3,3′-Dinitro­bis­phenol A

Sainath Babu; Chintan Pathak; Satvika Uppu; Conrad Jones; Frank R Fronczek; Rao M Uppu

doi:10.1107/S1600536811035458

. 2011 Sep 3;67(Pt 10):o2556–o2557. doi: 10.1107/S1600536811035458

3,3′-Dinitrobisphenol A

Sainath Babu ^a, Chintan Pathak ^a, Satvika Uppu ^b, Conrad Jones ^b, Frank R Fronczek ^c, Rao M Uppu ^a,^b,^*

PMCID: PMC3201564 PMID: 22065402

Abstract

The title compound [systematic name: 2,2′-dinitro-4,4′-(propane-2,2-diyl)diphenol], C₁₅H₁₄N₂O₆, crystallizes with two molecules in the asymmetric unit. Both have a trans conformation for their OH groups, and in each, the two aromatic rings are nearly orthogonal, with dihedral angles of 88.30 (3) and 89.62 (2)°. The nitro groups are nearly in the planes of their attached benzene rings, with C—C—N—O torsion angles in the range 1.21 (17)–4.06 (17)°, and they each accept an intramolecular O—H⋯O hydrogen bond from their adjacent OH groups. One of the OH groups also forms a weak intermolecular O—H⋯O hydrogen bond.

Related literature

For background information on bisphenol A and its uses and environmental effects, see: Hong-Mei & Nicell (2008 ▶); Lang et al. (2008 ▶); Masuda et al. (2005 ▶); Murrell (2006 ▶); Nakamura et al. (2011 ▶); Richter et al. (2007 ▶); Sakuyama et al. (2003 ▶); Toyoizumi et al. (2007 ▶); Vandenberg et al. (2009 ▶); Wang et al. (2007 ▶). For related structures, see: Bel’skii et al. (1983 ▶); Goldberg et al. (1991 ▶); Lim & Tanski (2007 ▶); Okada (1996 ▶); Wang et al. (1982 ▶). For graph-set analysis, see: Etter (1990 ▶).

Experimental

Crystal data

C₁₅H₁₄N₂O₆
M _r = 318.28
Triclinic,
a = 8.3989 (5) Å
b = 12.5738 (7) Å
c = 15.3757 (9) Å
α = 66.967 (2)°
β = 76.565 (2)°
γ = 77.833 (2)°
V = 1440.34 (14) Å³
Z = 4
Cu Kα radiation
μ = 0.98 mm⁻¹
T = 90 K
0.30 × 0.24 × 0.15 mm

Data collection

Bruker Kappa APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2004 ▶) T _min = 0.758, T _max = 0.867
17716 measured reflections
5276 independent reflections
5010 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.092
S = 1.04
5276 reflections
432 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811035458/hb6392sup1.cif

e-67-o2556-sup1.cif^{(27.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811035458/hb6392Isup2.hkl

e-67-o2556-Isup2.hkl^{(258.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811035458/hb6392Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O3	0.88 (2)	1.80 (2)	2.5947 (14)	149.6 (18)
O2—H2⋯O5	0.844 (19)	1.856 (18)	2.5955 (13)	145.3 (16)
O2—H2⋯O5ⁱ	0.844 (19)	2.380 (18)	2.9832 (13)	128.8 (14)
O7—H7⋯O9	0.91 (2)	1.72 (2)	2.5667 (17)	154 (2)
O8—H8⋯O11	0.85 (2)	1.81 (2)	2.5747 (14)	148.8 (19)

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Symmetry code: (i) Inline graphic .

