Crystal structures of two imidazole derivatives

Article abstract of DOI:10.1080/10587250307074

2-n-Butyl-5-chloro-3H-imidazole-4-carbaldehyde (BCIC), C₈H ₁₁ClN₂O. F.W.= 186.64, monoclinic, P2₁/c, a=7.2617(3)A, b= 13.2067(6)A, c=9.8491(4)A β = 101.76(1)°, V= 924.74(7)A³, Z=4, D_cal = 1.341 Mgm^-3, μ = 0.367mm^-1, F₀₀₀=392, λ (MoKα) = 0.71073A, final R1 and wR2 are 0.049 and 0.126, respectively. 2-n-Butyl-4-chloro-1 [(2-cyanobiphenyl-4-yl)methyl]-5- hydroxymethyl imidazok (BCCI), CvfliufilNnO, F.W. = 379.88, triclinic, P 1 a = 8.198(2)A, b = 10.997(3)A, c = 11.524(2)A, α= 90.83(2)°, β= 94.31(2)°, γ = 109.45(2)°, V= 976.0(2)A³, Z=2, D_cal = 1.293Mgm^-3, μ = 1.856mm^-1, F₀₀₀ = 400, λ (CuKα) = 1.5418A, final R1 and wR2 are 0.081 and 0.239, respectively. The imidazole ring in both the molecules is planar. The n-butyl group adopts a bent conformation in BCIC where it is in extended conformation in BCCI. The biphenyl ring system orients at an angle of 45.1(1)° in BCCI. The molecules are stabilized by N-H...N and O-H... N type hydrogen bonds in addition to van der Waals forces.

Full text of DOI:10.1080/10587250307074

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Crystal Structures of two
Imidazole Derivatives
P. Ambalavanan a , K. Palani a , M. N.
Ponnuswamyand a , R. A. Thirumuruhan a , H. S.
Yathirajan b , B. Prabhuswamy b , C. R. Raju b , P.
Nagaraja b & K. N. Mohana b
a Department of Crystallography and Biophysics ,
Universityof Madras , Guindy Campus, Chennai, 600
025, India
b Department of Studies in Chemistry , University of
Mysore , Manasagangotri, Mysore, 570 006, India
Published online: 18 Oct 2010.
To cite this article: P. Ambalavanan , K. Palani , M. N. Ponnuswamyand , R. A.
Thirumuruhan , H. S. Yathirajan , B. Prabhuswamy , C. R. Raju , P. Nagaraja & K. N.
Mohana (2003) Crystal Structures of two Imidazole Derivatives, Molecular Crystals and
Liquid Crystals, 393:1, 75-82, DOI: 10.1080/10587250307074
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Mol. Cryst. Liq. Cryst., Vol. 393, pp. 75–82
Copyright # 2003 Taylor & Francis
1542-1406/03 $12.00+.00
DOI: 10.1080/15421400390202962
CRYSTAL STRUCTURES OF TWO IMIDAZOLE
DERIVATIVES
P. Ambalavanan, K. Palani, M. N. Ponnuswamy,
and R. A. Thirumuruhan
Department of Crystallography and Biophysics, University
of Madras, Guindy Campus, Chennai–600 025, India
H. S. Yathirajan, B. Prabhuswamy, C. R. Raju, P. Nagaraja,
and K. N. Mohana
Department of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore–570 006, India
2-n-Butyl-5-chloro-3H-imidazole-4-carbaldehyde (BCIC), C8H11ClN2O. F.W. ¼
˚
˚
˚
186.64, monoclinic, P21/c, a ¼ 7.2617(3) A, b ¼ 13.2067(6) A, c ¼ 9.8491(4) A
b ¼ 101.76(1)ꢀ, V ¼ 924.74(7)A , Z ¼ 4, Dcal ¼ 1.341 Mgmꢁ3
,
m ¼ 0.367 mmꢁ1
,
3
˚
˚
F000 ¼ 392, l (MoKa) ¼ 0.71073 A, final R1 and wR2 are 0.049 and 0.126, respec-
tively. 2-n-Butyl-4-chloro-1 [(20-cyanobiphenyl-4-yl)methyl]-5-hydroxymethyl
˚
ꢀ
imidazole (BCCI), C22H22ClN3O, F.W. ¼ 379.88, triclinic, P 1, a ¼ 8.198(2) A,
ꢀ
ꢀ
ꢀ
˚
˚
b ¼ 10.997(3) A, c ¼ 11.524(2)A, a ¼ 90.83(2) , b ¼ 94.31(2) , g ¼ 109.45(2) , V ¼
976.0(2) A , Z ¼ 2, Dcal ¼ 1.293 Mgmꢁ3, m ¼ 1.856 mmꢁ1, F000 ¼ 400, l (CuKa) ¼
3
˚
˚
1.5418A, final R1 and wR2 are 0.081 and 0.239, respectively. The imidazole ring
in both the molecules is planar. The n-butyl group adopts a bent conformation in
BCIC where it is in extended conformation in BCCI. The biphenyl ring system
orients at an angle of 45.1(1)ꢀ in BCCI. The molecules are stabilized by N-H . . . N
and O-H. . . N type hydrogen bonds in addition to van der Waals forces.
Keywords: crystal structure; conformation; hydrogen bonding; BCIC; BCCI
One of the authors P. Ambalavanan would like to thank UGC for providing FDP under IX
plan period and also Commissioner of Collegiate Education, Chennai–600 006 for giving per-
mission to carry out the research work in the Department of Crystallography and Biophysics,
University of Madras.
75

