X-ray diffraction structures of regioisomers of N-methylated benzimidazole compounds with interest for the design of amyloid-avid probes

Article abstract of DOI:10.1007/s10870-012-0358-x

This work describes the compounds 5-bromo- 1-methyl-2-[N-methyl-N- (2′-O-tert-butylcarbonatethyl)-4′-aminophenyl]- 1H-benzo[d]imidazole (4) and 6-bromo-1 -methyl-2-[N-methyl-N-(2′-O-tert-butylcarbonatethyl)- 4′- aminophenyl]-1H-benzo[d]imidazole (5), C

Full text of DOI:10.1007/s10870-012-0358-x

J Chem Crystallogr (2012) 42:1052–1059
DOI 10.1007/s10870-012-0358-x
ORIGINAL PAPER
X-ray Diffraction Structures of Regioisomers of N-Methylated
Benzimidazole Compounds with Interest for the Design
of Amyloid-Avid Probes
•
Goreti Ribeiro Morais Isabel C. Santos
•
•
Isabel Santos Antonio Paulo
´
Received: 22 March 2012 / Accepted: 4 August 2012 / Published online: 18 August 2012
ꢀ Springer Science+Business Media, LLC 2012
Abstract This work describes the compounds 5-bromo-
1-methyl-2-[N-methyl-N-(20-O-tert-butylcarbonatethyl)-40-ami-
nophenyl]-1H-benzo[d]imidazole (4) and 6-bromo-1
-methyl-2-[N-methyl-N-(20-O-tert-butylcarbonatethyl)-40-
aminophenyl]-1H-benzo[d]imidazole (5), C22H26BrN3O3,
which correspond to two regioisomers that were obtained
by N-methylation of the corresponding 6-bromobenzimi-
dazole derivative. The structures of these two regioi-
somers have been confirmed in solution by NMR NOESY
experiments, as well as in the solid state using single
crystal X-ray diffraction analysis. The structures of 4 and
5 comprise two planar benzimidazole and benzene frag-
ments and a disordered aliphatic chain containing a ter-
minal carbamate group. Compound 4 crystallized in the
monoclinic P21/c group with unit cell parameters a =
Introduction
The benzimidazole ring, considered as a good pharmaco-
phore in medicinal chemistry, has been largely found in
biologically active compounds such as anti-bacterial [1],
antiprotozoal [2], anti-inflammatory [3] and cytotoxic
agents [4], to cite a few. Recently, we [5] and the Cui’s
group [6] have investigated benzimidazole compounds for
in vivo targeting of b-amyloid aggregates aiming at their
use in the design of 18F-labelled radioactive probes for the
early detection of Alzheimer’s disease by means of posi-
tron emission tomography. Like other amyloid targeting
agents, benzimidazole-containing compounds are planar
molecules with extended p-delocalized systems, which are
expected to enable their insertion between the b sheets of
amyloid aggregates. Initially, we have focused on styryl
benzimidazoles [5], and we have demonstrated that this
type of compounds interact specifically with different
fibrillar amyloid species emerging as useful structures for
the design of 18F-labelled amyloid radioprobes. However,
these styryl benzimidazoles were obtained as a mixture of
interconverting E/Z isomers, which might present different
in vivo biological behavior. To avoid this drawback we
have embarked in the study of arylbenzimidazoles and
correspondent N-methylated congeners, hoping to obtain
