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

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296

Methane­sulfonic acid salt forms of carbamazepine and 10,11-di­hydro­carbamazepine

aPharmorphix Limited, 250 Cambridge Science Park Milton Road, Cambridge CB4 0WE, England, and bDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, England
*Correspondence e-mail: chris.frampton@sial.com

(Received 4 September 2013; accepted 17 October 2013; online 31 October 2013)

New methane­sulfonic acid salt forms of the anti­convulsant and analgesic active pharmaceutical ingredient carbamazepine and its closely related structural analogue 10,11-di­hydro­carbamazepine have been prepared and characterized by single-crystal X-ray diffraction at 120 and 100 K, respectively {namely [(5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)methyl­idene]aza­nium methane­sulfonate, C15H13N2O+·CH3SO3, and [(10,11-di­hydro-5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)methyl­idene]aza­nium methane­sulfonate, C15H15N2O+·CH3SO3}. In light of the structural information obtained, the crystal structure of the carbamazepine tri­fluoro­acetic acid monosol­vate [dibenzo[b,f]azepine-5-carboxamide–tri­fluoro­acetic acid (1/1), C15H12N2O·CF3COOH] was redetermined at 100 and 270 K, and from this data it was concluded that the protonation state for this solvate species is best described as in an `inter­mediate state' with the acidic proton located almost at the mid-point between the acid and base.

1. Introduction

The anti­convulsant and analgesic pharmaceutical material carbamazepine [CBZ, (1)] and its closely related structural analogue 10,11-di­hydro­carbamazepine [DHCBZ, (2)] (see Scheme) have been used extensively as model compounds in a number of crystal engineering, cocrystallization and structure-prediction studies (Tiekink et al., 2010[Tiekink, E. R. T., Vittal, J. & Zaworotko, M. (2010). Editors. Organic Crystal Engineering: Frontiers in Crystal Engineering. Chichester, England: John Wiley & Sons Ltd.]). One reason for this is that these mol­ecules represent relatively simple structural examples of active pharmaceutical ingredients (APIs) which exhibit a single sterically accessible carboxamide functional group (–CONH2) available as a supra­molecular synthon for inter­molecular hydrogen bonding. CBZ has been shown to exist in five true polymorphic forms. Forms I–IV all utilize the carboxamide supra­molecular synthon to form a cyclic R22(8) homosynthon with only the syn-oriented (Allen et al., 1999[Allen, F. H., Motherwell, W. D. S., Raithby, P. R., Shields, G. P. & Taylor, R. (1999). New J. Chem. pp. 25-34.]) N—H group participating in the formation of the dimer (Grzesiak et al., 2003[Grzesiak, A. L., Lang, M., Kim, K. & Matzger, A. J. (2003). J. Pharm. Sci. 91, 1186-1190.]). The anti-oriented N—H group is not utilized in the formation of the supra­molecular complex thereby breaking Etter's first rule of hydrogen bonding which states `all good proton donors and acceptors are used in hydrogen bonding' (Etter, 1990[Etter, M. C. (1990). Acc. Chem. Res. 23, 120-126.]). More recently the preparation and structure determination of the computationally predicted (Florence, Johnston et al., 2006[Florence, A. J., Johnston, A., Price, S. L., Nowell, H., Kennedy, A. R. & Shankland, N. (2006). J. Pharm. Sci. 95, 1918-1930.]; Florence, Leech et al., 2006[Florence, A. J., Leech, C. K., Shankland, K., Shankland, N. & Johnston, A. (2006). CrystEngComm, 8, 746-747.]) catemeric Form V was achieved by using a seed crystal of the catemeric ortho­rhom­bic Form II of DHCBZ (Harrison et al., 2006[Harrison, W. T. A., Yathirajan, H. S. & Anilkumar, H. G. (2006). Acta Cryst. C62, o240-o242.]) to template growth of a crystal of Form V of CBZ from the vapour phase (Arlin et al., 2011[Arlin, J.-B., Price, L. S., Price, S. L. & Florence, A. J. (2011). Chem. Commun. 47, 7074-7076.]). In this example, the anti-oriented N—H group participates in the formation of the catemeric chain leaving the syn-oriented N—H donor uncoordinated. Fleischman et al. (2003[Fleischman, S. G., Kuduva, S. S., McMahon, J. A., Moulton, B., Bailey Walsh, R. D., Rodriquez-Hornedo, N. & Zaworotko, M. J. (2003). Cryst. Growth Des. 3, 909-919.]) reported the preparation and structural characterization of 13 supra­molecular complexes of CBZ and categorized the formation of the CBZ complexes into two different bonding strategies. The first strategy was one in which the integrity of the carboxamide R22(8) homosynthon was maintained and the free anti-orientated N—H group was available for further hydrogen-bonding inter­actions with a non-acid coformer, for example, acetone (Fig. 1[link]a). Other complexes categorized within this bonding strategy included those with dimethyl sulfoxide (DMSO), benzo­quinone, terephthalaldehyde, saccharin and nicotinamide. The second strategy results in the preferential formation of a heterosynthon with a carb­oxy­lic acid coformer over the formation of the homosynthon, for example, the acetic acid complex shown in Fig. 1[link](b).

[Figure 1]
Figure 1
CBZ bonding strategies, see §1[link] for further explanation.

In addition, five further examples of this bonding strategy with a carb­oxy­lic acid moiety were given, viz. the complexes with formic acid, butyric acid, trimesic acid, nitro­isophthalic acid and adamantane-1,3,5,7-tetra­carb­oxy­lic acid. The pKa values for these six acids all fall within the range 3.12–4.83 (Brown, 1955[Brown, H. C. (1955). In Determination of Organic Structures by Physical Methods, edited by E. A. Braude & F. C. Nachod. New York: Academic Press.]; Bjerrum, 1958[Bjerrum, J. (1958). Stability Constants of Metal-ion Complexes, with Solubil Products of Inorganic Substances. Part 2. Inorganic Ligands. London: Chemical Society.]). The Fleischman paper also reported the first described example of a crystal structure containing two independent amide–amide homosynthons in the mol­ecular complex of CBZ with formamide. A detailed systematic study of the packing motifs present in 23 carbamazepine structures and two close analogues was undertaken by Gelbrich & Hursthouse (2006[Gelbrich, T. & Hursthouse, M. B. (2006). CrystEngComm, 8, 448-460.]) using the XPac method. The analysis demonstrated that all the structures could be described by just four primary supra­molecular constructs. In a more recent paper, Childs et al. (2009[Childs, S. L., Wood, P. A., Rodriguez-Hornedo, N., Reddy, L. S. & Hardcastle, K. I. (2009). Cryst. Growth Des. 9, 1869-1888.]) expanded on this work and analysed the similarity relationships in the crystal packing motifs for a set of 50 crystal structures containing CBZ. The results demonstrated that all the CBZ complexes studied fall into one of three primary crystal-packing motifs, viz. the translation stack, inversion cup or coformer pairing. This study included a set of 13 new crystal structures which contained coformers that exhibited either a mono- or di­carb­oxy­lic acid functionality. One particular structure analysed as part of this clustering study was that of the tri­fluoro­acetic acid (TFA) solvate of CBZ (Fernandes et al., 2007[Fernandes, P., Bardin, J., Johnston, A., Florence, A. J., Leech, C. K., David, W. I. F. & Shankland, K. (2007). Acta Cryst. E63, o4269.]). This particular crystal structure, determined at 150 K, was analysed as a solvated species with the acidic H atom located on the carb­oxy­lic acid moiety, although an O—H distance restraint was required. The pKa value of TFA is reported to be ca −0.26 (Milne & Parker, 1981[Milne, J. B. & Parker, T. J. (1981). J. Solution Chem. 10, 479-487.]). All the solid forms of CBZ and DHCBZ so far described fall into the categories of polymorph and cocrystal/solvate. A classical salt form of CBZ, where the poorly ionizable carboxamide entity is formally protonated through the carbonyl O atom is rare and has lead to the assertion in the past that the CBZ drug substance is non-ionizable (Good & Rodriguez-Hornedo, 2009[Good, D. J. & Rodriguez-Hornedo, N. (2009). Cryst. Growth. Des. 9, 2252-2264.]; Bethune et al., 2009[Bethune, S. J., Huang, N., Jayasanker, A. & Rodriguez-Hornedo, N. (2009). Cryst. Growth Des. 9, 3976-3988.]; Huang & Rodriguez-Hornedo, 2011[Huang, N. & Rodriguez-Hornedo, N. (2011). CrystEngComm, 13, 5409-5422.]). However, a recent paper (Perumalla & Sun, 2012[Perumalla, S. R. & Sun, C. C. (2012). Chem. Eur. J. 18, 6462-6464.]) describes the first clear example of the classical salt form of CBZ, an HCl salt prepared through the use of either a methanol–HCl solution (1.25 M) or a 1,4-di­oxane–HCl solution (4.0 M). The use of an aqueous HCl reagent, even concentrated HCl, always resulted in the formation of the stable CBZ dihydrate. The single-crystal X-ray structure of this material clearly shows that protonation of the carbonyl group of the carboxamide synthon had been achieved [Cambridge Structural Database (CSD; Version 5.34, November 2012 release; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]) refcode XAYGIP]. In this paper, we present the single-crystal X-ray structures of the methane­sulfonic acid salt forms of CBZ {[(5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)methyl­idene]aza­nium methane­sul­fon­ate, (3)} and its structural analogue DHCBZ {[(10,11-di­hydro-5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)methyl­idene]aza­nium methane­sulfonate, (4)}. In light of the structural data obtained from these species and that mined from the CSD, the single-crystal X-ray structure of the TFA solvate of CBZ [dibenzo[b,f]azepine-5-carboxamide–tri­fluoro­acetic acid (1/1)] was redetermined at both 100 K [structure (5)] and 270 K [structure (6)] to investigate the protonation state of this material further.

[Scheme 1]

2. Experimental

2.1. Synthesis and crystallization

Carbamazepine, 10,11-di­hydro­carbamazepine and methane­sulfonic acid were obtained from Sigma–Aldrich (purity ≥ 99%). Salts (3) and (4) were prepared by maturation of a neat methane­sulfonic acid solution of either (1) or (2) according to the following method. (1) or (2) (50 mg) was weighed into a 1.5 ml HPLC vial. Methane­sulfonic acid (500 µl) was added to create a suspension at room temperature. The resulting slurry was then placed in a platform shaker incubator (Heidolph Titramax/Inkubator 1000) and subjected to a series of heating–cooling cycles under shaking from room temperature (RT) to 323 K (8 h cycles; heating to 323 K for 4 h and then cooling to RT for a further 4 h) for a maximum of 24 h. Single crystals of (3) and (4) suitable for X-ray diffraction studies were grown directly by slow evaporation of 10 µl of the maturated neat methane­sulfonic acid solution of either (1) or (2) on a microscope slide. Crystals of the CBZ–TFA complex, (5)/(6), were prepared from the crystallization of a neat TFA solution of (1). The complete list of structures contained within the CSD data set and their specifically defined parameters is available as Supplementary data.

2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1[link]. The positional coordinates of the N-bound H atoms were all located from a difference Fourier map and freely refined along with an isotropic displacement parameter. The remaining H atoms were positioned geometrically and refined using riding models (including free rotation about the methyl C—S bond), with C—H = 0.95–0.99 Å and Uiso(H) = 1.5Ueq(C) for methyl groups and 1.2Ueq(C) otherwise. The –CF3 rotational disorder present in structures (5) and (6) was refined using a two-part model with the F-atom parameters and the occupancies allowed to refine freely. The final refined occupancies of the two components converged at 0.738 (15):0.262 (15) and 0.505 (9):0.495 (9) for (5) and (6), respectively.

