Supramolecular architectures in 5,5′-substituted hydantoins: Crystal structures and Hirshfeld surface analyses

Article abstract of DOI:10.1021/cg100706n

A series of three 5,5′-substituted hydantoin derivatives (1-3) were synthesized, and their crystal structures were solved using single-crystal synchrotron/powder-crystal X-ray diffraction data with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures. A comparison of supramolecular assembly in the compounds with that in similar 5,5′-substituted hydantoins in the Cambridge Structural Database (CSD) has been presented. The crystal packing in compounds 1-3 containing complementary hydrogen bonding groups, i.e. the amino NH donors and carbonyl O acceptors, exhibits three types of supramolecular synthons. In the dipropyl substituted hydantoin (1), intermolecular N-H...O hydrogen bonds with only one carbonyl O atom acting as a double acceptor generate a one-dimensional C ¹₁(4)C¹₁(4)[R² ₂(8)] network propagating along the [100] direction, while in 3, a 5-spiro fused hydantoin, the cyclic R²₂(8) motifs self-organize through pairs of N-H...O hydrogen bonds to form a C ₂²(9)[R₂²(8)][R₂ ²(8)] framework running along the [1-10] direction. The molecular assembly in 2, with a dibutyl substitution at the hydantoin C-5 position, produces R⁴₄(17) synthons, which are edge-fused to form two-dimensional molecular sheets in the (100) plane. The formation of a supramolecular architecture built with an R⁴₄(17) synthon is unprecedented among the substituted hydantoin structures in the CSD.

Full text of DOI:10.1021/cg100706n

DOI: 10.1021/cg100706n
0
Supramolecular Architectures in 5,5 -Substituted Hydantoins:
Crystal Structures and Hirshfeld Surface Analyses
2
010, Vol. 10
4476–4484
†
Basab Chattopadhyay, Alok K. Mukherjee, N. Narendra, H. P. Hemantha,
‡
§
§
§
Vommina V. Sureshbabu, Madeliene Helliwell, and Monika Mukherjee*
,†
†
Department of Solid State Physics, Indian Association for the Cultivation of Science, Jadavpur,
Kolkata 700032, India, Department of Physics, Jadavpur University, Kolkata 700032, India,
‡
§
Peptide Research Laboratory, Department of Studies in Chemistry, Central College Campus,
Bangalore University, Bangalore-560 001, India, and Department of Chemistry,
University of Manchester, Manchester M13 9PL, United Kingdom
Received May 27, 2010; Revised Manuscript Received August 9, 2010
0
ABSTRACT: A series of three 5,5 -substituted hydantoin derivatives (1-3) were synthesized, and their crystal structures were
solved using single-crystal synchrotron/powder-crystal X-ray diffraction data with a detailed analysis of Hirshfeld surfaces and
fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures.
0
A comparison of supramolecular assembly in the compounds with that in similar 5,5 -substituted hydantoins in the Cambridge
Structural Database (CSD) has been presented. The crystal packing in compounds 1-3 containing complementary hydrogen
bonding groups, i.e. the amino NH donors and carbonyl O acceptors, exhibits three types of supramolecular synthons. In the
dipropyl substituted hydantoin (1), intermolecular N-H O hydrogen bonds with only one carbonyl O atom acting as a
3 3
3
2
1
1
double acceptor generate a one-dimensional C (4)C (4)[R (8)] network propagating along the [100] direction, while in 3,
1
1
2
2
a 5-spiro fused hydantoin, the cyclic R (8) motifs self-organize through pairs of N-H O hydrogen bonds to form a
3 3 3
2
2
2
2
2
2
C (9)[R (8)][R (8)] framework running along the [1-10] direction. The molecular assembly in 2, with a dibutyl substitution at
2
4
the hydantoin C-5 position, produces R (17) synthons, which are edge-fused to form two-dimensional molecular sheets in the
4
4
(100) plane. The formation of a supramolecular architecture built with an R (17) synthon is unprecedented among the
substituted hydantoin structures in the CSD.
4
1
1,12
Introduction
natural products,
nent with a rigid core.