compounds that do not form interconvertible isomers but
still present affinity for b-amyloid aggregates. During the
course of this work, N-methylation of a 6-bromobenzimi-
dazole derivative, compound 3, led to the formation of two
regiosomers, 5-bromo-1-methyl-2-[N-methyl-N-(20-O-tert-
butylcarbonatethyl)-40-aminophenyl]-1H-benzo[d]imidazole
(4) and 6-bromo-1-methyl-2-[N-methyl-N-(20-O-tert-butyl-
carbonatethyl)-40-aminophenyl]-1H-benzo[d]imidazole (5),
which were obtained in equal amount. Herein, we report on
the synthesis of compounds 4 and 5, as well as on the
˚
˚
˚
23.0178(7) A, b = 7.9106(2) A, c = 11.9758(3) A, b =
3
˚
93.340(2)8, V = 2176.90(10) A , Z = 4, D = 1.405 Mg/
m3. Compound 5 crystallized in the triclinic P-1 group
˚
with unit cell parameters a = 6.7187(3) A, b = 16.5203
˚
˚
(10) A, c = 21.3544(13) A, a = 109.279(2)8, b = 94.802
3
˚
(2)8, c = 98.871(2)8, V = 2187.4(2) A , Z = 4, D =
1.398 Mg/m3.
Keywords Benzimidazole derivatives ꢀ N-methylation ꢀ
Regioisomers ꢀ X-ray crystal structure
G. Ribeiro Morais ꢀ I. C. Santos ꢀ I. Santos ꢀ A. Paulo (&)
ˆ
Unidade de Ciencias Quımicas Radiofarmaceuticas, IST/ITN,
Instituto Superior Tecnico, Universidade Tecnica de Lisboa,
´
ˆ
´
´
´
Estrada Nacional 10, 2686-953 Sacavem, Portugal
e-mail: apaulo@itn.pt
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J Chem Crystallogr (2012) 42:1052–1059
1053
elucidation of their structures in solution by NMR NOESY
experiments and in the solid state by X-ray diffraction
studies. The assignment of these structures was essential
because these compounds are key intermediates in the syn-
thesis of novel fluorinated/radiofluorinated arylbenzimidaz-
oles compounds, which are currently under evaluation as
amyloid-probes.
formed was removed by filtration. The precipitate was
redissolved in MeOH, the solvent was concentrated and the
residue was purified by silica gel column chromatography
(n-hexane/EtOAc 1:1) to give 3 (793 mg, 80 %); Rf = 0.67
(n-hexane/EtOAc 1:2); 1H NMR (CDCl3, 300 MHz) d 1.44
(s, 9H, C(CH3)3), 3.01 (s, 3H, NCH3), 3.63 (t, 2H, J 6.0 Hz,
NCH2CH2OBoc), 4.22 (t, 2H, J 6.0 Hz, NCH2CH2OBoc),
6.68 (d, 2H, 3J 8.7 Hz, H-30), 7.26 (d, 1H, 3J 8.7 Hz, H-5),
7.38 (d, 1H, 3J 8.7 Hz, H-4), 7.64 (s, 1H, H-7), 7.89 (d, 2H,
3J 8.7 Hz, H-20); 13C NMR (CDCl3, 75 MHz) d 27.67 (3C,
C(CH3)3), 38.67 (NCH3), 50.73 (CH2), 63.49 (CH2), 82.49
(Cquart), 111.80 (2C, Carom), 115.27 (Cquart), 115.67 (Carom),
116.35 (Carom), 117.26 (Carom), 125.49 (Carom), 128.13 (2C,
Experimental Part
4-Bromo-diaminobenzene (1) was purchased from Sigma-
Aldrich. N-Methyl-N-((20-O-tert-butylcarbonate)ethyl)-4-
aminobenzaldehyde (2) was prepared according to the lit-
erature [5]. NMR spectra were recorded on a Varian Unity
300 NMR spectrometer at the frequencies of 300 MHz
(1H) and 75 MHz (13C). Chemical shifts are reported in
C
arom), 137.84 (Cquart), 139.88 (Cquart), 150.46 (Cquart),
153.33 (Cquart), 153.47 (C=O); ES? MS C21H24BrN303 (445)
m/z 446.2 [M?H]? (95 %), 447.2 [M?H]? (20 %), 448.2
[M?H]? (100 %), 468.2 [M?Na]? (30 %).