Table 1
Experimental details

  (3) (4) (5) (6)
Crystal data
Chemical formula C15H13N2O+·CH3O3S C15H15N2O+·CH3O3S C15H12N2O·C2HF3O2 C15H12N2O·C2HF3O2
Mr 332.37 334.38 350.29 350.29
Crystal system, space group Monoclinic, P21/c Monoclinic, P21/c Monoclinic, P21/n Monoclinic, P21/n
Temperature (K) 120 100 100 270
a, b, c (Å) 5.5673 (7), 15.7196 (19), 18.125 (2) 5.4477 (2), 15.7340 (7), 18.5034 (8) 14.9968 (12), 5.2660 (3), 20.1911 (12) 14.9970 (3), 5.3712 (1), 20.4441 (4)
β (°) 97.641 (4) 96.647 (4) 102.191 (7) 101.529 (2)
V3) 1572.1 (3) 1575.34 (11) 1558.60 (18) 1613.58 (5)
Z 4 4 4 4
Radiation type Mo Kα Mo Kα Cu Kα Cu Kα
μ (mm−1) 0.23 0.23 1.10 1.06
Crystal size (mm) 0.35 × 0.18 × 0.10 0.30 × 0.20 × 0.12 0.45 × 0.20 × 0.10 0.45 × 0.25 × 0.18
 
Data collection
Diffractometer Bruker SMART 1K CCD area-detector diffractometer Agilent SuperNova (Dual, Cu at zero, Atlas) diffractometer SuperNova (Dual, Cu at zero, Atlas) diffractometer SuperNova (Dual, Cu at zero, Atlas) diffractometer
Absorption correction Multi-scan (CrysAlis PRO; Agilent, 2011[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, Oxfordshire, England.]) Multi-scan (CrysAlis PRO; Agilent, 2011[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, Oxfordshire, England.]) Multi-scan (CrysAlis PRO; Agilent, 2011[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, Oxfordshire, England.])
Tmin, Tmax 0.766, 1.000 0.650, 1.000 0.738, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 13272, 3203, 2626 7104, 3215, 2783 7053, 3189, 2937 7096, 3302, 2957
Rint 0.033 0.021 0.030 0.021
(sin θ/λ)max−1) 0.625 0.625 0.625 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.098, 1.00 0.032, 0.090, 1.00 0.047, 0.137, 1.01 0.050, 0.155, 1.00
No. of reflections 3203 3215 3189 3302
No. of parameters 221 221 266 267
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.27, −0.40 0.38, −0.44 0.26, −0.29 0.34, −0.21
Computer programs: SMART (Bruker, 1999[Bruker (1999). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), CrysAlis PRO (Agilent, 2011[Agilent (2011). CrysAlis PRO. Agilent Technologies, Yarnton, Oxfordshire, England.]), SAINT (Bruker, 1999[Bruker (1999). SMART, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]).

3. Results and discussion

The crystal structures of (3) and (4) are mutually isomorphous, and are also isostructural but not isomorphous with the CBZ–AcOH and DHCBZ–AcOH structures (Fleischman et al., 2003[Fleischman, S. G., Kuduva, S. S., McMahon, J. A., Moulton, B., Bailey Walsh, R. D., Rodriquez-Hornedo, N. & Zaworotko, M. J. (2003). Cryst. Growth Des. 3, 909-919.]). The asymmetric units of (3) and (4) are shown in Fig. 2[link] and the extended supra­molecular structures are shown in Fig. 3[link]. Both structures demonstrate the expected heterosynthon with the exception that the H atom which was expected to reside on the methane­sulfonic acid group was located on the carbonyl O atom of the carboxamide functional group indicating that salt formation had occurred.

[Figure 2]
Figure 2
The asymmetric units of (a) (3) and (b) (4). Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines.
[Figure 3]
Figure 3
The unit-cell and extended supra­molecular structure for (a) (3) and (b) (4). The view shown is down the a axis of the unit cell. Hydrogen bonds are shown as dashed lines.

In both examples, the transferred H atom was clearly located by a difference Fourier synthesis and refined freely and converged with an acceptable isotropic displacement parameter; Uiso(H1A) = 0.061 (8) and 0.056 (7) Å2 for (3) and (4), respectively. The primary hydrogen-bonding inter­action is an R22(8) ring heterosynthon formed by a syn N—H⋯O hydrogen bond, with an O atom of a methane­sulfonate group acting as acceptor. The ring is completed through the formation of an O—H⋯O hydrogen bond from the proton­ated carboxamide carbonyl group to a second methane­sulfonate O atom. This heterosynthon is expanded about a crystallographic inversion centre into a four-component supra­molecular complex by the formation of a third hydrogen-bond N—H⋯O inter­action from the anti-orientated N—H moiety to the remaining O atom of the methane­sulfonate sulfonyl group, creating a central R44(12) ring about the inversion centre. Hydrogen-bond distances and angles for (3) and (4) are listed in Tables 2[link] and 3[link].

Table 2
Hydrogen-bond geometry (Å, °) for (3)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O2 0.98 (3) 1.53 (3) 2.5004 (18) 171 (3)
N2—H2C⋯O3i 0.85 (3) 2.11 (3) 2.885 (2) 152 (2)
N2—H2B⋯O4 0.86 (3) 2.11 (3) 2.924 (2) 159 (2)
Symmetry code: (i) -x+2, -y+1, -z+1.

Table 3
Hydrogen-bond geometry (Å, °) for (4)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O2 0.92 (3) 1.58 (3) 2.4941 (15) 168 (2)
N2—H2C⋯O3i 0.830 (19) 2.112 (19) 2.8830 (17) 154.4 (17)
N2—H2B⋯O4 0.87 (2) 2.02 (2) 2.8523 (17) 159.5 (17)
Symmetry code: (i) -x+2, -y+1, -z+1.

The impact of salt formation on both the CBZ and DHCBZ structures can be seen through a simple Conquest search of the CSD for CBZ and DHCBZ single-crystal X-ray structures with no disorder present or density modification methods applied, e.g. SQUEEZE (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]). The search returned a total of 83 entries. The C=O, C—N and C—NH2 bond lengths for each of these structures were mined from the database and a scatterplot (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]) of the C=O distance versus the C—N distance is shown in Fig. 4[link]. The mean C=O and C—N bond lengths determined from the CSD data set are 1.242 and 1.375 Å, respectively, whereas the values determined for (3) and (4) are 1.299 (2) and 1.3005 (17) Å (for C=O), and 1.338 (2) and 1.3390 (19) Å (for C—N), respectively, which are in agreement with the values obtained for the HCl salt [1.300 and 1.332 Å; CSD refcode XAYGIP (Perumalla & Sun, 2012[Perumalla, S. R. & Sun, C. C. (2012). Chem. Eur. J. 18, 6462-6464.])]. The open circles representing the CSD data set predominantly cluster in the lower-right quadrant of the scatterplot. The filled red circle represents the position on the scatterplot determined for (3), (4) and XAYGIP, which overlay almost exactly, and demonstrates a significant increase and decrease in the C=O and C—N bond lengths, respectively, as would be expected if transfer of the acidic proton had occurred. An inter­esting observation from the scatterplot is that of the CBZ–TFA solvate (GINFOZ; Fernandes et al., 2007[Fernandes, P., Bardin, J., Johnston, A., Florence, A. J., Leech, C. K., David, W. I. F. & Shankland, K. (2007). Acta Cryst. E63, o4269.]), which is marked on the plot as a filled green circle. The influence of the strong acidic solvate mol­ecule on the CBZ framework is apparent from the location of the point on the scatterplot. The position of the acidic H atom in this published structure appears to be located on the tri­fluoro­acetic acid moiety and although the positional parameters of this H atom were allowed to refine freely, they were subject to a distance restraint of 0.90 Å from the parent O atom.

[Figure 4]
Figure 4
A scatterplot of C=O versus C—N bond lengths for a data set of CBZ and DHCBZ fragments from the CSD. See §3[link] for an explanation of the symbols.

Redetermination of the CBZ–TFA structure at 100 K, (5), and 270 K, (6), was undertaken and the asymmetric units for (5) and (6) are shown in Fig. 5[link]. Both structures are similar to that published previously (Fernandes et al., 2007[Fernandes, P., Bardin, J., Johnston, A., Florence, A. J., Leech, C. K., David, W. I. F. & Shankland, K. (2007). Acta Cryst. E63, o4269.]), including the rotational disorder present in the –CF3 group. During the refinement of these structures, particular attention was paid to the determination of the positional coordinates of the acidic H atom and a Fourier difference map with no H atom included in the model was generated in the plane of the R22(8) heterosynthon for both the 100 and 270 K structures (Figs. 6[link] and 7[link], respectively). For both structures, the acidic H atom was placed in the position defined by the Fourier difference map and allowed to refine freely without the use of a distance restraint. For the 100 K structure, the acidic H atom refined to a position almost at the mid-point between atoms O1 and O2, thus exhibiting an inter­mediate-type structure, although showing a slight bias toward atom O1 of the CBZ moiety [O1—H2D = 1.18 (3) Å and O2—H2D 1.27 (3) Å]. For the 270 K structure, the situation is similar with respect to the formation of an inter­mediate-type structure; however, the bias has reversed with the acidic H atom now refining to show a slight bias toward atom O2 of the TFA moiety [O2—H2D = 1.17 (3) Å and O1—H2D = 1.27 (3) Å]. Hydrogen-bond distances and angles for (5) and (6) are listed in Tables 4[link] and 5[link], respectively. A structural precedent for the inter­mediate protonation state can be found in the urotropine N-oxide–formic acid structure, which was determined from multiple-temperature (123–295 K) single-crystal X-ray diffraction data and from neutron diffraction data at 123 K (Nygren et al., 2005[Nygren, C. L., Wilson, C. C. & Turner, J. F. C. (2005). J. Phys. Chem. 109, 1911-1919.]), and from the variable-temperature neutron diffraction study of the penta­chloro­phenol–4-methyl­pyridine complex (Steiner et al., 2001[Steiner, T., Majerz, I. & Wilson, C. C. (2001). Angew. Chem. Int. Ed. 40, 2651-2654.]).

Table 4
Hydrogen-bond geometry (Å, °) for (5)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2B⋯O3 0.86 (2) 2.04 (2) 2.8941 (18) 169.1 (18)
N2—H2C⋯O3i 0.87 (2) 2.31 (2) 2.9383 (16) 129.1 (16)
O1—H2D⋯O2 1.18 (3) 1.27 (3) 2.4322 (14) 168 (2)
O1—H2D⋯O3 1.18 (3) 2.57 (3) 3.4622 (15) 130.9 (17)
Symmetry code: (i) [-x+{\script{5\over 2}}, y+{\script{1\over 2}}, -z-{\script{1\over 2}}].

Table 5
Hydrogen-bond geometry (Å, °) for (6)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2B⋯O3 0.88 (2) 2.03 (2) 2.904 (2) 169.1 (19)
N2—H2C⋯O3i 0.89 (2) 2.36 (2) 3.003 (2) 129.2 (19)
O2—H2D⋯O1 1.17 (3) 1.27 (3) 2.4349 (16) 168 (2)
O1—H2D⋯O3 1.27 (3) 2.50 (3) 3.4435 (18) 128.9 (17)
Symmetry code: (i) [-x+{\script{5\over 2}}, y+{\script{1\over 2}}, -z-{\script{1\over 2}}].
[Figure 5]
Figure 5
The asymmetric units of (a) (5) and (b) (6) Displacement ellipsoids are drawn at the 50% probability level.
[Figure 6]
Figure 6
Difference Fourier map for structure (5) [100 K; contour level = 0.05 e Å−3; SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.])]. See §3[link] for details.
[Figure 7]
Figure 7
Difference Fourier map for structure (6) [270 K; contour level = 0.05 e Å−3; SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.])]. See §3[link] for details.

The design of pharmaceutical cocrystal materials to engineer enhanced physicochemical properties or stability into an API can utilize the acid–base inter­action as a driver for cocrystal formation and the ΔpKa value (pKa base − pKa acid) and is often used to predict the formation of either a salt or cocrystal from the reaction. If the ΔpKa value is less than 2 it is generally assumed that proton transfer will not occur and as such the result will be that a cocrystal phase will form rather than salt. In some cases, the ΔpKa value will be less than 1 and it is in these cases that the protonation state may not be clear and a continuum may exist between the extreme states of salt and cocrystal. The salt–cocrystal continuum has been the subject of recent investigations (Childs et al., 2007[Childs, S. L., Stahly, G. P. & Park, A. (2007). Mol. Pharm. 4, 323-338.]; Mohamed et al., 2009[Mohamed, S., Tocher, D. A., Vickers, M. & Karamertzanis, P. G. (2009). Cryst. Growth Des. 9, 2881-2889.]) and suggests that the formation of the salt, cocrystal and inter­mediate protonation states is not only dependant on the ΔpKa value, but also on the environment of the crystalline lattice. The observation of the inter­mediate protonation state complex has a direct impact on the field of pharmaceutical cocrystallization since the recent FDA Guidance for Industry on the Regulatory Classification of Pharmaceutical Co-Crystals (Guidance for Industry. Regulatory Classification of Co-Crystals, 2013)[Guidance for Industry. Regulatory Classification of Co-Crystals (2013). US Department of Health and Human Services Food and Drug Administration Center of Drug Evaluation and Research.], appears not to consider the possibility of materials adopting such a pro­ton­ation state.

