benzylidene)-malonic acid diethyl ester (3) was synthe-
sized and transformed to the malonate derivative as
described in our previous work [12]. 1H NMR spectra were
recorded on AC 300 MHz NMR Bruker Spectrometer at
ambient temperature and chemical shifts were reference to
the internal tetramethylsilane. Infrared spectra were recor-
ded in KBr pellets using a Perkin-Elmer 1310 spectropho-
tometer. Mass spectra were determined by platform II
Micromass (ESI?, CH3CN/H2O: 50/50) and elemental
analyses were performed by CNRST Service Central
d’Analyse (Rabat, Morocco).
Table 3 Torsion angles (°) for (4)
N1–C1–C2–H2
70.2(2)
O1–C3–C2–C6
-109.4(2)
N2–N1–C1–H1
N2–N1–C1–C2
N2–N1–C1–C9
O1–C3–C2–H2
-170.2(1)
-54.8(2)
72.2(2)
O1–C3–C2–H1
O3–C6–C2–H2
O3–C6–C2–H1
H1–C1–C2–H2
-12.1(2)
-176.6(2)
-31.5(2)
-174.3(1)
131.0(2)
123

J Chem Crystallogr (2010) 40:812–815
815
0
128.3/127.93 (5C, Ph), 105 (Ctert, C2 H, pyrazol), 61.57
(2C, 2CH2CH3), 60.35 (Ctert, PhC3HC2H), 57.52 (Ctert, Ph–
˚
Table 4 Electrostatic-bond parameters for 4 (A, °)
D–H
H_A
D_A
D–H_A
0
0
C3HC2H), 13.87 (C, C1 H3, pyrazol), 13.67 (C, C3 H3,
pyrazol), 13.64/10.06 (2C, 2CH2CH3). MS (IE): Calcd for
[M]? C19H24N2O4: 344.17, [M ? H]? (m/z) = 345 (11%),
83 (100%). Elemental analysis for C19H24N2O4 Calcd
(Found): C 66.27 (65.71), H 6.97 (5.80), N 8.13 (8.78).
C7–H7B_N2i
C10–H10_O1ii
C13–H13_Cg1iii
0.9900
0.9500
0.95
2.53
2.49
2.74
3.486 (2)
3.294 (2)
3.435 (2)
164
143
131
Symmetry codes: (i) 1 - x, -y, 1 - z; (ii) 1 - x, -y, 2 - z; (iii) -
1/2 ? x, -1/2 - y, z. Cg1 is a centroid of the five-membered ring
(N1/N2/C15–C17)
Supplementary Information
2-Benzylidene-malonic acid diethyl ester (3)
Crystallographic data for the structural analysis has been
deposited with the Cambridge crystallographic Data Cen-
tre, CCDC No. 734199 for compound (4). Copies of this
information can be obtained free of charge from The
Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ,
UK (fax: ?44-1223-336033; e-mail: deposit@ccdc.cam.
ac.uk or http://www.ccdc.cam.ac.uk).
To a solution of ethyl malonate 3 (15 g, 93 mmol) in
40 mL of ethanol, were added the respective aldehyde
[(benzaldehyde 1 (11.8 g, 110 mmol), 1.5 mL of piperi-
dine and 1 mL of glacial acetic acid. Then the mixture was
stirred at refluxing temperature of ethanol for 12 h, until
thin-layer chromatography indicated the complete consume
of the starting material. After removing solvent, the crude
product was washed with a saturated solution of sodium
bisulphite (20 mL). The product was extracted by diethyl
ether (2 9 20 mL), dried with sodium sulphate and evap-
orated to give the respective pure oil.
Acknowledgments This work was supported by grant from Project
´ ´
Global de Recherche de l’Universite Mohammed Premier/LCM
(Morocco).
Yellow oil. 71% of yield, Rf 0.7 (ether/hexane, 1/1). IR
(KBr, m cm-1): 2875–2982 (CH), 1722 (C=O), 1629 and
1497 (C=C), 1294–1254 (C–O). 1H-NMR (300 MHz,
CDCl3) d ppm: 7.72 (s, 1H, C=CH–Ph), 7.45–7.32 (m, 5H,
Ph), 4.32 (q, 2H, CH2–CH3, 3J = 7.2 Hz), 4.28 (q, H,
CH2–CH3, 3J = 7.2 Hz), 1.31 (t, 3H, CH2–CH3, 3J =
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2-[(phenyl)-(3,5-dimethyl-pyrazol)-1-yl-methyl]-
malonic acid diethyl ester (4)
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(C=O), 1586/1554 (C=C), 1460/1419 (C=N), 1269/1264
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3
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0
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¨
Bu¨yu¨kgu¨ngor O (2007) Acta Crystallogr E63:o1656–o1657
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3H, CH2CH3, 3J = 7.1 Hz). 13C-NMR (75.5 MHz, CDCl3)
0
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0
139.30 (Cquat, ph), 137.30 (Cquat, C3 , pyrazol), 128.50/
123