Hydantoin derivatives such as phenytoin, mephenythoin,
constitutes an ideal structural compo-
Noncovalent molecular interactions such as hydrogen
bonding and aromatic π-stacking form the basis for the design
of supramolecular assemblies in organic crystals. Molecular
functionalities, e.g. amino, hydroxyl, carbonyl, and ester, play
an important role in determining the spatial relationship
between neighboring molecules, leading to repetitive hydro-
1
,2
norantoin, methetoin, and ethotoin are used as anticonvulsive
13,14
drugs.
by 5-substituted hydantoins, antiviral, antidepressant, anti-
Among other medicinally useful properties exhibited
1
5,16
thrombic, and anticancer activities,
aggregation, human aldose reductase, and human leukocyte
clastase are worth mentioning.
are also important precursors to amino acids, via either acid-,
inhibition of platelet
3,4
gen bond patterns or supramolecular synthons. Many of
the synthons in molecular compounds involve N-H O,
1
7,18
Synthetically, hydantoins
3
3 3
N-H N, O-H O, and O-H N hydrogen bonds,
which provide the requisite robustness and reproducibility
3
3 3 3 3 3 3 3 3
19,20
base-, or enzyme-catalyzed hydrolysis.
Cambridge Structural Database (version 5.31, November
A search of the
5-7
to create new solid-state structures.
Compounds with
2
1
CSD 2009 release) with both hydantoin NH groups unsub-
highly symmetrical, rigid frameworks are versatile scaffolds,
because they can hold together interactive functional groups
for the formation of a variety of one-dimensional, two-
dimensional, or three-dimensional architectures based on
3
stituted and sp hybridization at the C5 position yielded
68 hits (excluding duplicate structure determinations), 35 of
0
which had a 5,5 -spiro-fusion, with the remaining 33 contain-
ing different substituent groups at the 5,5 -positions, except in
BEPNIT and PHYDAN, where the C5 atom had symme-
trical substitutions by either methyl or phenyl groups. A
symmetrical aliphatic chain (propyl, butyl, etc.) substitution
8-10
0
multiple noncovalent interactions.
It is useful to design
2
2
23
new compounds comprising a rigid core with multiple donor
atoms and having different types of substitutions and to study
their structural features as well as the interplay of noncovalent
interactions in building possible supramolecular assemblies.
This would undoubtedly enhance our understanding of the
factors that may be responsible for perturbing the usual
hydrogen bond motif characteristic of the rigid core in the
system under investigation. In this respect, the hydantoin or
imidazolidine-2,4-dione motif, possessing equal numbers of
N-H donors and CdO acceptors, and present in a number of
0
at the 5,5 positions is, however, yet to be reported.
In general, single-crystal X-ray diffractometry is the method
of choice when it comes to structure determination. For many
compounds of scientific interest, including the chain substituted
hydantoins, single crystals of appropriate size and quality
cannot always be grown within a reasonable time scale that
make them amenable to X-ray structure analysis. With the
recent developments in direct-space approaches for structure
24-27
solution, ab initio crystal structure analysis can nowadays
be accomplished from X-ray powder diffraction data,
*
Corresponding author. Telephone: þ91 33 2473 4971 ext 312. Fax:
28-31
þ91 33 2473 2805. E-mail: sspmm@iacs.res.in.
r
2010 American Chemical Society
pubs.acs.org/crystal
Published on Web 08/30/2010

Article
Crystal Growth & Design, Vol. 10, No. 10, 2010 4477
although significant challenges may arise when the molecule
possesses considerable flexibility or there are multiple mole-
cules in the asymmetric unit.
Compound 3. Yield 85%, mp 204 °C. Anal. HR-MS Calcd for
-
1
C
3
(
(
7
H
10
N
2
NaO
2
, 177.0640; found, 177.0648 [M þ Na]. IR (cm ):
1
220-3160, 1780, 1740. H NMR (300 MHz, DMSO-d
m, 4H), 1.92-2.12(m, 4H), 6.21(s, 1H), 7.84(br, 1H) ppm. C NMR
200 MHz, DMSO-d ): δ 23.8, 34.2, 69.5, 155.9, 173.2 ppm.
X-ray Powder Diffraction. X-ray powder diffraction data of
6
): δ 1.71-1.77
13
In this paper, the synthesis and structural characterization
0
6
of three 5,5 -substituted hydantoin derivatives (Scheme 1)
using X-raypowder andsynchrotron single-crystal diffraction
data are described, along with the DFT calculations, as a part
compounds 1-3 were collected on a Bruker D8 Advance powder
diffractometer using monochromatic Cu KR1 radiation (λ =
0
˚
.54056 A) selected with an incident beam germanium(111) mono-
1
of our wider strategy aimed at providing a library of 5,5 -
substituted hydantoin molecules capable of forming different
chromator. The diffraction patterns were recorded at 293(2) K with
a step size of 0.02° (2θ) and counting time of 20 s/step in the angular
range 8.0-100.0° (2θ) for 1 (3.0-100.0° for 2 and 3), using the
Bragg-Brentano geometry. The indexing of the powder pattern of
3
2
types of supramolecular assemblies. An investigation of
close intermolecular contacts between the molecules via Hirshfeld
surface analysis is also presented in order to reveal subtle
differencesand similaritiesof hydantoinmoleculesin thethree
crystal structures.