1
parts per million. H and 13C chemical shifts were refer-
enced with the residual solvent resonances relative to tet-
ramethylsilane. Electrospray ionisation mass spectrometry
(ESI–MS) was performed on a QITMS instrument in
positive ion mode. Analytical thin-layer chromatography
was performed on plates of precoated silica plates 60 F254
(Merck). Visualization of the plates was carried out using
UV light (254 and 365 nm) and/or iodine chamber. Col-
umn chromatography purification was carried out on silica
gel (Merck). Crystals of 4 and 5 suitable for X-ray dif-
fraction studies were obtained from slow evaporation of a
solution of the compounds in ethanol/diethyl ether. The
X-ray diffraction analysis has been performed on a Bruker
APEX-II CCD diffractometer, equipped with an Oxford
Cryosystems low-temperature device at 150 K in the x and
u scans mode, using graphite monochromatic Mo Ka
N-Methylation of 6-bromo-2-[N-methyl-N-(20-O-tert-
butylcarbonatethyl)-40-aminophenyl]-1H-
benzo[d]imidazole
To a solution of NaOH (720 mg, 18 mmol) in water
(1.5 mL) were added 3 (1.04 g, 2.3 mmol), acetone
(12 mL) and, dropwise with cooling in iced water, methyl
iodide (174 lL, 2.8 mmol). The reaction mixture was
stirred for 1 h at RT. Then, the solvents were evaporated,
the reaction mixture was diluted with water (100 mL) and
was extracted with CH2Cl2 (100 mL). The organic phase
was dried over Na2SO4, filtered and the filtrate was con-
centrated under vacuum to give a mixture of the regioi-
somers 4 and 5 (900 mg, 84 %). Compounds 4 and 5 have
been purified by column chromatography on silica gel
(n-hexane/EtOAc 1:1). After purification, 4 and 5 were
isolated in 38 and 37 % yield, respectively.
˚
radiation (0.71073 A). Empirical absorption correction was
carried out using SADABS [7]. Data collection and data
reduction for 4 and 5 were done with SMART and SAINT
programs [8]. The structure was solved by direct methods
with SIR97 [9] and refined by full-matrix least-squares
analysis with SHELXL97 [10] using the WINGX [11] suite
of programs. Non-hydrogen atoms were refined with
anisotropic thermal parameters whereas H-atoms were
placed in idealized positions and allowed to refine riding on
the parent C atom. Molecular graphics were prepared using
ORTEP3 [12] and MERCURY [13].
5-Bromo-1-methyl-2-[N-methyl-N-(20-O-tert-
butylcarbonatethyl)-40-aminophenyl]-1H-
benzo[d]imidazole (4)
Rf = 0.61(n-hexane/EtOAc 1:1); 1H NMR (CDCl3,
300 MHz) d 1.44 (s, 9H, C(CH3)3), 3.05 (s, 3H, NCH3),
3.67 (t, 2H, J 6.3 Hz, NCH2CH2OBoc), 3.82 (s, 3H,
NCH3), 4.24 (t, 2H, J 6.3 Hz, NCH2CH2OBoc), 6.80 (d,
2H, 3J 9.0 Hz, H-30), 7.18 (d, 1H, 3J 8.7 Hz, H-7), 7.34 (dd,
4
3
3
6-Bromo-2-[N-methyl-N-(20-O-tert-
butylcarbonatethyl)-40-aminophenyl]-1H-
benzo[d]imidazole (3)
1H, J 1.8 Hz and J 8.7 Hz, H-6), 7.63 (d, 2H, J 9.0 Hz,
4
H-20), 7.88 (d, 1H, J 1.8 Hz, H-4); 13C NMR (CDCl3,
75 MHz) d 27.70 (3C, C(CH3)3), 31.98 (NCH3), 38.70
(NCH3), 50.81 (CH2), 63.45 (CH2), 82.42 (Cquart), 110.49
(Cquart), 111.61 (2C, Carom), 115.12 (Carom), 116.88 (Carom),
121.96 (Carom), 125.06 (Carom), 130.62 (2C, Carom), 135.59
(Cquart), 144.05 (Cquart), 149.95 (Cquart), 153.37 (Cquart),
155.44 (C=O); ES? MS C22H26BrN303 (459) m/
A mixture of 4-bromo-1,2-diaminobenzene (1) (420 mg,
2.2 mmol), 2 (627 mg, 2.2 mmol), and Na2S2O5 (423 mg,
2.2 mmol) in DMF (7 mL) was refluxed for 90 min. Then,
iced water was added to the solution and the precipitate
123

1054
J Chem Crystallogr (2012) 42:1052–1059
Scheme 1 Synthesis of the N-
methylated benzimidazole
compounds
z 460.3[M?H]? (100 %), 461.3 [M?H]? (25 %), 462.3
[M?H]? (100 %), 482.2 [M?Na]? (17 %).
