The crystal structure of 3,5-diisopropyl-4-nitropyrazole from X-ray powder diffraction data

Article abstract of DOI:10.1016/S0022-2860(00)00766-3

The crystal structure of 3,5-diisopropyl-4-nitropyrazole, 3c, has been determined by a Patterson Search method from laboratory X-ray powder diffraction data. The crystal data are: monoclinic symmetry with the unit-cell parameters a = 19.530(5), b = 6.485(1) and c = 17.937(3) ?,β = 100.32(1)°, space group 12/a, C₉H₁₅N₃O₂, Z = 8, 293 K. After indexing the powder pattern by two methods, the unit-cell parameters found were refined by a least-squares technique. A whole pattern-fitting program was used to extract the integrated intensities. The structure was solved taking a related compound as a search model and the final Rietveld refinement converged to R_wp = 0.1971 and R_p = 0.1437. The structure presents a dimer conformation between N atoms through a hydrogen bond.

Full text of DOI:10.1016/S0022-2860(00)00766-3

Journal of Molecular Structure 562 (2001) 11±17
www.elsevier.nl/locate/molstruc
The crystal structure of 3,5-diisopropyl-4-nitropyrazole
from X-ray powder diffraction data
a,
L.E. Ochando , J.M. Amigo , J. Rius , D. Louer , Ch. Fontenas , J. Elguero
b
c
d
d
Âa
*
È
a
   Á
Seccion Departamental de Geologõa, Facultad de Quõmica, Universitat de Valencia, Avda Dr Moliner 50, E-46100 Burjassot, Spain
b
Á
Institut de Ciencia de Materials de Barcelona, CSIC, Campus de la UAB, E-08193 Bellaterra, Catalunya, Spain
c
Â
LCSIM (CNRS UMR 6511), Universite de Rennes I, 35042 Rennes, France
d
 Â
Instituto de Quõmica Medica, CSIC, Juan de la Cierva 3, E-28006 Madrid, Spain
Received 20 July 2000; revised 6 August 2000; accepted 6 August 2000
Abstract
The crystal structure of 3,5-diisopropyl-4-nitropyrazole, 3c, has been determined by a Patterson Search method from
laboratory X-ray powder diffraction data. The crystal data are: monoclinic symmetry with the unit-cell parameters a ˆ
ꢀ
19:530ꢀ5†; b ˆ 6:485ꢀ1† and c ˆ 17:937ꢀ3† A; b ˆ 100:32ꢀ1†8; space group I2/a, C9H15N3O2, Z ˆ 8, 293 K. After indexing
the powder pattern by two methods, the unit-cell parameters found were re®ned by a least-squares technique. A whole pattern-
®tting program was used to extract the integrated intensities. The structure was solved taking a related compound as a search
model and the ®nal Rietveld re®nement converged to Rwp ˆ 0.1971 and Rp ˆ 0.1437. The structure presents a dimer conforma-
tion between N atoms through a hydrogen bond. q 2001 Elsevier Science B.V. All rights reserved.
Keywords: X-ray powder diffraction; Patterson search method; Hydrogen bonding
1. Introduction
structure of the related phases. The present study
deals with the crystal structure of one variety of 3,5-
diisopropylpyrazoles 3, solved ab initio from conven-
tional monochromatic X-ray powder diffraction
patterns (Scheme 1).
N-Unsubstituted pyrazoles form hydrogen bond
networks of great complexity. Not less than four
fundamental motifs have been found so far: dimers,
trimers, tetramers and chains called catemers [1,2].
There are also several types of catemers depending
on the pitch [2]. The motif seems to depend on the
size of substituents at positions 3 and 5 of the pyrazole
ring [2]. We have already studied pyrazoles bearing at
these positions methyl 1 [3±5] and tert-butyl groups 2
[6]. To further understand the crystal chemistry of this
family of compounds it is of interest to know the
2. Experimental
A brief schematic synthesis of 3,5-diisopropylpyr-
azoles, all of them previously unknown, are reported
in Scheme 2.
Three forms of 3,5-diisopropylpyrazoles can be
synthesized depending on the experimental condi-
tions:
* Corresponding author. Tel.: 134-96-386-4603; fax: 134-96-
386-4372.
3,5-Diisopropylpyrazole 3a. Clean sodium (3.9 g,
169 mmol) is powdered under nitrogen ¯ow by
E-mail address: luis.e.ochando@uv.es (L.E. Ochando).
0022-2860/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(00)00766-3

