research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 12| December 2014| Pages 456-461
doi:10.1107/S1600536814023769

Crystal structures of 2-meth­­oxy­isoindoline-1,3-dione, 1,3-dioxoisoindolin-2-yl methyl carbonate and 1,3-dioxo-2,3-di­hydro-1H-benzo[de]isoquinolin-2-yl methyl carbonate: three anti­convulsant compounds

Fortune Ezemobi,a Henry North,b Kenneth R. Scott,c Anthohy K. Wutohc and Ray J. Butcherd*

aDepartment of Biology, College of Arts & Sciences, Howard University, 415 College Street NW, Washington, DC 20059, USA, bDepartment of Pharmaceutical Sciences, College of Pharmacy, Harding University, 915 E. Market Avenue, Box 12330, Searcy, Arkansas 72149, USA, cDepartment of Pharmaceutical Sciences, College of Pharmacy, Howard University, 2300 4th Street, NW, Washington, DC 20059, USA, and dDepartment of Chemistry, Howard University, 525 College Street NW, Washington, DC 20059, USA
*Correspondence e-mail: rbutcher99@yahoo.com

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 30 September 2014; accepted 28 October 2014; online 5 November 2014)

The title compounds, C9H7NO3, (1), C10H7NO5, (2), and C14H9NO5, (3), are three potentially anti­convulsant compounds. Compounds (1) and (2) are isoindoline derivatives and (3) is an iso­quinoline derivative. Compounds (2) and (3) crystallize with two independent mol­ecules (A and B) in their asymmetric units. In all three cases, the isoindoline and benzoiso­quinoline moieties are planar [r.m.s. deviations are 0.021 Å for (1), 0.04 and 0.018 Å for (2), and 0.033 and 0.041 Å for (3)]. The substituents attached to the N atom are almost perpendicular to the mean planes of the heterocycles, with dihedral angles of 89.7 (3)° for the N—O—Cmeth­yl group in (1), 71.01 (4) and 80.00 (4)° for the N—O—C(=O)O—Cmeth­yl groups in (2), and 75.62 (14) and 74.13 (4)° for the same groups in (3). In the crystal of (1), there are unusual inter­molecular C=O⋯C contacts of 2.794 (1) and 2.873 (1) Å present in mol­ecules A and B, respectively. There are also C—H⋯O hydrogen bonds and π–π inter­actions [inter-centroid distance = 3.407 (3) Å] present, forming slabs lying parallel to (001). In the crystal of (2), the A and B mol­ecules are linked by C—H⋯O hydrogen bonds, forming slabs parallel to (10-1), which are in turn linked via a number of π–π inter­actions [the most significant centroid–centroid distances are 3.4202 (7) and 3.5445 (7) Å], forming a three-dimensional structure. In the crystal of (3), the A and B mol­ecules are linked via C—H⋯O hydrogen bonds, forming a three-dimensional structure, which is consolidated by π–π inter­actions [the most significant inter-centroid distances are 3.575 (3) and 3.578 (3) Å].

CCDC references: 1031391; 1031392; 1031393

1. Chemical context

Traumatic brain injury (TBI) is a neurological disorder that is defined as damage to the brain resulting from external mechanical force, including accelerating, decelerating and rotating forces (Langlois et al., 2003[Langlois, J. A., Kegler, S. R., Butler, J. A., Gotsch, K. E., Johnson, R. L., Reichard, A. A., Webb, K. W., Coronado, V. G., Selassie, A. W. & Thurman, D. J. (2003). MMWR Surveill. Summ. 52, 1-20.], 2005[Langlois, J. A., Rutland-Brown, W. & Thomas, K. E. (2005). J. Head Trauma. Rehabil. 20, 229-238.]; Ashman et al., 2006[Ashman, T. A., Gordon, W. A., Cantor, J. B. & Hibbard, M. R. (2006). Mt Sinai J. Med. 73, 999-1005.]; Coronado et al., 2011[Coronado, V. G., Xu, L., Basavaraju, S. V., McGuire, L. C., Wald, M. M., Faul, M. D., Guzman, B. R. & Hemphill, J. D. (2011). MMWR Surveill. Summ. 60, 1-32.]). TBI also exacerbates seizure severity in individuals with pre-existing epilepsy (Ferraro et al., 1999[Ferraro, T. N., Golden, G. T., Smith, G. G., St Jean, P., Schork, N. J., Mulholland, N., Ballas, C., Schill, J., Buono, R. J. & Berrettini, W. H. (1999). J. Neurosci. 19, 6733-6739.]), being one example of the process of epileptogenesis (Christensen et al., 2009[Christensen, J., Pedersen, M. G., Pedersen, C. B., Sidenius, P., Olsen, J. & Vestergaard, M. (2009). Lancet, 373, 1105-1110.]). In this context, it has been demonstrated that early lesions in the central nervous system (CNS) alter the transport dynamic of the blood–brain barrier (BBB) and deteriorate the balance of the inhibitory and excitatory neurotransmitter system (Scantlebury et al., 2005[Scantlebury, M. H., Gibbs, S. A., Foadjo, B., Lema, P., Psarropoulou, C. & Carmant, L. (2005). Ann. Neurol. 58, 41-49.]]. This neuronal dysfunction predisposes to subsequent development of spontaneous recurrent seizures in the presence of prior subtle brain malformation (Love, 2005[Love, R. (2005). Lancet Neurol. 4, 458.]].

[Scheme 1]

TBI is the major cause of death in young individuals (14–24 years) from industrialized countries, with head injuries accounting for 25–33% of all trauma-related deaths (Abdul-Muneer et al., 2014[Abdul-Muneer, P. M., Namas, C. & James, H. (2014). Mol. Neurobiol. doi: 10.1007/s12035-014-8752-3.]). Disorders like memory loss, depression and seizures are some of the side effects to TBI. TBI affects people over 75 years of age because of falls and of 17–25 years of age because of accidents (Langlois et al., 2003[Langlois, J. A., Kegler, S. R., Butler, J. A., Gotsch, K. E., Johnson, R. L., Reichard, A. A., Webb, K. W., Coronado, V. G., Selassie, A. W. & Thurman, D. J. (2003). MMWR Surveill. Summ. 52, 1-20.], 2005[Langlois, J. A., Rutland-Brown, W. & Thomas, K. E. (2005). J. Head Trauma. Rehabil. 20, 229-238.]; Ashman et al., 2006[Ashman, T. A., Gordon, W. A., Cantor, J. B. & Hibbard, M. R. (2006). Mt Sinai J. Med. 73, 999-1005.]; Coronado et al., 2011[Coronado, V. G., Xu, L., Basavaraju, S. V., McGuire, L. C., Wald, M. M., Faul, M. D., Guzman, B. R. & Hemphill, J. D. (2011). MMWR Surveill. Summ. 60, 1-32.]). At present, there are no effective treatments available for TBI and there is thus a critical need to develop novel and effective strategies to alter the disease course. As indicated above, this health condition is quite similar to epilepsy in some instances and thus our earlier work (Alexander et al., 2013[Alexander, M. S., Scott, K. R., Harkless, J., Butcher, R. J. & Jackson-Ayotunde, P. L. (2013). Bioorg. Med. Chem. 21, 3272-3279.]; Jackson et al., 2012[Jackson, P. L., Hanson, C. D., Farrell, A. K., Butcher, R. J., Stables, J. P., Eddington, N. D. & Scott, K. R. (2012). Eur. J. Med. Chem. 51, 42-51.]; Edafiogho et al., 2007[Edafiogho, I. O., Kombian, S. B., Ananthalakshmi, K. V. V., Salama, N. N., Eddington, N. D., Wilson, T. L., Alexander, M. S., Jackson, P. L., Hanson, C. D. & Scott, K. R. (2007). J. Pharm. Sci. 96, 2509-2531.]) on developing anti­convulsant compounds for the treatment of epilepsy is relevant.

Our research on pharmacologically active compounds is a multi-pronged approach, which involves synthesis, chemical characterization, computer modeling, pharmacological evaluation, and structure determination (North et al., 2012[North, H., Scott, K. R., Stables, J. P. & Wang, X. S. (2012). Abstracts of Papers, 243rd ACS National Meeting & Exposition, San Diego, CA, United States, March 25-29, 2012, COMP-299.]; Gibson et al., 2009[Gibson, A., Harkless, J., Alexander, M. & Scott, K. R. (2009). Bioorg. Med. Chem. 17, 5342-5346.]). From this comprehensive approach, structure–activity correlations can be made to improve the existing pharmacologically active compounds. From our studies, we identified three imido­oxy derivatives as potential drug candidates for TBI that underwent anti­convulsant evaluation to test their ability to inhibit the onset of seizures in the in vivo MES, scPTZ test models. The MES (maximal electroshock seizure evaluation) test presented activity in animals in phase 1 testing.

2-Meth­oxy­isoindoline-1,3-dione, (1), studied by X-ray techniques, was inactive in MES and scPTZ in mice, but showed MES protection in rat studies at 50 mg kg−1 at 4 h and also protected 1/4 mice at three different time inter­vals (0.50, 1 and 2 h) in the 6 Hz test (Jackson, 2009[Jackson, P. L. (2009). PhD thesis, Howard University, Washington, DC, USA.]). For scPTZ studies, the compound was Class III (no activity at 300 mg kg−1). The compound is a dual MES/6Hz active compound. Compounds (2) and (3) showed similar activity.

The title compounds, containing either an isoindoline-1,3-dione moiety, (1) (Fig. 1[link]) and (2) (Fig. 2[link]), or an iso­quinoline-1,3-dione moiety, (3) (Fig. 3[link]), have been studied extensively for their anti­convulsant effects with promising results. Herein, we report on the crystal structures of these new structurally related compounds.

[Figure 1]
Figure 1
The mol­ecular structure of compound (1), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2]
Figure 2
The mol­ecular structures of the two independent mol­ecules (A and B) of compound (2), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The C—H⋯O hydrogen bond is shown as a dashed line (see Table 2[link] for details).
[Figure 3]
Figure 3
The mol­ecular structures of the two independent mol­ecules (A and B) of compound (3), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The C—H⋯O hydrogen bond is shown as a dashed line (see Table 3[link] for details).

2. Structural commentary

In compound (1), the isoindoline ring is planar [r.m.s. deviation = 0.017 (4) Å]. The meth­oxy O atom, O3, deviates from this plane by 0.176 (6) Å while the methyl C atom, C9, is out of the plane by 1.105 (9) Å. The meth­oxy substituent is oriented almost perpendicular to the indoline ring with the dihedral angle between the mean planes of the indoline ring and the meth­oxy substituent being 89.7 (3)°.

In compound (2), there are two mol­ecules (A and B) in the asymmetric unit. The isoindoline ring is planar [r.m.s. deviation = 0.0327 (9) for A and 0.0147 (9) Å for B] with the dione O atoms significantly out of the plane for mol­ecule A but not for mol­ecule B [0.172 (1) and 0.123 (1) Å for atoms O1 and O2, respectively, in A but by only 0.013 (1) and 0.002 (1) Å, respectively, in B]. The carbonato moiety is planar in both mol­ecules [r.m.s. deviations of 0.0066 (2) and 0.0027 (5) Å for A and B, respectively] and makes dihedral angles of 71.50 (3) and 80.03 (4)° with the benzoiso­quinoline ring in A and B, respectively, indicating that these substituents are oriented almost perpendicular to the benzoiso­quinoline ring system.