4. Conclusion

The crystalline products obtained from the maturation of CBZ and its close structural analogue DHCBZ in neat methane­sulfonic acid have been shown through single-crystal X-ray diffraction studies to be classical salt forms where the acidic proton has been transferred to the carboxamide carbonyl group. The structural data obtained were examined in relation to the data of other carbamazepine complexes mined from the CSD. From this comparison, a reinvestigation at 100 and 270 K of the crystal structure of the tri­fluoro­acetic acid solvate was undertaken, and it was observed that an inter­mediate pro­ton­ation state exists for this solvate material at both temperatures. Further work is currently in progress to determine the extent of salt formation for the CBZ/DHCBZ species and also on the inherent downstream physical properties of the new crystalline salt forms.

Supporting information


Introduction top

The anti­convulsant and analgesic pharmaceutical material carbamazepine [CBZ, (1)] and its closely related structural analogue 10,11-di­hydro­carbamazepine [DHCBZ, (2)] (see Scheme) have been used extensively as model compounds in a number of crystal engineering, co-crystallization and structure-prediction studies (Tiekink et al., 2010). One reason for this is that these molecules represent relatively simple structural examples of active pharmaceutical ingredients (APIs) which exhibit a single sterically accessible carboxamide functional group (–CONH2) available as a supra­molecular synthon for inter­molecular hydrogen bonding. CBZ has been shown to exist in five true polymorphic forms. Forms I–IV all utilize the carboxamide supra­molecular synthon to form a cyclic R22(8) homosynthon with only the syn-oriented (Allen et al., 1999), –NH participating in the formation of the dimer (Grzesiak et al., 2003). The anti-oriented –NH is not utilized in the formation of the supra­molecular complex thereby breaking Etter's first rule of hydrogen bonding which states `all good proton donors and acceptors are used in hydrogen bonding' (Etter, 1990). More recently the preparation and structure determination of the computationally predicted (Florence, Johnston et al., 2006; Florence, Leech et al., 2006) catemeric Form V was achieved by using a seed crystal of the catemeric orthorhombic Form II of DHCBZ (Harrison et al., 2006), to template growth of a crystal of Form V of CBZ from the vapour phase (Arlin et al., 2011). In this example, the anti-oriented –NH participates in the formation of the catemeric chain leaving the syn-oriented –NH donor uncoordinated. Fleischman et al. (2003) reported the preparation and structural characterization of 13 supra­molecular complexes of CBZ and categorized the formation of the CBZ complexes into two different bonding strategies. The first strategy was one in which the integrity of the carboxamide R22(8) homosynthon was maintained and the free anti-orientated –NH group was available for further hydrogen-bonding inter­actions with a non-acid coformer, for example acetone (Fig. 1a). Other complexes categorized within this bonding strategy included those with di­methyl sulfoxide (DMSO), benzo­quinone, terephthalaldehyde, saccharin and nicotinamide. The second strategy results in the preferential formation of a heterosynthon with a carb­oxy­lic acid coformer over the formation of the homosynthon, for example, the acetic acid complex shown in Fig. 1(b).

In addition, five further examples of this bonding strategy with a carb­oxy­lic acid moiety were given, the complexes with formic acid, butyric acid, trimesic acid, nitro­isophthalic acid and adamantane-1,3,5,7-tetra­carb­oxy­lic acid. The pKa values for these six acids all fall within the range 3.12–4.83 (Brown, 1955; Bjerrum, 1958). The Fleischman paper also reported the first described example of a crystal structure containing two independent amide–amide homosynthons in the molecular complex of CBZ with formamide. A detailed systematic study of the packing motifs present in 23 carbamazepine structures and two close analogues was undertaken by Gelbrich & Hursthouse (2006) using the XPac method. The analysis demonstrated that all the structures could be described by just four primary supra­molecular constructs. In a more recent paper, Childs et al. (2009) expanded on this work and analyzed the similarity relationships in the crystal packing motifs for a set of 50 crystal structures containing CBZ. The results demonstrated that all the CBZ complexes studied fall into one of three primary crystal packing motifs, the translation stack, inversion cup or coformer pairing. This study included a set of 13 new crystal structures which contained coformers that exhibited either a mono or di­carb­oxy­lic acid functionality. One particular structure analysed as part of this clustering study was that of the tri­fluoro­acetic acid (TFA) solvate of CBZ (Fernandes et al., 2007). This particular crystal structure, determined at 150 K, was analysed as a solvated species with the acidic H atom located on the carb­oxy­lic acid moiety, although an O—H distance restraint was required. The pKa value of TFA is reported to be ca -0.26 (Milne & Parker, 1981). All the solid forms of CBZ and DHCBZ so far described fall into the categories of polymorph and cocrystal/solvate. A classical salt form of CBZ, where the poorly ionizable carboxamide entity is formally protonated through the carbonyl O atom is rare and has lead to the assertion in the past that the CBZ drug substance is non-ionizable (Good & Rodriguez-Hornedo, 2009; Bethune et al., 2009; Huang & Rodriguez-Hornedo, 2011). However, a recent paper (Perumalla & Sun, 2012) describes the first clear example of the classical salt form of CBZ, an HCl salt prepared through the use of either a methanol–HCl solution (1.25 M) or a 1,4-dioxane–HCl solution (4.0 M). The use of an aqueous HCl reagent, even concentrated HCl, always resulted in the formation of the stable CBZ d ihydrate. The single-crystal X-ray structure of this material clearly shows that protonation of the carbonyl group of the carboxamide synthon had been achieved [Cambridge Structural Database (CSD; Version 5.34, released November 2012; Allen, 2002) refcode XAYGIP]. In this paper, we present the single-crystal X-ray structures of the methane­sulfonic acid salt forms of CBZ [(5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)­methyl­idene]aza­nium methane­sulfonate, (3)] and its structural analogue DHCBZ [(10,11-di­hydro-5H-dibenzo[b,f]azepin-5-yl)(hy­droxy)­methyl­idene]aza­nium methane­sulfonate, (4)]. In light of the structural data obtained from these species and that mined from the CSD, the single-crystal X-ray structure of the TFA solvate of CBZ [dibenzo[b,f]azepine-5-carboxamide–tri­fluoro­acetic acid (1/1)] was redetermined at both 100 [structure (5)] and 270 K [structure (6)] to investigate the protonation state of this material further.

Experimental top

Synthesis and crystallization top

Carbamazepine, 10,11-di­hydro­carbamazepine and methane­sulfonic acid were obtained from Sigma–Aldrich (purity 99%). Salts (3) and (4) were prepared by maturation of a neat methane­sulfonic acid solution of either (1) or (2) according to the following method. (1) or (2) (50 mg) was weighed into a 1.5 ml HPLC vial. Methane­sulfonic acid (500 µl) was added to create a suspension at room temperature. The resulting slurry was then placed in a platform shaker incubator (Heidolph Titramax/Inkubator 1000) and subjected to a series of heating–cooling cycles under shaking from room temperature (RT) to 323 K (8 h cycles; heating to 323 K for 4 h and then cooling to RT for a further 4 h) for a maximum of 24 h. Single crystals of (3) and (4) suitable for X-ray diffraction studies were grown directly by slow evaporation of 10 µl of the maturated neat methane­sulfonic acid solution of either (1) or (2) on a microscope slide. Crystals of the CBZ–TFA complex were prepared from the crystallisation of a neat TFA solution of (1). The complete list of structures contained within the CSD data set and their specifically defined parameters is available as Supplementary data.

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 1. The positional coordinates of the N-bound H atoms were all located from a Fourier difference map and freely refined along with an isotropic displacement parameter. The remaining H atoms were positioned geometrically and refined using riding models (including free rotation about the methyl C—S bond), with C–H = 0.95—0.99 Å and Uiso(H) = 1.5Ueq(C) for methyl groups and 1.2Ueq(C) otherwise. The –CF3 rotational disorder present in structures (5) and (6) was refined using a two-part model with only the F-atom parameterss and the occupancies allowed to refine freely. The final refined occupancies of the two components converged at 74:26 and 50:50 for (5) and (6), respectively.

Results and discussion top

The crystal structures of (3) and (4) are mutually isomorphous, and are also isostructural but not isomorphous with the CBZ–AcOH and DHCBZ–AcOH structures (Fleischman et al., 2003). The asymmetric units of (3) and (4) are shown in Fig. 2 and the extended supra­molecular structures are shown in Fig. 3. Both structures demonstrate the expected heterosynthon as shown with the exception that the H atom which was expected to reside on the methane­sulfonic acid group was located on the carbonyl O atom of the carboxamide functional group indicating that salt formation had occurred.

In both examples, the transferred H atom was clearly located by a difference Fourier synthesis and refined freely and converged with an acceptable isotropic displacement parameter; UisoH(1A) = 0.061 (8) and 0.056 (7) Å2 for (3) and (4), respectively. The primary hydrogen-bonding inter­action is an R22(8) ring heterosynthon formed by a syn N—H···O hydrogen bond with an O atom of a methane­sulfonate group acting as an acceptor. The ring is completed through the formation of an O—H···O hydrogen bond from the protonated carboxamide carbonyl group to a second methane­sulfonate O atom. This heterosynthon is expanded about a crystallographic inversion centre into a four-component supra­molecular complex by the formation of a third hydrogen-bond N—H···O inter­action from the anti-orientated –N—H moiety to the remaining O atom of the methane­sulfonaye sulfonyl group, creating a central R44(12) ring about the inversion centre. Hydrogen-bond distances and angles for (3) and (4) are listed in Tables 2 and 3.

The impact of salt formation on both the CBZ and DHCBZ structures can be seen through a simple Conquest search of the CSD for CBZ and DHCBZ single-crystal X-ray structures with no disorder present or density modification methods applied, e.g. SQUEEZE (Spek, 2009). The search returned a total of 83 entries. The CO, C—N and C—NH2 bond lengths for each of these structures were mined from the database and a scatterplot (Macrae et al., 2008), of the CO distance versus the C—N distance is shown in Fig. 4. The mean CO and C—N bond lengths determined from the CSD data set are 1.242 and 1.375 Å, respectively, whereas the values determined for (3) and (4) are 1.299 (2) and 1.301 (2) Å (for CO), and 1.338 (2) and 1.339 (2)Å (for C—N), which are in agreement with the values obtained for the HCl salt (CSD refcode XAYGIP; 1.300 and 1.332 Å). The open circles representing the CSD data set predominantly cluster in the lower-right quadrant of the scatterplot. The filled red circle represents the position on the scatterplot determined for (3) (4) and XAYGIP, which overlay almost exactly, and demonstrates a significant increase and decrease in the CO and C—N bond lengths, respectively, as would be expected if transfer of the acidic proton had occurred. An inter­esting observation from the scatterplot is that of the CBZ–TFA solvate (GINFOZ; Fernandes et al., 2007), which is marked on the plot as a filled green circle. The influence of the strong acidic solvate molecule on the CBZ framework is apparent from the location of the point on the scatterplot. The position of the acidic H atom in this published structure appears to be located on the tri­fluoro­acetic acid moiety and although the positional parameters of this H atom were allowed to refine freely, they were subject to a distance restraint of 0.90 Å from the parent O atom.