3
3
1
using the program TREOR showed an orthorhombic unit cell
˚
with a = 7.167(1), b = 13.964(1), and c = 10.957(3) A [M(20) = 49,
F(20) = 84 (0.003343, 72)]. Statistical analysis of the X-ray powder
3
4
data using the FINDSPACE module of EXPO2004 indicated
Pnma as the most probable space group, which was confirmed by a
successful structure determination. For compound 2, although the
powder XRD pattern (see Figure S1 in the Supporting Information)
Experimental Section
Synthesis. A mixture of a solution of appropriate ketone (0.1
mmol) [4-heptanone in (1), 5-nonanone in (2), and cyclopentanone
in (3)] in 50% aqueous methanol (50 mL), KCN (0.3 mmol), and
could be indexed on a monoclinic unit cell with a = 9.327(8), b =
˚
9
4
.575(4), c = 7.556(3) A, and β = 113.73(8)° [M(20) = 23, F(20) =
7 (0.014188, 30)], our attempts to solve the structure from powder
(
4 2 3
NH ) CO (0.5 mmol) was refluxed for 6-7 h. The resulting
XRD data were not successful. For compound 3, however, the powder
XRD pattern (see Figure S2 in the Supporting Information), which
contained only one low angle (2θ) peak of very large relative intensity
and a few small peaks with significant broadening (fwhm ≈ 0.2°),
could not be indexed reliably. The crystal structures of 2 and 3 were
solution was concentrated to half of its volume under vacuum and
cooled to 0 °C in an ice bath. The precipitate was filtered off, washed
with ice-cold water, and air-dried. Slow evaporation of a 1:1 water/
methanol solution of the crude product yielded the title hydantoin
derivatives (1, 2, and 3) in microcrystalline forms.
Compound 1. Yield 84%, mp 198 °C. Anal. HR-MS Calcd for
-1
C
3
9
H
16
N
2
NaO
2
, 207.1109; found, 207.1117 [M þ Na]. IR (cm ):
1
330-3180, 1728, 1710. H NMR (300 MHz, DMSO-d
J = 4.5 Hz, 6H), 1.42 (m, 4H), 1.88 (t, J = 4.0 Hz, 4H), 5.80 (br,
6
): δ 0.92 (t,
1
3
1
1
6
H), 8.71 (br, 1H) ppm. C NMR (200 MHz, DMSO-d ): δ 12.8,
6.8, 32.5, 63.4, 157.8, 174.2 ppm.
Compound 2. Yield 86%, mp 160 °C. Anal. HR-MS Calcd for
-
1
C
3
11
H
20
N
2
NaO
2
, 235.1422; found, 235.1418 [MþNa]. IR (cm ):
1
340-3200, 1730, 1710. H NMR (300 MHz, DMSO-d
6
): δ 0.82 (t,
J = 6.3 Hz, 6H), 1.12-1.29 (m, 4H), 1.44-1.52 (m, 4H), 2.01 (t, J =
1
.8 Hz, 4H), 5.20 (br, 1H), 7.41 (s, 1H) ppm. C NMR (200 MHz,
3
3
DMSO-d
6
): δ 13.5, 21.8, 26.8, 33.0, 66.4, 154.6, 175.2 ppm.
Scheme 1
9 16 2 2
Figure 1. Final Rietveld refinement plot of C H N O (1).
Table 1. Crystal Data and Structure Refinement Parameters for C
1
9
H N
16 2
O
2
20 2 2 7 10 2 2
(1), C11H N O (2), and C H N O (3)
2
3
chemical formula
M
temperature (K)
crystal system, space group, Z
C
9
H
16
N
2
O
2
C
11
H
20
N
2
O
2
7 10 2 2
C H N O
r
184.24
293(2)
orthorhombic, Pnma, 4
212.29
150(2)
monoclinic, Pc, 2
154.17
150(2)
triclinic, P1, 2
˚
a, b, c (A)
7.1577(5), 13.9721(9), 11.0211(10)
9.3072(12), 9.5775(12), 7.5116(9)
90, 113.735(1), 90
612.95(13)
1.150
0.69450
0.079
232
0.30 ꢀ 0.06 ꢀ 0.04
Station 9.8, SRS
10758, 1371, 1370
6.028(2), 6.086(2), 11.003(4)
91.834(4), 93.626(4), 115.228(4)
363.6(2)
1.408
0.69450
0.105
164
0.25 ꢀ 0.04 ꢀ 0.02
Station 9.8, SRS
3671, 2009, 1756
R, β, γ (deg)
volume (A )
90, 90, 90
1102.2(2)
1.110
3
˚
3
D (Mg/m )
˚
wavelength (A)
1.54056
-1
μ (mm
F(000)
crystal size (mm)
)
diffractometer
no. of measured, independent,
and observed reflections
Bruker D8 Advance
R
data/restraints/parameters
int,
θ
max
0.0635, 26.74
1371/2/140
0.0433
0.1135
1.096
0.0211, 30.41
2009/0/140
0.0449
0.1262
1.090
592/33/98
0.0477
0.0687
1.671
R
R
p
/R1
wp/wR(I)
2
χ /S

4
478 Crystal Growth & Design, Vol. 10, No. 10, 2010
Chattopadhyay et al.
