Structural studies of some push-pull N-arylbenzazoles

Article abstract of DOI:10.1039/c0dt00029a

X-Ray crystal structures, and calculated structures (at B3LYP/6-31G level) are reported for seven N-arylbenzazoles (two carbazoles, indoles and benzimidazoles, and one indazole) bearing electron withdrawing groups in the 2-position of the N-aryl ring. The

Full text of DOI:10.1039/c0dt00029a

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www.rsc.org/dalton | Dalton Transactions
Structural studies of some push–pull N-arylbenzazoles†‡
Lynne A. Crawford, Maria Ieva, Hamish McNab* and Simon Parsons*
Received 25th February 2010, Accepted 11th June 2010
First published as an Advance Article on the web 2nd July 2010
DOI: 10.1039/c0dt00029a
X-Ray crystal structures, and calculated structures (at B3LYP/6-31G level) are reported for seven
N-arylbenzazoles (two carbazoles, indoles and benzimidazoles, and one indazole) bearing electron
withdrawing groups in the 2-position of the N-aryl ring. The structures are markedly non-planar by
rotation around the N-aryl bond, with the substituent in most cases lying s-E in relation to the N-aryl
bond; intermolecular electrostatic interactions in the crystal rationalise the two examples in which an
s-Z conformation is observed. A large interplanar angle between the benzazole and the N-aryl planes is
associated with a small interplanar angle between the planes of the N-aryl group and the substituent
and vice versa.
way in which the systems cope with these competing influences.
Introduction
In the solid-state, crystal packing forces can provide a further
complication, and so the X-ray crystallographic studies have been
complemented by calculations of the gas-phase structures, made
at B3LYP/6-31G level.1
We report an analysis of the X-ray crystal structures of a range
of push–pull benzazole derivatives 1–7. These compounds all have
a benzazole core [either carbazole (1 and 2), indole (3 and 4),
benzimidazole (5 and 6) or indazole (7)] with an N-aryl group
bearing a strong electron withdrawing group [either carbomethoxy
(1, 3 and 5) or nitro (2, 4, 6 and 7)] in the 2-position of the N-aryl
ring.
Results and discussion
General
Compounds 1–4 and 6–7 were made from the corresponding
azole by standard SNAr procedures.2–6 Compound 5 required a
three-step procedure in which the final step was cyclisation of N-
(2-carbomethoxyphenyl)-o-phenylenediamine7 with formic acid.8
1
This compound shows unusual H NMR behaviour (ESI‡) in
which broadened areas of the spectrum are sharpened both at
higher and lower temperatures. This may be due to exchange
between two identical sites.
(1)
Plots of the X-ray crystal structures of 1–7 are given in
Fig. 1–7, respectively, and diagrams of corresponding calculated
structures are reported in the ESI.‡ All are significantly non-
planar, suggesting that push–pull conjugation is not a significant
feature in their structures. The solid-state structure of 1 shows
eight molecules in the unit cell at atmospheric pressure and its
pressure dependent polymorphism has been previously reported.2
The structure of 3 is disordered with ca. 10% showing an s-E
configuration around the N-aryl bond (ESI‡).
For maximum delocalisation of the azole nitrogen atom lone
pair, through to the electron withdrawing group, the systems would
ideally be planar. In compounds 1–7, this ideal state is impossible
owing to the peri-interactions of the N-aryl group and the fused
benzene ring of the benzazole, exacerbated by the presence of a
bulky ortho-substituent. It was therefore of interest to correlate the
Bond lengths and angles
Bond lengths and angles of 1–7 are generally unexceptional. The
bond lengths between the azole nitrogen atoms and the N-aryl
rings might have been expected to be short due to delocalisation.
Those of the eight molecules of 1 fall in the range 1.410(5)–
˚
˚
1.445(5) A (average 1.432 A); the average is close to the value for N-
School of Chemistry, The University of Edinburgh, West Mains
Road, Edinburgh, UK EH9 3JJ UK. E-mail: H.McNab@ed.ac.uk,
S.Parsons@ed.ac.uk; Fax: +44 131 650 4743; Tel: +44 131 650 4718; +44
131 650 5804
† This paper is dedicated to Professor David Rankin, in recognition of his
seminal contributions to structural science.
‡ Electronic supplementary information (ESI) available: NMR data for 5,
crystallographic data, Cartesian coordinates, calculated energies. See DOI:
10.1039/c0dt00029a
9
˚
phenylcarbazole itself (1.427 and 1.420 A, for the two molecules
in the unit cell). There is no obvious correlation between the C–N
bond lengths and the interplanar angle between the carbazole and
the N-aryl group. For compounds 2–7, the C–N bond length is in
˚
the range 1.409(5)–1.4282(18) A.
