New bis-pyrazole derivatives synthesized from aryl- and xylyl-linked bis(β-diketone) precursors

Article abstract of DOI:10.1080/00397910500446845

The synthesis and characterization of six new aryl-linked, and in one instance xylyl-linked, bis-pyrazoles are reported. The X-ray structures of two of these derivatives are also presented. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910500446845

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New bis‐Pyrazole Derivatives Synthesized
From Aryl‐ and Xylyl‐Linked bis(β‐Diketone)
Precursors
Michael J. Hayter a , David J. Bray a , Jack K. Clegg a & Leonard F. Lindoy a
a Centre for Heavy Metals Research , School of Chemistry, University of
Sydney , Australia
Published online: 16 Aug 2006.
To cite this article: Michael J. Hayter , David J. Bray , Jack K. Clegg & Leonard F. Lindoy (2006) New
bis‐Pyrazole Derivatives Synthesized From Aryl‐ and Xylyl‐Linked bis(β‐Diketone) Precursors, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:6,
707-714, DOI: 10.1080/00397910500446845
To link to this article: http://dx.doi.org/10.1080/00397910500446845
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Synthetic Communicationsw, 36: 707–714, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500446845
New bis-Pyrazole Derivatives Synthesized
From Aryl- and Xylyl-Linked
bis(b-Diketone) Precursors
Michael J. Hayter, David J. Bray, Jack K. Clegg, and
Leonard F. Lindoy
Centre for Heavy Metals Research, School of Chemistry,
University of Sydney, Australia
Abstract: The synthesis and characterization of six new aryl-linked, and in one
instance xylyl-linked, bis-pyrazoles are reported. The X-ray structures of two of
these derivatives are also presented.
Keywords: bis-Pyrazole, diketone, supramolecular, X-ray
INTRODUCTION
Our group has been investigating the use of aryl- and xylyl-linked bis-b-
diketone derivatives as components for constructing new multinuclear
metallo assemblies.[1,2] In an extension of this work we are currently under-
taking related studies employing bis-pyrazole derivatives derived from these
bis-b-diketones. It has long been known that pyrazole derivatives can be
readily prepared from b-diketones via condensation with hydrazine,[3,4] and
the preparation of the new bis-pyrazoles described in this report was based
on this synthetic procedure.
Although the preparation of pyrazole derivatives is well documented for
simple b-diketone precursors, there are only limited reports bis-b-diketones
being employed as precursors for bis-pyrazole derivatives.[5,6]
Received in the USA September 16, 2005
Address correspondence to Leonard F. Lindoy, Centre for Heavy Metals Research,
School of Chemistry, University of Sydney, 2006, N.S.W., Australia. Tel.: þ 61
2 9351 4400; Fax: þ61 2 9351 7067; E-mail: lindoy@chem.usyd.edu.au
707

708
M. J. Hayter et al.
We now report the synthesis and characterization of 1–7, which incorpor-
ate both meta- and para-substituted phenylene spacers (1–6) as well as, in the
case of 7, a meta-xylyl spacer (Schemes 1 and 2). This structural variation,
together with the use of different terminal R groups, gives the opportunity
to selectively “tune” the electronic and steric properties of these products
(and when used as ligands, also of any metal complexes derived from them)
as well as providing some control of their solubilities in different solvents.
RESULTS AND DISCUSSION
Compounds 1–7 were prepared from the corresponding bis(b-diketone)
species 8–13[2] and 14,[7] obtained by the published procedures. Nucleophilic
attack of two equivalents of hydrazine with the required bis(b-diketone)
precursor in hot ethanol in each case led to formation of the required bis-
pyrazole, with isolation of the product involving a solvent extraction step
(water/chloroform) followed by recrystallization from ethanol (except for 3,
which was obtained pure from the extraction step); yields ranged from 25 to
72% (Schemes 1 and 2).
All products were characterized by elemental microanalysis, FTIR spec-
1
troscopy, H NMR spectroscopy, and ESI-MS. Crystals of 5 and 7 were
obtained by slow evaporation of pyridine and methanol solutions, respect-
ively, and were used for X-ray diffraction studies to verify the nature of the
compounds in the solid state.
An ORTEP[8] plot of the X-ray structure of 5 is shown in Figure 1. The
pyrazole nitrogens are aligned mutually trans to each other. The mole-
cule crystallizes as a one-dimensional polymer, involving intermolecular
hydrogen bonding within the lattice. Figure 2 shows the hydrogen bonding
pattern for 5. In this case two molecules of the ligand are linked via two water
molecules; the remaining hydrogen atom on each molecule of water hydrogen
bonds to a lattice pyridine nitrogen forming a one-dimensional polymeric chain.
An ORTEP[8] representation of the X-ray crystal structure of 7 is given
in Figure 3. The pyrazole groups either side of the m-xylylene unit are
aligned at 1808 to each other.
The lattice structure takes the form of a two-dimensional polymer formed
from hydrogen bonding interactions. One pyrazole group of the molecule
hydrogen bonds to two methanol solvent molecules, which in turn interact
Scheme 1. General synthesis of bis-pyrazole ligands 1–7.