finally solvedvia singlecrystal X-ray analysisusing synchrotron data.
The agreement between the simulated powder pattern based on
single-crystal analysis and the observed X-ray powder profile (see
Figure S1 in the Supporting Information) for 2 indicates that the
crystal structure corresponds to the bulk phase. A similar conclusion
can be drawn for 3, although a high degree of preferred orientation is
apparent in the observed X-ray powder diffraction profile (see Figure
S2 in the Supporting Information).
The crystal structure of 1 was solved by global optimization of the
structural models in direct space using the simulated annealing
technique as implemented in the program DASH. Rietveld
3
5
3
6
37
refinement was carried out using the program GSAS with an
3
8
EXPGUI interface. The background was described by the shifted
Chebyshev function of the first kind with 36 points regularly
distributed over the entire 2θ range. The lattice parameters, back-
ground coefficients, and profile parameters were refined initially,
followed by the refinement of the positional coordinates of non-
hydrogen atoms with soft constraints on the bond lengths and bond
angles, and a planar restraint for the hydantoin fragment. A fixed
2
˚
isotropic displacement parameter of 0.04 A for all non-hydrogen
atoms was maintained. Hydrogen atoms were placed in the calcu-
2
lated positions with a common Biso value of 0.06 A . In the final
˚
stages of refinement, a preferred orientation correction using the
generalized spherical harmonic model (order 12) was applied. The
final Rietveld refinement converged to Rp = 0.0477 and Rwp =
0.0687 with an excellent agreement between the observed and the
calculated powder patterns (Figure 1).
Single Crystal X-ray Diffraction. Since the single crystals of 2 and
were too thin and weakly diffracting, intensity data were collected
3
˚
at 150(2) K with synchrotron radiation (λ = 0.69450 A) from
Station 9.8 at SRS Daresbury Laboratory using a Bruker SMART
APEX CCD diffractometer. Data reduction was performed using
39
3
9
the SAINT software. An empirical absorption correction SADABS
wasapplied. Structuresweresolvedbythedirectmethodsincorporated
in SHELXS-97 and refined by the full-matrix least-squares
40
2
40
methods based on F using SHELXL-97. For a successful structure
refinement of 2, a twin law (-1 0 -1/0 -1 0/0 0 1) had to be applied.
The refined twin fraction value of 0.500(4) indicates the presence
of two nearly overlapping monoclinic domains. The displacement
parameters of all non-H atoms were treated anisotropically. The
H-atoms in 2 were located from difference Fourier maps and
allowed to ride on the parent atom with fixed isotropic thermal
parameters [Uiso(H) = 1.2Ueqv(N/C) for NH and CH
2
groups and
Uiso(H) = 1.5Ueqv(C) for CH groups]. In 3, the H-atoms located
3
from the difference Fourier map were refined isotropically. Crystal
data and relevant refinement parameters of 1-3 are summarized in
Table 1.
Computational Details. The isolated molecule DFT calculations
were performed with full geometry optimization without any sym-
metry restriction. All calculations were carried out using the Dmol
3
41
code in the framework of a generalized-gradient approximation
42
(
X-ray refinement cycle. The geometries of the molecules were opti-
GGA). The starting atomic coordinates were taken from the final
4
3,44
mized using the hybrid exchange-correlation functional BLYP
and a double numeric plus polarization (DNP) basis set.
45-47
Hirshfeld Surface Analysis. Hirshfeld surfaces
and the asso-
plots were calculated using CrystalExplorer,
48-50
51
ciated 2D-fingerprint
which accepts a structure input file in CIF format. Bond lengths to
˚
hydrogen atoms were set to typical neutron values (C-H = 1.083 A,
˚
N-H = 1.009 A). For each point on the Hirshfeld isosurface, two
distances d
external to the surface and d
internal to the surface, are defined. The normalized contact distance
e
, the distance from the point to the nearest nucleus
i
, the distance to the nearest nucleus
(
d
norm) based on d
e
and d
i
is given by
vdW
i
vdW
vdW
e
vdW
ðdi - r
Þ
ðde - r
Þ
dnorm ¼
þ
r
r
e
i
vdW
vdW
where r
i
and r
e
are the van der Waals radii of the atoms. The
value of dnorm is negative or positive depending on intermolecular
contacts being shorter or longer than the van der Waals separations.
