Duncan
Graham
a,
Alan R.
Kennedy
*a,
Callum J.
McHugh
a,
W. Ewen
Smith
a,
William I. F.
David
b,
Kenneth
Shankland
b and
Norman
Shankland
cd
aDepartment of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland
bISIS Facility, CLRC Rutherford Appleton Laboratory, Chilton, Oxfordshire, OX11 0QX, England
cDepartment of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland
dCrystallografX Limited, 38 Queen Street, Glasgow G1 3DX, Scotland. E-mail: a.r.kennedy@strath.ac.uk; Fax: 0141 552 0876; Tel: 0141 548 2016
First published on 22nd October 2003
The crystal structures of three primary products from the selective reduction of 2,4,6-trinitrotoluene (TNT) have been determined by synchrotron X-ray powder diffraction (2-amino-4,6-dinitrotoluene) and single crystal X-ray diffraction (4-amino-2,6-dinitrotoluene and 2-hydroxyamino-4,6-dinitrotoluene). The molecular structure of 2-amino-4,6-dinitrotoluene, including rotational disorder of the 6-nitro group, was subsequently detailed to a higher resolution by a single-crystal analysis. In contrast to the known structures of TNT, the crystal structures of these amino species are dominated by hydrogen-bonded sheets connected via ring stacking, whilst that of 2-hydroxyamino-4,6-dinitrotoluene is dominated by the dual hydrogen-bonding acceptor/donator role of the hydroxyamine group.
Herein, we report on the crystal structures of the main amino and hydroxyamino products formed upon initial selective reduction of TNT, 2-amino-4,6-dinitrotoluene [1], 4-amino-2,6-dinitrotoluene [2] and 2-hydroxyamino-4,6-dinitrotoluene [3]. In TNT contaminated environments these reduction products are formed by the action of bacterial nitroreductase and, although they contribute significantly to the toxicity of contaminated soil, they are necessary intermediates en route to the non-toxic and fully reduced 2,4,6-triaminotoluene.1 The molecular recognition properties of these species are thus of interest with regard to their binding to nitroreductase enzymes as well as to soils and metal surfaces.
1 | 2 | 3 | |
---|---|---|---|
Formula | C7H7N3O4 | C7H7N3O4 | C7H7N3O5 |
Formula weight | 197.16 | 197.16 | 213.16 |
Crystal system | Monoclinic | Triclinic | Monoclinic |
Space group | P21/a |
P![]() |
P21/c |
a/Å | 6.7072(5) | 8.1036(3) | 15.0980(4) |
b/Å | 16.0387(11) | 8.0502(3) | 3.9219(1) |
c/Å | 8.1083(5) | 14.2752(5) | 16.4446(5) |
α/° | 75.097(2) | ||
β/° | 91.160(4) | 74.059(2) | 116.586(2) |
γ/° | 78.453(5) | ||
V/Å3 | 872.07(10) | 847.35(5) | 870.77(4) |
Z | 4 | 4 | 4 |
T/K | 295 | 150 | 150 |
2θ max./° | 50.04 | 54.94 | 57.20 |
Refl. measured | 7058 | 13402 | 10574 |
Refl. unique | 1515 | 3812 | 2227 |
R int | 0.034 | 0.036 | 0.057 |
R1 | 0.0645 | 0.0611 | 0.0417 |
wR2 | 0.1835 | 0.1852 | 0.1120 |
Refl. observed | 1111 | 3221 | 1628 |
Parameters | 143 | 271 | 145 |
GoF | 1.100 | 1.122 | 1.042 |
Initial attempts to solve the structure of 1 from single crystal data collected at 123 K failed. The problem was investigated by collecting X-ray powder diffraction (XRPD) data from a polycrystalline sample of 1 contained in a 1 mm capillary at station BM165 of the European Synchrotron Radiation Facility, Grenoble (λ=
0.8000 Å). At 105 K the sample was extremely line-broadened, whereas at 293 K the pattern exhibited acceptably sharp diffraction features (see A comparison of single crystal and XRPD analyses of crystal structure 1, below). A full data set was therefore collected at 293 K with a view to solving the crystal structure. An appropriate data collection scheme similar to the one described in ref. 6 was employed in order to increase preferentially the quality of short d-spacing reflections and thus increase the probability of solving the structure. The data were indexed to a monoclinic cell [a
=
6.703, b
=
16.031, c
=
8.106 Å, β
=
91.034°, V
=
870.9 Å3] using DICVOL91,7 with promising figures of merit, M(23)
=
30, F(23)
=
161. The volume of the unit cell suggested Z
=
4 and a preliminary examination of the predicted peak positions for this cell against the measured data indicated that the space group was P21/a. Diffraction data in the range 1.5–25.0° 2θ
(equating to ∼1.8 Å resolution) were fitted using the Pawley method in space group P21/a using DASH8 to give a profile χ2 of 7.6, with no significant misfit in the pattern. The crystal structure was then solved using the simulated annealing procedure described previously9 that is now implemented in DASH.