For compounds 2, 4 and 6, the lengths of the two N–O
bonds in the nitro group differ by around 1s or less in the
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Fig. 2 Plots of 2 showing (a) the crystallographic numbering scheme and
(b) a side view in which the heterocyclic ring is approximately orthogonal
to the plane of the paper.
Fig. 1 Plots of one of the eight molecules of 1 showing (a) the
crystallographic numbering scheme and (b) a side view in which the
heterocyclic ring is approximately orthogonal to the plane of the paper.
˚
nitro groups differ by ≥0.035 A in less than 1% of hits; although
X-ray structure; however the situation is very different for the
unusual, this situation is therefore not unprecedented.
indazole derivative 7, in which these parameters differ by some 5s
˚
˚
[1.196(5) A and 1.231(5) A]. This difference is not reflected in the
Interplanar angles
˚
˚
calculated structure (N111–O112 1.260 A; N111–O111 1.265 A.
There are no obvious inter- or intra-molecular interactions to
account for this difference in the crystal; indeed, if the two N–
O distances are strongly restrained to be equal, R1 increases by
only 0.004. It is possible that the high mosacity in the crystal used
for data collection compromised the peak shapes, degrading the
accuracy of the integrated intensities. A search of the Cambridge
Crystallographic database (ESI‡) reveals that the N–O bonds of
Compounds 1–7 are composed of three, essentially planar, sub-
units, viz the benzazole (or dibenzazole) ring, the N-aryl group
and the nitro (or carbomethoxy) substituent. It is clear from the
side views shown in Fig. 1–7, that there are substantial angles
between the planes of the benzazole and the N-aryl group, and
between those of the N-aryl group and the substituent (Table 1).
These results are broadly supported by the calculations (ESI‡).
Table 1 Interplanar angles (◦) for 1–8
Benzazole-N-aryl (X-ray)
Benzazole-N-aryl (calc.)a
N-aryl-substituent (X-ray)
N-aryl-substituent (calc.)a
1b
65.78(13)
78.09(14)
59.81(14)
60.04(13)
62.42(13)
80.77(13)
81.12(13)
74.05(14)
61.11(5)
115.13(8)
47.17(4)
116.40(3)
68.64(5)
63.96
33.6(2)
21.8(2)
39.3(2)
38.9(2)
38.4(2)
21.7(2)
21.7(2)
20.7(2)
40.48(9)
37.21(6)
41.11(6)
34.49(3)
47.31(17)
47.35(27)
18.64
2
56.70
54.72
70.54
66.59
64.25
47.00
32.94
10.75
33.77
21.86
24.66
35.55
3c
4
5d
6
7
40.29(11)
a Dihedral angles reported; calculated at B3LYP/6-31G level. b Eight independent molecules in the unit cell. c Major conformer; substituent is s-Z.
d Substituent is s-Z.
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Fig. 4 Plots of 4 showing (a) the crystallographic numbering scheme and
(b) a side view in which the heterocyclic ring is approximately orthogonal
to the plane of the paper.
similar electrostatic potentials, with an electron rich region close
to the s-Z carbonyl group creating a pocket for the electron
deficient region of the N-aryl group, thus controlling the packing
forces.
Fig. 3 Plots of the major rotamer of 3 showing (a) the crystallographic
numbering scheme and (b) a side view in which the heterocyclic ring
is approximately orthogonal to the plane of the paper. The coordinates
plotted in this figure have been inverted relative to the asymmetric unit for
consistency with other figures in this paper. This operation is consistent
with the space group.
Data for the X-ray structures shown in Table 1 suggest that
structures with a large benzazole-N-aryl angle tend to show a small
N-aryl-substituent angle. These parameters are plotted in Fig. 10
and show modest correlation with a straight line fit (R2 = 0.64).
The point furthest from the line is for the 2-methylbenzimidazole
6, where increased steric factors may introduce further complica-
tions. If this point is ignored, R2 improves to 0.85. The correlation
is also somewhat better if the eight conformers of 1 are treated
separately from 2–7 (R2 0.91) (ESI‡). Calculations on 1, in which
the benzazole–N-aryl angle is fixed, also show a relation between
the two interplanar angles though in this case the correlation
shows a very good exponential fit (R2 0.99). Unfortunately, the
experimental data do not cover a wide enough range (restricted
to benzazole–N-aryl interplanar angles of ca. 40–80◦) for any
exponential correlation to become evident. Overall, these results
suggest that in the cases where conjugation from the benzazole
nitrogen atom is reduced by a large interplanar angle, the systems
can compensate by increasing the interaction between the N-
aryl group and the substituent, by reducing these interplanar
angles.