76
P. Ambalavanan et al.
INTRODUCTION
Imidazole is a heterocyclic five-membered ring containing nitrogen atoms.
Various imidazole derivatives are found to possess biological activities.
Interestingly, it is to be noted that biotin, a heterocyclic sulfur-containing
B-complex vitamin, is fused of imidazole and thiophene rings and partici-
pates as a coenzyme in the carboxylation reaction [1].
Imidazole is a protonated five-membered ring, which promotes che-
mical reactions depending on the specific physical conditions at enzyme
catalytic sites [2]. Imidazoles and benzimidazoles are the components of
important structures used in pharmaceuticals, agrochemicals, dyestuffs,
and high temperature polymer products. The crystal structure of cis-1-{[4-
(1-Imidazolylmethyl) cyclohexyl] methyl} imidazole-succinic acid complex
has been determined since it is an active nonsteroidal aromatase inhibitor
[3, 4].
With a view to understand the conformation of the imidazole moiety
and the influence of substituents at different positions of this five-
membered ring, the crystal structure determination of two imidazole
derivatives have been carried out. The chemical diagrams of BCIC and
BCCI are shown in Figure 1.
X-RAY DATA COLLECTION, STRUCTURE SOLUTION,
AND REFINEMENT
Data Collection
Intensity data were collected on a Siemens SMART CCD [5] area detector
diffractometer using graphite monochromated MoKa radiation for BCIC.
FIGURE 1 Chemical diagrams of BCIC and BCCI.

Crystal Structures of Two Imidazole Derivatives
77
The entire data collection was covered over a hemisphere of reciprocal
space by a combination of three sets of exposure, each having a different f
angle (0, 88, and 180ꢀ) for the crystal and each exposure time of 10 s
covered 0.3ꢀ in o. The crystal-to-detector distance was 4 cm and the
detector swing angle was ꢁ35ꢀ. Coverage of unique set was complete by
over 99%. Crystal decay, monitored by repeating thirty initial frames at the
end of the data collection and analyzing the duplicate reflections, was
found to be negligible.
For BCCI, the data were collected on a CAD4 diffractometer [6] using
graphite monochromated CuKa radiation. Accurate unit cell parameters
were derived from least-squares analysis using 25 reflections. In order to
check the intensity deterioration due to the radiation damage or crystal
degradation, three standard reflections were monitored for every 1 h or for
every hundred reflections, whichever is the earliest. The intensity data
were corrected for Lorentz, polarization, and absorption effects [7].
Structure Solution and Refinement
Both the structures were solved using direct methods in SHELXS97 [8] and
refined in SHELXL97 [9]. Hydrogen atoms were placed at the calculated
positions but not refined. The final cycles of full-matrix least-squares
refinement were carried out applying anisotropic thermal parameters for
all nonhydrogen atoms. The geometrical parameters were calculated
using PARST [10], and the molecular graphics were drawn through
ZORTEP [11].
RESULTS AND DISCUSSION
The crystal and refinement data are given in Table I. Figures 2 and 3 show
the ZORTEP plot of the molecules of BCIC and BCCI with thermal ellip-
soids at 30% probability level. The bond lengths and bond angles of the
imidazole moiety in BCIC and BCCI are comparable with the standard
˚
˚
values [12, 13]. The C-C1 distances (C4-C112¼) 1.712(2) A and 1.723(4) A
are within the range of values reported in the literature [14].
In BCIC molecule, the imidazole ring, carbaldehyde group, and C1 atom
lie in the same plane except the n-butyl chain which adopts a bent
conformation as can be seen from the conformational angles (N3-C2-C6-
C7¼) 63.5(2)ꢀ, (C2-C6-C7-C8¼) 61.8(2)ꢀ, and (C6-C7-C8-C9¼) 71.0(2)ꢀ.
In BCCI molecule, the 2-n-butyl substitution at C2 lies almost in the plane
of the imidazole moiety. This facilitates the atom C7 to form a C-H . . . N
˚
hydrogen bonding with the imidazole nitrogen N3 (C7 . . . N3¼)2.861(6)A
and (C7-H7B . . . N3¼88.3(3)ꢀ). The n-butyl group of BCCI is in an