6-bromo-1-methyl-2-[N-methyl-N-(20-O-tert-
butylcarbonatethyl)-40-aminophenyl]-1H-
benzo[d]imidazole (5)
Rf = 0.54 (n-hexane/EtOAc 1:1); 1H NMR (CDCl3,
300 MHz) d 1.43 (s, 9H, C(CH3)3), 3.04 (s, 3H, NCH3),
3.66 (t, 2H, J 6.3 Hz, NCH2CH2OBoc), 3.79 (s, 3H,
NCH3), 4.24 (t, 2H, J 6.3 Hz, NCH2CH2OBoc), 6.79 (d,
Fig. 1 NOESY interactions in the regioisomers 4 and 5
Table 1 Crystallographic data
and structure refinement for
compounds 4 and 5
4
5
Crystal size (mm)
0.25 9 0.10 9 0.03
0.30 9 0.20 9 0.03
Colourless, plate
150(2)
Crystal colour, shape
Temperature (K)
Empirical formula
Molecular mass
Crystal system
Colourless, plate
150(2)
C
22H26N3O3Br
C22H26N3O3Br
460.37
460.37
Monoclinic
Triclinic
Space group
P21/c
P-1
˚
a (A)
23.0178(7)
6.7187(3)
˚
b (A)
7.9106(2)
16.5203(10)
21.3544(13)
109.2279(3)
94.802(2)
˚
c (A)
11.9756(3)
a (ꢁ)
b (ꢁ)
c (ꢁ)
90
93.340(2)
90
98.871(2)
3
˚
V (A )
2176.9(1)
2187.4(2)
Z, Dcalcd. (Mg/m3)
4, 1.405
4, 1.398
l (mm-1
)
1.916
1.906
F(000)
952
952
Theta range (ꢁ)
Index range (h,k,l)
Refl. collected/unique
T max/min
3.13–25.03
2.88–25.03
-7/7, -19/19, -25/25
17855/7612[Rint = 0.0450]
0.9450/0.5986
7612/637
-26/27, -9/8, -13/14
12177/3824[Rint = 0.0362]
0.9448/0.6459
3824/295
Data/parameters
G.O.F. on F2
1.040
1.125
R [I [ 2r(I)]
Dqmax/min [eA-3
R1 = 0.0455, wR2 = 0.1046
0.594/–0.518
R1 = 0.0748, wR2 = 0.1957
2.112/–2.002
]
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J Chem Crystallogr (2012) 42:1052–1059
1055
Table 2 Selected bond lengths
˚
Compound 4
[A] and angles [ꢁ] for 4 and 5
Br1–C1
N1–C4
N1–C7
N1–C8
N2–C5
N2–C8
N3–C12
C8–C9
1.913(4)
1.376(4)
1.455(3)
1.380(4)
1.379(5)
1.328(4)
1.372(5)
1.453(5)
C(6)–C(1)–Br(1)
C(2)–C(1)–Br(1)
C(4)–N(1)–C(8)
C(4)–N(1)–C(7)
C(8)–N(1)–C(7)
C(8)–N(2)–C(5)
N(2)–C(8)–N(1)
N(2)–C(8)–C(9)
N(1)–C(8)–C(9)
118.8(2)
118.2(3)
106.8(2)
125.1(3)
127.8(3)
105.2(3)
112.5(3)
125.1(3)
122.4(3)
Compound 5
Br(1)–C(1)
