3-[5-(4-Bromophenyl)-1H-pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one- (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile (2/1): A stoichiometric cocrystal of a reaction product with one of its early precursors

Article abstract of DOI:10.1107/S0108270106033968

The title compound, 2C₁₇H₁₈BrN₃O· C₉H₅BrClN, was crystallized from the reaction between 5,5-dimethylcyclohexane-1,3-dione, triethyl orthoformate and 5-amino-3-(4-bromophenyl)pyrazole, which had itself been prepared from the reaction between (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile and hydrazine. The compound is a stoichiometric 2:1 cocrystal of the reaction product 3-[5-(4-bromophenyl)-1H-pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one and the early reactant (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile. The two independent molecules of cyclohex-2-en-1-one are linked by N-H...N and N-H...O hydrogen bonds into complex bilayers and the molecules of acrylonitrile are trapped within large cavities in the substructure formed by the cyclohex-2-en-1-one molecules.

Full text of DOI:10.1107/S0108270106033968

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
been hoped, would yield a pyrazolo[3,4-b]quinoline deriva-
tive. The pyrazole component of this reaction had itself been
prepared using the reaction of (Z)-3-(4-bromophenyl)-3-
chloroacrylonitrile (component R) and hydrazine (see
scheme), and evidently the excess of component R had been
carried right through the synthesis, leading to the isolation of
the cocrystal, compound (I).
ISSN 0108-2701
3-[5-(4-Bromophenyl)-1H-pyrazol-
3-ylamino]-5,5-dimethylcyclohex-
2-en-1-one±(Z)-3-(4-bromophenyl)-
3-chloroacrylonitrile (2/1): a stoichio-
metric cocrystal of a reaction product
with one of its early precursors
a
b
c
Â
Silvia Cruz, Jairo Quiroga, Jose M. de la Torre, Justo
Cobo,c John N. Lowd and Christopher Glidewelle*
a
Â
Departamento de Quõmica, Universidad de Narino, Ciudad universitaria, Torobajo,
Ä
b
Â
Â
AA 1175 Pasto, Colombia, Grupo de Investigacion de Compuestos Heterocõclicos,
Â
Departamento de Quõmica, Universidad de Valle, AA 25360 Cali, Colombia,
c
Â
Â
Â
Â
Departamento de Quõmica Inorganica y Organica, Universidad de Jaen, 23071
Jaen, Spain, dDepartment of Chemistry, University of Aberdeen, Meston Walk, Old
Â
Aberdeen AB24 3UE, Scotland, and eSchool of Chemistry, University of St Andrews,
Fife KY16 9ST, Scotland
Correspondence e-mail: cg@st-andrews.ac.uk
Received 8 August 2006
Accepted 23 August 2006
Online 12 September 2006
The title compound, 2C17H18BrN3OÁC9H5BrClN, was crystal-
lized from the reaction between 5,5-dimethylcyclohexane-1,3-
dione, triethyl orthoformate and 5-amino-3-(4-bromo-
phenyl)pyrazole, which had itself been prepared from the
reaction between (Z)-3-(4-bromophenyl)-3-chloroacrylo-
nitrile and hydrazine. The compound is a stoichiometric 2:1
cocrystal of the reaction product 3-[5-(4-bromophenyl)-1H-
pyrazol-3-ylamino]-5,5-dimethylcyclohex-2-en-1-one and the
early reactant (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile.
The two independent molecules of cyclohex-2-en-1-one are
linked by NÐHÁ Á ÁN and NÐHÁ Á ÁO hydrogen bonds into
complex bilayers and the molecules of acrylonitrile are
trapped within large cavities in the substructure formed by
the cyclohex-2-en-1-one molecules.
For the sake of convenience, we shall refer to the molecules
containing N11, N21 and N31 (Fig. 1) as types 1±3, respec-
tively. The cocrystal thus contains two molecules, those of
types 1 and 2, of the expected product P, along with one
molecule, that of type 3, of the precursor compound R.
Although the atomic displacement parameters of molecule 3
are generally higher than those of molecules 1 and 2, re®ne-
ment of the site occupancy for component R con®rmed that
the occupancy is unity and that the composition of the
cocrystal is stoichiometrically 2:1. While the two independent
molecules of component P are linked into bilayers by a
combination of NÐHÁ Á ÁN and NÐHÁ Á ÁO hydrogen bonds,
there are no direction-speci®c intermolecular interactions
involving the molecules of component R. Hence, this
component is, in effect, captive within the supramolecular
structure generated by component P, in the manner of a
clathrate, and the molecule of R thus has somewhat greater
freedom of movement than the molecules of P.
The non-aromatic carbocyclic rings in the type 1 and 2
molecules both adopt envelope conformations, folded across
the vectors C134Á Á ÁC136 and C234Á Á ÁC236. The ring-puck-
ering parameters (Cremer & Pople, 1975) for the atom
sequences C131±C136 and C231±C236 are ꢀ = 52.2 (4)ꢀ and
' = 234.7 (5)ꢀ for the type 1 molecule, and ꢀ = 128.5 (4)ꢀ and
' = 48.3 (5)ꢀ for the type 2 molecule, so that the two molecules
of P in the selected asymmetric unit are nearly enantiomeric.
Comment
We report here the molecular and supramolecular structure of
the title compound, (I), which is a stoichiometric cocrystal of
two molecules of 3-[3-(4-bromophenyl)-1H-pyrazol-5-yl-
amino]-5,5-dimethyl-2-cyclohexen-1-one, hereinafter desig-
nated P (for product) and one molecule of one of its upstream
precursors, viz. (Z)-3-(4-bromophenyl)-3-chloroacrylonitrile,
which had evidently been carried through the entire synthetic
sequence and which is hereinafter designated R (for reactant).
The compound was obtained from the reaction between
5-amino-3-(4-bromophenyl)pyrazole, 5,5-dimethylcyclohexane-
1,3-dione (dimedone) and triethyl orthoformate, which, it had
o608 # 2006 International Union of Crystallography
DOI: 10.1107/S0108270106033968
Acta Cryst. (2006). C62, o608±o611