Redetermination of the CBZ–TFA structure at 100 K, (5), and 270 K, (6), was undertaken and the asymmetric units for (5) and (6) are shown in Fig. 5. Both structures are similar to that previously published (Fernandes et al., 2007), including the rotational disorder present in the –CF3 group. During the refinement of these structures, particular attention was paid to the determination of the positional coordinates of the acidic H atom and a Fourier difference map with no H atom included in the model was generated in the plane of the R22(8) heterosynthon for both the 100 and 270 K structures (Figs. 6 and 7, respectively). For both structures, the acidic H atom was placed in the position defined by the Fourier difference map and allowed to refine freely without the use of a distance restraint. For the 100 K structure, the acidic H atom refined to a position almost at the mid-point between atoms O1 and O2, thus exhibiting an inter­mediate-type structure, although showing a slight bias toward atom O1 of the CBZ moiety [O1—H2D = 1.18 (3) Å and O2—H2D 1.27 (3) Å]. For the 270 K structure, the situation is similar in the respect of the formation of an inter­mediate-type structure; however, the bias has now reversed with the acidic H atom now refining to show a slight bias toward atom O2 of the TFA moiety [O2—H2D = 1.17 (3) Å and O1—H2D = 1.27 (3) Å]. Hydrogen-bond distances and angles for (5) and (6) are listed in Tables 4 and 5, respectively. A structural precedent for the inter­mediate protonation state can be found in the urotropine N-oxide–formic acid structure, which was determined from multiple-temperature (123–295 K) single-crystal X-ray diffraction data and from neutron diffraction data at 123 K (Nygren et al., 2005), and from the variable-temperature neutron diffraction study of the penta­chloro­phenol–4-methyl­pyridine complex (Steiner et al., 2001). The design of pharmaceutical cocrystal materials to engineer enhanced physicochemical properties or stability into an API can utilize the acid–base inter­action as a driver for cocrystal formation and the ΔpKa value, (pKa base–pKa acid) is often used to predict the formation of either a salt or cocrystal from the reaction. If the ΔpKa value is less than 2 it is generally assumed that proton transfer will not occur and as such the result will be that a cocrystal phase will form rather than salt. In some cases, the ΔpKa value will be less than 1 and it is in these cases that the protonation state may not be clear and a continuum may exist between the extreme states of salt and cocrystal. The salt–cocrystal continuum has been the subject of recent investigations (Childs et al., 2007; Mohamed et al., 2009) and suggests that the formation of the salt, cocrystal and inter­mediate protonation states is not only dependant on the ΔpKa value but also on the environment of the crystalline lattice. The observation of the inter­mediate protonation state complex has a direct impact on the field of pharmaceutical cocrystallization since the recent FDA Guidance for Industry on the Regulatory Classification of Pharmaceutical Co-Crystals (Guidance for Industry. Regulatory Classification of Co-Crystals, 2013), appears not to consider the possibility of materials adopting such a protonation state.

Conclusion

The crystalline products obtained from the maturation of CBZ and its close structural analogue DHCBZ in neat methane­sulfonic acid have been shown through single-crystal X-ray diffraction studies to be classical salt forms where the acidic proton has been transferred to the carboxamide carbonyl group. The structural data obtained were examined in relation to the data of other carbamazepine complexes mined from the CSD. From this comparison, a reinvestigation at 100 and 270 K of the crystal structure of the tri­fluoro­acetic acid solvate was undertaken, and it was observed that an inter­mediate protonation state exists for this solvate material at both temperatures. Further work is currently in progress to determine the extent of salt formation for the CBZ/DHCBZ species and also on the inherent downstream physical properties of the new crystalline salt forms.

Related literature top

For related literature, see: Allen (2002); Allen et al. (1999); Arlin et al. (2011); Bethune et al. (2009); Bjerrum (1958); Brown (1955); Childs et al. (2007, 2009); Etter (1990); Fernandes et al. (2007); Fleischman et al. (2003); Florence, Johnston, Price, Nowell, Kennedy & Shankland (2006); Florence, Leech, Shankland, Shankland & Johnston (2006); Gelbrich & Hursthouse (2006); Good & Rodriguez-Hornedo (2009); Grzesiak et al. (2003); Harrison et al. (2006); Huang & Rodriguez-Hornedo (2011); Macrae et al. (2008); Milne & Parker (1981); Mohamed et al. (2009); Nygren et al. (2005); Perumalla & Sun (2012); Spek (2009); Steiner et al. (2001); Tiekink et al. (2010).

Computing details top

Data collection: SMART (Bruker, 1999) for (3); CrysAlis PRO (Agilent, 2011) for (4), (5), (6). Cell refinement: SMART and SAINT (Bruker, 1999) for (3); CrysAlis PRO (Agilent, 2011) for (4), (5), (6). Data reduction: SAINT (Bruker, 1999) and SHELXTL (Sheldrick, 2008) for (3); CrysAlis PRO (Agilent, 2011) for (4), (5), (6). For all compounds, program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2008).

Figures top
[Figure 1] Fig. 1. CBZ bonding strategies, see section 3 for further explanation.
[Figure 2] Fig. 2. The asymmetric units of (a) (3) and (b) (4). Displacement ellipsoids are drawn at the 50% probability level.
[Figure 3] Fig. 3. The unit-cell and extended supramolecular structure for (a) (3) and (b) (4). The view shown is down the a axis of the unit cell.
[Figure 4] Fig. 4. A scatterplot of CO versus C—N bond lengths for a data set of CBZ and DHCBZ fragments from the CSD. See section 3 for an explanation of the symbols.
[Figure 5] Fig. 5. The asymmetric units of (a) (5) and (6) Displacement ellipsoids are drawn at the 50% probability level.
[Figure 6] Fig. 6. Fourier difference map for structure (5) (100 K). See section 3 for details.
[Figure 7] Fig. 7. Fourier difference map for structure (6) (270 K). See section 3 for details.
(3) [(5H-Dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium methanesulfonate top
Crystal data top
C15H13N2O+·CH3O3SF(000) = 696
Mr = 332.37Dx = 1.404 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 5.5673 (7) ÅCell parameters from 876 reflections
b = 15.7196 (19) Åθ = 2.6–27.9°
c = 18.125 (2) ŵ = 0.23 mm1
β = 97.641 (4)°T = 120 K
V = 1572.1 (3) Å3Prism, colourless
Z = 40.35 × 0.18 × 0.10 mm
Data collection top
Bruker SMART 1K CCD area-detector
diffractometer
2626 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.033
Graphite monochromatorθmax = 26.4°, θmin = 1.7°
Detector resolution: 8.192 pixels mm-1h = 66
ω scansk = 1919
13272 measured reflectionsl = 2222
3203 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.037Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.098H atoms treated by a mixture of independent and constrained refinement
S = 1.00 w = 1/[σ2(Fo2) + (0.053P)2 + 0.750P]
where P = (Fo2 + 2Fc2)/3
3203 reflections(Δ/σ)max = 0.001
221 parametersΔρmax = 0.27 e Å3
0 restraintsΔρmin = 0.40 e Å3
Crystal data top
C15H13N2O+·CH3O3SV = 1572.1 (3) Å3
Mr = 332.37Z = 4
Monoclinic, P21/cMo Kα radiation
a = 5.5673 (7) ŵ = 0.23 mm1
b = 15.7196 (19) ÅT = 120 K
c = 18.125 (2) Å0.35 × 0.18 × 0.10 mm
β = 97.641 (4)°
Data collection top
Bruker SMART 1K CCD area-detector
diffractometer
2626 reflections with I > 2σ(I)
13272 measured reflectionsRint = 0.033
3203 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0370 restraints
wR(F2) = 0.098H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.27 e Å3
3203 reflectionsΔρmin = 0.40 e Å3
221 parameters
Special details top