12
L.E. Ochando, et al. / Journal of Molecular Structure 562 (2001) 11±17
Scheme 1.
melting and agitating it during cooling. To the gray
powder is added 200 ml of dry diethylether. Then,
under re¯ux, 10 ml (1 eq.) of ethanol (dried over
concentrating the ethereal solution due to volatility
of the product. 17.2 g of the yellow oil containing
2,5-dimethyl-hepta-3,5-dione are obtained. The oil is
dissolved in 200 ml of ethanol. 9.5 ml (more than
1.5 eq.) hydrazine hydrate and 1 ml concentrated
hydrochloric acid are added. The reaction mixture is
heated under re¯ux overnight and then concentrated
to dryness. The oily residue, dissolved in dichloro-
methane, is washed with a saturated solution of
sodium bicarbonate. The aqueous layer is extracted
with dichloromethane. Combined organic layers are
washed with water and brine. After drying over
sodium sulfate and evaporation of the solvent, 1.8 g
(6%) of an oil that solidi®es slowly is obtained, m.p.
788C. Attempts to crystallize it reverts it to its syrupy
appearance.
Ê
4 A molecular sieves) is added dropwise. The solution
is left under re¯ux for 4 h. The reaction mixture being
then a suspension of a white solid. The diethylether is
distilled off. To the dry sodium ethoxide, heated to
808C, is added 45 ml (approximately 2 eq.) of ethyl
2-methyl propionate in one portion. Immediately, a
dropwise addition of 18.8 ml (1 eq.) of 3-methyl-2-
butanone is started. At that stage, the reaction should
be protected from moisture with a silica gel drying
tube. After the completion of the addition the solution
is heated for 1 h and left for cooling. Upon cooling the
reaction mixture becomes a solid. Water is added and
the organic layer is separated and dissolved in diethy-
lether. The organic layer is extracted several times
with water. Combined aqueous layers are acidi®ed
with 10% sulfuric acid. The diketone is extracted
with diethylether. Special care must be taken when
1H NMR (d ppm, CDCl3): 8.10 (br, 1H), 5.88 (s,
1H), 2.96 (h, 2H), 1.26 (s, 12H). 13C NMR (d ppm,
CDCl3): 98.3 (C4), 26.8, 22.6 (3,5-iPr groups).
3,5-Diisopropyl-4-bromopyrazole 3b. To a solution
Scheme 2.