N(1)–C(5)
N(1)–C(7)
N(1)–C(8)
N(2)–C(4)
N(2)–C(8)
N(3)–C(12)
C(8)–C(9)
1.909(6)
1.382(7)
1.451(7)
1.381(7)
1.388(7)
1.328(7)
1.376(7)
1.468(8)
C(6)–C(1)–Br(1)
C(2)–C(1)–Br(1)
C(8)–N(1)–C(5)
C(8)–N(1)–C(7)
C(5)–N(1)–C(7)
C(8)–N(2)–C(4)
N(2)–C(8)–N(1)
N(2)–C(8)–C(9)
N(1)–C(8)–C(9)
C(28)–C(23)–Br(2)
C(24)–C(23)–Br(2)
C(27)–N(4)–C(30)
C(27)–N(4)–C(29)
C(30)–N(4)–C(29)
C(30)–N(5)–C(26)
N(5)–C(30)–N(4)
N(5)–C(30)–C(31)
N(4)–C(30)–C(31)
118.4(4)
118.7(4)
107.1(4)
128.9(5)
123.3(5)
105.1(5)
112.3(5)
123.5(5)
124.1(5)
117.8(5)
118.6(5)
106.5(5)
125.1(5)
128.3(5)
104.9(4)
113.0(5)
123.6(5)
123.4(5)
Br(2)–C(23)
N(4)–C(27)
N(4)–C(29)
N(4)–C(30)
N(5)–C(26)
N(5)–C(30)
N(6)–C(34)
C(30)–C(31)
1.905(6)
1.370(7)
1.457(7)
1.377(7)
1.381(7)
1.323(7)
1.373(7)
1.476(8)
Table 3 Intermolecular short contacts in the crystal structure of compound 4
Intrastack
Interstack
O1ꢀꢀꢀH2…
O2AꢀꢀꢀH2…
C2ꢀꢀꢀH15A
C2ꢀꢀꢀH16B
C2ꢀꢀꢀH16D
2.538
2.714
2.780
2.830
2.645
2 - x, ‘ ? y, ‘ - z
2 - x, ‘ ? y, ‘ - z
2 - x, ‘ ? y, ‘ - z
2 - x, ‘ ?y, ‘ - z
2 - x, ‘ ? y, ‘ - z
BR1ꢀꢀꢀH16B
BR1ꢀꢀꢀH22B
C6ꢀꢀꢀH13
3.047
3.044
2.827
2.900
2.704
3.166(9)
2.531
2 - x, 2 - y, 1 - z
2 - x, 2 - y, 1 - z
2 - x, 2 - y, 1 - z
x, 1.5 - y, -‘ ? z
x, 1.5 - y, -‘ ? z
x, 1.5 - y, -‘ ? z
x, 1.5 - y, -‘ ? z
C3ꢀꢀꢀH6
H7BꢀꢀꢀN2
C15ꢀꢀꢀC17A
C15ꢀꢀꢀH17C
3
2H, J 9.0 Hz, H-30), 7.33 (dd, 1H, 4J 1.8 Hz and
(63 %), 461.3 [M?H]? (26 %), 462.3 [M?H]? (100 %),
482.2 [M?Na]? (32 %), 484.2 [M?Na]? (34 %).
3J 8.4 Hz, H-5), 7.46 (d, 1H, J 1.8 Hz, H-7), 7.60 (d, 1H,
3J 8.4 Hz, H-4), 7.62 (d, 2H, J 9.0 Hz, H-20); 13C NMR
4
3
(CDCl3, 75 MHz) d 27.69 (3C, C(CH3)3), 31.95(NCH3),
38.68 (NCH3), 50.80 (CH2), 63.44 (CH2), 82.39 (Cquart),
111.58 (2C, Carom), 112.43 (Carom), 115.10 (Carom), 120.43
(Carom), 125.3 (Carom), 130.54 (2C, Carom), 137.77 (Cquart),
141.94 (Cquart), 149.87 (Cquart), 153.36 (Cquart), 155.16
(C=O); ES? MS C22H26BrN303 (459) m/z 460.3 [M?H]?