bis-Pyrazole Derivatives
709
Scheme 2.
Figure 1. ORTEP plot of 5 shown with 50% probability ellipsoids. Solvate molecules
are omitted for clarity.

710
M. J. Hayter et al.
Figure 2. Schematic representation of 5 showing hydrogen bonding to form a one-
i
˚
dimensional chain. Hydrogen bond distances: N(2)-O(1) 2.7891(16) A, O(1)-N(1)
ii
˚
˚
2.8472(17) A, O(1)-N(3) 2.8716(19) A. i 2x þ 2, 2y þ 2, 2z þ 1; ii 2x þ 1,
y þ 1/2, 2z þ 3/2.
with the another molecule. The other pyrazole interacts with adjacent
pyrazoles in the lattice resulting in the formation of infinite two-dimensional
sheets. Part of one of these sheets showing the hydrogen bonding interactions
is shown in Figure 4.
X-RAY STRUCTURE DETERMINATIONS
Data for 5 were collected at 150(2) K with v scans to approximately 568 2u
using a Bruker SMART 1000 diffractometer employing graphite-monochromated
Figure 3. ORTEP plot of 7 shown with 50% probability ellipsoids.

bis-Pyrazole Derivatives
711
Figure 4. Representation of the X-ray crystal structure of 7 showing the intermole-
cular hydrogen bonding as well as the hydrogen bonding to methanol solvate molecules
to produce a two-dimensional chain. Hydrogen bond distances: N(1)-O(1)i 2.7929(11)
ii
iii
˚
˚
˚
A, N(3)-N(4) 2.8953(11) A, O(1)-N(2) 2.7410(11) A. i. x, 2y 2 1/2, z 2 1/2;
ii. 2x þ 1, y þ 1/2, 2z þ 3/2; iii. 2x, y 2 1/2, 2z þ 1.
˚
Mo-Ka radiation generated from a sealed tube (0.71073A). For 7, data were
collected at 150(2) K with w and v scans to approximately 568 2u using a
Bruker-Nonius APEX2-X8-FR591 diffractometer employing graphite-
monochromated Mo-Ka radiation generated from
a rotating anode
˚
(0.71073 A). Data integration and reduction were undertaken with SAINT and
XPREP[9,10] and subsequent computations were carried out using the WinGX-
32 graphical user interface.[11] Multiscan empirical absorption corrections
were applied to the data using the program SADABS.[12] The structures were
solved by direct methods using SIR97[13] and then refined and extended with
SHELXL-97.[14] Nonhydrogen atoms were refined anisotropically. Carbon-
bound hydrogen atoms were included in idealized positions and refined using
a riding model. Oxygen-bound hydrogen atoms were first located in the differ-
ence Fourier map and were refined with bond length and angle restraints.
Crystal Structure and Refinement Data
R1 ¼ SkFoj–jFck/SjFoj for Fo . 2s(Fo) and wR2 ¼ fS[w(F2o–Fc2)2]/
1/2
S[w(F2c)2]g
where w ¼ 1/[s2(Fo2) þ (AP)2 þ BP], P ¼ (Fo2 þ 2F2c)/3, and
A and B are listed with the crystal data for each structure.
.
.
.
.
5 2Py 2(H2O). Formula C20H26N4 2Py 2(H2O), M ¼ 516.68, monocli-
˚
nic, space group P21/c, a ¼ 10.1140(18), b ¼ 14.021(2), c ¼ 11.0090(19) A,