Experimental. Single-crystal X-ray data for (3) was measured at 120 K on a Bruker SMART 1 K X-ray diffractometer equipped with an Oxford Cryosystems Cryostream cooler using graphite-monochromated Mo Kα (λ = 0.71073 Å) radiation.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.7116 (2)0.68279 (8)0.37938 (6)0.0228 (3)
H1A0.784 (5)0.6329 (19)0.3586 (15)0.061 (8)*
N10.5566 (3)0.73258 (9)0.47872 (8)0.0194 (3)
N20.8099 (3)0.61525 (10)0.49083 (9)0.0244 (3)
H2B0.916 (4)0.5868 (15)0.4709 (13)0.036 (6)*
H2C0.799 (4)0.6132 (15)0.5370 (14)0.039 (6)*
C10.4652 (3)0.80545 (11)0.43571 (10)0.0221 (4)
C20.2549 (3)0.79903 (13)0.38618 (10)0.0261 (4)
H2A0.16640.74720.38150.031*
C30.1743 (4)0.86908 (14)0.34326 (11)0.0333 (5)
H3A0.03050.86540.30870.040*
C40.3046 (4)0.94449 (14)0.35096 (12)0.0365 (5)
H4A0.24970.99240.32150.044*
C50.5133 (4)0.95038 (13)0.40107 (12)0.0342 (5)
H5A0.60051.00250.40560.041*
C60.5995 (4)0.88092 (12)0.44550 (10)0.0260 (4)
C70.8218 (4)0.88805 (12)0.49865 (11)0.0297 (4)
H7A0.94450.92420.48440.036*
C80.8718 (4)0.84968 (12)0.56468 (11)0.0288 (4)
H8A1.02660.86080.59180.035*
C90.7130 (3)0.79217 (12)0.59973 (10)0.0237 (4)
C100.7161 (4)0.79098 (13)0.67723 (10)0.0294 (4)
H10A0.82810.82590.70760.035*
C110.5587 (4)0.73972 (13)0.70993 (10)0.0302 (4)
H11A0.56260.74020.76250.036*
C120.3952 (4)0.68761 (13)0.66703 (10)0.0278 (4)
H12A0.28540.65340.68990.033*
C130.3928 (3)0.68570 (12)0.59029 (10)0.0235 (4)
H13A0.28290.64960.56030.028*
C140.5517 (3)0.73682 (11)0.55793 (9)0.0205 (4)
C150.6949 (3)0.67510 (11)0.44989 (9)0.0197 (4)
S11.11791 (7)0.52090 (3)0.34676 (2)0.01901 (13)
O20.8898 (2)0.56267 (8)0.31431 (7)0.0261 (3)
O31.0868 (2)0.43046 (8)0.35405 (7)0.0289 (3)
O41.2186 (2)0.56268 (9)0.41551 (7)0.0278 (3)
C161.3180 (4)0.53606 (15)0.28087 (12)0.0344 (5)
H16A1.47670.51200.29980.052*
H16B1.33530.59710.27170.052*
H16C1.25400.50760.23430.052*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0302 (7)0.0229 (7)0.0155 (6)0.0044 (5)0.0041 (5)0.0004 (5)
N10.0259 (8)0.0173 (7)0.0150 (7)0.0002 (6)0.0025 (6)0.0008 (6)
N20.0309 (9)0.0258 (8)0.0163 (8)0.0070 (7)0.0026 (6)0.0002 (7)
C10.0304 (10)0.0188 (9)0.0189 (9)0.0039 (7)0.0102 (7)0.0005 (7)
C20.0276 (10)0.0311 (10)0.0210 (9)0.0047 (8)0.0082 (7)0.0020 (8)
C30.0344 (11)0.0426 (13)0.0245 (10)0.0155 (9)0.0099 (8)0.0054 (9)
C40.0508 (13)0.0317 (11)0.0302 (11)0.0186 (10)0.0173 (10)0.0101 (9)
C50.0535 (13)0.0215 (10)0.0315 (11)0.0043 (9)0.0197 (10)0.0029 (8)
C60.0365 (10)0.0212 (9)0.0227 (9)0.0029 (8)0.0130 (8)0.0002 (7)
C70.0388 (11)0.0207 (9)0.0319 (11)0.0100 (8)0.0135 (9)0.0064 (8)
C80.0316 (10)0.0252 (10)0.0296 (10)0.0077 (8)0.0043 (8)0.0072 (8)
C90.0277 (10)0.0218 (9)0.0220 (9)0.0009 (7)0.0046 (7)0.0043 (7)
C100.0374 (11)0.0287 (10)0.0215 (9)0.0026 (8)0.0018 (8)0.0089 (8)
C110.0401 (11)0.0357 (11)0.0154 (9)0.0014 (9)0.0059 (8)0.0032 (8)
C120.0307 (10)0.0324 (11)0.0219 (10)0.0007 (8)0.0088 (8)0.0003 (8)
C130.0239 (9)0.0251 (10)0.0214 (9)0.0016 (7)0.0023 (7)0.0012 (7)
C140.0247 (9)0.0211 (9)0.0155 (8)0.0033 (7)0.0023 (7)0.0020 (7)
C150.0220 (8)0.0190 (9)0.0176 (8)0.0038 (7)0.0006 (7)0.0020 (7)
S10.0188 (2)0.0212 (2)0.0170 (2)0.00055 (16)0.00206 (15)0.00143 (16)
O20.0258 (7)0.0319 (7)0.0196 (6)0.0080 (5)0.0009 (5)0.0044 (5)
O30.0359 (8)0.0240 (7)0.0257 (7)0.0002 (6)0.0006 (6)0.0002 (5)
O40.0261 (7)0.0329 (8)0.0228 (7)0.0017 (6)0.0024 (5)0.0066 (6)
C160.0296 (11)0.0449 (13)0.0308 (11)0.0090 (9)0.0114 (8)0.0047 (9)
Geometric parameters (Å, º) top
O1—C151.299 (2)C7—H7A0.9500
O1—H1A0.98 (3)C8—C91.467 (3)
N1—C151.338 (2)C8—H8A0.9500
N1—C11.440 (2)C9—C141.399 (2)
N1—C141.441 (2)C9—C101.403 (3)
N2—C151.311 (2)C10—C111.381 (3)
N2—H2B0.86 (3)C10—H10A0.9500
N2—H2C0.85 (3)C11—C121.384 (3)
C1—C21.381 (3)C11—H11A0.9500
C1—C61.401 (3)C12—C131.390 (3)
C2—C31.388 (3)C12—H12A0.9500
C2—H2A0.9500C13—C141.382 (3)
C3—C41.387 (3)C13—H13A0.9500
C3—H3A0.9500S1—O31.4404 (14)
C4—C51.380 (3)S1—O41.4534 (13)
C4—H4A0.9500S1—O21.4803 (13)
C5—C61.403 (3)S1—C161.754 (2)
C5—H5A0.9500C16—H16A0.9800
C6—C71.468 (3)C16—H16B0.9800
C7—C81.336 (3)C16—H16C0.9800
C15—O1—H1A113.0 (16)C14—C9—C8121.97 (16)
C15—N1—C1120.41 (14)C10—C9—C8120.93 (17)
C15—N1—C14120.56 (14)C11—C10—C9120.90 (18)
C1—N1—C14116.77 (13)C11—C10—H10A119.5
C15—N2—H2B116.6 (15)C9—C10—H10A119.5
C15—N2—H2C119.4 (16)C10—C11—C12120.78 (17)
H2B—N2—H2C123 (2)C10—C11—H11A119.6
C2—C1—C6122.42 (17)C12—C11—H11A119.6
C2—C1—N1120.11 (16)C11—C12—C13119.56 (18)
C6—C1—N1117.46 (16)C11—C12—H12A120.2
C1—C2—C3119.30 (19)C13—C12—H12A120.2
C1—C2—H2A120.4C14—C13—C12119.38 (17)
C3—C2—H2A120.4C14—C13—H13A120.3
C4—C3—C2119.7 (2)C12—C13—H13A120.3
C4—C3—H3A120.1C13—C14—C9122.21 (16)
C2—C3—H3A120.1C13—C14—N1119.58 (16)
C5—C4—C3120.47 (19)C9—C14—N1118.20 (15)
C5—C4—H4A119.8O1—C15—N2122.00 (16)
C3—C4—H4A119.8O1—C15—N1116.21 (15)
C4—C5—C6121.3 (2)N2—C15—N1121.78 (16)
C4—C5—H5A119.4O3—S1—O4113.88 (8)
C6—C5—H5A119.4O3—S1—O2111.52 (8)
C1—C6—C5116.78 (19)O4—S1—O2110.66 (8)
C1—C6—C7122.47 (17)O3—S1—C16106.95 (10)
C5—C6—C7120.75 (18)O4—S1—C16108.35 (9)
C8—C7—C6127.61 (18)O2—S1—C16104.96 (9)
C8—C7—H7A116.2S1—C16—H16A109.5
C6—C7—H7A116.2S1—C16—H16B109.5
C7—C8—C9126.90 (18)H16A—C16—H16B109.5
C7—C8—H8A116.6S1—C16—H16C109.5
C9—C8—H8A116.6H16A—C16—H16C109.5
C14—C9—C10117.10 (17)H16B—C16—H16C109.5
C15—N1—C1—C284.2 (2)C14—C9—C10—C112.7 (3)
C14—N1—C1—C2112.73 (18)C8—C9—C10—C11176.96 (19)
C15—N1—C1—C694.7 (2)C9—C10—C11—C120.6 (3)
C14—N1—C1—C668.3 (2)C10—C11—C12—C131.2 (3)
C6—C1—C2—C31.2 (3)C11—C12—C13—C140.9 (3)
N1—C1—C2—C3177.70 (16)C12—C13—C14—C91.3 (3)
C1—C2—C3—C40.4 (3)C12—C13—C14—N1177.54 (16)
C2—C3—C4—C50.1 (3)C10—C9—C14—C133.0 (3)
C3—C4—C5—C60.1 (3)C8—C9—C14—C13176.56 (18)
C2—C1—C6—C51.4 (3)C10—C9—C14—N1175.83 (16)
N1—C1—C6—C5177.55 (15)C8—C9—C14—N14.6 (3)
C2—C1—C6—C7179.41 (17)C15—N1—C14—C1386.7 (2)
N1—C1—C6—C71.7 (3)C1—N1—C14—C13110.34 (19)
C4—C5—C6—C10.8 (3)C15—N1—C14—C992.3 (2)
C4—C5—C6—C7179.96 (18)C1—N1—C14—C970.7 (2)
C1—C6—C7—C834.2 (3)C1—N1—C15—O19.3 (2)
C5—C6—C7—C8146.6 (2)C14—N1—C15—O1171.65 (15)
C6—C7—C8—C90.9 (3)C1—N1—C15—N2169.74 (16)
C7—C8—C9—C1433.7 (3)C14—N1—C15—N27.4 (3)
C7—C8—C9—C10145.9 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O20.98 (3)1.53 (3)2.5004 (18)171 (3)
N2—H2C···O3i0.85 (3)2.11 (3)2.885 (2)152 (2)
N2—H2B···O40.86 (3)2.11 (3)2.924 (2)159 (2)
Symmetry code: (i) x+2, y+1, z+1.
(4) [(9,10-Dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium methanesulfonate top
Crystal data top
C15H15N2O+·CH3O3SF(000) = 704
Mr = 334.38Dx = 1.410 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 5.4477 (2) ÅCell parameters from 3424 reflections
b = 15.7340 (7) Åθ = 3.3–29.5°
c = 18.5034 (8) ŵ = 0.23 mm1
β = 96.647 (4)°T = 100 K
V = 1575.34 (11) Å3Lath, colourless
Z = 40.30 × 0.20 × 0.12 mm
Data collection top
Agilent SuperNova (Dual, Cu at zero, Atlas)
diffractometer
3215 independent reflections
Radiation source: SuperNova (Mo) X-ray Source2783 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.021
Detector resolution: 10.5598 pixels mm-1θmax = 26.4°, θmin = 1.7°
ω scansh = 66
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
k = 1918
Tmin = 0.766, Tmax = 1.000l = 2322
7104 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.090H atoms treated by a mixture of independent and constrained refinement
S = 1.00 w = 1/[σ2(Fo2) + (0.0485P)2 + 0.7P]
where P = (Fo2 + 2Fc2)/3
3215 reflections(Δ/σ)max = 0.001
221 parametersΔρmax = 0.38 e Å3
0 restraintsΔρmin = 0.44 e Å3
Crystal data top
C15H15N2O+·CH3O3SV = 1575.34 (11) Å3
Mr = 334.38Z = 4
Monoclinic, P21/cMo Kα radiation
a = 5.4477 (2) ŵ = 0.23 mm1
b = 15.7340 (7) ÅT = 100 K
c = 18.5034 (8) Å0.30 × 0.20 × 0.12 mm
β = 96.647 (4)°
Data collection top
Agilent SuperNova (Dual, Cu at zero, Atlas)
diffractometer
3215 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
2783 reflections with I > 2σ(I)
Tmin = 0.766, Tmax = 1.000Rint = 0.021
7104 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0320 restraints
wR(F2) = 0.090H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.38 e Å3
3215 reflectionsΔρmin = 0.44 e Å3
221 parameters
Special details top