Results and Discussion
As shown in Scheme 1, the benzimidazole precursor
(compound 3) has been synthesized in good yield
(g = 80 %) by the cyclocondensation reaction between the
123

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J Chem Crystallogr (2012) 42:1052–1059
Table 4 Intermolecular short contacts in the crystal structure of compound 5
Molecule 1–Molecule 1
Molecule 2–Molecule 2
O2ꢀꢀꢀC15
3.097(7)
2.703
x - 1, y, z
BR2ꢀꢀꢀC40
C40ꢀꢀꢀH43A
O5ꢀꢀꢀH43A
C30ꢀꢀꢀH29B
3.458(9)
2.849
2 - x, 1 - y, 2 - z
1 - x, 1 - y, 1 - z
1 - x, 1 - y, 1 - z
2 - x, 1 - y, 2 - z
O2ꢀꢀꢀH15A
O3ꢀꢀꢀH17A…
x - 1, y, z
2.581
2 - x, 2 - y, -z
2.445
2.813
Molecule 1–Molecule 2
N2ꢀꢀꢀH35
C10ꢀꢀꢀH36
C12ꢀꢀꢀH29A
C13ꢀꢀꢀH29A
N5ꢀꢀꢀH16A
2.641
2.867
2.844
2.694
2.725
2.893
2.849
2 - x, 1 - y, 1 - z
2 - x, 1 - y, 1 - z
2 - x, 1 - y, 1 - z
2 - x, 1 - y, 1 - z
1 - x, 1 - y, 1 - z
1 - x, 1 - y, 1 - z
2 - x, 1 - y, 1 - z
C35ꢀꢀꢀH14
C28ꢀꢀꢀH16B
Fig. 2 ORTEP diagram of compound 4 drawn at the 40 % probability level with the atomic numbering scheme. H atoms have been omitted for
clarity
commercially available o-phenylenediamine derivative 1
with the substituted benzaldehyde 2. The N-alkylation of 3
with methyl iodide proceeded smoothly (g = 84 %) lead-
ing to the formation of regioisomers 4 and 5, which were
obtained in roughly equal amount after proper purification
by column chromatography. The regioisomers 4 and 5 are
key compounds for the synthesis of fluorinated/radio-
fluorinated benzimidazole derivatives with potential rele-
vance for the design of amyloid-avid probes. The chemical
structures of 4 and 5, particularly the relative positions of
the bromide substituent and N–CH3 group in the benz-
imidazole rings, were confirmed in solution by NMR
NOESY experiments and in the solid state by X-ray dif-
fraction analysis.
of the benzimidazole ring. By contrast, a NOESY effect
was observed for compound 5 between the doublet
signal at 7.46 ppm (Ha) and the singlet at 3.79 ppm
(NCH3), which is consistent with the formation of the
other regioisomer containing the bromide at the
6-position.
The molecular structures of regioisomers 4 and 5 were
confirmed by X-ray diffraction analysis, and corroborated
the data obtained in solution by the 2D NOESY experi-
ments. Compound 4 crystallizes in the monoclinic system,
space group P21/c, with one molecule in the asymmetric
unit located in a general position. Compound 5 crystallizes
in the triclinic system, space group P-1, with two inde-
pendent molecules in the asymmetric unit, which are
located in general positions and can be considered chemi-
cally equivalent. The crystal data and final refinement
details for compounds 4 and 5 are given in Table 1. A
selection of bond lengths and angles for 4 and for the two
independent molecules of 5 is given in Table 2. The rele-
vant short intermolecular contacts for 4 and 5 are provided
in Tables 3 and 4. The respective ORTEP diagrams are
presented in Figs. 2 and 3.