In all cases except 7 (which has only a lone pair on the site
adjacent to the N-aryl group) the angle between the benzazole and
the N-aryl ring is greater than that between the N-aryl group and
the substituent. The carbazole 1 and the 2-methylbenzimidazole 6,
with non-hydrogen substituents on the site adjacent to the N-aryl
group, correspondingly have the largest benzazole-N-aryl angle.
Although the same trends are evident, there is little quantitative
correspondence between the calculated and X-ray interplanar
angles.
In all of the calculated structures, and in most of the solid-state
structures, the position of the substituent is s-E with respect to the
N-C(aryl) bond. However, in the two carbomethoxy compounds,
3 (major conformer) and 5, an s-Z configuration is adopted so
that the substituent lies in the direction of the fused benzene ring
(Fig. 3 and 5). Calculations on 3 suggest that the energy surface
created by N-aryl bond rotation is very flat (ESI‡) (difference
of less than 7 kJ mol-1 between energy maximum and minimum
in the dihedral angle range 30–150◦) and so crystal packing
could readily account for these differences. Indeed, it is likely
that electrostatic interactions are responsible for the conformation
of these molecules in the crystal. Thus the Hirshfield surfaces
shown in Fig. 8 and 9 demonstrate that 3 and 5 show very
Conclusions
We have shown, by consideration of a range of related
N-arylbenzazole structures with electron withdrawing sub-
stituents in the 2-position of the aryl ring, that the non-planarity
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Fig. 6 Plots of 6 showing (a) the crystallographic numbering scheme and
(b) a side view in which the heterocyclic ring is approximately orthogonal
to the plane of the paper.
Fig. 5 Plots of 5 showing (a) the crystallographic numbering scheme and
(b) a side view in which the heterocyclic ring is approximately orthogonal
to the plane of the paper.
ether (3 ¥ 50 cm3), dried (MgSO4) and the solvent removed under
red◦uced pressure to give 5 (60%) mp 88–89 ◦C (from toluene) [lit.,8
3
4
5
88 C] dH (250 MHz) 8.08 (1H, ddd, J 7.7, J 1.7, J 0.3), 8.00
3
3
4
(1H, br s), 7.85 (1H, br d, J 6.9), 7.70 (1H, td, J 7.5, J 1.6),
3
4
of the systems severely limits push–pull conjugation between the
nitrogen atom of the azole and the electron withdrawing sub-
stituent. The unexpected s-Z configurations of the carbomethoxy
compounds 3 and 5 in the solid-state (not reproduced as global
minima in the calculated structures) may be explained by inter-
molecular electrostatic interactions. Interplanar angles between
the benzazole and the N-aryl group, and between the N-aryl group
and the substituent are linearly related in the solid-state.
7.58 (1H, td, J 7.7, J 1.4), 7.14–7.48 (4H, m) and 3.46 (3H, s);
dC (63 MHz) 165.63 (quat), 143.32, 135.08 (quat), 133.19, 131.82,
128.95, 128.28, 123.46, 122.35, 120.22, 109.68 and 52.29 (CH3) (3
quaternaries missing – see ESI‡); m/z 252 (M+, 100%), 220 (55),
192 (39), 166 (15), 140 (13), 92 (32), 83 (15) and 76 (22). This
compound has been reported in a patent.8
2-Methyl-1-(2-nitrophenyl)-1H-benzimidazole 6
Experimental
2-Methylbenzimidazole (0.01 mol) and 2-fluoronitrobenzene
◦
(0.01 mol) were heated at 125 C for 8 h in DMF (15 cm3)
NMR spectra were recorded for solutions in CDCl3. Chemical
shifts are quoted relative to TMS and coupling constants are
given in Hertz. 13C NMR signals refer to one CH resonance
unless otherwise stated. Mass spectra were recorded under electron
impact conditions.