Experimental. Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.35.8 (release 07-03-2011 CrysAlis171 .NET) (compiled Mar 7 2011,18:06:32) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Single-crystal X-ray data for structures (4), (5) and (6) were measured at 100 K [270 K for structure (6)], on an Oxford Diffraction (Agilent Technologies) SuperNova X-ray diffractometer equipped with an Oxford Cryosystems Cobra low-temperature device using either Mo Kα (λ = 0.71073 Å) radiation from a SuperNova Mo X-ray microsource (Nova) for (4) or Cu Kα (λ = 1.54173 Å) radiation from a SuperNova Cu X-ray microsource (Nova) for (5) and (6) and focusing mirror optics (Agilent, 2011).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.73850 (19)0.67537 (7)0.37232 (5)0.0155 (2)
H1A0.816 (4)0.6288 (17)0.3548 (14)0.056 (7)*
N10.5897 (2)0.73580 (8)0.46781 (6)0.0129 (3)
N20.8547 (2)0.62104 (8)0.48580 (7)0.0159 (3)
H2B0.959 (3)0.5867 (12)0.4689 (10)0.019 (4)*
H2C0.848 (3)0.6210 (11)0.5304 (11)0.017 (4)*
C10.4756 (3)0.80112 (10)0.42031 (8)0.0141 (3)
C20.2727 (3)0.77834 (10)0.37107 (8)0.0162 (3)
H2A0.21650.72110.36870.019*
C30.1533 (3)0.83903 (10)0.32569 (8)0.0187 (3)
H3A0.01530.82380.29200.022*
C40.2370 (3)0.92249 (10)0.32975 (8)0.0194 (3)
H4A0.15700.96460.29860.023*
C50.4381 (3)0.94424 (10)0.37942 (8)0.0173 (3)
H5A0.49231.00170.38190.021*
C70.7832 (3)0.91600 (10)0.47730 (8)0.0167 (3)
H7A0.72520.96440.50500.020*
H7B0.90610.93890.44700.020*
C80.9199 (3)0.85443 (10)0.53251 (8)0.0182 (3)
H8A1.00930.81200.50590.022*
H8B1.04430.88670.56480.022*
C60.5634 (3)0.88445 (9)0.42593 (8)0.0140 (3)
C90.7518 (3)0.80844 (10)0.57854 (8)0.0158 (3)
C100.7465 (3)0.82293 (10)0.65272 (8)0.0203 (3)
H10A0.85650.86310.67740.024*
C110.5815 (3)0.77906 (10)0.69067 (8)0.0219 (3)
H11A0.57940.78960.74110.026*
C120.4196 (3)0.72000 (10)0.65603 (8)0.0195 (3)
H12A0.30630.69080.68250.023*
C130.4238 (3)0.70375 (10)0.58226 (8)0.0162 (3)
H13A0.31590.66280.55790.019*
C140.5882 (3)0.74844 (9)0.54505 (8)0.0137 (3)
C150.7298 (2)0.67538 (9)0.44226 (8)0.0129 (3)
S11.14613 (6)0.50621 (2)0.351758 (19)0.01365 (11)
O20.95704 (19)0.56144 (7)0.31122 (5)0.0181 (2)
O31.0521 (2)0.42143 (7)0.36193 (6)0.0201 (2)
O41.25031 (19)0.54714 (7)0.41908 (6)0.0203 (2)
C161.3818 (3)0.49719 (11)0.29503 (9)0.0213 (3)
H16A1.52150.46600.32050.032*
H16B1.43640.55400.28230.032*
H16C1.31900.46660.25060.032*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0183 (5)0.0182 (5)0.0099 (5)0.0029 (4)0.0014 (4)0.0011 (4)
N10.0144 (6)0.0143 (6)0.0097 (6)0.0004 (5)0.0005 (5)0.0005 (5)
N20.0192 (6)0.0185 (7)0.0099 (6)0.0047 (5)0.0011 (5)0.0000 (5)
C10.0142 (7)0.0177 (7)0.0109 (7)0.0028 (6)0.0038 (5)0.0010 (6)
C20.0139 (7)0.0200 (8)0.0150 (7)0.0011 (6)0.0026 (6)0.0010 (6)
C30.0153 (7)0.0285 (9)0.0122 (7)0.0020 (6)0.0002 (6)0.0002 (6)
C40.0203 (7)0.0249 (8)0.0136 (7)0.0077 (6)0.0037 (6)0.0049 (6)
C50.0212 (7)0.0169 (7)0.0151 (7)0.0015 (6)0.0070 (6)0.0021 (6)
C70.0184 (7)0.0163 (7)0.0155 (7)0.0030 (6)0.0026 (6)0.0003 (6)
C80.0153 (7)0.0211 (8)0.0174 (7)0.0029 (6)0.0011 (6)0.0015 (6)
C60.0145 (7)0.0175 (7)0.0108 (7)0.0012 (6)0.0050 (5)0.0003 (6)
C90.0152 (7)0.0167 (7)0.0148 (7)0.0026 (6)0.0010 (6)0.0010 (6)
C100.0246 (8)0.0187 (8)0.0162 (8)0.0014 (6)0.0035 (6)0.0023 (6)
C110.0315 (8)0.0230 (8)0.0114 (7)0.0067 (7)0.0024 (6)0.0005 (6)
C120.0214 (7)0.0230 (8)0.0151 (7)0.0048 (6)0.0068 (6)0.0042 (6)
C130.0149 (7)0.0168 (7)0.0164 (7)0.0012 (6)0.0001 (6)0.0013 (6)
C140.0146 (7)0.0156 (7)0.0109 (7)0.0043 (6)0.0009 (5)0.0001 (5)
C150.0120 (6)0.0139 (7)0.0126 (7)0.0032 (5)0.0006 (5)0.0010 (5)
S10.01256 (18)0.0164 (2)0.01192 (19)0.00119 (13)0.00112 (14)0.00096 (13)
O20.0180 (5)0.0222 (6)0.0136 (5)0.0051 (4)0.0008 (4)0.0021 (4)
O30.0220 (5)0.0204 (6)0.0179 (5)0.0028 (4)0.0023 (4)0.0019 (4)
O40.0183 (5)0.0247 (6)0.0169 (5)0.0033 (4)0.0028 (4)0.0040 (5)
C160.0162 (7)0.0262 (9)0.0227 (8)0.0004 (6)0.0078 (6)0.0010 (7)
Geometric parameters (Å, º) top
O1—C151.3005 (17)C7—H7B0.9900
O1—H1A0.92 (3)C8—C91.506 (2)
N1—C151.3390 (19)C8—H8A0.9900
N1—C141.4440 (18)C8—H8B0.9900
N1—C11.4452 (18)C9—C141.394 (2)
N2—C151.3101 (19)C9—C101.395 (2)
N2—H2B0.87 (2)C10—C111.387 (2)
N2—H2C0.830 (19)C10—H10A0.9500
C1—C21.395 (2)C11—C121.386 (2)
C1—C61.396 (2)C11—H11A0.9500
C2—C31.383 (2)C12—C131.392 (2)
C2—H2A0.9500C12—H12A0.9500
C3—C41.389 (2)C13—C141.383 (2)
C3—H3A0.9500C13—H13A0.9500
C4—C51.389 (2)S1—O31.4489 (11)
C4—H4A0.9500S1—O41.4578 (11)
C5—C61.399 (2)S1—O21.4833 (11)
C5—H5A0.9500S1—C161.7556 (15)
C7—C61.523 (2)C16—H16A0.9800
C7—C81.536 (2)C16—H16B0.9800
C7—H7A0.9900C16—H16C0.9800
C15—O1—H1A114.8 (16)C1—C6—C7126.21 (13)
C15—N1—C14121.07 (12)C5—C6—C7117.22 (13)
C15—N1—C1120.84 (12)C14—C9—C10117.59 (14)
C14—N1—C1116.91 (11)C14—C9—C8118.27 (13)
C15—N2—H2B119.9 (12)C10—C9—C8124.13 (14)
C15—N2—H2C122.2 (12)C11—C10—C9120.35 (14)
H2B—N2—H2C117.6 (17)C11—C10—H10A119.8
C2—C1—C6121.93 (14)C9—C10—H10A119.8
C2—C1—N1117.83 (13)C12—C11—C10120.98 (14)
C6—C1—N1120.21 (13)C12—C11—H11A119.5
C3—C2—C1120.02 (14)C10—C11—H11A119.5
C3—C2—H2A120.0C11—C12—C13119.65 (14)
C1—C2—H2A120.0C11—C12—H12A120.2
C2—C3—C4119.42 (14)C13—C12—H12A120.2
C2—C3—H3A120.3C14—C13—C12118.68 (14)
C4—C3—H3A120.3C14—C13—H13A120.7
C5—C4—C3119.85 (14)C12—C13—H13A120.7
C5—C4—H4A120.1C13—C14—C9122.75 (13)
C3—C4—H4A120.1C13—C14—N1120.05 (13)
C4—C5—C6122.21 (14)C9—C14—N1117.17 (13)
C4—C5—H5A118.9O1—C15—N2122.38 (13)
C6—C5—H5A118.9O1—C15—N1116.06 (13)
C6—C7—C8119.66 (13)N2—C15—N1121.53 (13)
C6—C7—H7A107.4O3—S1—O4113.84 (7)
C8—C7—H7A107.4O3—S1—O2111.70 (6)
C6—C7—H7B107.4O4—S1—O2110.63 (6)
C8—C7—H7B107.4O3—S1—C16107.30 (7)
H7A—C7—H7B106.9O4—S1—C16107.90 (7)
C9—C8—C7113.54 (12)O2—S1—C16104.95 (7)
C9—C8—H8A108.9S1—C16—H16A109.5
C7—C8—H8A108.9S1—C16—H16B109.5
C9—C8—H8B108.9H16A—C16—H16B109.5
C7—C8—H8B108.9S1—C16—H16C109.5
H8A—C8—H8B107.7H16A—C16—H16C109.5
C1—C6—C5116.57 (13)H16B—C16—H16C109.5
C15—N1—C1—C273.83 (17)C14—C9—C10—C110.5 (2)
C14—N1—C1—C2118.42 (14)C8—C9—C10—C11178.48 (14)
C15—N1—C1—C6108.14 (16)C9—C10—C11—C120.2 (2)
C14—N1—C1—C659.61 (17)C10—C11—C12—C130.6 (2)
C6—C1—C2—C30.4 (2)C11—C12—C13—C141.1 (2)
N1—C1—C2—C3178.40 (13)C12—C13—C14—C90.7 (2)
C1—C2—C3—C40.1 (2)C12—C13—C14—N1177.29 (13)
C2—C3—C4—C50.4 (2)C10—C9—C14—C130.1 (2)
C3—C4—C5—C60.6 (2)C8—C9—C14—C13179.01 (13)
C6—C7—C8—C952.33 (18)C10—C9—C14—N1178.13 (13)
C2—C1—C6—C50.2 (2)C8—C9—C14—N10.93 (19)
N1—C1—C6—C5178.17 (12)C15—N1—C14—C1388.80 (17)
C2—C1—C6—C7179.67 (13)C1—N1—C14—C13103.48 (15)
N1—C1—C6—C72.4 (2)C15—N1—C14—C993.07 (16)
C4—C5—C6—C10.3 (2)C1—N1—C14—C974.65 (16)
C4—C5—C6—C7179.23 (13)C14—N1—C15—O1172.74 (12)
C8—C7—C6—C13.8 (2)C1—N1—C15—O15.50 (19)
C8—C7—C6—C5176.77 (13)C14—N1—C15—N25.7 (2)
C7—C8—C9—C1468.68 (18)C1—N1—C15—N2172.91 (13)
C7—C8—C9—C10110.31 (16)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O20.92 (3)1.58 (3)2.4941 (15)168 (2)
N2—H2C···O3i0.830 (19)2.112 (19)2.8830 (17)154.4 (17)
N2—H2B···O40.87 (2)2.02 (2)2.8523 (17)159.5 (17)
Symmetry code: (i) x+2, y+1, z+1.
(5) Dibenzo[b,f]azepine-5-carboxamide–trifluoroacetic acid (1/1) top
Crystal data top
C15H12N2O·C2HF3O2F(000) = 720
Mr = 350.29Dx = 1.493 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54178 Å
a = 14.9968 (12) ÅCell parameters from 3607 reflections
b = 5.2660 (3) Åθ = 3.0–75.6°
c = 20.1911 (12) ŵ = 1.10 mm1
β = 102.191 (7)°T = 100 K
V = 1558.60 (18) Å3Lath, colourless
Z = 40.45 × 0.20 × 0.10 mm
Data collection top
SuperNova, Dual, Cu at zero, Atlas
diffractometer
3189 independent reflections
Radiation source: SuperNova (Cu) X-ray Source2937 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.030
Detector resolution: 10.5598 pixels mm-1θmax = 74.5°, θmin = 3.4°
ω scansh = 1818
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
k = 36
Tmin = 0.650, Tmax = 1.000l = 2525
7053 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.047Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H atoms treated by a mixture of independent and constrained refinement
S = 1.01 w = 1/[σ2(Fo2) + (0.0945P)2 + 0.550P]
where P = (Fo2 + 2Fc2)/3
3189 reflections(Δ/σ)max = 0.001
266 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = 0.29 e Å3
Crystal data top
C15H12N2O·C2HF3O2V = 1558.60 (18) Å3
Mr = 350.29Z = 4
Monoclinic, P21/nCu Kα radiation
a = 14.9968 (12) ŵ = 1.10 mm1
b = 5.2660 (3) ÅT = 100 K
c = 20.1911 (12) Å0.45 × 0.20 × 0.10 mm
β = 102.191 (7)°
Data collection top
SuperNova, Dual, Cu at zero, Atlas
diffractometer
3189 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
2937 reflections with I > 2σ(I)
Tmin = 0.650, Tmax = 1.000Rint = 0.030
7053 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0470 restraints
wR(F2) = 0.137H atoms treated by a mixture of independent and constrained refinement
S = 1.01Δρmax = 0.26 e Å3
3189 reflectionsΔρmin = 0.29 e Å3
266 parameters
Special details top