A satisfactory fit to the data could not be obtained with a structural model in which all atoms occupied fully ordered positions. However, the fit to the data improved significantly when the 6-nitro group was treated as being disordered. Each O-atom was allowed to occupy two separate positions with site occupancy factors (SOF’s) constrained to sum to unity. Since the amount of useable diffraction data was insufficient to refine the SOF’s accurately, the structure was solved using different fixed values of the SOF’s and the solution returning the best fit to the data (Table 2, Model 4) was taken to be the most probable solution.
Model | SOF's | Profile χ2 | Intensities χ2 |
---|---|---|---|
1 | 100![]() ![]() |
41 | 203 |
2 | 90![]() ![]() |
36 | 174 |
3 | 80![]() ![]() |
33 | 157 |
4 | 70![]() ![]() |
32 | 154 |
5 | 60![]() ![]() |
33 | 160 |
6 | 50![]() ![]() |
34 | 163 |
A single crystal data collection on 1 was subsequently repeated, but this time with the sample temperature held at 293 K. The structure solved and refined satisfactorily to give SOF's for the O-atoms of the 6-nitro group equal to 79.8(8)∶
20.2(8), in good agreement with the XRPD data. The solution and refinement details were as for 2 and 3, with the O-atoms of the minor disordered component refined isotropically.
1 | 2 | 3 | ||
---|---|---|---|---|
a SOF(O4)![]() ![]() |
||||
![]() |
![]() |
![]() |
||
C2-C1-C6 | 116.5(2) | 111.7(2) | 111.6(2) | 116.1(1) |
C2-C1-C7 | 118.3(2) | 124.0(2) | 124.3(2) | 119.9(1) |
C6-C1-C7 | 125.1(2) | 124.1(2) | 123.9(2) | 124.0(1) |
C1-C2-C3 | 119.4(2) | 125.6(2) | 125.7(2) | 121.3(1) |
C1-C2-N1 | 120.6(2) | 120.0(2) | 119.8(2) | 116.6(1) |
C3-C2-N1 | 120.0(2) | 114.4(2) | 114.6(2) | 122.1(1) |
C2-C3-C4 | 119.9(2) | 119.8(2) | 119.9(2) | 118.3(1) |
C3-C4-C5 | 123.3(2) | 117.3(2) | 117.2(2) | 123.4(1) |
C3-C4-N2 | 118.3(2) | 121.3(2) | 120.9(2) | 118.3(1) |
C5-C4-N2 | 118.4(2) | 121.4(2) | 121.9(2) | 118.2(1) |
C4-C5-C6 | 115.6(2) | 120.1(2) | 119.8(2) | 115.7(1) |
C5-C6-C1 | 125.3(2) | 125.6(2) | 125.8(2) | 125.1(1) |
C5-C6-N3 | 115.2(2) | 114.6(2) | 114.9(2) | 116.2(1) |
C1-C6-N3 | 119.5(2) | 119.9(2) | 119.2(2) | 118.6(1) |
C7C1C2N1 | 0.7(4) | 8.5(3) | −9.5(4) | 1.9(2) |
C7C1C6N3 | −2.6(5) | −8.5(3) | 12.1(4) | 4.0(2) |
C3C4N2O2 | 178.4(3) | — | — | −2.9(2) |
C1C2N1O1 | — | 36.3(3) | −34.6(3) | −169.7(1) |
C1C6N3O4 | −51.2(5)a | −38.2(3) | 38.2(3) | 54.6(2) |
These marked distortions from the ideal sp2 geometry, ranging from 111.6(2)° to 125.8(2)°, are in fact entirely in keeping with expectations based on Domenicano's assessment12 of structural substituent effects in benzene derivatives. Following Domenicano and utilising the angular substituent parameters for –CH3, –NO2and –NH2,12 it can be seen that ten of the twelve independent pairs of predicted and observed internal ring angles in 1 and 2 agree to within three e.s.d's (≈1°). The remaining two observed angles (at C1 and C4 in 2) are both 1.4° narrower than predicted. This discrepancy may be due to a “push–pull” effect with substituents interacting cooperatively through the aromatic ring, such that the overall observed effect is greater than the expected sum of parts.12,13 Similar predictions for angular deviations in 3 are not possible as a search of the Cambridge Structural Database14 found no examples of aromatic hydroxyamines. However, a useful comparison can be made between 1 and 3. Replacing NH2 in 1 with NHOH in 3 causes the internal angle at C2 to widen by 1.9° and the angle at C3 to narrow by 1.6° (the other internal angles agree to within two e.s.d’s). This suggests that the NHOH group has considerably less electron-donating character than NH2,12 as would be expected on simple chemical grounds.
Compound 2 has a non-crystallographic mirror plane running through C7C1C4N2 in Fig. 1, which is rendered to emphasise the non-coplanarity of the nitro groups to the aromatic ring. In 1 and 3 (Fig. 2), the nitro groups ortho to the methyl group are similarly twisted out of the ring plane, while the nitro groups para to methyl are essentially coplanar with the ring (Table 3). This difference is attributable to steric interaction between adjacent methyl and nitro groups. An interesting consequence of the distorted geometry at C1 in 2 is the fact that the methyl C-atom is displaced out of the ring plane by a significant amount in each independent molecule (0.175(3) Å and 0.145(3) Å cf. 0.024(4) Å in 1 and 0.039(2) Å in 3).