In compound (3), there are also two mol­ecules (A and B) in the asymmetric unit. In both mol­ecules, the benzoiso­quinoline ring systems are planar (r.m.s. deviations for A and B = 0.033 and 0.015 Å, respectively). The meth­oxy O atom deviates from this plane by 0.126 (1) for atom O5A in A and 0.156 (1) Å for atom O5B in B. The methyl carbonate moieties are planar [r.m.s. deviations of 0.007 (1) and 0.003 (1) Å for A and B, respectively] and these substituents are oriented almost perpendicular to the iso­quinoline rings, making dihedral angles of 71.50 (3) and 80.04 (4)° for A and B, respectively. As in (2), these dihedral angles are significantly smaller than that found for (1).

3. Supra­molecular features

In the crystal of (1), there are C—H⋯O hydrogen bonds (Fig. 4[link] and Table 1[link]) and π–π inter­actions present, forming slabs lying parallel to (001) [Cg1⋯Cg2i,ii = 3.407 (3) Å; Cg1 and Cg2 are the centroids of rings N1/C1/C2/C7/C8 and C2–C7, respectively; symmetry codes: (i) x − 1, y, z; (ii) x + 1, y, z].

Table 1
Hydrogen-bond geometry (Å, °) for (1)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C4—H4A⋯O2i 0.95 2.38 3.190 (4) 143
C9—H9A⋯O1ii 0.98 2.54 3.428 (7) 151
C9—H9B⋯O1iii 0.98 2.53 3.260 (8) 131
Symmetry codes: (i) x-1, y+1, z; (ii) [-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 4]
Figure 4
A view along the a axis of the crystal packing of compound (1), showing the formation of the three-dimensional array by an extensive network of C—H⋯O hydrogen bonds (shown as dashed lines; see Table 1[link] for details).

In the crystal of (2), the A and B mol­ecules are linked by C—H⋯O hydrogen bonds (Fig. 5[link] and Table 2[link]), forming slabs parallel to (10[\overline{1}]). The slabs are in turn linked via π–π inter­actions, forming a three-dimensional structure with centroid–centroid distances of 3.4202 (7) for Cg1⋯Cg5ii and 3.5445 (7) Å for Cg2⋯Cg4ii [Cg1, Cg2, Cg4 and Cg5 are the centroids of rings N1A/C1A/C2A/C7A/C8A, C2A–C7A, N1B/C1B/C2B/C7B/C8B and C2B–C7B, respectively; symmetry code: (ii) x + 1, y, z − 1].

Table 2
Hydrogen-bond geometry (Å, °) for (2)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C5A—H5AA⋯O3Bi 0.95 2.54 3.3341 (15) 141
C6A—H6AA⋯O4Aii 0.95 2.51 3.4091 (15) 158
C3B—H3BA⋯O2Aiii 0.95 2.59 3.2281 (14) 125
C6B—H6BA⋯O3Aiv 0.95 2.55 3.3086 (14) 137
C10B—H10F⋯O2Bv 0.98 2.57 3.4956 (16) 157
Symmetry codes: (i) -x, -y+1, -z; (ii) -x+1, -y+1, -z; (iii) -x+1, -y+1, -z+1; (iv) -x+1, -y+2, -z+1; (v) -x, -y+2, -z+1.
[Figure 5]
Figure 5
A view along the a axis of the crystal packing of compound (2), showing the three-dimensional array formed by an extensive network of C—H⋯O hydrogen bonds (dashed lines; see Table 2[link] for details).

In the crystal of (3), the A and B mol­ecules are linked by C—H⋯O hydrogen bonds (Fig. 6[link] and Table 3[link]), forming a three-dimensional structure, which is consolidated by π–π inter­actions [Cg1⋯Cg3iii = 3.578 (3), Cg2⋯Cg3iii = 3.575 (3) Å and Cg9⋯Cg10iv; Cg1, Cg2, Cg3, Cg9 and Cg10 are the centroids of rings N1A/C1A–C5A, C2A/C3A/C6A–C9A, C3A/C4A/C9A–C12A, C2B/C3B/C6B–C9B and C3B/C4B/C9B–C12B, respectively; symmetry codes: (iii) x, −y + [{1\over 2}], z − [{1\over 2}]; (iv) x, −y + [{3\over 2}], z + [{1\over 2}]].

Table 3
Hydrogen-bond geometry (Å, °) for (3)[link]

D—H⋯A D—H H⋯A D⋯A D—H⋯A
C6A—H6AA⋯O4Ai 0.95 2.51 3.159 (5) 125
C7B—H7BA⋯O2Bii 0.95 2.51 3.229 (5) 133
C10B—H10B⋯O5Bii 0.95 2.60 3.428 (5) 146
C11B—H11B⋯O1Aiii 0.95 2.48 3.270 (6) 141
C14A—H14A⋯O1Biv 0.98 2.51 3.481 (5) 169
C14B—H14E⋯O4Aiv 0.98 2.51 3.306 (6) 138
Symmetry codes: (i) [x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]; (ii) [-x, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]; (iii) -x, -y+1, -z; (iv) [x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}].
[Figure 6]
Figure 6
For mol­ecule A in compound (2), perpendicular inter­actions between atoms O1A and C9A (shown as dashed lines) link the mol­ecules into inversion dimers [symmetry code: (A) − x + 1, − y + 2, −z].

Inter­estingly, in the crystal of (2) one of the two dione moieties for each mol­ecule (O1A and O1B) has a short inter­molecular inter­actions with the central C atom of the carbonato group [O1A⋯C9A = 2.794 (1), O1B⋯C9B = 2.873 (1) Å], which is perpendicular to the carbonato plane indicating that both atoms, C9A and C9B, must have significant positive character. These inter­actions link the mol­ecules into dimers as shown in Figs. 6[link] and 7[link], respectively. This is also noticed to a lesser extent in (3) (Fig. 8[link]) for mol­ecule A (but not for mol­ecule B), where a longer inter­molecular inter­action of 3.060 (3) Å is observed between atoms O2A and C13A, resulting in weakly associated dimers similar to that seen in the case of (2).

[Figure 7]
Figure 7
For mol­ecule B in compound (2), perpendicular inter­actions between atoms O1B and C9B (shown as dashed lines) link the mol­ecules into inversion dimers [symmetry code: (A) −x, −y + 1, −z − 1].
[Figure 8]
Figure 8
A view along the a axis of the crystal packing of compound (3), showing the formation of the three-dimensional array by an extensive network of C—H⋯O hydrogen bonds (dashed lines; see Table 3[link] for details).

4. Database survey

A search of the Cambridge Structural Database (Version 5.35; Groom & Allen, 2014[Groom, C. R. & Allen, F. H. (2014). Angew. Chem. Int. Ed. 53, 662-671.]) for the indoline skeleton gave 26 hits. In all cases, the geometrical parameters of the indoline skeleton are similar to those observed in compounds (1) and (2). In the case of the iso­quinoline structure, there are only two structures containing the planar iso­quinoline moiety with similar geometrical parameters to the present structure, (3).

5. Synthesis and crystallization

Compound (1):

To a freshly prepared solution of sodium (2.3 g, 0.10 mol) in absolute ethanol (60 ml) was added a solution of N-hy­droxy­phthalimide (16.3 g, 0.10 mol) in absolute ethanol (350 ml), and the red reaction mixture was stirred at room temperature for 30 min. The brick-red precipitate was collected, washed with water, and dried in the oven at 373 K for 30 min to give 17.45 g (95%) of sodium phthalimide oxide as brick-red crystals; m.p. > 573 K. To the solution of sodium phthalimide oxide (0.92 g, 5 mmol) in water (15 ml) was added acetone (10 ml), followed by a solution of bromo­methane (0.66 g, 7 mmol). The reaction mixture was stirred at room temperature for 16 h, during which the red color disappeared. On standing at room temperature for 48 h, the product solidified in the aqueous mixture and was collected. Recrystallization from 2-propanol gave 0.72 g (78%) of compound (1) as plate-like colorless crystals: m.p. 395–397 K; 1H NMR (CDC13) δ 3.36 (s, 3H, J = 6 Hz, OCH3), 5.52, s, 1 H,CH, 7.87 (m, 4 H, phthalimido ring).

Compound (2):

To a solution of sodium phthalimide oxide (0.92 g, 5 mmol) in water (15 ml) was added acetone (10 ml), followed by a solution of bromo­(meth­oxy)methanone (0.97 g, 7 mmol). The reaction mixture was stirred at room temperature for 16 h, during which the red color disappeared. On standing at room temperature for 48 h, the product solidified in the aqueous mixture and was collected. Recrystallization from ethanol gave 0.82 g (74%) of compound (2) as colorless crystals: m.p. 410–411 K; 1H NMR (CDC13) δ 3.8 (s, 3H,OCH3), 7.86 (m, 4H, phthalimido ring).

Compound (3):

To a solution of sodium naphthalimide oxide, (1.18 g, 5 mmol), in water (50 ml), was added bromo­(meth­oxy)methanone (1.25g, 7 mmol) in acetone (10 ml). The red reaction mixture was stirred at room temperature. The red color disappeared within 5 min and the reaction mixture was filled with a white precipitate. After standing for 4 h, the white precipitate was collected, washed with water, and recrystallized from ethanol to give 1.46 g (89%) of compound (3) as colorless crystals: m.p. 483–485 K; 1H NMR (CDCl3) δ 3.79 (s, 3H, OCH3), 5.66 (s, 1H, CH), 7.65–8.50 (m, 6 H, naphthal­imido ring).

6. Refinement

Crystal data, data collection and structure refinement details for (1), (2) and (3) are summarized in Table 4[link]. For all three compounds, the H atoms were positioned geometrically and refined as riding: C—H = 0.93–0.99 Å with Uiso(H) = 1.5Ueq(C) for methyl H atoms and = 1.2Ueq(C) for other H atoms.

Table 4
Experimental details

  (1) (2) (3)
Crystal data
Chemical formula C9H7NO3 C10H7NO5 C14H9NO5
Mr 177.16 221.17 271.22
Crystal system, space group Orthorhombic, P212121 Triclinic, P[\overline{1}] Monoclinic, P21/c
Temperature (K) 123 123 123
a, b, c (Å) 4.2987 (4), 7.0243 (10), 27.587 (4) 7.0363 (4), 11.0082 (5), 12.4239 (6) 16.512 (3), 18.579 (3), 7.6156 (13)
α, β, γ (°) 90, 90, 90 98.884 (4), 96.159 (4), 93.009 (4) 90, 99.434 (17), 90
V (Å3) 832.98 (19) 942.95 (8) 2304.6 (7)
Z 4 4 8
Radiation type Mo Kα Cu Kα Mo Kα
μ (mm−1) 0.11 1.10 0.12
Crystal size (mm) 0.66 × 0.23 × 0.04 0.35 × 0.25 × 0.08 0.44 × 0.12 × 0.07
 
Data collection
Diffractometer Agilent Xcalibur (Ruby, Gemini) SuperNova (Dual, Cu at zero, Atlas) Agilent Xcalibur (Ruby, Gemini)
Absorption correction Analytical (CrysAlis PRO; Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.]) Multi-scan (CrysAlis PRO; Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.]) Analytical (CrysAlis PRO; Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.])
Tmin, Tmax 0.946, 0.996 0.807, 1.000 0.995, 0.999
No. of measured, independent and observed [I > 2σ(I)] reflections 5145, 2259, 1989 6437, 3803, 3516 9949, 4156, 1898
Rint 0.087 0.018 0.091
(sin θ/λ)max (Å−1) 0.727 0.631 0.600
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.099, 0.229, 1.13 0.033, 0.089, 1.06 0.080, 0.224, 1.00
No. of reflections 2259 3803 4156
No. of parameters 119 291 363
H-atom treatment H-atom parameters constrained H-atom parameters constrained H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.50, −0.34 0.29, −0.21 0.33, −0.39
Computer programs: CrysAlis PRO (Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.]), SUPERFLIP (Palatinus & Chapuis, 2007[Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.]), SHELXS2013, SHELXL2013 and SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and SUPERFLIP (Palatinus et al. 2007[Palatinus, L. & Chapuis, G. (2007). J. Appl. Cryst. 40, 786-790.]).