Experimental. Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.35.19 (release 27-10-2011 CrysAlis171 .NET) (compiled Oct 27 2011,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Single-crystal X-ray data for structures (4), (5) and (6) were measured at 100 K [270 K for structure (6)], on an Oxford Diffraction (Agilent Technologies) SuperNova X-ray diffractometer equipped with an Oxford Cryosystems Cobra low-temperature device using either Mo Kα (λ = 0.71073 Å) radiation from a SuperNova Mo X-ray microsource (Nova) for (4) or Cu Kα (λ = 1.54173 Å) radiation from a SuperNova Cu X-ray microsource (Nova) for (5) and (6) and focusing mirror optics (Agilent, 2011).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
N11.01040 (8)0.3899 (2)0.19315 (5)0.0204 (3)
N21.13634 (9)0.1950 (3)0.22083 (6)0.0247 (3)
H2B1.1857 (14)0.109 (4)0.2068 (10)0.029 (5)*
H2C1.1209 (13)0.258 (4)0.2615 (11)0.030 (5)*
O11.11508 (7)0.1982 (2)0.11242 (5)0.0244 (2)
C10.95601 (9)0.4422 (3)0.14367 (6)0.0197 (3)
C20.97975 (10)0.6438 (3)0.09929 (7)0.0230 (3)
H2A1.02900.75220.10330.028*
C30.93124 (10)0.6866 (3)0.04891 (7)0.0249 (3)
H3A0.94680.82540.01860.030*
C40.85989 (10)0.5256 (3)0.04289 (7)0.0256 (3)
H4A0.82760.55200.00780.031*
C50.83597 (9)0.3273 (3)0.08796 (7)0.0243 (3)
H5A0.78720.21820.08330.029*
C60.88225 (9)0.2835 (3)0.14061 (7)0.0208 (3)
C70.85101 (9)0.0800 (3)0.18921 (7)0.0232 (3)
H7A0.82260.06080.17270.028*
C80.85782 (9)0.0688 (3)0.25451 (7)0.0233 (3)
H8A0.83450.08010.27860.028*
C90.89710 (9)0.2598 (3)0.29261 (7)0.0215 (3)
C100.86126 (10)0.2862 (3)0.36231 (7)0.0248 (3)
H10A0.81530.17200.38410.030*
C110.89142 (10)0.4749 (3)0.40005 (7)0.0266 (3)
H11A0.86580.48990.44710.032*
C120.95892 (10)0.6419 (3)0.36917 (7)0.0269 (3)
H12A0.97870.77350.39490.032*
C130.99757 (10)0.6168 (3)0.30068 (7)0.0242 (3)
H13A1.04420.73000.27940.029*
C140.96744 (9)0.4245 (3)0.26327 (6)0.0204 (3)
C151.08910 (9)0.2580 (3)0.17442 (7)0.0204 (3)
O21.23590 (7)0.1025 (2)0.06761 (5)0.0278 (3)
H2D1.1757 (19)0.053 (6)0.0964 (13)0.067 (8)*
O31.28746 (8)0.1351 (3)0.16402 (6)0.0371 (3)
C161.28569 (10)0.1916 (3)0.10585 (7)0.0253 (3)
C17A1.35264 (11)0.3987 (3)0.07195 (8)0.0311 (4)0.738 (15)
F1A1.3372 (3)0.4807 (8)0.01191 (14)0.0412 (7)0.738 (15)
F2A1.34620 (19)0.6059 (4)0.11052 (17)0.0452 (8)0.738 (15)
F3A1.4373 (2)0.3211 (7)0.0597 (3)0.0433 (8)0.738 (15)
C17B1.35264 (11)0.3987 (3)0.07195 (8)0.0311 (4)0.262 (15)
F1B1.3244 (10)0.536 (3)0.0352 (13)0.084 (5)0.262 (15)
F2B1.3867 (17)0.507 (5)0.1213 (4)0.109 (9)0.262 (15)
F3B1.4281 (7)0.257 (3)0.0392 (8)0.060 (3)0.262 (15)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0196 (5)0.0241 (6)0.0183 (5)0.0002 (4)0.0055 (4)0.0007 (4)
N20.0222 (6)0.0325 (6)0.0202 (6)0.0037 (5)0.0064 (5)0.0020 (5)
O10.0245 (5)0.0302 (5)0.0189 (5)0.0061 (4)0.0057 (4)0.0013 (4)
C10.0203 (6)0.0212 (6)0.0178 (6)0.0035 (5)0.0048 (5)0.0035 (5)
C20.0255 (7)0.0220 (6)0.0210 (6)0.0005 (5)0.0035 (5)0.0021 (5)
C30.0298 (7)0.0244 (7)0.0196 (6)0.0051 (6)0.0028 (5)0.0011 (5)
C40.0241 (6)0.0337 (7)0.0198 (6)0.0082 (6)0.0066 (5)0.0018 (5)
C50.0201 (6)0.0307 (7)0.0227 (6)0.0020 (5)0.0057 (5)0.0045 (5)
C60.0207 (6)0.0213 (6)0.0203 (6)0.0036 (5)0.0042 (5)0.0038 (5)
C70.0209 (6)0.0219 (6)0.0273 (7)0.0015 (5)0.0060 (5)0.0033 (5)
C80.0222 (6)0.0211 (6)0.0259 (7)0.0022 (5)0.0035 (5)0.0019 (5)
C90.0223 (6)0.0207 (6)0.0220 (6)0.0024 (5)0.0063 (5)0.0009 (5)
C100.0228 (7)0.0291 (7)0.0225 (6)0.0014 (6)0.0045 (5)0.0036 (5)
C110.0276 (7)0.0339 (8)0.0183 (6)0.0056 (6)0.0048 (5)0.0019 (5)
C120.0307 (7)0.0275 (7)0.0242 (7)0.0024 (6)0.0099 (6)0.0048 (5)
C130.0257 (7)0.0239 (7)0.0240 (7)0.0009 (5)0.0073 (5)0.0000 (5)
C140.0213 (6)0.0215 (6)0.0193 (6)0.0028 (5)0.0062 (5)0.0001 (5)
C150.0204 (6)0.0206 (6)0.0208 (6)0.0030 (5)0.0053 (5)0.0013 (5)
O20.0280 (5)0.0332 (6)0.0238 (5)0.0095 (4)0.0094 (4)0.0020 (4)
O30.0386 (6)0.0493 (7)0.0260 (5)0.0165 (5)0.0129 (5)0.0021 (5)
C160.0240 (7)0.0279 (7)0.0246 (7)0.0026 (6)0.0061 (5)0.0040 (5)
C17A0.0282 (7)0.0329 (8)0.0335 (8)0.0054 (6)0.0091 (6)0.0017 (6)
F1A0.0432 (14)0.0448 (14)0.0396 (12)0.0211 (11)0.0180 (9)0.0185 (8)
F2A0.0524 (13)0.0290 (10)0.0523 (12)0.0110 (9)0.0066 (8)0.0112 (7)
F3A0.0210 (8)0.0354 (13)0.0723 (19)0.0016 (8)0.0071 (10)0.0129 (11)
C17B0.0282 (7)0.0329 (8)0.0335 (8)0.0054 (6)0.0091 (6)0.0017 (6)
F1B0.056 (5)0.059 (7)0.141 (13)0.012 (5)0.032 (8)0.063 (8)
F2B0.139 (14)0.134 (14)0.049 (3)0.117 (13)0.009 (5)0.008 (5)
F3B0.036 (3)0.068 (5)0.067 (6)0.019 (3)0.007 (3)0.011 (4)
Geometric parameters (Å, º) top
N1—C151.3529 (18)C7—H7A0.9500
N1—C141.4380 (16)C8—C91.4636 (19)
N1—C11.4433 (16)C8—H8A0.9500
N2—C151.3306 (18)C9—C141.3971 (19)
N2—H2B0.86 (2)C9—C101.4034 (19)
N2—H2C0.87 (2)C10—C111.385 (2)
O1—C151.2696 (17)C10—H10A0.9500
O1—H2D1.18 (3)C11—C121.386 (2)
C1—C21.3865 (19)C11—H11A0.9500
C1—C61.3980 (19)C12—C131.388 (2)
C2—C31.388 (2)C12—H12A0.9500
C2—H2A0.9500C13—C141.3944 (19)
C3—C41.390 (2)C13—H13A0.9500
C3—H3A0.9500O2—C161.2718 (18)
C4—C51.382 (2)O2—H2D1.27 (3)
C4—H4A0.9500O3—C161.2174 (19)
C5—C61.4059 (19)C16—C17A1.541 (2)
C5—H5A0.9500C17A—F3A1.306 (3)
C6—C71.4618 (19)C17A—F2A1.332 (3)
C7—C81.345 (2)C17A—F1A1.352 (4)
C15—N1—C14121.55 (11)C14—C9—C10117.30 (12)
C15—N1—C1119.45 (11)C14—C9—C8123.75 (12)
C14—N1—C1117.14 (10)C10—C9—C8118.92 (12)
C15—N2—H2B116.5 (13)C11—C10—C9121.48 (13)
C15—N2—H2C119.6 (13)C11—C10—H10A119.3
H2B—N2—H2C123.3 (18)C9—C10—H10A119.3
C15—O1—H2D119.3 (13)C10—C11—C12120.01 (13)
C2—C1—C6121.78 (12)C10—C11—H11A120.0
C2—C1—N1119.21 (12)C12—C11—H11A120.0
C6—C1—N1118.99 (12)C11—C12—C13119.97 (13)
C1—C2—C3119.67 (13)C11—C12—H12A120.0
C1—C2—H2A120.2C13—C12—H12A120.0
C3—C2—H2A120.2C12—C13—C14119.59 (13)
C2—C3—C4119.82 (13)C12—C13—H13A120.2
C2—C3—H3A120.1C14—C13—H13A120.2
C4—C3—H3A120.1C13—C14—C9121.55 (12)
C5—C4—C3120.05 (13)C13—C14—N1119.75 (12)
C5—C4—H4A120.0C9—C14—N1118.68 (12)
C3—C4—H4A120.0O1—C15—N2122.30 (13)
C4—C5—C6121.39 (13)O1—C15—N1118.10 (12)
C4—C5—H5A119.3N2—C15—N1119.60 (12)
C6—C5—H5A119.3C16—O2—H2D114.4 (12)
C1—C6—C5117.20 (13)O3—C16—O2129.11 (14)
C1—C6—C7123.57 (12)O3—C16—C17A117.16 (13)
C5—C6—C7119.23 (12)O2—C16—C17A113.73 (12)
C8—C7—C6127.61 (13)F3A—C17A—F2A108.4 (2)
C8—C7—H7A116.2F3A—C17A—F1A105.9 (3)
C6—C7—H7A116.2F2A—C17A—F1A104.9 (2)
C7—C8—C9127.39 (13)F3A—C17A—C16112.24 (19)
C7—C8—H8A116.3F2A—C17A—C16111.09 (16)
C9—C8—H8A116.3F1A—C17A—C16113.91 (19)
C15—N1—C1—C281.15 (16)C10—C11—C12—C131.3 (2)
C14—N1—C1—C2114.12 (14)C11—C12—C13—C140.6 (2)
C15—N1—C1—C697.09 (15)C12—C13—C14—C91.9 (2)
C14—N1—C1—C667.64 (16)C12—C13—C14—N1176.91 (12)
C6—C1—C2—C32.0 (2)C10—C9—C14—C133.5 (2)
N1—C1—C2—C3176.17 (12)C8—C9—C14—C13174.75 (13)
C1—C2—C3—C40.6 (2)C10—C9—C14—N1175.30 (11)
C2—C3—C4—C51.5 (2)C8—C9—C14—N16.4 (2)
C3—C4—C5—C60.2 (2)C15—N1—C14—C1382.35 (17)
C2—C1—C6—C53.64 (19)C1—N1—C14—C13113.26 (14)
N1—C1—C6—C5174.56 (11)C15—N1—C14—C996.48 (15)
C2—C1—C6—C7175.64 (12)C1—N1—C14—C967.91 (16)
N1—C1—C6—C76.17 (19)C14—N1—C15—O1168.32 (12)
C4—C5—C6—C12.7 (2)C1—N1—C15—O14.28 (19)
C4—C5—C6—C7176.59 (12)C14—N1—C15—N211.6 (2)
C1—C6—C7—C828.7 (2)C1—N1—C15—N2175.60 (12)
C5—C6—C7—C8150.59 (15)O3—C16—C17A—F3A69.8 (3)
C6—C7—C8—C90.9 (2)O2—C16—C17A—F3A109.9 (3)
C7—C8—C9—C1429.8 (2)O3—C16—C17A—F2A51.7 (3)
C7—C8—C9—C10148.46 (15)O2—C16—C17A—F2A128.6 (2)
C14—C9—C10—C112.8 (2)O3—C16—C17A—F1A169.9 (2)
C8—C9—C10—C11175.55 (13)O2—C16—C17A—F1A10.4 (3)
C9—C10—C11—C120.5 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O30.86 (2)2.04 (2)2.8941 (18)169.1 (18)
N2—H2C···O3i0.87 (2)2.31 (2)2.9383 (16)129.1 (16)
O1—H2D···O21.18 (3)1.27 (3)2.4322 (14)168 (2)
O1—H2D···O31.18 (3)2.57 (3)3.4622 (15)130.9 (17)
Symmetry code: (i) x+5/2, y+1/2, z1/2.
(6) Dibenzo[b,f]azepine-5-carboxamide–trifluoroacetic acid (1/1) top
Crystal data top
C15H12N2O·C2HF3O2F(000) = 720
Mr = 350.29Dx = 1.442 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54178 Å
a = 14.9970 (3) ÅCell parameters from 3984 reflections
b = 5.3712 (1) Åθ = 3.0–75.8°
c = 20.4441 (4) ŵ = 1.06 mm1
β = 101.529 (2)°T = 270 K
V = 1613.58 (5) Å3Lath, colourless
Z = 40.45 × 0.25 × 0.18 mm
Data collection top
SuperNova, Dual, Cu at zero, Atlas
diffractometer
3302 independent reflections
Radiation source: SuperNova (Cu) X-ray Source2957 reflections with I > 2σ(I)
Mirror monochromatorRint = 0.021
Detector resolution: 10.5598 pixels mm-1θmax = 74.5°, θmin = 3.4°
ω scansh = 1817
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
k = 46
Tmin = 0.738, Tmax = 1.000l = 2425
7096 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.050H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.155 w = 1/[σ2(Fo2) + (0.0975P)2 + 0.320P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
3302 reflectionsΔρmax = 0.34 e Å3
267 parametersΔρmin = 0.21 e Å3
0 restraintsExtinction correction: SHELXTL (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0047 (7)
Crystal data top
C15H12N2O·C2HF3O2V = 1613.58 (5) Å3
Mr = 350.29Z = 4
Monoclinic, P21/nCu Kα radiation
a = 14.9970 (3) ŵ = 1.06 mm1
b = 5.3712 (1) ÅT = 270 K
c = 20.4441 (4) Å0.45 × 0.25 × 0.18 mm
β = 101.529 (2)°
Data collection top
SuperNova, Dual, Cu at zero, Atlas
diffractometer
3302 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2011)
2957 reflections with I > 2σ(I)
Tmin = 0.738, Tmax = 1.000Rint = 0.021
7096 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0500 restraints
wR(F2) = 0.155H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.34 e Å3
3302 reflectionsΔρmin = 0.21 e Å3
267 parameters
Special details top

Experimental. CrysAlisPro, Agilent Technologies, Version 1.171.35.19 (release 27-10-2011 CrysAlis171 .NET) (compiled Oct 27 2011,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm.