78
P. Ambalavanan et al.
TABLE I Crystal Data for BCIC and BCCI
Parameter
BCIC
BCCI
C22H22Cl N3O
Empirical formula
Formula weight
Temperature(K)
Wavelength
C8H11Cl N2O
186.64
293(2)
379.88
293(2)
1.5418A
˚
0.71073A
˚
Crystal system
Space group
Unit cell dimensions
Monoclinic
P21/c
Triclinic
ꢀ
P 1
˚
˚
a ¼ 7.2617(3)A
a ¼ 8.198(2)A
˚
˚
b ¼ 13.2067(6)A
b ¼ 10.997(3)A
˚
˚
c ¼ 9.8491(4)A
c ¼ 11.524(2)A
a ¼ 90.83(2)ꢀ
b ¼ 94.31(2)ꢀ
g ¼ 109.45(2)ꢀ
b ¼ 101.76(1)ꢀ
3
3
˚
924.74(7)A
˚
Volume
Z
976.0(4)A
4
2
Calculated density
Absorption coefficient
F(000)
1.341 Mg/m3
0.367 mmꢁ1
392
1.293 Mg/m3
1.856 mmꢁ1
400
Crystal size
y - range for data collection
Index ranges
0.2460.1460.08 mm
2.62 to 28.29ꢀ
ꢁ9 ꢃ h ꢃ 9
ꢁ13 ꢃ k ꢃ 17
ꢁ11 ꢃ 1 ꢃ 13
6383
0.3560.2060.10 mm
3.85 to 71.92ꢀ
ꢁ10 ꢃ h ꢃ 9
0 ꢃ k ꢃ 13
ꢁ14 ꢃ 1 ꢃ 14
4023
Reflections collected
Independent reflections
Observed reflections
[I > 2s(I)]
2268 [R(int) ¼ 0.0597]
1664
3821 [R(int) ¼ 0.0891]
2423
Refinement method
Full-matrix least-squares
on F2
0.946
Full-matrix least-squares
on F2
1.086
Goodness-of-fit on F2
Final R-indices [I > 2s(I)]
R-indices (all data)
R1 ¼ 0.049, wR2 ¼ 0.126
R1 ¼ 0.0634, wR2 ¼ 0.1333
R1 ¼ 0.081, wR2 ¼ 0.239
R1 ¼ 0.1247, wR2 ¼ 0.2757
extended conformation as evidenced by the conformational angles (N1-C2-
C6-C7¼)176.4(5)ꢀ. (C2-C6-C7-C8¼)ꢁ177.1(5)ꢀ, and (C6-C7-C8-C9¼)
178.5(5)ꢀ.
The imidazole ring is planar in both the molecules (maximum deviation
˚
˚
0.005(2)A for N3 in BCIC and 0.008(5)A for C5 in BCCI). This is also
supported by the minimum q2 values of 0.009(2) for BCIC and 0.005(4) for
BCCI [10]. In BCCI, the sum of the bond angles around N1 is 360.0ꢀ, which
confirms that the atom N1 is in sp2 hybridized state. The bond length N1-
C13 is comparable with the standard value [15].
In BCCI, the two phenyl rings (biphenyl ring system) are planar (max-
˚
imum deviation ꢂ 0.014(5)A), and the mutual orientation of these phenyl