The parameter dnorm displays a surface with a red-white-blue
color scheme, where bright red spots highlight shorter contacts,

Article
Crystal Growth & Design, Vol. 10, No. 10, 2010 4479
Figure 2. ORTEP diagrams of C
9
H
16
N
O
2 2
(1), C11H
20
N
O
2 2
(2), and C
7
10
H N
2
O
2
(3).
Table 3. Hydrogen Bonds and C-H
3 3 O Interactions in C9
H
N
16 2
O
2
(1), C11
H
20
N
2
O
2
(2), and C
7
H N
10 2
O
2
(3)
3
A/A
˚
˚
˚
A/A
interaction
D-H/A
H
D
D-H A/deg
symmetry code
3
3 3
3 3 3
3 3 3
(
1)
1
1
3
N1-H1 O2
0.86
0.86
0.93
1.95
2.02
2.69
2.790(3)
2.863(3)
3.582(3)
166
167
162
- /
2
þ x, /
2
- y, /
2
- z
3
3
3 3
3 3
3
1
1
3
N3-H3 O2
/
2
1
- /
þ x, /
2
- y, /
2
- z
, -z þ /
1
1
C6-H6A
3 3 O4
2
þ x, -y þ /
2
2
(
2)
1
N1-H1 O2
0.86
0.86
0.97
2.06
1.97
2.66
2.826(3)
2.827(3)
3.583(3)
147
173
159
x, -y þ 1, z - /
2
3
3
3 3
3 3
3
1
N3-H3 O4
x, -y, z þ /
2
1
C6-H6A
3 3 O4
x, -y, þz - /
2
(3)
N1-H1 O2
0.93(2)
0.93(2)
0.96(2)
0.97(2)
1.93(2)
1.97(2)
2.63(2)
2.69(2)
2.843(1)
2.890(1)
3.278(2)
3.298(2)
167(2)
174(2)
125(2)
121(2)
-x, -y þ 1, -z þ 1
-x þ 1, -y, -z þ 1
-x þ 1, -y þ 1, -z þ 1
-x, -y, -z þ 1
3
3 3
N3-H3 O4
3
3 3
C9-H9B O2
3
3 3
C6-H6B O2
3
3 3
1
1
2
Figure 3. Formation of the parallel C
1
(4)C
1
(4)[R
2
(8)] network in C
9
H
16
N
O
2 2
(1). H-atoms of the propyl chains are omitted for clarity.
white areas represent contacts around the van der Waals separation,
and blue regions are devoid of close contacts.
2 and 3, respectively. In 2, the dibutyl chain (C6-C13), with
the maximum deviation of 0.057(3) A for the C10 atom from
˚
the least-squares plane through the chain atoms (C6-C13), is
twisted with respect to the hydantoin ring; the dihedral angle
between the hydantoin and dibutyl moieties is 86.8(1)°.
The cyclopentane ring in 3 adopts a half-chair conformation
Results and Discussion
The asymmetric unit of 1 crystallizing in the orthorhombic
space group Pnma (Table 1) consists of half of the hydantoin
moiety (lying on the mirror plane) and one propyl chain
5
2
˚
with ring puckering parameters Q=0.407(2) A and j=
340.7(2)°, respectively. The bond lengths (Table 2) of the
hydantoin fragment in 1-3 agree well with the mean values
(
Figure 2). The orientation of the -(CH ) CH chain with
2
2
3
respect to the hydantoin fragment in 1 is established by the
dihedral angle of 57.9(3)°, between the two planar fragments.
As expected, the hydantoin moieties in 2 and 3 (Figure 2) are
53
of relevant bond distances obtained with MOGUL from
searches based on related molecular fragments run on the
CSD. The presence of a spiro center (C5) explains the
˚
essentially planar with a rms deviations of 0.02 and 0.01 A in

4
480 Crystal Growth & Design, Vol. 10, No. 10, 2010
Chattopadhyay et al.