![]() | ||
Fig. 1 The structure of one of the crystallographically independent molecules of 2, with ellipsoids rendered at 50% probability. |
![]() | ||
Fig. 2 The structure of 3, with ellipsoids rendered at 50% probability. |
![]() | ||
Fig. 3 A section of the hydrogen-bonded B layer of 2. |
In both 1 and 2 these internally hydrogen-bonded layers are bound to the next layer by offset face-to-face π-stacking. 3 is of a markedly different structural type (Fig. 4). A simple translation along b gives stacks of aromatic rings with a large face-to- face spacing of 3.922 Å (cf. the much shorter face-to-face distances (3.3–3.5 Å) in 1 and 2). Adjacent stacks along the c direction are tilted with respect to each other and are bound into pairs of stacks by the strong O–H⋯O hydrogen-bonds that zig-zag between neighbouring hydroxy groups. The amine H-atom forms a similarly patterned, but longer range, connection to the 4-nitro group of a second neighbouring stack.
![]() | ||
Fig. 4 Crystal packing in 3 viewed along the b axis. |
Given the polynitro nature of TNT and its derivatives reported herein, we expected to find evidence of nitro–nitro O⋯N contacts as described by Wozniak et al.15 However, upon examination of the twenty independent nitro groups of TNT and its derivatives, only those in 2 had O⋯N contacts shorter than (the formally repulsive) O⋯O or O⋯C contacts. The closest such contact occurs in 3
(O5⋯O5*=
2.806 Å
cf. sum of van der Waals radii
=
3.04 Å16 to 3.12 Å17), but, even taken as a group, the formally repulsive O⋯O contacts are typically shorter than the formally attractive N⋯O contacts (N⋯O range 3.041 Å to 3.102 Å). This counter-intuitive behaviour of the nitro group was recently noted by Szczęsna and Urbańczyk-Lipkowska,18 who suggested that short O⋯O contacts were favoured by intramolecular resonance assisted hydrogen-bonding (RAHB). This does not seem applicable to the structures of TNT and its derivatives, which have no intramolecular RAHB. In these compounds, an anisotropic van der Waals radius19 for nitro-O seems a plausible mechanism by which to account for unexpectedly short intermolecular O⋯O contacts.
![]() | ||
Fig. 5 Crystal structure 1, showing the disordered 6-nitro group projecting between parallel sheets of molecules. |
A comparison of the XRPD and single-crystal structures (Fig. 6) shows excellent agreement with respect to the position and orientation of the molecule in the unit cell, and the orientation of the 6-nitro group at higher occupancy. Unsurprisingly, the orientation of the lower occupancy 6-nitro group is less well determined. Subsequent structure determinations that included a preferred orientation correction improved the overall fit to the data (with a decrease in profile χ2 from ∼32 to ∼26), but did not alter the rank order of the disordered models (as listed in Table 2) or improve on the orientation of the lower occupancy 6-nitro group.
![]() | ||
Fig. 6 The crystal structure of 1 determined from XRPD data (red) overlaid upon the corresponding single-crystal solution (green). Each O-atom of the 6-nitro group is disordered between high occupancy (80% single crystal; 70% XRPD) and low occupancy sites and the two structure solutions are in good agreement on the position of the higher occupancy site. Note that the H-atoms of the 1-methyl group in the XRPD solution have been placed in calculated positions. |
Other authors have shown that the results obtained from global optimisation can sometimes indicate the presence of conformational disorder.20,21 Huq and Stephens,21 for example, found that two distinct conformations of ranitidine gave equally good fits to XRPD data obtained from a polycrystalline sample of ranitidine hydrochloride and went on to show that these matched the conformations found in the disordered structure determined by single crystal diffraction. Here, we have taken the approach that residual misfit in the diffraction pattern derived from a fully ordered model might well arise from disorder in the actual structure and have used global optimisation to prove this hypothesis by simultaneously optimising models that include contributions from atoms with fractional occupancies.
Large deformations from ideal sp2 geometry are observed in the aromatic rings of 1, 2 and 3 and this is entirely in line with expectations based on a knowledge of structural substituent effects in benzene derivatives. The introduction of stronger hydrogen-bond donors to TNT results in solid-state structures with layer architectures as opposed to the herring bone motifs seen in TNT itself. 1 and 2 form hydrogen bonded sheets connected via N–H and C–H hydrogen-bond donation to nitro acceptors. These sheets are held to each other by π-stacking and by dipole–dipole interactions between nitro groups. The stronger hydrogen-bonding in 3 (with its donating and accepting NHOH group) gives a different structure dominated by NHOH–NHOH dimers.
Footnote |
† CCDC reference numbers 220762–220764. See http://www.rsc.org/suppdata/nj/b3/b309792g/ for crystallographic data in .cif or other electronic format. |
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2004 |