712
M. J. Hayter et al.
3
b ¼110.963(3)8, V ¼ 1457.8(4) A , Dc ¼ 1.177 g cm23, Z ¼ 2, crystal size
˚
0.615 ꢀ 0.466 ꢀ 0.125 mm, colorless, habit blade, temperature 150(2) K,
l(MoKa) ¼ 0.71073 A, m(MoKa) 0.076 mm21
,
T(empirical)min,max
¼
˚
0.877117, 1.00000, 2umax ¼ 56.64, hkl range 213 to 13, 218 to 18, 214
to 14, N ¼ 14083, Nind ¼ 3510 (Rmerge 0.0218), Nobs ¼ 2897 (I . 2s(I)),
Nvar ¼ 111, residuals R1 (F, 2s) ¼ 0.0512, wR2 (F2, all) ¼ 0.1399, A ¼
2
23
˚
0.0838, B ¼ 0.4638, GoF (all) ¼ 1.036, Drmin,max ¼ 0.681, 20.193 e A
.
.
.
7 MeOH. Formula C18H22N4 MeOH, M ¼ 326.44, monoclinic, space
˚
group P21/c, a ¼ 17.887(2), b ¼ 5.5530(7), c ¼ 19.796(2) A, b ¼
114.991(6)8, V ¼ 1782.2(4) A , Dc ¼ 1.217 g cm23, Z ¼ 4, crystal size
3
˚
0.3 ꢀ 0.25 ꢀ 0.15 mm, colorless, habit prism, temperature 150(2) K, l
(MoKa) ¼ 0.71073 A, m (MoKa) 0.078 mm21, T (empirical)min,max
¼
˚
0.90558666, 0.99000, 2umax ¼ 66.64, hkl range 227 to 27, 28 to 8, 230
to 30, N ¼ 26834, Nind ¼ 6826 (Rmerge 0.0320), Nobs ¼ 5400 (I . 2s(I)),
Nvar ¼ 223, residuals R1 (F, 2s) ¼ 0.0471, wR2 (F2, all) ¼ 0.1409, A ¼
0.090, B ¼ 0.3123, GoF (all) ¼ 1.050, Drmin,max ¼ 0.438, 20.329 e2
.
23
˚
A
EXPERIMENTAL
General
1H NMR spectra were recorded in d6-DMSO at 300 K on a Bruker Avance
DPX300 spectrometer at 300 MHz. dH values are recorded in ppm and are
relative to Me4Si at 0 ppm. Low-resolution electrospray ionisation mass
spectra (ESI-MS) were obtained on a Finnigan LCQ-8 spectrometer. FT-IR
(KBr) spectra were collected using a Bio-Rad FTS-40 spectrometer.
General Synthesis for Compounds 1–7
Hydrazine monohydrate (2.5 mol equiv) in ethanol (10 mL) was added
dropwise to a refluxing ethanol (40 mL) solution of the appropriate
bis(b-diketone) (1 mol equiv). The solution was refluxed for 3 h and cooled
before partitioning between chloroform (400 mL) and water (400 mL). The
organic phase was separated, washed with water (2 ꢀ 200 mL), and dried
(MgSO4) before concentrating under reduced pressure. Pure samples of the
corresponding bis(pyrazole) compounds were then obtained by recrystalliza-
tion from ethanol, except in the case of 3, which was obtained pure directly
from evaporation of the chloroform solution.
1,3-di(3-Methyl-5-pyrazolyl)-benzene (1) (57%) as pale yellow needles.
Elemental analysis found: C, 65.37; H, 6.26; N, 21.41%. Calc. for
C14H14N4ꢁ H2O: C, 65.60; H, 6.29; N, 21.86%. 1H NMR d: 11.73 (br s, –NH,
2H), 7.28 (s, aromatic, H), 6.79 (dd, aromatic, 2H), 6.53 (t, aromatic, H),