Supporting information

CCDC references: 1031391; 1031392; 1031393

Crystal structure: contains datablocks 1, 2, 3. DOI: 10.1107/S1600536814023769/su2795sup1.cif

Structure factors: contains datablock 1. DOI: 10.1107/S1600536814023769/su27951sup2.hkl

Structure factors: contains datablock 2. DOI: 10.1107/S1600536814023769/su27952sup3.hkl

Structure factors: contains datablock 3. DOI: 10.1107/S1600536814023769/su27953sup4.hkl

Supporting information file. DOI: 10.1107/S1600536814023769/su27951sup5.cml

Supporting information file. DOI: 10.1107/S1600536814023769/su27952sup6.cml

Supporting information file. DOI: 10.1107/S1600536814023769/su27953sup7.cml

checkCIF report


Chemical context top

Traumatic brain injury (TBI) is a neurological disorder that is defined as damage to the brain resulting from external mechanical force, including accelerating, decelerating and rotating forces (Langlois et al., 2003, 2005; Ashman et al., 2006; Coronado et al., 2011). TBI also exacerbates seizure severity in individuals with pre-existing epilepsy (Ferraro et al., 1999), being one example of the process of epileptogenesis (Christensen et al., 2009). In this context, it has been demonstrated that early lesions in the central nervous system (CNS) alter the transport dynamic of the blood–brain barrier (BBB) and deteriorate the balance of the inhibitory and excitatory neurotransmitter system (Scantlebury et al., 2005]. This neuronal dysfunction predisposes to subsequent development of spontaneous recurrent seizures in the presence of prior subtle brain malformation (Love, 2005].

TBI is the major cause of death in young individuals (14–24 years) from industrialized countries, with head injuries accounting for 25–33% of all trauma-related deaths (Abdul-Muneer et al., 2014). Disorders like memory loss, depression and seizures are some of the side effects to TBI. TBI affects people over 75 years of age because of falls and of 17–25 years of age because of accidents (Langlois et al., 2003, 2005; Ashman et al., 2006; Coronado et al., 2011). At present, there are no effective treatments available for TBI and there is thus a critical need to develop novel and effective strategies to alter the disease course. As indicated above, this health condition is quite similar to epilepsy in some instances and thus our earlier work (Alexander et al., 2013; Jackson et al., 2012; Edafiogho et al., 2007) on developing anti­convulsant compounds for the treatment of epilepsy is relevant.

Our research on pharmacologically active compounds is a multi-pronged approach, which involves synthesis, chemical characterization, computer modeling, pharmacological evaluation, and structure determination (North et al., 2012; Gibson et al., 2009). From this comprehensive approach, structure–activity correlations can be made to improve the existing pharmacologically active compounds. From our studies, we identified three imido­oxy derivatives as potential drug candidates for TBI that underwent anti­convulsant evaluation to test their ability to inhibit the onset of seizures in the in vivo MES, scPTZ test models. The MES (maximal electroshock seizure evaluation) test presented activity in animals in phase 1 testing.

2-Meth­oxy­isoindoline-1,3-dione, (1), studied by X-ray, was inactive in MES and scPTZ in mice, but showed MES protection in rat studies at 50 mg kg-1 at 4 h and also protected 1/4 mice at three different time inter­vals (0.50, 1 and 2 h) in the 6 Hz test (Jackson, 2009). For scPTZ studies, the compound was Class III (no activity at 300 mg kg-1). The compound is a dual MES/6Hz active compound. Compounds (2) and (3) showed similar activity.

The title compounds, containing either an isoindoline-1,3-dione moiety, (1) and (2), or an iso­quinoline-1,3-dione moiety, (3), have been studied extensively for their anti­convulsant effects with promising results. Herein, we report on the crystal structures of these new structurally related compounds.

Structural commentary top

In compound (1), the isoindoline ring is planar [r.m.s. deviation = 0.017 (4) Å]. The meth­oxy O atom, O3, deviates from this plane by 0.176 (6) Å while the methyl C atom, C9, is out of the plane by 1.105 (9) Å. The meth­oxy substituent is oriented almost perpendicular to the indoline ring with the dihedral angle between the mean planes of the indoline ring and the meth­oxy substituent being 89.7 (3)°.

In compound (2), there are two molecules (A and B) in the asymmetric unit. The isoindoline ring is planar [r.m.s. deviation = 0.0327 (9) for A and 0.0147 (9) Å for B] with the dione O atoms significantly out of the plane for molecule A but not for molecule B [0.172 (1) and 0.123 (1) Å for atoms O1 and O2, respectively, in A but by only 0.013 (1) and 0.002 (1) Å, respectively, in B]. The carbonato moiety is planar in both molecules [r.m.s. deviations of 0.0066 (2) and 0.0027 (5) Å for A and B, respectively] and makes dihedral angles of 71.50 (3) and 80.03 (4)° with the benzoiso­quinoline ring in A and B, respectively, indicating that these substituents are oriented almost perpendicular to the benzoiso­quinoline ring system.

In compound (3), there are also two molecules (A and B) in the asymmetric unit. In both molecules, the benzoiso­quinoline ring systems are planar (r.m.s. deviations for A and B = 0.033 and 0.015 Å, respectively). The meth­oxy O atom deviates from this plane by 0.126 (1) for atom O5A in A and 0.156 (1) Å for atom O5B in B. The methyl carbonate moieties are planar (r.m.s. deviations of 0.007 and 0.003 Å for A and B, respectively) and these substituents are oriented almost perpendicular to the iso­quinoline rings, making dihedral angles of 71.50 (3) and 80.04 (4)° for A and B, respectively. As in (2), these dihedral angles are significantly smaller than that found for (1).

Supra­molecular features top

In the crystal of (1), there are C—H···O hydrogen bonds (Fig. 4 and Table 1) and π–π inter­actions present, forming slabs lying parallel to (001) [Cg1···Cg2i,ii = 3.407 (3) Å; Cg1 and Cg2 are the centroids of rings N1/C1/C2/C7/C8 and C2–C7, respectively; symmetry codes: (i) x-1, y, z; (ii) x+1, y, z].

In the crystal of (2), the A and B molecules are linked by C—H···O hydrogen bonds (Fig. 5 and Table 2), forming slabs parallel to (101). The slabs are in turn linked via π–π inter­actions, forming a three-dimensional structure with centroid–centroid distances of 3.4202 (7) for Cg1···Cg5ii and 3.5445 (7) Å for Cg2···Cg4ii [Cg1, Cg2, Cg4 and Cg5 are the centroids of rings N1A/C1A/C2A/C7A/C8A, C2A–C7A, N1B/C1B/C2B/C7B/C8B and C2B–C7B, respectively; symmetry code: (ii) x+1, y, z-1].

In the crystal of (3), the A and B molecules are linked by C—H···O hydrogen bonds (Fig. 6 and Table 3), forming a three-dimensional structure, which is consolidated by π–π inter­actions [Cg1···Cg3iii = 3.578 (3), Cg2···Cg3iii = 3.575 (3) Å and Cg9···Cg10iv; Cg1, Cg2, Cg3, Cg9 and Cg10 are the centroids of rings N1A/C1A–C5A, C2A/C3A/C6A–C9A, C3A/C4A/C9A–C12A, C2B/C3B/C6B–C9B and C3B/C4B/C9B–C12B, respectively; symmetry codes: (iii) x, -y+1/2, z-1/2; (iv) x, -y+3/2, z+1/2].

Inter­estingly, in the crystal of (2) one of the two dione moieties for each molecule (O1A and O1B) has a short inter­molecular inter­actions with the central C atom of the carbonato group [O1A···C9A = 2.794 (1), O1B···C9B = 2.873 (1) Å], which is perpendicular to the carbonato plane indicating that both atoms, C9A and C9B, must have significant positive character. These inter­actions link the molecules into dimers as shown in Figs. 6 and 7, respectively. This is also noticed to a lesser extent in (3) for molecule A (but not for molecule B), where a longer inter­molecular inter­action of 3.060 (3) Å is observed between atoms O2A and C13A, resulting in weakly associated dimers similar to that seen in the case of (2).

Database survey top

A search of the Cambridge Structural Database (Version 5.35; Groom & Allen, 2014) for the indoline skeleton gave 26 hits. In all cases, the geometrical parameters of the indoline skeleton are similar to those observed in compounds (1) and (2). In the case of the iso­quinoline structure, there are only two structures containing the planar iso­quinoline moiety with similar geometrical parameters to the present structure, (3).

Synthesis and crystallization top

Compound (1):

To a freshly prepared solution of sodium (2.3 g, 0.10 mol) in absolute ethanol (60 ml) was added a solution of N-hy­droxy­phthalimide (16.3 g, 0.10 mol) in absolute ethanol (350 ml), and the red reaction mixture was stirred at room temperature for 30 min. The brick-red precipitate was collected, washed with water, and dried in the oven at 373 K for 30 min to give 17.45 g (95%) of sodium phthalimide oxide as brick-red crystals; m.p. > 573 K. To the solution of sodium phthalimide oxide (0.92 g, 5 mmol) in water (15 ml) was added acetone (10 ml), followed by a solution of bromo­methane (0.66 g, 7 mmol). The reaction mixture was stirred at room temperature for 16 h, during which the red color disappeared. On standing at room temperature for 48 h, the product solidified in the aqueous mixture and was collected. Recrystallization from 2-propanol gave 0.72 g (78%) of compound (1) as plate-like colorless crystals: m.p. 395–397 K; 1H NMR (CDC13) δ 3.36 (s, 3H, J = 6 Hz, OCH3), 5.52, s, 1 H,CH, 7.87 (m, 4 H, phthalimido ring).

Compound (2):

To a solution of sodium phthalimide oxide (0.92 g, 5 mmol) in water (15 ml) was added acetone (10 ml), followed by a solution of bromo­(meth­oxy)­methanone (0.97 g, 7 mmol). The reaction mixture was stirred at room temperature for 16 h, during which the red color disappeared. On standing at room temperature for 48 h, the product solidified in the aqueous mixture and was collected. Recrystallization from ethanol gave 0.82 g (74%) of compound (2) as colorless crystals: m.p. 410–411 K; 1H NMR (CDC13) δ 3.8 (s, 3H,OCH3), 7.86 (m, 4 H, phthalimido ring).

Compound (3):

To a solution of sodium naphthalimide oxide, (1.18 g, 5 mmol), in water (50 ml), was added bromo­(meth­oxy)­methanone (1.25g, 7 mmol) in acetone (10 ml). The red reaction mixture was stirred at room temperature. The red color disappeared within 5 min and the reaction mixture was filled with a white precipitate. After standing for 4 h, the white precipitate was collected, washed with water, and recrystallized from ethanol to give 1.46 g (89%) of compound (3) as colorless crystals: m.p. 483–485 K; 1H NMR (CDCl3) δ 3.79 (s, 3H, OCH3), 5.66 (s, 1H, CH), 7.65–8.50 (m, 6 H, naphthalimido ring).