0
a
Table 4. Supramolecular Synthons in 5,5 -Substituted Hydantoin Structures Retrieved from the CSD with Space Groups Given in Parentheses
1
1
2
2
2
2
2
3
C
1
(4)C
1
(4)[R
2
(8)]
C
2
(9)[R
2
(8)] [R
(8)]
fused R
3
(12) rings
CSD ref code
space group)
CSD ref code
(space group)
CSD ref code
(space group)
LABTIR
(
substituents (R
= propyl,
= propyl
= methyl,
= methyl
= methyl,
= ethyl
= methyl,
1
,R
2
)/R
substituents (R
1
,R )/R
2
1 2
substituents (R ,R )/R
compound (1)
Pnma)
BEPNIT
P2
ADUQOF
P2
NIWRAN
Pbca)
AHORIY
P2
R
1
compound (3)
(P1)
QOPYOK
R = cyclopentane
R = cyclohexane
R = cyclooctane
R
R
R
1
= phenyl,
= ethyl
= phenyl,
= phenyl
= hydroxyl,
= ethyl acetate
R = 6-fluorochroman
(
R
2
(P2
PHYDAN
(Pn2 a)
PIPVAL
(P2
DAFFIZ
(P2
1
2
1
1
2 )
R
2
R
R
R
R
1
1
(
1
2
1
2
1
)
)
R
2
(P2 /c)
OCSHYD
(C2/c)
1
1
R
2
1
1
(
2
1 1
2
1
R
2
1
)
R
2
1
UGEYIO
(P1)
BCOCHY
(C2/m)
R = ((cyclobutylmethoxy)methyl)-
benzene
R = bicyclo(3.3.0)octane
(
R
2
= fluorophenyl
= isobutene,
1
2
1
1
2 )
1
(
2
1 1
2
1
)
R
2
= 4-methoxy-2,2-
dimethyl-
tetrahydrofuro[3,4-d]-
[
1,3]dioxole
= phenyl,
HPHCMS
P2
R
1
GRNSHY
(P1)
R = 9-phenethyl-9-azabicyclo-
[3.3.1]nonane
(
1
)
R
2
= phenyl(7,7-
dimethyl-2-
oxobicyclo[2.2.1]
heptan-1-yl)
methanesulfonate
XERTUJ
P2
R=2,2,4,6-
tetramethyl-
tetrahydro-3aH-
(
1
)
[1,3]dioxolo[4,5-c]-
pyran
OGUVIV
P2
R=tert-butyl-
1,2,3,4,5,6,7,8-
octahydroanthracen-
(
1
)
1-ylcarbamate
a
0
R = spiro-fused ring substitution at the 5-position; R
1
, R
2
are substitutions at the 5,5 -positions, respectively.
˚
lengthening of the C4-C5 distance [1.520(3)-1.525(2) A] in
-3. The C-N bond distance (Table 2) involving the spiro-
appear to be consistent with electronegativity. The net charges
on O2 [-0.477 in 3 to -0.478 in 1] and O4 [-0.451 in 1 to
-0.461 in 2] suggest that more negative charge is received by
the atom O2 than by O4.
1
carbon atom (C5) reveals that the N1-C5 bond is σ in
character, while the other C-N bonds show dominantly π
characterduetothe π-electron delocalization in the hydantoin
fragment. Bending of one of the two carbonyl bonds is
common in hydantoin derivatives. In 1-3, the O2-C2-N1
angle [129.0(1)-129.7(2)°] is significantly greater than O2-
C2-N3 [123.0(2)-123.8(1)°], while the equivalent bond
angles around C4 are practically identical [125.5(2)-126.8(2)°].
The asymmetry of exterior bond angles around the C2 atom
can be attributed to the fact that the N3 atom shares its lone
pair between the C2 and C4 atoms, while the N1 atom is
involved in a π-resonance with the C2-O2 carbonyl group
only. This observation is in accordance with the different
acidic properties of two NH residues in hydantoin derivatives,
The molecular packing in compounds 1-3 exhibits strong
intermolecular N-H O hydrogen bonds and weak C-H
O
3
3 3
3 3 3
interactions (Table 3). The N-H O hydrogen bonds facil-
3
3 3
itate self- assembly of hydantoin molecules, forming different
types of supramolecular architectures in 1-3; additional
reinforcement within each framework is provided by the C-
H...O interactions. In 1, the amino N1 atom in the molecule at
(x, y, z) acts as a donor to the carbonyl O2 atom of the
1
1
3
molecule at (- / þ x, / - y, / - z), whose amino N3 atom
2
2
2
in turn donates a proton to the O2 atom in the molecule at
(x, y, z), thus generating an R (8) ring (Table 3 and Figure 3);
2
2
the oxygen atom (O4) of another possible carbonyl (C4dO4)
acceptor remains unused in the hydrogen bonding pattern,
except for forming a weak interaction with the C-atom (C6) of
5
4,55
with N3-H3 being more acidic than N1-H1.