Acknowledgments

This publication was made possible by National Institutes of Health Grant No. P20RR16456 (the BRIN Program of the National Center for Research Resources), National Science Foundation Grant No. HRD-1043316 (the HBCU-UP ACE implementation program), and the US Department of Education Grant No. PO31B040030 (Title III, Part B - Strengthening Historically Black Graduate Institutions). The contents of this publication are solely the responsibility of authors and do not necessarily represent the official views of the NSF, NIH or the US Department of Education.

supplementary crystallographic information

Comment

Bisphenol A (BPA), a persistent organic pollutant in urban environments, ranks among the top 2% of high volume chemicals produced in the United States (Vandenberg et al., 2009). It is used in the making of printing materials, polycarbonate plastics and resins, all of which can become portals for human exposure. Studies using experimental animals have repeatedly shown that low level exposures to BPA can cause liver and brain damage, impaired insulin secretion, and a dysfunctional reproductive system (Richter et al., 2007). A recent report by Lang and colleagues (Lang et al., 2008), who analyzed the results of the first major epidemiologic study conducted by the National Health and Nutrition Examination Survey (NHANES) in 2003–2004, suggests wide-spread exposure to BPA in noninstitutionalized US populations where urinary levels of BPA are positively associated with higher incidence of cardiovascular diseases, diabetes, and abnormal concentrations of liver enzymes.

Bisphenol A can under go metabolic transformation by enzymes of cytochrome P450 system (Nakamura et al., 2011), peroxidases (Hong-Mei & Nicell, 2008; Sakuyama et al., 2003), and neutrophil and macrophage derived oxidants such as hypochlorous acid (Wang et al., 2007) and peroxynitrite (B.Martin, S. Babu, C. Pathak & R. Uppu, unpublished work). It is likely that the various putative metabolites of BPA formed in these reactions can act as secondary toxins and relay, at least, in part, the toxic effects of BPA. It has been shown, for instance, that nitrated and chlorinated products of BPA, which could be formed in vivo in hypochlorous acid and peroxynitrite mediated oxidations, exhibit higher toxicity than BPA itself and often elaborate mutagenic and/or genotoxic effects (Masuda et al., 2005; Toyoizumi et al., 2007). To better understand the molecular targets for nitrated products of BPA and the likely disruption of endocrine function, in the present report we have synthesized 3,3'-dinitrobisphenol A, (I), using acetone/nitric acid mixtures and characterized the product by IR, NMR, and GC-MS following necessary purification and recrystallization from ethanol. The structural co-ordinates obtained from the crystallographic studies are presented here with the anticipation that they could be used in computational studies aimed at understanding the molecular docking and energetics of binding to possible targets such as the androgen and estrogen receptors and serum proteins.

The two independent molecules in the asymmetric unit are illustrated in Fig. 1. In both, the conformation is trans, placing the OH groups on the opposite sides of the molecule. The phenyl groups are twisted with respect to the central C(CH₃)₂ group such that they are nearly perpendicular. The dihedral angle formed by the two phenyl planes is 89.62 (2)° in the molecule containing C1 through C15 and 88.30 (3)° in the second molecule. The nitro groups lie near the planes of the phenyl groups and form intramolecular hydrogen bonds with the adjacent OH groups. The C1—C2—N1—O3 torsion angle is 4.06 (17)°, and analogous torsion angles involving the other nitro groups are 2.11 (17)° for N2, 3.73 (18)° for N3, and 1.21 (17)° for N4. The intramolecular hydrogen bonds have O···O distances in the range 2.5667 (17) - 2.5955 (13) Å. One OH group, O2 also has an intermolecular acceptor at a longer distance, O2···O5 (at 2 - x, -y, 2 - z), 2.9832 (13) Å, forming centrosymmetric R²₂(4) rings (Etter, 1990), as shown in Fig. 2.

Similar intramolecular hydrogen bonds are found in the crystal structure of 2,2',6,6'-tetranitro-4,4-isopropylidenediphenol (Wang et al., 1982), which has two nitro groups adjacent to each OH. As in the title structure, the hydrogen- bonded nitro group lies near the plane of the phenyl group, while the other nitro group twists 46.5 (3)° out of plane.

Experimental

Chemicals and solvents used in the synthesis and recrystallization of 3,3'-dinitrobisphenol A were obtained as follows: BPA and DMSO-d6 from Sigma-Aldrich (St. Louis, MO); HNO3 (70% w/v; density: 1.42 g/ml) from Fisher Scientific (Fairlawn, NJ); acetone from Mallinckrodt (Phillipsburg, NJ); and TRI-SIL/TBT reagent (a special formulation of silylation mixture consisting of TMS-imidazole with bis-TMS-acetamide and trimethylchlorosilane) from Pierce (Rockford, IL). Water used was ultrapure with resistance 18.2 MO/cm.