Refinement top

Crystal data, data collection and structure refinement details for (1), (2) and (3) are summarized in Table 4. For all three compounds, the H atoms were positioned geometrically and refined as riding: C—H = 0.93–0.99 Å with Uiso(H) = 1.5Ueq(C) for methyl H atoms and = 1.2Ueq(C) for other H atoms.

Related literature top

For related literature, see: Abdul-Muneer, Namas & James (2014); Alexander et al. (2013); Ashman et al. (2006); Cambridge (2013); Christensen et al. (2009); Coronado et al. (2011); Edafiogho et al. (2007); Ferraro et al. (1999); Gibson et al. (2009); Jackson (2009); Jackson et al. (2012); Langlois et al. (2003, 2005); Love (2005); North et al. (2012); Scantlebury et al. (2005).

Computing details top

For all compounds, data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012). Program(s) used to solve structure: SUPERFLIP (Palatinus & Chapuis, 2007) for (1); SHELXS2013 (Sheldrick, 2008) for (2); SUPERFLIP (Palatinus et al. 2007) for (3). For all compounds, program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
The molecular structure of compound (1), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

The molecular structures of the two independent molecules (A and B) of compound (2), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The C—H···O hydrogen bond is shown as a dashed line (see Table 2 for details).

The molecular structures of the two independent molecules (A and B) of compound (3), with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The C—H···O hydrogen bond is shown as a dashed line (see Table 3 for details).

A view along the a axis of the crystal packing of compound (1), showing the formation of the three-dimensional array by an extensive network of C—H···O hydrogen bonds (shown as dashed lines; see Table 1 for details).

A view along the a axis of the crystal packing of compound (2), showing the three-dimensional array formed by an extensive network of C—H···O hydrogen bonds (dashed lines; see Table 2 for details).

For molecule A in compound (2), perpendicular interactions between atoms O1A and C9A (shown as dashed lines) link the molecules into inversion dimers (symmetry code: - x + 1, - y + 2, -z).

For molecule B in compound (2), perpendicular interactions between atoms O1B and C9B (shown as dashed lines) link the molecules into inversion dimers (symmetry code: -x, -y + 1, -z - 1).