As a
consequence of the asymmetric π-electron clouds on N1-
C2 and N3-C2 and of the latter bond being more electron
rich, the lone pair residing on O2 could experience a repulsion
causing the observed bending of O2 toward N3.
The molecular-orbital optimization for compounds 1-3
with Dmol corroborates the near equality of CdO distances
Table 2). The DFT calculation generally yields longer bond
lengths compared to the crystallographic values; the largest
difference between the calculated and experimentally deter-
the propyl group. The one-dimensional N-H O hydrogen
3 3
3
bonded network propagates along the [100] direction and can
5
6,57
1
be represented using the graph-set notation
1
as C (4)
1
2
C (4)[ R (8)]. The spreading of parallel chains separated by
1 2
3
˚
11.0 A in 1 is such that the hydantoin sites in the neighboring
chains are oriented toward each other in the same way as the
hydrophobic propyl groups (Figure 3). A search of the CSD for
5,5 -disubstituted hydantoin structures with a similar hydro-
gen bonding pattern returned seven hits (Table 4), where
(
0
˚
mined distances is 0.041 A for the C4-C5 bond in 1 (Table 2).
The difference between the observed and calculated bond
distances can be attributed to the inadequacies of the DFT
method and also the fact that theoretical calculations have
been carried out with isolated molecules in the gaseous phase
whereas the experimental values correspond to the crystalline
state in which the packing forces play a significant role. The
atomic charges estimated from Mulliken population analysis
the electron-rich O2 atom simultaneously accepts both N1-
H1 3 3 3
O2 and N3-H3 O2 hydrogen bonds, while the other
3 3 3
carbonyl oxygen atom (O4) of hydantoin does not take part in
any classical hydrogen bonding. Incidentally, except the pre-
5
sent compound (1) and NIWRAN, the other six entries in
Table 4 exhibiting a C (4) C (4)[R (8)] synthon belonged to
the Sohnke space groups.
8
1
1
1
1
2
2

Article
Crystal Growth & Design, Vol. 10, No. 10, 2010 4481
4
4 20 2 2
Figure 4. Two-dimensional molecular sheet with fused R (17) rings in C11H N O (2). H-atoms of the butyl chains are omitted for clarity.
2
2
2
Figure 5. Parallel C
2
(9)[R
2
(8)] [R
2
(8)] motifs propagating along the [1-10] direction in C
7
H
10
N
2
O
2
(3).
1
1
1
and ( / , 0, / ), respectively. The R (8) rings are alternately
2
Intermolecular N1-H1 O2 (x, -y þ 1, z - / ) and N3-
3
3 3
2
2
2
2
1
H3 O4 (x, -y, z þ / ) hydrogen bonds link the molecules
3 3
linked into an infinite one-dimensional MNMN... polymeric
chain propagating along the the [1-10] direction (Figure 5)
with a graph-set description of C (9)[R (8)][R (8)]. The
adjacent polymeric chains are separated by 3.3 A (Figure 5).
A similar hydrogen bonding pattern has been reported in the
experimental as well as the predicted (results of a third
blind test of crystal structure prediction) structures of unsub-
stituted hydantoin molecules (CSD code PAHYON) and also
3
2
1
1
in 2 into zigzag polymeric C (4) chains propagating along the
2
2
2
[001] direction. Two pairs of N-H O hydrogen bonds
3 3
interconnect four hydantoin molecules, forming an R (17)
3
2 2 2
4
˚
4
4
4
˚
˚
synthon (Figure 4) of dimension 6.3 Aꢀ7.8 A. The R (17)
6
2
63
rings are edge-fused to generate a two-dimensional molecular
assembly in the (100) plane. The parallel molecular sheets in
2
layer separation of 9.3 A. The formation of an R (17) synthon
are stacked along the crystallographic a-axis with an inter-
4
˚
0
in five 5,5 -spiro-substituted hydantoin systems in the CSD
4
built by hydantoin molecules is unprecedented in the literature.
0
(Table 4). It is interestingto note thatallofthem, including the
present compound 3, crystallize in centrosymmetric space
groups.
A CSD search among the 5,5 -substituted hydantoins for an
n
R m(X) synthon (m,n > 2 and X > 8) involving more than two
molecules returned only four hits, having the CSD ref-codes
The Hirshfeld surfaces of substituted (1-3) and unsubsti-
tuted (4) hydantoin compounds are illustrated in Figure 6,
5
9
60
23
61
DAFFIZ, LABTIR, PHYDAN, and PIPVAL. In all
62
3
cases, the supramolecular synthon was, however, R (12).