Compounds 1,2 2,3 3,4,5 44 and 76 were prepared according to
literature procedures.
with stirring, in the presence of anhydrous potassium carbonate
(0.01 mol). The reaction mixture was poured into water (100 cm3)
and extracted with dichloromethane (6 ¥ 30 cm3). The combined
organic layers were washed with water (3 ¥ 15 cm3), dried (MgSO4)
and concentrated in vacuo to provide 6 (78%), mp 110–111 ◦C;
(Found: C, 66.05; H, 4.25; N, 16.75. C14H11N3O2 requires C, 66.4;
3
4
H, 4.35; N, 16.6%); dH (360 MHz) 8.21 (1H, dd, J 8.1, J 1.5),
3
4
7.87 (1H, td, J 7.8, J 1.6), 7.75–7.80 (2H, m), 7.54 (1H, dd,
1-(2-Carbomethoxyphenyl)-1H-benzimidazole 5
4
3
4
3J 7.8, J 1.5), 7.18–7.32 (2H, m), 6.92 (1H, dd, J 8.1, J 1.1)
and 2.47 (3H, s); dC (90 MHz) 152.04 (quat), 147.31 (quat), 143.23
(quat), 136.83 (quat), 134.87, 131.53, 131.05, 130.03 (quat), 126.35,
123.54, 123.23, 119.79, 109.43 and 14.47 (CH3); m/z 253 (M+,
57%), 236 (8), 206 (23), 181 (42), 132 (100), 104 (28), 91 (39) and
77 (40).
Methyl 2-(2-aminophenylamino)benzoate7 (1 mmol) and formic
acid (10 cm3) were heated for 2 h at 130 ◦C. The solution was
cooled and ether was added. The solution was extracted with HCl
(2 M, 3 ¥ 50 cm3). The aqueous layer was made alkaline with
aqueous potassium carbonate solution and then extracted with
7150 | Dalton Trans., 2010, 39, 7147–7152
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Fig. 9 (a) Views of Hirshfeld surfaces mapped with the individual
electrostatic potentials of 5 and (b) a view showing how the electron rich
region close to the carbonyl oxygen atom of the ester group creates a
pocket suitable for the more electron-deficient area of the N-aryl group of
an adjacent molecule. Colours and ranges were the same as Fig. 8.
Fig. 7 Plots of 7 showing (a) the crystallographic numbering scheme and
(b) a side view in which the heterocyclic ring is approximately orthogonal
to the plane of the paper. The coordinates plotted in this figure have been
inverted relative to the asymmetric unit for consistency with other figures
in this paper. This corresponds to an inversion twinning operation.
Fig. 10 Plot of benzazole–N-aryl interplanar angle versus
N-aryl-substituent interplanar angle for
1 (8 molecules) and 2–7
(X-ray data).
blue corresponding to net positive charge. Wavefunctions were
calculated using STO-3G basis sets.
Crystal structures
Crystallographic data for compounds 1–7 are available on the
Cambridge Database, having been previously deposited by us.
REFCODES are 1 (CARZIF), 2 (SEMTAG), 3 (CARZOL), 4
(PELDUG), 5 (CARZUR), 6 (PELFES) and 7 (PELDOA). Data
for 1 have been previously published.2 Crystal and refinement
statistics are recorded as Table 1 in the ESI.‡ Searches of the
Cambridge Database11 used version 5.31 with updates to Novem-
ber 2009. Structures were solved and refined using SHELXTL,12
and visualised with XP12 and MERCURY.13 Structure analyses
were accomplished with PLATON.14
Fig. 8 (a) Views of Hirshfeld surfaces mapped with the individual
electrostatic potentials of the main conformer of 3 and (b) a view showing
how the electron rich region close to the carbonyl oxygen atom of the ester
group creates a pocket suitable for the more electron-deficient area of the
N-aryl group of an adjacent molecule. Positive regions are shown in blue,
and negative in red. The range mapped was 0.05 au.
Calculations
Calculations were carried out at B3LYP/6-31G level using the
Gaussian set of programs.1 Tables of coordinates and energies are
given in the ESI.‡
Hirshfeld surface plots10 were calculated using the program
CrystalExplorer.10c Electrostatic potentials were mapped over the
range 0.05 au with red corresponding to net negative charge and
Acknowledgements
We are grateful to EPSRC and to EaStChem for the award
of Research Studentships (to L. A. C. and M. I., respec-
tively). We also acknowledge Dr Alice Dawson and the late
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Dr Andrew Parkin, for their assistance in the determination
of some of the crystal structures. This work has made use of
the resources provided by the EaStCHEM Research Computing
Facility (http://www.eastchem.ac.uk/rcf). This facility is partially
supported by the eDIKT initiative (http://www.edikt.org).
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7152 | Dalton Trans., 2010, 39, 7147–7152
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