A view along the a axis of the crystal packing of compound (3), showing the formation of the three-dimensional array by an extensive network of C—H···O hydrogen bonds (dashed lines; see Table 3 for details).
(1) 2-Methoxyisoindoline-1,3-dione top
Crystal data top
C9H7NO3Dx = 1.413 Mg m−3
Mr = 177.16Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 1634 reflections
a = 4.2987 (4) Åθ = 3.3–31.1°
b = 7.0243 (10) ŵ = 0.11 mm−1
c = 27.587 (4) ÅT = 123 K
V = 832.98 (19) Å3Plate, colorless
Z = 40.66 × 0.23 × 0.04 mm
F(000) = 368
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer		2259 independent reflections
Radiation source: Enhance (Mo) X-ray Source1989 reflections with I > 2σ(I)
Detector resolution: 10.5081 pixels mm-1Rint = 0.087
ω scansθmax = 31.1°, θmin = 3.3°
Absorption correction: analytical
(CrysAlis PRO; Agilent, 2012)		h = −5→5
Tmin = 0.946, Tmax = 0.996k = −10→9
5145 measured reflectionsl = −25→38
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.099H-atom parameters constrained
wR(F2) = 0.229 w = 1/[σ2(Fo2) + (0.0842P)2 + 1.043P]
where P = (Fo2 + 2Fc2)/3
S = 1.13(Δ/σ)max < 0.001
2259 reflectionsΔρmax = 0.50 e Å−3
119 parametersΔρmin = −0.33 e Å−3
Crystal data top
C9H7NO3V = 832.98 (19) Å3
Mr = 177.16Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 4.2987 (4) ŵ = 0.11 mm−1
b = 7.0243 (10) ÅT = 123 K
c = 27.587 (4) Å0.66 × 0.23 × 0.04 mm
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer		2259 independent reflections
Absorption correction: analytical
(CrysAlis PRO; Agilent, 2012)		1989 reflections with I > 2σ(I)
Tmin = 0.946, Tmax = 0.996Rint = 0.087
5145 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0990 restraints
wR(F2) = 0.229H-atom parameters constrained
S = 1.13Δρmax = 0.50 e Å−3
2259 reflectionsΔρmin = −0.33 e Å−3
119 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.6646 (10)0.6034 (6)0.30567 (13)0.0417 (10)
O20.6859 (9)0.0978 (4)0.41116 (14)0.0358 (9)
O30.9419 (9)0.2430 (6)0.32341 (14)0.0413 (10)
N10.7177 (10)0.3273 (6)0.35101 (15)0.0293 (9)
C10.6031 (12)0.5105 (7)0.34055 (17)0.0284 (10)
C20.3946 (11)0.5531 (6)0.38248 (16)0.0229 (9)
C30.2197 (12)0.7156 (6)0.39295 (18)0.0306 (11)
H3A0.21100.81990.37110.037*
C40.0601 (13)0.7184 (6)0.4364 (2)0.0318 (11)
H4A−0.05910.82780.44450.038*
C50.0684 (12)0.5655 (6)0.46879 (18)0.0275 (10)
H5A−0.04360.57220.49840.033*
C60.2410 (10)0.4030 (6)0.45760 (16)0.0250 (9)
H6A0.24650.29770.47920.030*
C70.4026 (11)0.3989 (6)0.41468 (16)0.0229 (9)
C80.6130 (11)0.2513 (6)0.39447 (17)0.0247 (9)
C90.8051 (17)0.1214 (10)0.2870 (2)0.0532 (18)
H9A0.96930.07010.26610.080*
H9B0.65830.19520.26740.080*
H9C0.69480.01620.30280.080*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.039 (2)0.049 (2)0.0379 (19)−0.010 (2)0.0000 (17)0.0107 (16)
O20.0325 (19)0.0155 (14)0.059 (2)0.0085 (16)−0.0026 (17)0.0010 (15)
O30.028 (2)0.051 (2)0.045 (2)0.005 (2)0.0082 (16)−0.0136 (17)
N10.022 (2)0.030 (2)0.036 (2)0.0038 (17)0.0013 (16)−0.0028 (16)
C10.0186 (19)0.034 (2)0.033 (2)−0.007 (2)−0.0037 (18)0.0048 (18)
C20.0163 (18)0.0171 (19)0.035 (2)−0.0029 (16)−0.0069 (17)0.0032 (16)
C30.031 (3)0.0115 (18)0.049 (3)−0.0008 (18)−0.014 (2)0.0041 (17)
C40.028 (3)0.013 (2)0.054 (3)0.0040 (19)−0.011 (2)−0.0085 (19)
C50.021 (2)0.019 (2)0.043 (3)−0.0001 (17)−0.0024 (19)−0.0055 (18)
C60.019 (2)0.0183 (19)0.038 (2)−0.0048 (18)−0.0031 (18)−0.0007 (16)
C70.021 (2)0.0122 (17)0.035 (2)0.0024 (19)−0.0075 (17)−0.0009 (16)
C80.0183 (19)0.019 (2)0.037 (2)−0.0023 (17)−0.0044 (18)−0.0035 (17)
C90.050 (4)0.062 (4)0.047 (3)−0.011 (4)0.010 (3)−0.025 (3)
Geometric parameters (Å, º) top
O1—C11.193 (6)C4—C51.398 (7)
O2—C81.214 (5)C4—H4A0.9500
O3—N11.364 (5)C5—C61.396 (6)
O3—C91.444 (7)C5—H5A0.9500
N1—C81.387 (6)C6—C71.373 (6)
N1—C11.407 (6)C6—H6A0.9500
C1—C21.494 (7)C7—C81.484 (6)
C2—C31.397 (6)C9—H9A0.9800
C2—C71.401 (6)C9—H9B0.9800
C3—C41.381 (8)C9—H9C0.9800
C3—H3A0.9500
N1—O3—C9110.9 (4)C6—C5—H5A120.0
O3—N1—C8123.0 (4)C4—C5—H5A120.0
O3—N1—C1122.0 (4)C7—C6—C5118.5 (4)
C8—N1—C1114.5 (4)C7—C6—H6A120.8
O1—C1—N1126.0 (5)C5—C6—H6A120.8
O1—C1—C2130.4 (5)C6—C7—C2121.2 (4)
N1—C1—C2103.6 (4)C6—C7—C8130.3 (4)
C3—C2—C7120.9 (4)C2—C7—C8108.5 (4)
C3—C2—C1130.3 (4)O2—C8—N1125.9 (4)
C7—C2—C1108.7 (4)O2—C8—C7129.4 (5)
C4—C3—C2117.3 (4)N1—C8—C7104.7 (4)
C4—C3—H3A121.3O3—C9—H9A109.5
C2—C3—H3A121.3O3—C9—H9B109.5
C3—C4—C5122.1 (4)H9A—C9—H9B109.5
C3—C4—H4A119.0O3—C9—H9C109.5
C5—C4—H4A119.0H9A—C9—H9C109.5
C6—C5—C4120.0 (5)H9B—C9—H9C109.5
C9—O3—N1—C893.4 (6)C5—C6—C7—C2−0.4 (7)
C9—O3—N1—C1−94.8 (6)C5—C6—C7—C8177.1 (4)
O3—N1—C1—O16.7 (8)C3—C2—C7—C6−0.4 (7)
C8—N1—C1—O1179.1 (5)C1—C2—C7—C6177.4 (4)
O3—N1—C1—C2−173.7 (4)C3—C2—C7—C8−178.4 (4)
C8—N1—C1—C2−1.2 (5)C1—C2—C7—C8−0.6 (5)
O1—C1—C2—C3−1.7 (9)O3—N1—C8—O2−6.2 (7)
N1—C1—C2—C3178.6 (5)C1—N1—C8—O2−178.5 (4)
O1—C1—C2—C7−179.2 (5)O3—N1—C8—C7173.2 (4)
N1—C1—C2—C71.1 (5)C1—N1—C8—C70.9 (5)
C7—C2—C3—C40.9 (7)C6—C7—C8—O21.5 (8)
C1—C2—C3—C4−176.4 (5)C2—C7—C8—O2179.2 (5)
C2—C3—C4—C5−0.5 (7)C6—C7—C8—N1−177.9 (5)
C3—C4—C5—C6−0.2 (7)C2—C7—C8—N1−0.1 (5)
C4—C5—C6—C70.7 (7)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4A···O2i0.952.383.190 (4)143
C9—H9A···O1ii0.982.543.428 (7)151
C9—H9B···O1iii0.982.533.260 (8)131
Symmetry codes: (i) x−1, y+1, z; (ii) −x+2, y−1/2, −z+1/2; (iii) −x+1, y−1/2, −z+1/2.
(2) 1,3-Dioxoisoindolin-2-yl methyl carbonate top
Crystal data top
C10H7NO5Z = 4
Mr = 221.17F(000) = 456
Triclinic, P1Dx = 1.558 Mg m−3
a = 7.0363 (4) ÅCu Kα radiation, λ = 1.54184 Å
b = 11.0082 (5) ÅCell parameters from 4882 reflections
c = 12.4239 (6) Åθ = 3.6–76.2°
α = 98.884 (4)°µ = 1.10 mm−1
β = 96.159 (4)°T = 123 K
γ = 93.009 (4)°Prism, colorless
V = 942.95 (8) Å30.35 × 0.25 × 0.08 mm
Data collection top
SuperNova (Dual, Cu at zero, Atlas)
diffractometer		3803 independent reflections
Radiation source: SuperNova (Cu) X-ray Source3516 reflections with I > 2σ(I)
Detector resolution: 5.3250 pixels mm-1Rint = 0.018
ω scansθmax = 76.7°, θmin = 3.6°
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)		h = −6→8
Tmin = 0.807, Tmax = 1.000k = −12→13
6437 measured reflectionsl = −15→15
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.033H-atom parameters constrained
wR(F2) = 0.089 w = 1/[σ2(Fo2) + (0.0493P)2 + 0.2145P]
where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max < 0.001
3803 reflectionsΔρmax = 0.29 e Å−3
291 parametersΔρmin = −0.21 e Å−3
Crystal data top
C10H7NO5γ = 93.009 (4)°
Mr = 221.17V = 942.95 (8) Å3
Triclinic, P1Z = 4
a = 7.0363 (4) ÅCu Kα radiation
b = 11.0082 (5) ŵ = 1.10 mm−1
c = 12.4239 (6) ÅT = 123 K
α = 98.884 (4)°0.35 × 0.25 × 0.08 mm
β = 96.159 (4)°
Data collection top
SuperNova (Dual, Cu at zero, Atlas)
diffractometer		3803 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)		3516 reflections with I > 2σ(I)
Tmin = 0.807, Tmax = 1.000Rint = 0.018
6437 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0330 restraints
wR(F2) = 0.089H-atom parameters constrained
S = 1.06Δρmax = 0.29 e Å−3
3803 reflectionsΔρmin = −0.21 e Å−3
291 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O1A0.58069 (12)0.94400 (7)−0.10814 (7)0.02474 (19)
O2A0.70600 (12)0.59365 (8)0.03549 (7)0.02446 (19)
O3A0.71408 (11)0.85375 (7)0.08575 (6)0.02145 (18)
O4A0.45369 (12)0.79308 (7)0.16556 (7)0.02328 (18)
O5A0.69506 (12)0.92945 (8)0.25353 (7)0.02361 (18)
N1A0.62655 (14)0.78226 (9)−0.01005 (8)0.0207 (2)
C1A0.57541 (15)0.83540 (10)−0.10425 (9)0.0194 (2)
C2A0.52332 (15)0.72621 (10)−0.19136 (9)0.0191 (2)
C3A0.44765 (16)0.72094 (11)−0.29960 (9)0.0224 (2)
H3AA0.41980.7936−0.32890.027*
C4A0.41381 (17)0.60441 (12)−0.36426 (10)0.0256 (2)
H4AA0.36170.5976−0.43890.031*
C5A0.45539 (17)0.49821 (11)−0.32085 (10)0.0255 (2)
H5AA0.43210.4202−0.36670.031*
C6A0.53058 (16)0.50392 (11)−0.21126 (10)0.0226 (2)
H6AA0.55820.4315−0.18150.027*
C7A0.56299 (15)0.61941 (10)−0.14801 (9)0.0190 (2)
C8A0.64135 (15)0.65422 (10)−0.03083 (9)0.0191 (2)
C9A0.60062 (16)0.85373 (10)0.17055 (9)0.0194 (2)
C10A0.6040 (2)0.94039 (12)0.35373 (10)0.0295 (3)
H10A0.68540.99500.41240.044*
H10B0.58590.85880.37490.044*
H10C0.47930.97470.34150.044*
O1B−0.08991 (12)0.51108 (8)0.60519 (7)0.02492 (19)
O2B−0.11026 (13)0.93213 (8)0.64789 (7)0.0288 (2)
O3B−0.16633 (12)0.71284 (8)0.49226 (6)0.02337 (18)
O4B0.14891 (12)0.77011 (8)0.48293 (7)0.02594 (19)
O5B−0.07693 (12)0.72731 (8)0.33471 (6)0.02271 (18)
N1B−0.11179 (15)0.72022 (9)0.60321 (8)0.0242 (2)
C1B−0.06927 (15)0.61621 (10)0.65099 (9)0.0192 (2)
C2B−0.00046 (15)0.66970 (10)0.76699 (9)0.0184 (2)
C3B0.06678 (16)0.61061 (10)0.85235 (9)0.0204 (2)
H3BA0.07030.52350.84300.025*
C4B0.12944 (16)0.68463 (11)0.95314 (9)0.0229 (2)
H4BA0.17720.64701.01350.027*
C5B0.12339 (16)0.81246 (11)0.96696 (9)0.0232 (2)
H5BA0.16730.86031.03640.028*
C6B0.05364 (16)0.87132 (10)0.88024 (9)0.0215 (2)
H6BA0.04820.95830.88940.026*
C7B−0.00701 (15)0.79761 (10)0.78058 (9)0.0194 (2)
C8B−0.08039 (16)0.83365 (10)0.67376 (9)0.0213 (2)
C9B−0.00857 (16)0.74035 (10)0.43860 (9)0.0201 (2)
C10B0.06721 (18)0.74950 (12)0.26295 (10)0.0269 (3)
H10D0.00970.73060.18630.040*
H10E0.17290.69670.27450.040*
H10F0.11610.83620.27960.040*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O1A0.0279 (4)0.0182 (4)0.0291 (4)0.0039 (3)0.0032 (3)0.0063 (3)
O2A0.0259 (4)0.0239 (4)0.0252 (4)0.0039 (3)0.0015 (3)0.0092 (3)
O3A0.0221 (4)0.0214 (4)0.0190 (4)−0.0023 (3)−0.0001 (3)0.0006 (3)
O4A0.0230 (4)0.0202 (4)0.0266 (4)0.0001 (3)0.0024 (3)0.0045 (3)
O5A0.0266 (4)0.0226 (4)0.0199 (4)0.0007 (3)−0.0017 (3)0.0016 (3)
N1A0.0254 (5)0.0175 (5)0.0178 (4)0.0002 (4)−0.0014 (4)0.0016 (4)
C1A0.0164 (5)0.0207 (5)0.0223 (5)0.0033 (4)0.0037 (4)0.0057 (4)
C2A0.0158 (5)0.0204 (5)0.0217 (5)0.0021 (4)0.0038 (4)0.0039 (4)
C3A0.0191 (5)0.0265 (6)0.0228 (5)0.0030 (4)0.0024 (4)0.0071 (4)
C4A0.0208 (5)0.0336 (6)0.0212 (5)0.0009 (5)0.0017 (4)0.0012 (5)