L.E. Ochando, et al. / Journal of Molecular Structure 562 (2001) 11±17
13
Table 1
X-ray powder diffraction data of 3,5-di-isopropyl-4-nitropyrazole
carbon in ethanol affords 0.52 g (52%) of a
slightly yellow oil.
1H NMR (d ppm, CDCl3): 10.65 (br, 1H), 3.07 (h,
2H), 1.30 (d, 12H). 13C NMR (d ppm, CDCl3): 90.6
(C-4), 26.1, 21.2 (3,5-iPr groups).
Ê
dobs (A)
h k l
2uobs (8)
2ucalc (8)
Iobs
2 0 0
0 0 2
10.681
11.640
14.324
16.746
16.896
17.193
19.881
20.595
20.989
21.448
22.641
23.386
23.941
24.144
24.702
26.294
27.344
27.512
28.282
29.921
31.397
32.459
33.576
34.294
35.087
35.339
35.807
36.056
36.358
36.546
36.642
37.616
38.965
40.036
40.311
40.369
43.175
43.695
45.107
10.685
11.637
14.333
16.741
16.900
17.187
19.873
20.594
20.984
21.463
22.640
23.395
23.939
24.142
24.699
26.290
27.349
27.511
28.274
29.929
31.396
32.468
33.585
34.304
35.117
35.301
35.815
36.028
36.371
36.568
36.647
37.613
38.977
40.040
40.315
40.378
43.178
43.673
45.114
9.6101
8.8206
7.1745
6.1426
6.0884
5.9840
5.1815
5.0038
4.9108
4.8068
4.5567
4.4135
4.3125
4.2769
4.1817
3.9326
3.7842
3.7616
3.6612
3.4649
3.3058
3.2004
3.0968
3.0339
2.9674
2.9469
2.9096
2.8902
2.8670
2.8527
2.8455
2.7744
2.6819
2.6130
2.5959
2.5923
2.4311
2.4036
2.3321
100
19
6
3,5-Diisopropyl-4-nitropyrazole 3c. To 0.5 g
(3.3 mmol) of 3,5-diisopropylpyrazole 3a in a 25 ml
round-bottom ¯ask cooled to 08C is added slowly
1.4 ml of 96% sulfuric acid. Once the entire product
dissolved, 0.7 ml of 90% nitric acid is added. The
reaction mixture is left at 08C for 30 min and then
heated to 1008C for 2 h. Thin Layer Chromatography
(TLC) analysis shows the completion of the reaction.
The reaction mixture once cold is neutralized with a
saturated solution of sodium bicarbonate. The
resulting suspension is extracted with dichloro-
methane. The organic layer is dried over sodium
sulfate and yields after evaporation 0.54 g (83%) of
a white powdered solid, m.p. 1128C.
1H NMR (d ppm, CDCl3): 3.72 (h, 2H), 1.36 (d,
12H). 13C NMR (d ppm, CDCl3): 153.4 (C-3 and C-
5), 128.9 (C-4), 26.4, 21.0 (3,5-iPr groups).
Of these three compounds, only 3c yields a micro-
crystalline powder by slow evaporation of a saturated
solution in ethanol.
22 0 2
1 1 0
10
4
0 1 1
2 0 2
3
21 1 2
2 1 1
1 1 2
56
2
22
, 1
4
4 0 0
3 1 0
0 0 4
10
5
22 0 4
23 1 2
22 1 3
4 0 2
4
81
8
2 1 3
7
2 0 4
4
4 1 1
24 1 3
5 1 0
6
14
3
26 0 2
22 1 5
4 1 3
2
5
2
22 0 6
5 1 2
2
4
Two powder diffraction data sets were used for the
study. For indexing purposes and, also, to have a
reference material for the calibration of the second
instrument, data set (I) was collected with a high-reso-
lution powder diffractometer (Siemens D500) using
the parafocusing Bragg±Brentano Geometry. Pure
26 1 1
23 2 1
25 1 4
2 2 2
1
, 1
4
2
26 0 4
1 2 3
2
1
2 0 6
1
ꢀ
CuKa1 ꢀl ˆ 1:5405981 A† radiation was produced
0 2 4
1 1 6
3
with an incident-beam curved-crystal Ge monochro-
mator and asymmetric focusing (short focal distance,
124 mm; long focal distance, 216 mm). The instru-
ment resolution function has been described else-
where [7] and the alignment of the diffractometer
was checked with standard reference materials [8].
To reduce peak displacements due to the effect of
specimen transparency in re¯ection geometry, a thin
layer of the powder was deposited on a silicon plate.
The powder diffraction pattern was scanned in steps of
0.028 (2u) with a ®xed counting time 27 s per step.
Peak positions were obtained with the pro®le ®tting
program pro®le from Socabim.
1
22 2 4
6 1 3
1
2
24 2 4
23 2 5
2
3
of 0.56 g (3.7 mmol) 3,5-diisopropylpyrazole 3a in
5 ml glacial acetic acid is added 0.2 ml (1 eq.)
bromine via a syringe. The solution is re¯uxed
for 3 h and becomes brown. After cooling, the
reaction mixture is concentrated, dissolved in
dichloromethane and washed with a saturated
solution of sodium bicarbonate, with water and
®nally with brine. After drying over sodium
sulfate and evaporation under reduced pressure a
brown oil is obtained. Discoloration by activated
The second data set (II) was collected with a high-
resolution powder diffractometer using the Debye±
ꢀ
Scherrer Geometry. Pure CoKa1 ꢀl ˆ 1:78892 A†