Crystal Structures of Two Imidazole Derivatives
79
FIGURE 2 ZORTEP diagram of BCIC.
rings is 45.1(1)ꢀ, a common feature observed in many biphenyl derivatives
[16]. In the biphenyl ring system, the endocyclic bond angles at C16 and
C20 are contracted to 118.0(4)ꢀ and 118.3(4)ꢀ, respectively, due to steric
hindrance between the rings. The cyano group (CꢄN) attached to the
phenyl ring is linear (C25-C26-N27¼177.8(5)ꢀ). The two phenyl rings
(biphenyl group) are oriented at angles of 85.3(2)ꢀ and 80.6(2)ꢀ with
respect to the imidazole moiety.
In BCIC, the molecules are linked by a three-dimensional network of
N-H . . . N type hydrogen bonds. But the O-H . . . N type hydrogen bonds
stabilize the molecules in BCCI crystal. Weak intermolecular interactions of
the type C-H . . . O and C-H . . . N are also observed in the crystals of both
BCIC and BCCI.
Preparation of BCIC
A mixture of glycine (0.55 mol, 41.7 g), methanol (175.0 ml), and water
(10 ml) was cooled to 0ꢀC under stirring. Two drops of 30% NaOH was
added into the mixture (pH 8.0–9.5). To this mixture, a solution of methyl
pentanimidate (0.55 mol, 64.0 g) in toluene (106 ml) was added and stirred
for 15 min. The mixture was stirred overnight. The pH of the mixture was
then adjusted from 10.1 to 7.0 (conc. H2SO4) and charged with toluene
(500 ml). The methanol was distilled completely and the mixture was
cooled to 0ꢀC. To the cooled mixture was added with POCl3 (1.55 mol,

80
P. Ambalavanan et al.
FIGURE 3 ZORTEP diagram of BCCI.
238.0 g) and DMF (1.55 mol, 113.6 g) at 80ꢀC. The mixture was heated at
100ꢀC for 2 h, cooled to room temperature and poured into ice water
(370 ml) (temp. 30ꢀC) with vigorous stirring for 2 h. The organic layer was
separated after adjusting the pH of the mixture of 7.2. It was washed with
water (2650 ml), dried over anhydrous Na2SO4 concentrated, and cooled
to ꢁ10ꢀC for 2 h. The product separated was filtered off, washed with
ice-cold toluene, and dried to get 57.5 g (55%) of pure product. It was
recrystallized from CC14 to get white needles.
Preparation of BCCI
A solution of 2-n-butyl-4-chloro-5-formylimidazole (0.05 mol, 9.32 g) in
methanol (40 ml) was cooled at 0ꢀC. Sodiumborohydride (0.0125 mol,
0.4727 g) was added slowly with stirring. the reaction mixture was then

Crystal Structures of Two Imidazole Derivatives
81
stirred at room temperature for 2–3 h. After completion of reaction (TLC),
the mixture was concentrated to about 10 ml and poured into ice water
(100 ml). The white product formed was filtered, washed, with water and
dried under vacuum at 50ꢀC to get 90% (8.4 g) of 2-n-butyl-4-chloro-5-
hydroxymethyl imidazole. To a suspension of sodium methoxide (0.03 mol,
1.62 g) in DMF (25 ml) was added 2-n-butyl-4-chloro-5-hydroxymethy-
limidazole (0.03 mol, 5.655 g) in DMF (25 ml). The mixture was stirred at
25ꢀC for 30 min. To this mixture was added in drops, a solution of 4-bro-
momethyl-20-cyanobiphenyl (0.025 mol, 6.80 g) in DMF (25 ml). The mix-
ture was stirred at room temperature for 24 h. The mixture was evaporated
to a residue under vacuum and dissolved in ethyl acetate (70 ml), washed
with brine solution (20 ml), water (50 ml), dried using Na2SO4, and eva-
porated to get a crude product which was purified by column chromato-
graphy using n-hexane-ethylacetate mixture (7:2) as the eluent to get the
title product in 40% yield (3.11 g). It was recrystallized from CCl4 to get
white needles. Both BCCI and BCIC are white crystalline solids and serve as
important key intermediates for preparing antihypertensive drug Losartan
potassium [17]. Both compounds are soluble in chloroform, tetra-
hydrofuran, acetone, etc. It answers the tests for primary alcoholic and
chloro groups.
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