C5A0.0226 (5)0.0251 (6)0.0266 (6)−0.0011 (4)0.0047 (4)−0.0029 (5)
C6A0.0209 (5)0.0199 (5)0.0270 (6)0.0008 (4)0.0055 (4)0.0024 (4)
C7A0.0163 (5)0.0202 (5)0.0210 (5)0.0011 (4)0.0040 (4)0.0039 (4)
C8A0.0167 (5)0.0181 (5)0.0235 (5)0.0010 (4)0.0042 (4)0.0047 (4)
C9A0.0219 (5)0.0161 (5)0.0206 (5)0.0046 (4)−0.0001 (4)0.0046 (4)
C10A0.0387 (7)0.0284 (6)0.0210 (5)0.0059 (5)0.0034 (5)0.0019 (5)
O1B0.0289 (4)0.0194 (4)0.0248 (4)0.0009 (3)0.0027 (3)−0.0011 (3)
O2B0.0352 (5)0.0208 (4)0.0308 (4)0.0050 (3)0.0000 (4)0.0070 (3)
O3B0.0251 (4)0.0280 (4)0.0163 (4)−0.0002 (3)−0.0002 (3)0.0039 (3)
O4B0.0239 (4)0.0249 (4)0.0272 (4)0.0005 (3)−0.0025 (3)0.0027 (3)
O5B0.0236 (4)0.0258 (4)0.0192 (4)0.0026 (3)0.0009 (3)0.0058 (3)
N1B0.0348 (5)0.0211 (5)0.0156 (4)0.0012 (4)−0.0006 (4)0.0023 (4)
C1B0.0169 (5)0.0207 (5)0.0205 (5)0.0012 (4)0.0040 (4)0.0032 (4)
C2B0.0155 (5)0.0193 (5)0.0201 (5)0.0006 (4)0.0035 (4)0.0015 (4)
C3B0.0184 (5)0.0195 (5)0.0241 (5)0.0018 (4)0.0037 (4)0.0046 (4)
C4B0.0196 (5)0.0283 (6)0.0214 (5)0.0031 (4)0.0022 (4)0.0054 (4)
C5B0.0195 (5)0.0275 (6)0.0211 (5)0.0010 (4)0.0023 (4)−0.0009 (4)
C6B0.0196 (5)0.0194 (5)0.0244 (5)0.0010 (4)0.0044 (4)−0.0006 (4)
C7B0.0167 (5)0.0205 (5)0.0214 (5)0.0017 (4)0.0037 (4)0.0035 (4)
C8B0.0203 (5)0.0205 (5)0.0227 (5)0.0013 (4)0.0029 (4)0.0021 (4)
C9B0.0237 (5)0.0154 (5)0.0209 (5)0.0034 (4)0.0000 (4)0.0033 (4)
C10B0.0300 (6)0.0279 (6)0.0248 (6)0.0036 (5)0.0079 (5)0.0062 (5)
Geometric parameters (Å, º) top
O1A—C1A1.2027 (14)O1B—C1B1.2023 (14)
O2A—C8A1.2048 (14)O2B—C8B1.1998 (15)
O3A—N1A1.3849 (12)O3B—N1B1.3794 (12)
O3A—C9A1.3885 (14)O3B—C9B1.3980 (14)
O4A—C9A1.1914 (15)O4B—C9B1.1890 (15)
O5A—C9A1.3148 (14)O5B—C9B1.3116 (14)
O5A—C10A1.4517 (15)O5B—C10B1.4555 (14)
N1A—C8A1.4045 (14)N1B—C1B1.4002 (15)
N1A—C1A1.4087 (14)N1B—C8B1.4027 (15)
C1A—C2A1.4891 (15)C1B—C2B1.4888 (15)
C2A—C3A1.3837 (15)C2B—C3B1.3817 (16)
C2A—C7A1.3956 (15)C2B—C7B1.3958 (15)
C3A—C4A1.3986 (17)C3B—C4B1.3982 (16)
C3A—H3AA0.9500C3B—H3BA0.9500
C4A—C5A1.3928 (18)C4B—C5B1.3945 (17)
C4A—H4AA0.9500C4B—H4BA0.9500
C5A—C6A1.3975 (17)C5B—C6B1.3989 (17)
C5A—H5AA0.9500C5B—H5BA0.9500
C6A—C7A1.3815 (16)C6B—C7B1.3833 (16)
C6A—H6AA0.9500C6B—H6BA0.9500
C7A—C8A1.4845 (15)C7B—C8B1.4908 (15)
C10A—H10A0.9800C10B—H10D0.9800
C10A—H10B0.9800C10B—H10E0.9800
C10A—H10C0.9800C10B—H10F0.9800
N1A—O3A—C9A111.33 (8)N1B—O3B—C9B110.40 (9)
C9A—O5A—C10A114.27 (9)C9B—O5B—C10B113.62 (9)
O3A—N1A—C8A121.52 (9)O3B—N1B—C1B122.20 (9)
O3A—N1A—C1A120.85 (9)O3B—N1B—C8B121.91 (9)
C8A—N1A—C1A114.42 (9)C1B—N1B—C8B115.69 (9)
O1A—C1A—N1A125.64 (11)O1B—C1B—N1B125.87 (10)
O1A—C1A—C2A131.20 (10)O1B—C1B—C2B131.10 (10)
N1A—C1A—C2A103.13 (9)N1B—C1B—C2B103.02 (9)
C3A—C2A—C7A121.36 (11)C3B—C2B—C7B121.65 (10)
C3A—C2A—C1A129.54 (10)C3B—C2B—C1B129.07 (10)
C7A—C2A—C1A109.10 (9)C7B—C2B—C1B109.26 (9)
C2A—C3A—C4A117.42 (11)C2B—C3B—C4B117.10 (10)
C2A—C3A—H3AA121.3C2B—C3B—H3BA121.5
C4A—C3A—H3AA121.3C4B—C3B—H3BA121.5
C5A—C4A—C3A120.97 (11)C5B—C4B—C3B121.40 (10)
C5A—C4A—H4AA119.5C5B—C4B—H4BA119.3
C3A—C4A—H4AA119.5C3B—C4B—H4BA119.3
C4A—C5A—C6A121.41 (11)C4B—C5B—C6B121.06 (11)
C4A—C5A—H5AA119.3C4B—C5B—H5BA119.5
C6A—C5A—H5AA119.3C6B—C5B—H5BA119.5
C7A—C6A—C5A117.16 (11)C7B—C6B—C5B117.24 (11)
C7A—C6A—H6AA121.4C7B—C6B—H6BA121.4
C5A—C6A—H6AA121.4C5B—C6B—H6BA121.4
C6A—C7A—C2A121.67 (11)C6B—C7B—C2B121.55 (10)
C6A—C7A—C8A129.38 (10)C6B—C7B—C8B129.39 (10)
C2A—C7A—C8A108.95 (9)C2B—C7B—C8B109.03 (10)
O2A—C8A—N1A124.89 (11)O2B—C8B—N1B125.16 (11)
O2A—C8A—C7A131.55 (11)O2B—C8B—C7B131.84 (11)
N1A—C8A—C7A103.55 (9)N1B—C8B—C7B103.00 (9)
O4A—C9A—O5A129.96 (11)O4B—C9B—O5B130.60 (11)
O4A—C9A—O3A125.15 (10)O4B—C9B—O3B124.73 (10)
O5A—C9A—O3A104.85 (9)O5B—C9B—O3B104.66 (9)
O5A—C10A—H10A109.5O5B—C10B—H10D109.5
O5A—C10A—H10B109.5O5B—C10B—H10E109.5
H10A—C10A—H10B109.5H10D—C10B—H10E109.5
O5A—C10A—H10C109.5O5B—C10B—H10F109.5
H10A—C10A—H10C109.5H10D—C10B—H10F109.5
H10B—C10A—H10C109.5H10E—C10B—H10F109.5
C9A—O3A—N1A—C8A−84.35 (12)C9B—O3B—N1B—C1B−96.65 (12)
C9A—O3A—N1A—C1A117.04 (10)C9B—O3B—N1B—C8B78.04 (12)
O3A—N1A—C1A—O1A−8.90 (17)O3B—N1B—C1B—O1B−6.58 (18)
C8A—N1A—C1A—O1A−168.93 (10)C8B—N1B—C1B—O1B178.42 (11)
O3A—N1A—C1A—C2A169.42 (9)O3B—N1B—C1B—C2B174.59 (9)
C8A—N1A—C1A—C2A9.39 (12)C8B—N1B—C1B—C2B−0.41 (13)
O1A—C1A—C2A—C3A−7.3 (2)O1B—C1B—C2B—C3B3.3 (2)
N1A—C1A—C2A—C3A174.49 (11)N1B—C1B—C2B—C3B−178.00 (11)
O1A—C1A—C2A—C7A172.60 (11)O1B—C1B—C2B—C7B−178.47 (11)
N1A—C1A—C2A—C7A−5.58 (11)N1B—C1B—C2B—C7B0.27 (12)
C7A—C2A—C3A—C4A−0.50 (16)C7B—C2B—C3B—C4B−0.42 (16)
C1A—C2A—C3A—C4A179.42 (10)C1B—C2B—C3B—C4B177.66 (10)
C2A—C3A—C4A—C5A−0.12 (17)C2B—C3B—C4B—C5B0.31 (16)
C3A—C4A—C5A—C6A0.57 (18)C3B—C4B—C5B—C6B0.19 (17)
C4A—C5A—C6A—C7A−0.38 (17)C4B—C5B—C6B—C7B−0.57 (16)
C5A—C6A—C7A—C2A−0.24 (16)C5B—C6B—C7B—C2B0.46 (16)
C5A—C6A—C7A—C8A−179.74 (10)C5B—C6B—C7B—C8B−177.49 (11)
C3A—C2A—C7A—C6A0.70 (17)C3B—C2B—C7B—C6B0.03 (16)
C1A—C2A—C7A—C6A−179.24 (10)C1B—C2B—C7B—C6B−178.39 (10)
C3A—C2A—C7A—C8A−179.71 (10)C3B—C2B—C7B—C8B178.36 (10)
C1A—C2A—C7A—C8A0.35 (12)C1B—C2B—C7B—C8B−0.06 (12)
O3A—N1A—C8A—O2A10.35 (17)O3B—N1B—C8B—O2B5.73 (18)
C1A—N1A—C8A—O2A170.23 (10)C1B—N1B—C8B—O2B−179.25 (11)
O3A—N1A—C8A—C7A−169.10 (9)O3B—N1B—C8B—C7B−174.64 (9)
C1A—N1A—C8A—C7A−9.22 (12)C1B—N1B—C8B—C7B0.37 (13)
C6A—C7A—C8A—O2A5.2 (2)C6B—C7B—C8B—O2B−2.4 (2)
C2A—C7A—C8A—O2A−174.35 (11)C2B—C7B—C8B—O2B179.42 (12)
C6A—C7A—C8A—N1A−175.40 (11)C6B—C7B—C8B—N1B177.99 (11)
C2A—C7A—C8A—N1A5.05 (11)C2B—C7B—C8B—N1B−0.17 (12)
C10A—O5A—C9A—O4A−0.38 (17)C10B—O5B—C9B—O4B2.22 (17)
C10A—O5A—C9A—O3A−178.02 (8)C10B—O5B—C9B—O3B−178.74 (8)
N1A—O3A—C9A—O4A5.52 (14)N1B—O3B—C9B—O4B−2.43 (15)
N1A—O3A—C9A—O5A−176.69 (8)N1B—O3B—C9B—O5B178.46 (8)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C5A—H5AA···O3Bi0.952.543.3341 (15)141
C6A—H6AA···O4Aii0.952.513.4091 (15)158
C3B—H3BA···O2Aiii0.952.593.2281 (14)125
C6B—H6BA···O3Aiv0.952.553.3086 (14)137
C10B—H10F···O2Bv0.982.573.4956 (16)157
Symmetry codes: (i) −x, −y+1, −z; (ii) −x+1, −y+1, −z; (iii) −x+1, −y+1, −z+1; (iv) −x+1, −y+2, −z+1; (v) −x, −y+2, −z+1.
(3) 1,3-Dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl methyl carbonate top
Crystal data top
C14H9NO5F(000) = 1120
Mr = 271.22Dx = 1.563 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 16.512 (3) ÅCell parameters from 1261 reflections
b = 18.579 (3) Åθ = 3.4–26.9°
c = 7.6156 (13) ŵ = 0.12 mm−1
β = 99.434 (17)°T = 123 K
V = 2304.6 (7) Å3Needle, colorless
Z = 80.44 × 0.12 × 0.07 mm
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer		4156 independent reflections
Radiation source: Enhance (Mo) X-ray Source1898 reflections with I > 2σ(I)
Detector resolution: 10.5081 pixels mm-1Rint = 0.091
ω scansθmax = 25.3°, θmin = 3.3°
Absorption correction: analytical
(CrysAlis PRO; Agilent, 2012)		h = −15→19
Tmin = 0.995, Tmax = 0.999k = −22→21
9949 measured reflectionsl = −9→9
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.080H-atom parameters constrained
wR(F2) = 0.224 w = 1/[σ2(Fo2) + (0.0796P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
4156 reflectionsΔρmax = 0.33 e Å−3
363 parametersΔρmin = −0.39 e Å−3
Crystal data top
C14H9NO5V = 2304.6 (7) Å3
Mr = 271.22Z = 8
Monoclinic, P21/cMo Kα radiation
a = 16.512 (3) ŵ = 0.12 mm−1
b = 18.579 (3) ÅT = 123 K
c = 7.6156 (13) Å0.44 × 0.12 × 0.07 mm
β = 99.434 (17)°
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer		4156 independent reflections
Absorption correction: analytical
(CrysAlis PRO; Agilent, 2012)		1898 reflections with I > 2σ(I)
Tmin = 0.995, Tmax = 0.999Rint = 0.091
9949 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0800 restraints
wR(F2) = 0.224H-atom parameters constrained
S = 1.00Δρmax = 0.33 e Å−3
4156 reflectionsΔρmin = −0.39 e Å−3
363 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O1A0.3491 (2)0.31532 (15)0.1257 (5)0.0428 (9)
O2A0.5630 (2)0.44236 (15)0.4206 (4)0.0441 (9)
O3A0.4152 (2)0.43894 (14)0.2299 (4)0.0384 (9)
O4A0.3270 (2)0.41710 (15)0.4258 (4)0.0413 (9)
O5A0.31114 (19)0.50794 (14)0.2257 (4)0.0367 (8)
N1A0.4539 (3)0.37502 (17)0.2925 (5)0.0375 (10)
C1A0.4144 (3)0.3116 (2)0.2245 (7)0.0370 (12)
C2A0.4578 (3)0.2448 (2)0.2868 (6)0.0334 (11)
C3A0.5339 (3)0.2484 (2)0.4016 (6)0.0335 (11)
C4A0.5716 (3)0.3145 (2)0.4574 (6)0.0359 (12)
C5A0.5329 (3)0.3829 (2)0.3934 (6)0.0344 (12)
C6A0.4237 (3)0.1799 (2)0.2309 (6)0.0361 (12)
H6AA0.37220.17850.15430.043*
C7A0.4646 (3)0.1149 (2)0.2864 (7)0.0400 (13)
H7AA0.44150.07000.24510.048*
C8A0.5375 (3)0.1174 (2)0.3996 (7)0.0369 (12)
H8AA0.56420.07350.43760.044*
C9A0.5748 (3)0.1828 (2)0.4622 (7)0.0365 (12)
C10A0.6507 (3)0.1873 (2)0.5762 (7)0.0411 (13)
H10A0.67860.14430.61710.049*
C11A0.6852 (3)0.2519 (2)0.6293 (6)0.0385 (12)
H11A0.73650.25340.70690.046*
C12A0.6457 (3)0.3158 (2)0.5705 (6)0.0378 (12)
H12A0.67010.36060.60870.045*
C13A0.3473 (3)0.4514 (2)0.3079 (7)0.0354 (12)
C14A0.2353 (3)0.5276 (2)0.2859 (6)0.0427 (13)
H14A0.21340.57170.22530.064*
H14B0.24590.53580.41470.064*
H14C0.19530.48860.25830.064*
O1B0.1669 (2)0.82517 (15)0.5198 (4)0.0392 (8)
O2B−0.0410 (2)0.95254 (15)0.2005 (4)0.0468 (10)
O3B0.1021 (2)0.94818 (14)0.4052 (4)0.0384 (9)
O4B0.1866 (2)0.92546 (16)0.2003 (4)0.0434 (9)
O5B0.1998 (2)1.02184 (14)0.3847 (4)0.0392 (9)
N1B0.0622 (3)0.88420 (17)0.3479 (5)0.0363 (10)
C1B0.1017 (3)0.8213 (2)0.4202 (7)0.0359 (12)
C2B0.0594 (3)0.7545 (2)0.3564 (6)0.0325 (11)
C3B−0.0186 (3)0.7576 (2)0.2461 (6)0.0358 (12)
C4B−0.0567 (3)0.8244 (2)0.1926 (6)0.0349 (12)
C5B−0.0156 (3)0.8933 (2)0.2436 (7)0.0376 (12)
C6B0.0945 (3)0.6896 (2)0.4060 (6)0.0363 (12)
H6BA0.14620.68790.48200.044*
C7B0.0547 (3)0.6251 (2)0.3450 (7)0.0392 (13)
H7BA0.08030.58020.37800.047*
C8B−0.0194 (3)0.6266 (2)0.2403 (7)0.0400 (13)
H8BA−0.04540.58250.20160.048*
C9B−0.0595 (3)0.6923 (2)0.1864 (6)0.0356 (12)
C10B−0.1376 (3)0.6966 (2)0.0811 (7)0.0432 (13)