organic compounds
However, this choice has no signi®cance, as the space group
accommodates equal numbers of both enantiomers of the type
1 and 2 molecules. For an idealized envelope conformation,
the ring-puckering parameters are 54.7ꢀ (or 125.3ꢀ for the
enantiomorphic ring) and ' = (60k)ꢀ (where k = zero or
integer). The dihedral angle between the planes of the aryl
and pyrazole rings is 19.0 (2)ꢀ in the type 1 molecule and
18.4 (2)ꢀ in the type 2 molecule, and the corresponding torsion
angles (Table 1) indicate the near-enantiomeric relationship of
the two reference molecules. The type 3 molecule is nearly
planar, as shown by the leading torsion angles. The bond
distances and interbond angles present no unusual features.
The molecules of component P are linked into bilayers by
three NÐHÁ Á ÁO hydrogen bonds and one NÐHÁ Á ÁN
hydrogen bond (Table 2), and the formation of the bilayer is
readily analysed, ®rstly in terms of the formation of single
sheets by the three NÐHÁ Á ÁO hydrogen bonds only, and then
of the pairwise linking of these sheets by the NÐHÁ Á ÁN
hydrogen bond. Within the selected asymmetric unit, the two
independent molecules of component P are linked by an NÐ
HÁ Á ÁO hydrogen bond. In addition, atom N11 in the type 1
molecule at (x, y, z) acts as hydrogen-bond donor to atom O13
bond donor to atom O23 in the type 2 molecule at ( 12 + x, 21 + y,
z), so generating by translation a second C(9) chain, this time
built from type 2 molecules and running parallel to the [110]
direction. The combination of the [110] and [110] chains,
linked by the NÐHÁ Á ÁO hydrogen bond within the asym-
metric unit, generates a sheet of R88(44) rings parallel to (001)
(Fig. 2).
Four such sheets pass through each unit cell, lying in the
domains 0.05 < z < 0.29, 0.21 < z < 0.55, 0.45 < z < 0.79 and
0.71 < z < 1.05. Pairs of these sheets, related by twofold
rotation axes, are linked by paired NÐHÁ Á ÁN hydrogen bonds
involving type 2 molecules only. Atom N23 in the type 2
molecule at (x, y, z), which lies in the domain 0.45 < z < 0.79,
acts as hydrogen-bond donor to atom N22 in the type 2 mol-
ecule at (1 x, y, 32 z), which lies in the domain 0.71 < z <
1.05. The resulting R22(8) motif (Fig. 3), generated by the
3
twofold rotation axis along (12, y, ), thus links pairs of (001)
4
sheets to form bilayers. Two bilayers pass through each unit
cell, in the domains 0.45 < z < 1.05 and 0.05 < z < 0.55,
3
1
generated by the twofold rotation axes at z = and z = ,
respectively, but there are no direction-speci®c interactions
between the bilayers.
4
4
1
in the type 1 molecule at (12 + x, + y, z), so generating by
The bilayers built from the molecules of types 1 and 2
occupy ca 71% of the total unit-cell volume, as indicated by
the VOID calculation in PLATON (Spek, 2003), equivalent to
2
translation a C(9) (Bernstein et al., 1995) chain of type
1 molecules running parallel to the [110] direction. Similarly,
atom N21 in the type 2 molecule at (x, y, z) acts as hydrogen-
3
3
Ê
Ê
ca 377 A per molecule of component P, leaving ca 319 A per
molecule of component R. Thus, for the molecules of
Figure 2
A stereoview of part of the crystal structure of compound (I), showing the
formation of a hydrogen-bonded sheet parallel to (001) built from the
type 1 and 2 molecules only. For the sake of clarity, H atoms not involved
in the motif shown have been omitted.
Figure 1
Figure 3
The three independent molecules in compound (I), showing the atom-
labelling scheme, viz. (a) the type 1 molecule of component P, (b) the
type 2 molecule of component P and (c) the molecule of component R.
Displacement ellipsoids are drawn at the 30% probability level and H
atoms are shown as small spheres of arbitrary radii.
Part of the crystal structure of compound (I), showing the R22(8) motif,
built from type 2 molecules only, which links the (001) sheets into
bilayers. For the sake of clarity, the unit-cell outline and H atoms not
involved in the motif shown have been omitted. Atoms marked with an
asterisk (*) are at the symmetry position (1 x, y, 32 z).
ꢁ
Acta Cryst. (2006). C62, o608±o611
Cruz et al.
2C17H18BrN3OÁC9H5BrClN o609