In 3, pairs of N1-H1 O2 (-x, -y þ 1, -z þ 1) and
showing surfaces that have been mapped over a dnorm range of
˚
3
-0.5 to 1.5 A. The dominant interactions between amine N-H
3
3 3
N3-H3 O4 (-x þ 1, -y, -z þ 1) hydrogen bonds between
and carbonyl O atoms in 1-4 can be seen in the Hirshfeld
surfaces as the bright red areas marked as a and b in Figure 6.
The light red spots labeled as care due to C-H3 3 3 O interactions
3
3 3
molecules related by inversion and translation generate centro-
2
2
1
symmetric R (8) dimeric rings M and N centered at (0, / , / )
1
2
2

4
482 Crystal Growth & Design, Vol. 10, No. 10, 2010
Chattopadhyay et al.
Figure 6. Hirshfeld surfaces for C
PAHYON).
9
H
16
N
O
2 2
(1), C11H
20
N
2
O
2
7
(2), C H
10
N
O
2 2
3
(3), and C H
4
N
O
2 2
(4) (unsubstituted hydantoin, CSD code
Figure 8. Relative contributions of various intermolecular contacts
to the Hirshfeld surface area in C (1), C11 (2),
(3), and some related structures retrieved from the
9
H
16
N
O
2 2
20 2 2
H N O
7 10 2 2
C H N O
CSD.
(Figure 6). Other visible spots in the Hirshfeld surfaces
correspond to H H contacts. The N-H O intermole-
3
3 3
3 3 3
cular interactions appear as two distinct spikes in the 2D
fingerprint plots (Figure 7), labeled correspondingly as a and
b. Prominent pairs of sharp spikes of almost equal lengths in
˚
˚
the region 1.6 A < (d þ d ) < 2.4 A in the fingerprint plots
e
i
(
(
Figure 7) are characteristics of nearly equal N(donor) O-
3 3
3
˚
acceptor) distances (2.84 ( 0.05 A) and a cyclic hydrogen-
n
64
bonded R m(X) synthon. The upper spike a (Figure 7)
corresponds to the donor spike (amino H-atoms from hydantoin
interacting with O-atoms of the carbonyl groups), with
the lower spike b being an acceptor spike (O-atoms from
hydantoin interacting with the H-atoms of NH groups). The
˚
˚
˚
˚
points in the (d , d ) regions of (1.5 A, 1.2 A) and (1.2 A, 1.5 A)
i
e
in the fingerprint plots of 1-3 are due to C-H O inter-
3
3 3
actions (Figure 7). A significant difference between the mole-
cular interactionsin three hydantoin derivatives (1-3) and the
6
2
unsubstituted hydantoin (4) in terms of H H interactions
3
3 3
is reflected in the distribution of scattered points in the
˚
fingerprint plots, which spread only up to d = d = 2.1 A in
i
e
˚ ˚
compared to d = d = 2.4 A in 1, d = d = 2.6 A in 2, and
i e i e
4
˚
d = d = 2.2 A in 3.
i
e
The relative contribution of the different interactions to the
Hirshfeld surface was calculated for 1-3 as well as a number
of unsubstituted and 5,5 -substituted hydantoins (Figure 8)
0
available in the CSD. Due to varying the number and the
types of carbon containing substituents, they are not directly
comparable across the compounds, but it offers some insight
into the effect of different substituents on the hydantoin
Figure 7. Fingerprint plots: full (left) and resolved into O H/
3 3
3
H
O contacts for C
9
H
16
N
2
O
2
(1), C11
(4) (unsubstituted hydantoin, CSD code PAHYON)
showing percentages of O H/H
20 2 2 7 10 2 2
H N O (2), C H N O
3
3 3
(
3),andC H N O
3 4 2 2
3 3 3 O contacts contribution to the
backbone. No significant C-H π or π-π interactions are
3 3 3
3
3 3
total Hirshfeld surface area of molecules.
observed in 1-3, with C H close contacts varying from
3
3 3

Article
.9% in 3 to 2.6% in 1. In the unsubstitued hydantoin (4), the
Crystal Growth & Design, Vol. 10, No. 10, 2010 4483
0
the X-ray powder diffractometer in the Department of Physics,
Jadavpur University, is gratefully acknowledged.
H
actions account for 56.5% to the Hirshfeld surface area
H interactions contribute 21.8% and the O H inter-
3
3 3
3 3 3
Supporting Information Available: Three crystallographic files
CIF); observed and simulated X-ray powder diffraction patterns.
(Figures 7 and 8). With different aliphatic and aromatic
(
substituents at the hydantoin C5-position, the contribution
of H H interactions to the Hirshfeld surface increases
steadily up to well over 70% in 2 with a corresponding
This material is available free of charge via the Internet at http://
pubs.acs.org.
3
3 3
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6
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