H10B−0.16520.65350.03950.052*
C11B−0.1745 (3)0.7611 (2)0.0371 (7)0.0459 (13)
H11B−0.22820.7626−0.03070.055*
C12B−0.1335 (3)0.8257 (2)0.0917 (7)0.0415 (13)
H12B−0.15920.87050.05850.050*
C13B0.1661 (3)0.9614 (2)0.3143 (7)0.0365 (12)
C14B0.2722 (3)1.0450 (2)0.3140 (7)0.0454 (14)
H14D0.29531.08800.37790.068*
H14E0.25691.05620.18710.068*
H14F0.31321.00630.32920.068*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O1A0.037 (2)0.0392 (18)0.047 (2)0.0021 (16)−0.0087 (18)−0.0011 (15)
O2A0.044 (2)0.0267 (16)0.058 (2)−0.0019 (16)−0.0013 (18)−0.0040 (15)
O3A0.037 (2)0.0299 (16)0.046 (2)0.0043 (15)−0.0004 (17)0.0045 (14)
O4A0.048 (2)0.0313 (16)0.044 (2)0.0042 (16)0.0033 (18)0.0056 (16)
O5A0.039 (2)0.0245 (15)0.045 (2)0.0049 (15)0.0022 (17)0.0062 (14)
N1A0.038 (3)0.0219 (19)0.049 (3)0.0043 (18)−0.003 (2)−0.0012 (17)
C1A0.041 (4)0.029 (2)0.040 (3)0.001 (2)0.003 (3)0.000 (2)
C2A0.034 (3)0.026 (2)0.040 (3)−0.003 (2)0.005 (2)0.001 (2)
C3A0.036 (3)0.027 (2)0.037 (3)0.002 (2)0.005 (2)0.003 (2)
C4A0.036 (3)0.032 (2)0.038 (3)−0.002 (2)0.000 (2)−0.002 (2)
C5A0.038 (3)0.031 (3)0.033 (3)−0.003 (2)0.004 (2)0.000 (2)
C6A0.036 (3)0.035 (3)0.037 (3)−0.006 (2)0.005 (2)−0.001 (2)
C7A0.043 (4)0.029 (2)0.048 (3)−0.002 (2)0.010 (3)−0.006 (2)
C8A0.043 (4)0.029 (2)0.038 (3)0.004 (2)0.006 (3)0.002 (2)
C9A0.037 (3)0.029 (2)0.044 (3)0.002 (2)0.007 (3)−0.005 (2)
C10A0.039 (3)0.035 (3)0.048 (4)0.007 (2)0.006 (3)0.002 (2)
C11A0.029 (3)0.045 (3)0.039 (3)0.002 (2)−0.005 (2)−0.001 (2)
C12A0.042 (3)0.034 (2)0.037 (3)0.000 (2)0.004 (3)−0.009 (2)
C13A0.036 (3)0.031 (2)0.038 (3)−0.004 (2)0.003 (3)−0.003 (2)
C14A0.041 (3)0.037 (3)0.046 (3)0.002 (2)−0.002 (3)0.002 (2)
O1B0.035 (2)0.0361 (17)0.044 (2)0.0022 (16)−0.0005 (17)−0.0033 (15)
O2B0.050 (3)0.0270 (17)0.059 (3)0.0022 (16)−0.0037 (19)0.0046 (15)
O3B0.040 (2)0.0257 (16)0.048 (2)−0.0046 (15)0.0019 (18)−0.0046 (14)
O4B0.050 (2)0.0384 (18)0.041 (2)−0.0032 (16)0.0047 (18)−0.0054 (16)
O5B0.046 (2)0.0265 (16)0.043 (2)−0.0059 (15)0.0031 (17)−0.0044 (14)
N1B0.037 (3)0.0213 (19)0.046 (3)−0.0027 (18)−0.006 (2)−0.0020 (17)
C1B0.033 (3)0.036 (3)0.037 (3)0.005 (2)0.002 (3)0.001 (2)
C2B0.035 (3)0.027 (2)0.035 (3)0.001 (2)0.002 (2)−0.007 (2)
C3B0.040 (3)0.030 (2)0.038 (3)0.001 (2)0.005 (2)0.003 (2)
C4B0.033 (3)0.032 (2)0.038 (3)−0.004 (2)0.001 (2)0.000 (2)
C5B0.040 (4)0.032 (3)0.041 (3)−0.001 (2)0.006 (3)−0.002 (2)
C6B0.039 (3)0.031 (2)0.039 (3)0.001 (2)0.008 (2)0.003 (2)
C7B0.047 (4)0.025 (2)0.046 (3)0.002 (2)0.010 (3)0.003 (2)
C8B0.040 (4)0.030 (2)0.050 (4)−0.004 (2)0.006 (3)−0.002 (2)
C9B0.037 (3)0.036 (3)0.032 (3)−0.005 (2)0.003 (2)−0.002 (2)
C10B0.041 (4)0.037 (3)0.049 (3)−0.009 (2)0.000 (3)0.005 (2)
C11B0.042 (3)0.048 (3)0.045 (3)−0.006 (3)−0.001 (3)0.001 (2)
C12B0.040 (4)0.037 (3)0.046 (3)0.001 (2)0.002 (3)0.006 (2)
C13B0.036 (3)0.030 (3)0.042 (3)0.002 (2)0.000 (3)0.007 (2)
C14B0.044 (4)0.037 (3)0.055 (4)−0.010 (2)0.007 (3)0.001 (2)
Geometric parameters (Å, º) top
O1A—C1A1.211 (6)O1B—C1B1.212 (5)
O2A—C5A1.215 (5)O2B—C5B1.204 (5)
O3A—C13A1.371 (5)O3B—C13B1.377 (5)
O3A—N1A1.395 (4)O3B—N1B1.394 (4)
O4A—C13A1.193 (5)O4B—C13B1.188 (5)
O5A—C13A1.316 (5)O5B—C13B1.326 (5)
O5A—C14A1.449 (5)O5B—C14B1.455 (5)
N1A—C1A1.403 (6)N1B—C5B1.405 (6)
N1A—C5A1.408 (6)N1B—C1B1.406 (6)
C1A—C2A1.473 (6)C1B—C2B1.468 (6)
C2A—C6A1.370 (6)C2B—C6B1.365 (6)
C2A—C3A1.409 (6)C2B—C3B1.419 (6)
C3A—C4A1.410 (6)C3B—C4B1.419 (6)
C3A—C9A1.432 (6)C3B—C9B1.427 (6)
C4A—C12A1.377 (7)C4B—C12B1.371 (7)
C4A—C5A1.471 (6)C4B—C5B1.472 (6)
C6A—C7A1.413 (6)C6B—C7B1.408 (6)
C6A—H6AA0.9500C6B—H6BA0.9500
C7A—C8A1.362 (7)C7B—C8B1.347 (7)
C7A—H7AA0.9500C7B—H7BA0.9500
C8A—C9A1.410 (6)C8B—C9B1.417 (6)
C8A—H8AA0.9500C8B—H8BA0.9500
C9A—C10A1.405 (7)C9B—C10B1.404 (7)
C10A—C11A1.361 (6)C10B—C11B1.362 (6)
C10A—H10A0.9500C10B—H10B0.9500
C11A—C12A1.392 (6)C11B—C12B1.406 (6)
C11A—H11A0.9500C11B—H11B0.9500
C12A—H12A0.9500C12B—H12B0.9500
C14A—H14A0.9800C14B—H14D0.9800
C14A—H14B0.9800C14B—H14E0.9800
C14A—H14C0.9800C14B—H14F0.9800
C13A—O3A—N1A110.9 (3)C13B—O3B—N1B111.0 (3)
C13A—O5A—C14A113.6 (3)C13B—O5B—C14B114.6 (4)
O3A—N1A—C1A115.4 (4)O3B—N1B—C5B114.5 (3)
O3A—N1A—C5A115.4 (3)O3B—N1B—C1B114.9 (4)
C1A—N1A—C5A128.4 (4)C5B—N1B—C1B130.2 (4)
O1A—C1A—N1A119.6 (4)O1B—C1B—N1B120.2 (4)
O1A—C1A—C2A125.8 (4)O1B—C1B—C2B125.7 (4)
N1A—C1A—C2A114.6 (5)N1B—C1B—C2B114.0 (5)
C6A—C2A—C3A120.9 (4)C6B—C2B—C3B120.2 (4)
C6A—C2A—C1A119.3 (5)C6B—C2B—C1B119.8 (5)
C3A—C2A—C1A119.8 (4)C3B—C2B—C1B119.9 (4)
C2A—C3A—C4A122.2 (4)C2B—C3B—C4B121.4 (4)
C2A—C3A—C9A119.0 (4)C2B—C3B—C9B119.3 (4)
C4A—C3A—C9A118.8 (5)C4B—C3B—C9B119.2 (5)
C12A—C4A—C3A120.5 (4)C12B—C4B—C3B120.1 (4)
C12A—C4A—C5A119.1 (4)C12B—C4B—C5B118.5 (4)
C3A—C4A—C5A120.4 (5)C3B—C4B—C5B121.4 (5)
O2A—C5A—N1A120.3 (4)O2B—C5B—N1B120.7 (4)
O2A—C5A—C4A125.9 (5)O2B—C5B—C4B126.7 (5)
N1A—C5A—C4A113.8 (4)N1B—C5B—C4B112.5 (4)
C2A—C6A—C7A120.5 (5)C2B—C6B—C7B120.4 (5)
C2A—C6A—H6AA119.7C2B—C6B—H6BA119.8
C7A—C6A—H6AA119.7C7B—C6B—H6BA119.8
C8A—C7A—C6A119.3 (4)C8B—C7B—C6B120.5 (4)
C8A—C7A—H7AA120.3C8B—C7B—H7BA119.8
C6A—C7A—H7AA120.3C6B—C7B—H7BA119.8
C7A—C8A—C9A122.3 (4)C7B—C8B—C9B121.7 (4)
C7A—C8A—H8AA118.8C7B—C8B—H8BA119.1
C9A—C8A—H8AA118.8C9B—C8B—H8BA119.1
C10A—C9A—C8A123.8 (4)C10B—C9B—C8B123.8 (4)
C10A—C9A—C3A118.3 (4)C10B—C9B—C3B118.4 (4)
C8A—C9A—C3A117.9 (5)C8B—C9B—C3B117.8 (5)
C11A—C10A—C9A121.6 (4)C11B—C10B—C9B121.5 (5)
C11A—C10A—H10A119.2C11B—C10B—H10B119.2
C9A—C10A—H10A119.2C9B—C10B—H10B119.2
C10A—C11A—C12A120.3 (5)C10B—C11B—C12B120.2 (5)
C10A—C11A—H11A119.9C10B—C11B—H11B119.9
C12A—C11A—H11A119.9C12B—C11B—H11B119.9
C4A—C12A—C11A120.5 (4)C4B—C12B—C11B120.5 (5)
C4A—C12A—H12A119.7C4B—C12B—H12B119.8
C11A—C12A—H12A119.7C11B—C12B—H12B119.8
O4A—C13A—O5A128.5 (4)O4B—C13B—O5B128.3 (5)
O4A—C13A—O3A126.0 (4)O4B—C13B—O3B126.9 (4)
O5A—C13A—O3A105.6 (4)O5B—C13B—O3B104.7 (4)
O5A—C14A—H14A109.5O5B—C14B—H14D109.5
O5A—C14A—H14B109.5O5B—C14B—H14E109.5
H14A—C14A—H14B109.5H14D—C14B—H14E109.5
O5A—C14A—H14C109.5O5B—C14B—H14F109.5
H14A—C14A—H14C109.5H14D—C14B—H14F109.5
H14B—C14A—H14C109.5H14E—C14B—H14F109.5
C13A—O3A—N1A—C1A75.2 (5)C13B—O3B—N1B—C5B−107.2 (4)
C13A—O3A—N1A—C5A−113.9 (4)C13B—O3B—N1B—C1B79.7 (5)
O3A—N1A—C1A—O1A−3.6 (6)O3B—N1B—C1B—O1B−2.2 (6)
C5A—N1A—C1A—O1A−173.0 (5)C5B—N1B—C1B—O1B−173.9 (5)
O3A—N1A—C1A—C2A177.8 (4)O3B—N1B—C1B—C2B−179.2 (3)
C5A—N1A—C1A—C2A8.3 (7)C5B—N1B—C1B—C2B9.1 (7)
O1A—C1A—C2A—C6A0.3 (8)O1B—C1B—C2B—C6B−1.7 (8)
N1A—C1A—C2A—C6A178.8 (4)N1B—C1B—C2B—C6B175.1 (4)
O1A—C1A—C2A—C3A179.8 (5)O1B—C1B—C2B—C3B177.2 (4)
N1A—C1A—C2A—C3A−1.6 (6)N1B—C1B—C2B—C3B−6.0 (7)
C6A—C2A—C3A—C4A178.2 (4)C6B—C2B—C3B—C4B180.0 (4)
C1A—C2A—C3A—C4A−1.3 (7)C1B—C2B—C3B—C4B1.1 (7)
C6A—C2A—C3A—C9A−1.1 (7)C6B—C2B—C3B—C9B−0.5 (7)
C1A—C2A—C3A—C9A179.4 (4)C1B—C2B—C3B—C9B−179.4 (4)
C2A—C3A—C4A—C12A179.6 (4)C2B—C3B—C4B—C12B−177.4 (4)
C9A—C3A—C4A—C12A−1.1 (7)C9B—C3B—C4B—C12B3.1 (7)
C2A—C3A—C4A—C5A−1.3 (7)C2B—C3B—C4B—C5B2.3 (7)
C9A—C3A—C4A—C5A178.0 (4)C9B—C3B—C4B—C5B−177.2 (4)
O3A—N1A—C5A—O2A−0.2 (7)O3B—N1B—C5B—O2B4.6 (6)
C1A—N1A—C5A—O2A169.3 (4)C1B—N1B—C5B—O2B176.3 (4)
O3A—N1A—C5A—C4A179.8 (3)O3B—N1B—C5B—C4B−177.6 (3)
C1A—N1A—C5A—C4A−10.7 (7)C1B—N1B—C5B—C4B−5.9 (7)
C12A—C4A—C5A—O2A5.6 (8)C12B—C4B—C5B—O2B−3.0 (8)
C3A—C4A—C5A—O2A−173.4 (5)C3B—C4B—C5B—O2B177.3 (5)
C12A—C4A—C5A—N1A−174.3 (4)C12B—C4B—C5B—N1B179.4 (4)
C3A—C4A—C5A—N1A6.6 (7)C3B—C4B—C5B—N1B−0.3 (7)
C3A—C2A—C6A—C7A−0.5 (7)C3B—C2B—C6B—C7B1.4 (7)
C1A—C2A—C6A—C7A179.0 (4)C1B—C2B—C6B—C7B−179.7 (4)
C2A—C6A—C7A—C8A1.5 (7)C2B—C6B—C7B—C8B−1.5 (7)
C6A—C7A—C8A—C9A−0.9 (7)C6B—C7B—C8B—C9B0.6 (8)
C7A—C8A—C9A—C10A−178.7 (5)C7B—C8B—C9B—C10B−178.4 (5)
C7A—C8A—C9A—C3A−0.6 (7)C7B—C8B—C9B—C3B0.3 (7)
C2A—C3A—C9A—C10A179.8 (4)C2B—C3B—C9B—C10B178.4 (4)
C4A—C3A—C9A—C10A0.5 (7)C4B—C3B—C9B—C10B−2.1 (7)
C2A—C3A—C9A—C8A1.6 (7)C2B—C3B—C9B—C8B−0.4 (7)
C4A—C3A—C9A—C8A−177.7 (4)C4B—C3B—C9B—C8B179.2 (4)
C8A—C9A—C10A—C11A178.2 (4)C8B—C9B—C10B—C11B178.1 (5)
C3A—C9A—C10A—C11A0.2 (8)C3B—C9B—C10B—C11B−0.6 (8)
C9A—C10A—C11A—C12A−0.3 (7)C9B—C10B—C11B—C12B2.3 (8)
C3A—C4A—C12A—C11A1.0 (8)C3B—C4B—C12B—C11B−1.4 (8)
C5A—C4A—C12A—C11A−178.0 (4)C5B—C4B—C12B—C11B178.9 (4)
C10A—C11A—C12A—C4A−0.3 (7)C10B—C11B—C12B—C4B−1.3 (8)
C14A—O5A—C13A—O4A−2.6 (7)C14B—O5B—C13B—O4B−1.5 (7)
C14A—O5A—C13A—O3A177.5 (3)C14B—O5B—C13B—O3B177.3 (3)
N1A—O3A—C13A—O4A6.8 (6)N1B—O3B—C13B—O4B0.7 (7)
N1A—O3A—C13A—O5A−173.3 (3)N1B—O3B—C13B—O5B−178.1 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C6A—H6AA···O4Ai0.952.513.159 (5)125
C7B—H7BA···O2Bii0.952.513.229 (5)133
C10B—H10B···O5Bii0.952.603.428 (5)146
C11B—H11B···O1Aiii0.952.483.270 (6)141
C14A—H14A···O1Biv0.982.513.481 (5)169
C14B—H14E···O4Aiv0.982.513.306 (6)138
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x, y−1/2, −z+1/2; (iii) −x, −y+1, −z; (iv) x, −y+3/2, z−1/2.
Hydrogen-bond geometry (Å, º) for (1) top
D—H···AD—HH···AD···AD—H···A
C4—H4A···O2i0.952.383.190 (4)143
C9—H9A···O1ii0.982.543.428 (7)151
C9—H9B···O1iii0.982.533.260 (8)131
Symmetry codes: (i) x−1, y+1, z; (ii) −x+2, y−1/2, −z+1/2; (iii) −x+1, y−1/2, −z+1/2.
Hydrogen-bond geometry (Å, º) for (2) top
D—H···AD—HH···AD···AD—H···A
C5A—H5AA···O3Bi0.952.543.3341 (15)141
C6A—H6AA···O4Aii0.952.513.4091 (15)158
C3B—H3BA···O2Aiii0.952.593.2281 (14)125
C6B—H6BA···O3Aiv0.952.553.3086 (14)137
C10B—H10F···O2Bv0.982.573.4956 (16)157
Symmetry codes: (i) −x, −y+1, −z; (ii) −x+1, −y+1, −z; (iii) −x+1, −y+1, −z+1; (iv) −x+1, −y+2, −z+1; (v) −x, −y+2, −z+1.
Hydrogen-bond geometry (Å, º) for (3) top
D—H···AD—HH···AD···AD—H···A
C6A—H6AA···O4Ai0.952.513.159 (5)125
C7B—H7BA···O2Bii0.952.513.229 (5)133
C10B—H10B···O5Bii0.952.603.428 (5)146
C11B—H11B···O1Aiii0.952.483.270 (6)141
C14A—H14A···O1Biv0.982.513.481 (5)169
C14B—H14E···O4Aiv0.982.513.306 (6)138
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x, y−1/2, −z+1/2; (iii) −x, −y+1, −z; (iv) x, −y+3/2, z−1/2.