organic compounds
Crystal data
2C17H18BrN3OÁC9H5BrClN
Z = 8
Dx = 1.489 Mg m
Mo Kꢂ radiation
ꢃ = 2.92 mm
T = 293 (2) K
Block, colourless
0.44 Â 0.26 Â 0.20 mm
3
Mr = 963.01
Monoclinic, C2=c
1
Ê
a = 13.4390 (4) A
Ê
b = 13.8680 (4) A
Ê
c = 46.1620 (15) A
ꢁ = 93.050 (2)ꢀ
V = 8591.1 (5) A
3
Ê
Data collection
Bruker±Nonius KappaCCD area-
detector diffractometer
' and ! scans
Absorption correction: multi-scan
(SADABS; Sheldrick, 2003)
Tmin = 0.338, Tmax = 0.557
49869 measured re¯ections
9729 independent re¯ections
5997 re¯ections with I > 2ꢄ(I)
Rint = 0.037
Figure 4
A space-®lling stereoview of part of the crystal structure of compound (I),
showing only the type 1 and 2 molecules in the domain 14 < z < 43 and the
resulting cavities.
ꢀmax = 27.5ꢀ
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.051
wR(F2) = 0.136
w = 1/[ꢄ2(Fo2) + (0.0539P)2
+ 16.273P]
2
where P = (Fo + 2Fc2)/3
S = 1.03
9729 re¯ections
505 parameters
H-atom parameters constrained
(Á/ꢄ)max = 0.002
3
Ê
Áꢅmax = 0.62 e A
3
Ê
0.73 e A
Áꢅmin
=
Table 1
Selected torsion angles (ꢀ).
N11ÐC15ÐC151ÐC152
N21ÐC25ÐC251ÐC252
17.8 (5)
16.9 (5)
C32ÐC31ÐC37ÐC38
C31ÐC37ÐC38ÐC39
6.1 (6)
177.1 (4)
Figure 5
A space-®lling stereoview of part of the crystal structure of compound (I),
showing the pairwise arrangement of the type 3 molecules in the domain
1
3
< z < .
4
4
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
3
component P, the mean volume per non-H atom is ca 17.1 A ,
Ê
3
satisfactorily close to the average value of 18 A proposed by
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
Kempster & Lipson (1972) for light-atom structures, while the
mean volume available per non-H atom for component R is ca
N11ÐH11Á Á ÁO13i
N13ÐH13Á Á ÁO23
N21ÐH21Á Á ÁO23ii
N23ÐH23Á Á ÁN22iii
0.86
0.86
0.86
0.86
1.96
2.02
1.96
2.16
2.801 (3)
2.880 (3)
2.798 (3)
3.009 (3)
166
177
164
169
3
26.6 A , some 50% higher. The use of element-speci®c atomic
Ê
volumes (Hofmann, 2002) leads to estimated volumes for the
3
molecules of components P and R of 406.7 and 210.5 A ,
Symmetry codes: (i) x ‡ 21; y ‡ 21; z; (ii) x 12; y ‡ 21; z; (iii) x ‡ 1; y; z ‡ 23.
Ê
respectively, which differ from the available volumes esti-
mated by PLATON by ca 8 and 34%, respectively. The
substantial molecular volume available to the molecules for
component R, coupled with the absence of any direction-
speci®c intermolecular forces involving the molecules of R,
may account for the apparently large atomic displacement
parameter values for component R.
The systematic absences permitted C2/c and Cc as possible space
groups; C2/c was selected and con®rmed by the successful structure
analysis. All H atoms were located in difference maps and then
treated as riding atoms, with distances CÐH = 0.93 (aromatic and
Ê
Ê
alkenic), 0.96 (CH3) or 0.97 A (CH2) and NÐH = 0.86 A, and with
Uiso(H) = kUeq(C,N), where k = 1.5 for the methyl groups and 1.2 for
all other H atoms.