Nitration of BPA was performed according to the method of Murrell (2006) with minor modifications (Fig. 3). Briefly, BPA (5.1 g; 22.4 mmol) was dissolved in 50 ml of acetone in a round-bottom flask and HNO₃ (4.2 ml; 66.3 mmol) was added drop-wise over a period of 30 min with continuous mixing. Throughout the course of nitration, the temperature of the flask was maintained at 0–5°C using an ice-water bath. At the end of HNO₃ addition, the reaction mixture was brought to room temperature over a period of 1 h, while the contents were continuously stirred and then quenched in cold water. The yellow/orange precipitate was filtered and washed with an ice cold mixture of acetone and water (3:1). The precipitate was dried for 24 h at 37°C and purified further by recrystallization from ethanol.

The nitro product of BPA was dissolved in DMSO-d6 and analyzed for ¹H– and ¹³C-NMR spectra using a Bruker Avance II 400 MHz spectrometer. The ¹H-NMR showed peaks with chemical shifts (in p.p.m.) at δ: 10.86 (s, 2H), 7.71 (d, J = 2.54 Hz, 2H), 7.32 (dd, J = 2.50 and 2.50 Hz, 2H), 7.01(d, J = 8.55 Hz, 2H), and 1.60 (s, 6H) (Fig. 4). ¹³C-NMR spectrum showed chemical shifts (in p.p.m.) at δ: 30.28, (–CH₃); 41.76 (C7), 119.62(C1), 122.51(C4), 134.55 (C6), 136.57(C3), and 141.01(C5), 150.83 (C2) (Fig. 5). The chemicals shifts and assignments of C and H shown are consistent with the structure shown in Fig. 1. Following silylation using the TRI-SIL/TBT reagent, the nitroproduct of BPA was analyzed by GC-MS using an Agilent Technologies 7890 A gas chromatograph equipped with an Agilent Technologies 5975 C V L triple-axis MSD and a HP-5MS capillary column (length: 30 m; internal diameter: 0.25 mm; and film thickness: 0.25 µm). Helium was used as the carrier gas (total flow: 3 ml/min; split ratio: 1:50) with temperature programming as follows: 40 °C for 2 min (isothermal); 20 °C/min up to 150 °C (ramp 1), 150 °C for 3 min (isothermal); 20 °C/min up to 300 °C (ramp 2), and 300 °C for 2 min (isothermal) (total run time: 20 min; temperature of the inlet port: 270°C). Under these conditions, the silylated product of nitro-BPA resolved as a single peak with a retention time of 19.61 min (Fig. 6). The ion chromatogram of the product eluting at 19.61 min showed a molecular ion (M^+.) at m/z 462 (2.14%; relative to the base peak) and other fragments at m/z values of 447 (100%; base peak; [M-15]⁺ or [M—CH₃]⁺), 252 (2.64%; [M-210]⁺ or [M—C₉H₁₂NO₃Si]⁺), and 73 (42.54%; [M-389]⁺ or [M—C₁₈H₂₁N₂O₆Si]⁺ (Fig. 7). The proposed routes of fragmentation of the molecular ion of silylated 3,3'-dinitrobisphenol A, giving various daughter ions, are given in Fig. 8.

Yellow needles of 3,3'-dinitrobisphenol A were obtained from ethanol.

Figures

Fig. 1. — The molecular structure of (I) with ellipsoids at the 50% level, with H atoms having arbitrary radius.

Fig. 2. — The unit cell, showing hydrogen bonding.

Fig. 3. — Nitration of bisphenol A by nitric acid/acetone mixtures at 0–5°C.

Fig. 4. — 1H-NMR spectrum of 3,3'-dinitrobisphenol A.

Fig. 5. — 13C-NMR spectrum of 3,3'-dinitrobisphenol A.

Fig. 6. — Ion chromatogram of the silylated product of 3,3'- dinitrobisphenol A.

Fig. 7. — Electron ionization fragmentation of the silylated product of 3,3'-dintrobisphenol A.

Fig. 8. — Proposed routes of fragmentation of the molecular ion of silylated 3,3'-dinitrobisphenol A.