bis-Pyrazole Derivatives
713
5.65 (s, Hg, 2H), 1.43 (s, –CH3, 6H). (ESI-MS): m/z 239.3 [M þ H]þ. FTIR
(KBr): 3191, 3001, 2933, 1576, 1448, 1285, 1156, 687 cm21
.
1,3-di(3-tert-butyl-5-pyrazolyl)-benzene (2) (72%), as a white microcrystal-
line powder. Elemental analysis found: C, 74.33; H, 8.10; N 17.20%. Calc. for
C20H26N4: C, 74.50; H, 8.13; N, 17.38%. 1H NMR d: 12.65 (br s, –NH, 2H),
8.14 (s, aromatic, H), 7.67 (dd, aromatic, 2H), 7.39 (t, aromatic, H), 6.55 (s,
Hg, 2H), 1.32 (s, –CH3, 18H). (ESI-MS): m/z 323.5 [M þ H]þ. FTIR
(KBr): 3218, 2962, 1457, 1279, 1170, 790 cm21
.
1,3-di(3-Phenyl-5-pyrazolyl)-benzene (3) (25%) as a white powder. Elemetal
analysis found: C, 71.55; H, 4.61; N, 13.63%. Calc. for C24H18N4ꢁ 0.4CHCl3:
1
C, 71.44; H, 4.52; N, 13.66%. H NMR d: 13.47 (br s, –NH, 2H), 8.38
(s, aromatic, H), 8.35 (s, chloroform, 3H) 7.86 (t, aromatic, 4H), 7.82
(d, aromatic, 2H), 7.55(d, aromatic, 4H), 7.48 (t, aromatic, H), 7.36 (dd,
aromatic, 2H), 7.29 ppm (s, Hg, 2H). (ESI-MS): m/z 363.5 [M þ H]þ. FTIR
(KBr): 3634, 3073, 2986, 2889, 1457, 1175, 759 cm21
.
1,4-di(3-Methyl-5-pyrazolyl)-benzene (4) (38%) as pale yellow needles.
Elemental analysis found: C, 68.93; H, 5.92; N, 21.82%. Calc. for
C14H14N4ꢁ 0.4EtOH: C, 69.24; H, 6.42; N, 21.82%. H NMR d: 12.54 (br s,
1
–NH, 2H), 7.75 (s, aromatic, 4H), 6.45 (s, Hg, 2H), 2.04 ppm (s, –CH3,
6H). (ESI-MS): m/z 239.3 [M þ H]þ. FTIR (KBr): 3218, 1585, 1455, 848,
790 cm21
.
1,4-di(3-tert-Butyl-l,5-pyrazolyl)-benzene (5) (69%) as a white microcrys-
talline powder. Elemental analysis found: C, 74.55; H, 8.07; N, 16.79%.
1
Calc. for C20H26N4: C, 74.50; H, 8.13; N, 17.38%. H NMR d: 12.59 (br s,
–NH, 2H), 7.78 (s, aromatic, 4H), 6.49 (s, Hg, 2H), 1.23 (s, –CH3, 18H).
(ESI-MS): m/z 323.5 [M þ H]þ. FTIR (KBr): 3216, 2964, 1558, 1457,
1244, 794 cm21. Crystals of sufficient quality for an X-ray structure
.
.
analysis of formula C20H26N4 2Py 2(H2O) were obtained by slow evapor-
ation of a pyridine solution over several days.
1,4-di(3-Phenyl-5-pyrazolyl)-benzene (6) (38%) as a yellow microcrystal-
line powder. Elemental analysis found: C, 79.38; H, 5.18; N, 15.17%. Calc.
1
for C24H18N4: C, 79.54; H, 5.01; N, 15.46%. H NMR d: 13.82 (br s, –NH,
2H), 8.35 (s, aromatic, 4H), 8.27 (d, aromatic, 4H), 7.83 (t, aromatic, 4H),
7.75 (d, aromatic, 2H), 7.66 (s, Hg, 2H). (ESI-MS): m/z 363.5 [M þ H]þ.
FTIR (KBr): 3141, 3092, 2889, 2829, 1472, 1184, 974, 753 cm21
.
3,30-(1,3-Xylylene)-bis(3-methyl-5-pyrazolyl) (7) (63%) as pale yellow
needles. Elemental analysis found: C, 72.62; H, 7.68; N, 18.46%. Calc. for
C18H22N4ꢁ 0.2EtOH: C, 72.78; H, 7.71; N, 18.46%. H NMR d: 11.94 (br s,
1
–NH, 2H), 7.13 (t, aromatic, H), 6.89 (dd, aromatic, 2H), 6.87 (s, aromatic,

714
M. J. Hayter et al.
H), 3.58 (s, –CH2, 4H), 2.01 ppm (s, –CH3, 6H). (ESI-MS): m/z 295.4
[M þ H]þ. FTIR (KBr): 3108, 2966, 2906, 1586, 1298, 1046, 811 cm21
.
Crystals of sufficient quality for X-ray structure analysis of formula
.
C18H22N4 MeOH were obtained by the slow evaporation of a methanol
solution over several days.
ACKNOWLEDGMENTS
We to thank the Australian Research Council for financial support. We also
thank J. C. McMurtrie for assistance.
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