The 29% of the cell volume not occupied by the bilayers
forms four large centrosymmetric cavities per unit cell,
Data collection: COLLECT (Nonius, 1999); cell re®nement:
DENZO (Otwinowski & Minor, 1997) and COLLECT; data reduc-
tion: DENZO and COLLECT; program(s) used to solve structure:
SIR2004 (Burla et al., 2005); program(s) used to re®ne structure:
OSCAIL (McArdle, 2003) and SHELXL97 (Sheldrick, 1997);
molecular graphics: PLATON (Spek, 2003); software used to prepare
material for publication: SHELXL97 and PRPKAPPA (Ferguson,
1999).
1
1
1
1 1
4 2
centred at (Æ , Æ , 0) and (Æ , Ç , ) (Fig. 4), each of which
4
4
4
accommodates two molecules of component R related to one
another by inversion (Fig. 5).
Experimental
A solution of 5-amino-3-(4-bromophenyl)pyrazole [1.0 mmol, itself
prepared from the reaction of (Z)-3-(4-bromophenyl)-3-chloro-
acrylonitrile with excess hydrazine; see scheme in Comment],
5,5-dimethylcyclohexane-1,3-dione (dimedone; 1.0 mmol) and triethyl
orthoformate (1.0 mmol) in ethanol (20 ml) was heated under re¯ux
for 10 h. The reaction mixture was cooled to ambient temperature
and crystals of the title compound, (I), were collected by ®ltration.
X-ray data were collected at the EPSRC National Crystal-
lography Service, University of Southampton, England; the
authors thank the staff for all their help and advice. JC and
Â
JMT thank the Consejerõa de Innovacion, Ciencia y Empresa
(Junta de Andalucõa, Spain) and the Universidad de Jaen for
Â
Â
Â
Â
®nancial support. JMT also thanks Universidad de Jaen for a
ꢁ
o610 Cruz et al. 2C17H18BrN3OÁC9H5BrClN
Acta Cryst. (2006). C62, o608±o611

organic compounds
Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De
Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38,
381±388.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354±1358.
Ferguson, G. (1999). PRPKAPPA. University of Guelph, Canada.
Hofmann, D. W. M. (2002). Acta Cryst. B58, 489±493.
Kempster, C. J. E. & Lipson, H. (1972). Acta Cryst. B28, 3674.
McArdle, P. (2003). OSCAIL for Windows. Version 10. Crystallography
Centre, Chemistry Department, NUI Galway, Ireland.
Nonius (1999). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,
Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M.
Sweet, pp. 307±326. New York: Academic Press.
scholarship grant supporting a short stay at the EPSRC
National Crystallography Service, University of Southampton.
JQ and SC thank COLCIENCIAS, UNIVALLE (Universidad
del Valle, Colombia) and UDENAR (Universidad de NarinÄo,
Colombia) for ®nancial support.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FA3037). Services for accessing these data are
described at the back of the journal.
È
Sheldrick, G. M. (1997). SHELXL97. University of Gottingen, Germany.
Sheldrick, G. M. (2003). SADABS. Version 2.10. University of Gottingen,
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ꢁ
Acta Cryst. (2006). C62, o608±o611
Cruz et al.
2C17H18BrN3OÁC9H5BrClN o611