Figure 1 shows the numbering of the different protons
from the benzimidazole rings of compounds 4 and 5. For
compound 4, a strong NOESY effect was observed
between the doublet at 7.18 ppm, due to the Hc proton,
and the singlet at 3.82 ppm from the NCH3 protons. This
finding showed that these protons are spatially nearby
and indicated that we were in the presence of the reg-
ioisomer having the bromide substituent at the 5-position
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J Chem Crystallogr (2012) 42:1052–1059
1057
Fig. 3 ORTEP diagram of two independent molecules (1 and 2) of compound 5 drawn at the 40 % probability level with the atomic numbering
scheme. H atoms have been omitted for clarity
The structures of 4 and 5 are defined by two planar
benzimidazole and benzene fragments and an aliphatic
chain containing a terminal tert-butyloxycarbonyl (BOC)
protecting group. As shown in Figs. 2 and 3 these frag-
ments are essentially planar being the respective r.m.s
˚
deviation of fitted atoms 0.0194 and 0.0033 A for com-
˚
pound 4, 0.0072 and 0.0060 A for molecule 1 of compound
120.0(5)8 for molecules 1 and 2 of compound 5, respec-
tively) are consistent with an sp2 hybridization for these
atoms. The benzimidazole ring and the substituted phenyl
ring make a dihedral angle of 50.9 (1)8 in compound 4.
The same dihedral angle show values of 42.4(1) and
39.2(1)8 for the independent molecules 1 and 2 of com-
pound 5, respectively. In this way, the steric interactions
between the imidazolyl N–CH3 group and the phenyl
substituent at the 2-position are minimized. The aliphatic
chains in the molecules of compound 5 adopt different
orientations, as can be can be seen by the quite different
torsion angles C18–O2–C17–C16 (99.2(6)8) and C40–
˚
5, and 0.0084 and 0.0187 A for molecule 2 of compound 5.
In compound 4 three atoms (O2, C16, C17/O2A, C16A,
C17A) of the aliphatic chain are disordered over two sites
with occupancies 0.45:0.55. In compound 5 only one of
the molecules presents disorder. In this case atoms of the
aliphatic chain of molecule 2 (C37–C38–C39–O5–C40–
O4–O6–C41–C42–C43–C44: C37A–C38A–C39A–O5A–
C40A–O4A–O6A–C41A–C42A–C43A–C44A) are disor-
dered over two positions with occupancies 0.50:0.50. The
intramolecular bond lengths and angles of the benzimid-
azole ring in compounds 4 and 5 are comparable to those
reported for other benzimidazole-containing compounds
[14]. In particular, the averaged angle around the nitrogen
atom from the imidazolyl N–CH3 groups (av. angle of
119.9(3)8 for compound 4; av. angles of 119.8(5)8 and
O5–C39–C38 (178.3(6)8) in molecules
respectively.
1
and 2,
The crystal structure of compound 4 is shown in Fig. 4.
The molecules are stacked along b axis with short inter-
molecular contacts between atoms of the aliphatic chain
and benzimidazole rings (Fig. 4b). Along the stack there
are no contacts between benzimidazole and/or benzene
rings. Along the c axis neighboring molecules are linked by
several short contacts (Fig. 4c), forming layers of parallel
stacks in the bc plane. Along the a axis there are no
123

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J Chem Crystallogr (2012) 42:1052–1059
Fig. 4 Crystal structure of compound 4; a View along the stacking axis b; partial views emphasizing the intrastack b and interstack c short
contacts
Fig. 5 Crystal structure of compound 5 viewed along the a axis, showing the short contacts between the symmetry equivalent molecules of 1
(green) and 2 (blue) extending along the cb plane (Color figure online)
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J Chem Crystallogr (2012) 42:1052–1059
1059
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Supplementary Materials
Crystallographic data for the structures of 4 and 5 have
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CCDC-871178, respectively. Copies of the data can be
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Acknowledgments The authors thank Dr. Joaquim Marc¸alo for
Mass Spectroscopy measurements. This work was funded by Fun-
ˆ
dac¸a˜o para a Ciencia e Tecnologia (FCT), Portugal (PTDC/QUI/
102049/2008). GRM thanks the FCT for the ‘‘Ciencia 2008 program.
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