14
L.E. Ochando, et al. / Journal of Molecular Structure 562 (2001) 11±17
Table 2
radiation was produced with an incident-beam
curved-crystal quartz monochromator and asym-
metric focusing (short focal distance, 180 mm; long
focal distance, 560 mm) with a capillary sample. The
powder diffraction pattern was scanned in steps of
0.0258 (2u) with a ®xed counting time of 200 s per
step in the range from 8 to 308 and 400 s per step in the
range from 30.025 to 598 (2u). Then, the full pattern
was scaled to the lower counting times. Such a proce-
dure improves signi®cantly the counting statistics at
high angles. After data collection the stability of the
X-ray source was checked by recording the ®rst lines
of the pattern. Peak positions were obtained with the
pro®le ®tting program pro®le from Socabim.
Details of the rigid-body least-squares re®nement from X-ray
powder data of 3,5-di-isopropyl-4-nitropyrazole. sꢀf†; sꢀc†; sꢀw†
are the estimated standard deviations of the Euler angles describing
the molecular rotation
Range of 2u (8)
Space group
Z
8±59
I2/a
8
Ê
Unit cell dimensions (A)
a ˆ 19.530(5)
b ˆ 6.485(1)
c ˆ 17.937(3)
b ˆ 100.32(1)
2234.6(4)
91 (unambig.)
0.8579
Ê 3
Volume (A )
Number of re¯ections
Scale factor
FWHM (8)
Overall B (A )
0.089
Ê 2
6.33
0.253
s(f) (8)
s(c) (8)
s(w) (8)
Residuals
0.204
3. Structure solution
0.235
a
The powder diffraction data (data set I) were
indexed with the two programs dicvol91 [9] and
treor90 [10]. The same monoclinic unit cell, with
Rp
0.144
0.197
0.306
4.619
b
Rwp
c
RB
x2d
high ®gures of merit M20 ˆ 29 and F20
ˆ
a
64ꢀ0:004; 78† for dicvol91 and M18 ˆ 27 and F18
ˆ
R-pattern:
X
56ꢀ0:0042; 77† for treor90, was obtained from both
programs. After a least-squares reviewing of the data
available of the pattern, the re®ned unit cell para-
uyoꢀi† 2 ycꢀi†u
i
X
Rp
ˆ
:
yoꢀi†
i
ꢀ
ꢀ
meters were: a ˆ 19:530ꢀ5† A; b ˆ 6:485ꢀ1† A and
ꢀ
ꢀ 3
c ˆ 17:937ꢀ3† A; b ˆ 100:32ꢀ1†8; V ˆ 2234:6ꢀ4† A :
The ®nal ®gures of merit are M20 ˆ 20:3 and
F30 ˆ 35:1ꢀ0:0067; 127†; the list of observed and
calculated peak positions is given in Table 1. The
most probable space group is I2/a (C2/c).
b
R-weighted pattern:
X
0
1
1=2
2
wꢀi†ꢀyoꢀi† 2 ycꢀi††
B
B
@
C
C
A
i
X
Rwp
ˆ
2
wꢀi†yoꢀi†
i
Ninety-one unambiguously indexed and 106
systematically overlapped integrated intensities were
extracted from data set II by means of the whole
pattern ®tting program ajust [11] in the range of 8±
598 (2u).
Patterson search methods have been widely used
for solving crystal structures from powder data
when, as in the present case, only low-resolution
diffraction data are available [12]. The molecular
fragment used for the Patterson search was taken
from the compound 3,5-di-tert-buthyl-4-nitropirazole
(C11H19N3O2) [6], which crystallizes in a monoclinic
with wꢀi† ˆ 1=yoꢀi†:
c
R-Bragg factor:
nref
X
uIoꢀj† 2 Icꢀj†u
j
RB
ˆ
:
nref
X
Ioꢀj†
j
Chi-squared factor: x2 ˆ Rwp=Rexp; where the R-expected factor
d
is
0
1
1=2
B
B
@
C
C
A
ꢀN 2 P†
X
Rexp
ˆ
:
2
wꢀi†yoꢀi†
ꢀ
ꢀ
structure [a ˆ 10:6407ꢀ4† A; b ˆ 9:6180ꢀ4† A; c ˆ
i
ꢀ
ꢀ 3
12:6649ꢀ5† A; b ˆ 107:962ꢀ3†8; V ˆ 1233:0ꢀ1† A ],
space group P21/c, with four molecules in the asym-
metric unit ꢀZ ˆ 4†:

L.E. Ochando, et al. / Journal of Molecular Structure 562 (2001) 11±17
15
Table 3
Fractional coordinates of non-methyl-hydrogen atoms for 3,5-di-
isopropyl-4-nitropyrazole with e.s.d.'s in parentheses
The search model was oriented and placed in
the monoclinic unit cell by the program rots96
[13]. The subsequent rigid-body Rietveld re®ne-
ment was performed with the program ribols
[14] using a Pearson-VII pro®le function with
the shape parameter m ˆ 1:6; which dropped to a
pro®le factor Rwp ˆ 19:7%: As shown in Table 2,
the parameters re®ned are the angles describing
the molecular orientations. To complete the struc-
ture, the hydrogen atoms of the central atom of
the isopropyl groups and of the nitrogen atom
were generated geometrically by the shelxl-93
program [15]. The details of the ®nal re®nement
are given in Table 2. The ®nal coordinates
including three hydrogen atoms are listed in
Table 3. The observed X-ray diffraction pattern
and the difference pro®le between observed and
calculated patterns are shown in Fig. 1. The mole-
cular conformation with atom labeling and the unit
Atom
x/a
y/b
z/c
N1
0.4349 (4)
0.4204
0.4644 (4)
0.4268 (4)
0.4509
H1
0.5652
N2
0.5023 (4)
0.5067 (4)
0.4397 (4)
0.3943 (4)
0.3168 (4)
0.2770 (4)
0.3012
0.4003 (4)
0.2493 (4)
0.2211 (4)
0.3593 (4)
0.4021 (4)
0.2739 (4)
0.3691
0.4402 (4)
0.3910 (4)
0.3469 (4)
0.3718 (4)
0.3491 (4)
0.3989 (4)
0.2954
C3
C4
C5
C6
C7
H8
C9
0.3022 (4)
0.4223 (4)
0.3622 (4)
0.4687 (4)
0.5745 (4)
0.5987
0.6304 (4)
0.0826 (4)
0.0732 (4)
20.0195 (4)
0.1326 (4)
0.1872
0.3609 (4)
0.2838 (4)
0.2508 (4)
0.2651 (4)
0.3926 (4)
0.3534
N10
O11
O12
C13
H14
C15
C16
0.6211 (4)
0.5612 (4)
0.1599 (4)
20.0979 (4)
0.4697 (4)
0.3795 (4)
Fig. 1. Observed diffraction pattern and difference pro®le between observed and calculated patterns for 3,5-di-isopropyl-4-nitropyrazole.

16
L.E. Ochando, et al. / Journal of Molecular Structure 562 (2001) 11±17
SSPT (solid state proton transfer) considering that
3,5-di-tert-butyl-4-nitropyrazole, a dimer [6], shows
proton disorder [17].
Unfortunately, compound 3c does not present SSPT
and the N±H proton is clearly localized, may be due to
the fact that the two isopropyl groups have different
orientations. Even in the case where only one position
for the proton is found, the possibility exists to study
the disorder by looking at the internal angles of the
pyrazole pentagon, especially those at N1 and N2
[18]. In compound 3c these angles amount to
113.69(^0.65)8 and 106.45(^0.36)8, respectively.
The difference is 7.28, instead of 98 for a pyrazole in
the gas phase (ED, MW or high level ab initio calcu-
lations) [18]. Therefore, a small amount of disorder
cannot be ruled out.
Fig. 2. Molecular conformation of the title compound, with atom
labeling.
cell packing of the ®nal crystal structure of the title
compound are represented in Figs. 2 and 3, respec-
tively.
Acknowledgements
The authors acknowledge the EU for the network
Location and Transfer of Hydrogen (No. CHRX CT
940582). LEO, JMA, JR and DL are also indebted to
4. Discussion
Â
the D.G.E.S. for economic support (Accion Integrada
Hispano-Francesa number HF1997-0226/Action Inte-
Â
gree PICASSO No. 98149).
One of the most fascinating properties of N-unsub-
stituted pyrazole crystals is the possibility that they
present dynamic disorder involving the NH proton of
the N±H´´´N hydrogen bond. This only happens in
cyclic structures (dimers, trimers and tetramers) and
never in catemers. Moreover, in most cases, the
substituents at positions 3 and 5 should be identical
[1,2,16]. Therefore, the dimer formed by 3,5-diiso-
propyl-4-nitropyrazole was a good candidate for
Â
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È
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