Experimental details

(1)(2)(3)
Crystal data
Chemical formulaC9H7NO3C10H7NO5C14H9NO5
Mr177.16221.17271.22
Crystal system, space groupOrthorhombic, P212121Triclinic, P1Monoclinic, P21/c
Temperature (K)123123123
a, b, c (Å)4.2987 (4), 7.0243 (10), 27.587 (4)7.0363 (4), 11.0082 (5), 12.4239 (6)16.512 (3), 18.579 (3), 7.6156 (13)
α, β, γ (°)90, 90, 9098.884 (4), 96.159 (4), 93.009 (4)90, 99.434 (17), 90
V (Å3)832.98 (19)942.95 (8)2304.6 (7)
Z448
Radiation typeMo KαCu KαMo Kα
µ (mm−1)0.111.100.12
Crystal size (mm)0.66 × 0.23 × 0.040.35 × 0.25 × 0.080.44 × 0.12 × 0.07
Data collection
DiffractometerAgilent Xcalibur (Ruby, Gemini)
diffractometer		SuperNova (Dual, Cu at zero, Atlas)
diffractometer		Agilent Xcalibur (Ruby, Gemini)
diffractometer
Absorption correctionAnalytical
(CrysAlis PRO; Agilent, 2012)		Multi-scan
(CrysAlis PRO; Agilent, 2012)		Analytical
(CrysAlis PRO; Agilent, 2012)
Tmin, Tmax0.946, 0.9960.807, 1.0000.995, 0.999
No. of measured, independent and
observed [I > 2σ(I)] reflections		5145, 2259, 1989 6437, 3803, 3516 9949, 4156, 1898
Rint0.0870.0180.091
(sin θ/λ)max (Å−1)0.7270.6310.600
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.099, 0.229, 1.13 0.033, 0.089, 1.06 0.080, 0.224, 1.00
No. of reflections225938034156
No. of parameters119291363
H-atom treatmentH-atom parameters constrainedH-atom parameters constrainedH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.50, −0.330.29, −0.210.33, −0.39

Computer programs: CrysAlis PRO (Agilent, 2012), SUPERFLIP (Palatinus & Chapuis, 2007), SHELXS2013 (Sheldrick, 2008), SUPERFLIP (Palatinus et al. 2007), SHELXL2013 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

 

Acknowledgements

FE wishes to acknowledge Dr Ivan Edafiogho, University of Saint Joseph SOP and Professor Emeritus Kenneth R. Scott, for their generous donation of the compounds studied. The authors are indebted to Mr James P. Stables (retired), Epilepsy Branch, Division of Convulsive, Developmental and Neuromuscular Disorders, National Institute of Neurological Disorders and Stroke, for helpful discussions and initial data. The authors wish to acknowledge Drs Ivan Edafiogho and Mariano S. Alexander, for their generous assistance and support in completing this project. RJB is grateful to the NSF–MRI program (grant CHE-0619278) for funds to purchase the diffractometer and the Howard University Nanoscience Facility for access to liquid nitro­gen.

References

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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

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ISSN: 2056-9890
Volume 70| Part 12| December 2014| Pages 456-461
doi:10.1107/S1600536814023769
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