Single-crystal X-ray data for structures (4), (5) and (6) were measured at 100 K [270 K for structure (6)], on an Oxford Diffraction (Agilent Technologies) SuperNova X-ray diffractometer equipped with an Oxford Cryosystems Cobra low-temperature device using either Mo Kα (λ = 0.71073 Å) radiation from a SuperNova Mo X-ray microsource (Nova) for (4) or Cu Kα (λ = 1.54173 Å) radiation from a SuperNova Cu X-ray microsource (Nova) for (5) and (6) and focusing mirror optics (Agilent, 2011).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/UeqOcc. (<1)
N11.00960 (8)0.3794 (2)0.19199 (6)0.0445 (3)
N21.13368 (10)0.1840 (3)0.22070 (7)0.0594 (4)
H2B1.1836 (16)0.095 (4)0.2079 (10)0.061 (5)*
H2C1.1187 (15)0.251 (4)0.2610 (12)0.068 (6)*
O11.11367 (8)0.1877 (2)0.11365 (5)0.0561 (3)
C10.95582 (9)0.4336 (3)0.14274 (7)0.0438 (3)
C20.97930 (12)0.6319 (3)0.09996 (8)0.0541 (4)
H2A1.02760.73490.10440.065*
C30.93064 (14)0.6769 (4)0.05025 (8)0.0626 (5)
H3A0.94580.81140.02150.075*
C40.85988 (12)0.5224 (4)0.04340 (8)0.0641 (5)
H4A0.82820.55020.00940.077*
C50.83609 (11)0.3274 (4)0.08673 (8)0.0595 (4)
H5A0.78830.22400.08150.071*
C60.88219 (10)0.2802 (3)0.13878 (7)0.0477 (3)
C70.85093 (11)0.0798 (3)0.18596 (9)0.0544 (4)
H7A0.82290.05410.16940.065*
C80.85761 (11)0.0651 (3)0.25014 (9)0.0533 (4)
H8A0.83470.07880.27270.064*
C90.89671 (10)0.2486 (3)0.28882 (7)0.0465 (3)
C100.86112 (11)0.2709 (3)0.35739 (8)0.0559 (4)
H10A0.81620.16080.37770.067*
C110.89126 (12)0.4521 (4)0.39514 (8)0.0610 (4)
H11A0.86690.46300.44060.073*
C120.95721 (14)0.6172 (4)0.36603 (9)0.0626 (4)
H12A0.97610.74280.39150.075*
C130.99580 (12)0.5967 (3)0.29858 (8)0.0550 (4)
H13A1.04120.70670.27890.066*
C140.96626 (9)0.4112 (3)0.26084 (7)0.0441 (3)
C151.08751 (9)0.2478 (3)0.17424 (7)0.0449 (3)
O21.23698 (9)0.0982 (3)0.06931 (6)0.0671 (4)
H2D1.179 (2)0.035 (5)0.0965 (13)0.098 (8)*
O31.28638 (13)0.1342 (4)0.16454 (7)0.0975 (6)
C161.28630 (12)0.1862 (4)0.10722 (9)0.0605 (4)
C17A1.35519 (16)0.3780 (5)0.07339 (12)0.0776 (6)0.505 (9)
F1A1.3430 (5)0.4494 (14)0.0135 (3)0.118 (2)0.505 (9)
F2A1.3469 (6)0.5914 (9)0.1084 (3)0.141 (3)0.505 (9)
F3A1.4339 (3)0.3150 (14)0.0614 (6)0.152 (4)0.505 (9)
C17B1.35519 (16)0.3780 (5)0.07339 (12)0.0776 (6)0.495 (9)
F1B1.3224 (6)0.5483 (14)0.0464 (6)0.160 (5)0.495 (9)
F2B1.4066 (4)0.4498 (14)0.11635 (19)0.112 (3)0.495 (9)
F3B1.4203 (4)0.2479 (14)0.0311 (2)0.136 (3)0.495 (9)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0373 (6)0.0557 (7)0.0402 (6)0.0012 (5)0.0068 (4)0.0028 (5)
N20.0486 (7)0.0859 (10)0.0458 (7)0.0122 (7)0.0141 (6)0.0052 (7)
O10.0484 (6)0.0776 (8)0.0420 (5)0.0165 (5)0.0083 (4)0.0035 (5)
C10.0400 (7)0.0505 (7)0.0403 (7)0.0070 (5)0.0063 (5)0.0077 (6)
C20.0574 (9)0.0565 (8)0.0457 (8)0.0018 (7)0.0043 (6)0.0040 (6)
C30.0728 (11)0.0676 (10)0.0448 (8)0.0186 (9)0.0054 (7)0.0014 (7)
C40.0544 (9)0.0928 (13)0.0461 (8)0.0238 (9)0.0127 (7)0.0066 (8)
C50.0423 (8)0.0840 (12)0.0539 (9)0.0081 (7)0.0137 (6)0.0154 (8)
C60.0392 (7)0.0551 (8)0.0488 (8)0.0063 (6)0.0087 (6)0.0109 (6)
C70.0464 (8)0.0545 (8)0.0624 (9)0.0065 (6)0.0114 (7)0.0101 (7)
C80.0476 (8)0.0488 (8)0.0616 (9)0.0067 (6)0.0064 (7)0.0008 (7)
C90.0409 (7)0.0494 (7)0.0481 (8)0.0023 (6)0.0065 (5)0.0009 (6)
C100.0459 (8)0.0685 (10)0.0505 (8)0.0022 (7)0.0027 (6)0.0059 (7)
C110.0580 (9)0.0786 (11)0.0441 (8)0.0077 (8)0.0048 (7)0.0052 (7)
C120.0711 (11)0.0667 (10)0.0512 (9)0.0015 (8)0.0155 (8)0.0130 (7)
C130.0564 (9)0.0580 (9)0.0509 (8)0.0092 (7)0.0114 (7)0.0037 (7)
C140.0408 (7)0.0504 (7)0.0407 (7)0.0014 (5)0.0073 (5)0.0026 (5)
C150.0386 (7)0.0540 (8)0.0420 (7)0.0033 (6)0.0077 (5)0.0003 (6)
O20.0637 (7)0.0861 (9)0.0551 (7)0.0268 (7)0.0202 (6)0.0084 (6)
O30.0980 (12)0.1415 (15)0.0589 (8)0.0577 (11)0.0295 (8)0.0087 (9)
C160.0546 (9)0.0746 (11)0.0536 (9)0.0118 (8)0.0142 (7)0.0039 (8)
C17A0.0693 (12)0.0863 (15)0.0803 (14)0.0246 (11)0.0225 (11)0.0025 (11)
F1A0.122 (5)0.134 (5)0.104 (3)0.070 (4)0.037 (3)0.049 (3)
F2A0.160 (6)0.082 (3)0.175 (5)0.039 (3)0.018 (4)0.033 (3)
F3A0.0488 (17)0.137 (5)0.267 (10)0.008 (2)0.026 (4)0.089 (6)
C17B0.0693 (12)0.0863 (15)0.0803 (14)0.0246 (11)0.0225 (11)0.0025 (11)
F1B0.118 (4)0.102 (5)0.276 (13)0.035 (4)0.080 (7)0.099 (7)
F2B0.107 (4)0.138 (5)0.094 (2)0.074 (4)0.031 (2)0.001 (2)
F3B0.097 (4)0.216 (6)0.081 (2)0.072 (4)0.021 (2)0.028 (3)
Geometric parameters (Å, º) top
N1—C151.3516 (19)C7—H7A0.9300
N1—C141.4378 (18)C8—C91.458 (2)
N1—C11.4401 (18)C8—H8A0.9300
N2—C151.327 (2)C9—C141.393 (2)
N2—H2B0.88 (2)C9—C101.402 (2)
N2—H2C0.89 (2)C10—C111.374 (3)
O1—C151.2643 (18)C10—H10A0.9300
O1—H2D1.27 (3)C11—C121.372 (3)
C1—C21.378 (2)C11—H11A0.9300
C1—C61.393 (2)C12—C131.389 (2)
C2—C31.386 (2)C12—H12A0.9300
C2—H2A0.9300C13—C141.386 (2)
C3—C41.376 (3)C13—H13A0.9300
C3—H3A0.9300O2—C161.265 (2)
C4—C51.372 (3)O2—H2D1.17 (3)
C4—H4A0.9300O3—C161.205 (2)
C5—C61.403 (2)C16—C17A1.524 (3)
C5—H5A0.9300C17A—F3A1.205 (5)
C6—C71.459 (2)C17A—F1A1.331 (6)
C7—C81.338 (2)C17A—F2A1.344 (5)
C15—N1—C14121.49 (12)C14—C9—C10117.47 (14)
C15—N1—C1119.54 (11)C14—C9—C8123.41 (14)
C14—N1—C1116.98 (11)C10—C9—C8119.09 (14)
C15—N2—H2B117.4 (13)C11—C10—C9121.34 (16)
C15—N2—H2C119.3 (15)C11—C10—H10A119.3
H2B—N2—H2C123 (2)C9—C10—H10A119.3
C15—O1—H2D120.3 (12)C12—C11—C10120.25 (15)
C2—C1—C6121.67 (14)C12—C11—H11A119.9
C2—C1—N1119.48 (14)C10—C11—H11A119.9
C6—C1—N1118.84 (13)C11—C12—C13120.03 (16)
C1—C2—C3119.67 (17)C11—C12—H12A120.0
C1—C2—H2A120.2C13—C12—H12A120.0
C3—C2—H2A120.2C14—C13—C12119.58 (16)
C4—C3—C2119.95 (17)C14—C13—H13A120.2
C4—C3—H3A120.0C12—C13—H13A120.2
C2—C3—H3A120.0C13—C14—C9121.25 (14)
C5—C4—C3120.06 (16)C13—C14—N1119.89 (13)
C5—C4—H4A120.0C9—C14—N1118.84 (13)
C3—C4—H4A120.0O1—C15—N2122.09 (14)
C4—C5—C6121.57 (17)O1—C15—N1118.60 (13)
C4—C5—H5A119.2N2—C15—N1119.31 (13)
C6—C5—H5A119.2C16—O2—H2D113.8 (13)
C1—C6—C5116.98 (16)O3—C16—O2128.58 (18)
C1—C6—C7123.47 (14)O3—C16—C17A117.77 (17)
C5—C6—C7119.53 (15)O2—C16—C17A113.64 (16)
C8—C7—C6127.95 (15)F3A—C17A—F1A101.7 (6)
C8—C7—H7A116.0F3A—C17A—F2A109.3 (5)
C6—C7—H7A116.0F1A—C17A—F2A103.3 (4)
C7—C8—C9127.52 (15)F3A—C17A—C16116.7 (3)
C7—C8—H8A116.2F1A—C17A—C16114.0 (3)
C9—C8—H8A116.2F2A—C17A—C16110.7 (3)
C15—N1—C1—C281.92 (18)C10—C11—C12—C132.0 (3)
C14—N1—C1—C2113.89 (15)C11—C12—C13—C141.0 (3)
C15—N1—C1—C696.79 (16)C12—C13—C14—C91.8 (3)
C14—N1—C1—C667.40 (17)C12—C13—C14—N1176.28 (15)
C6—C1—C2—C32.0 (2)C10—C9—C14—C133.4 (2)
N1—C1—C2—C3176.65 (13)C8—C9—C14—C13174.33 (15)
C1—C2—C3—C40.7 (2)C10—C9—C14—N1174.70 (13)
C2—C3—C4—C51.5 (3)C8—C9—C14—N17.6 (2)
C3—C4—C5—C60.2 (3)C15—N1—C14—C1382.98 (19)
C2—C1—C6—C53.6 (2)C1—N1—C14—C13113.15 (16)
N1—C1—C6—C5175.03 (13)C15—N1—C14—C995.12 (17)
C2—C1—C6—C7175.40 (14)C1—N1—C14—C968.75 (18)
N1—C1—C6—C75.9 (2)C14—N1—C15—O1167.38 (14)
C4—C5—C6—C12.7 (2)C1—N1—C15—O13.9 (2)
C4—C5—C6—C7176.33 (15)C14—N1—C15—N212.1 (2)
C1—C6—C7—C828.7 (3)C1—N1—C15—N2175.53 (14)
C5—C6—C7—C8150.31 (18)O3—C16—C17A—F3A70.1 (8)
C6—C7—C8—C91.0 (3)O2—C16—C17A—F3A108.5 (7)
C7—C8—C9—C1429.1 (3)O3—C16—C17A—F1A171.6 (5)
C7—C8—C9—C10148.54 (18)O2—C16—C17A—F1A9.8 (5)
C14—C9—C10—C112.4 (2)O3—C16—C17A—F2A55.7 (6)
C8—C9—C10—C11175.46 (16)O2—C16—C17A—F2A125.7 (5)
C9—C10—C11—C120.3 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O30.88 (2)2.03 (2)2.904 (2)169.1 (19)
N2—H2C···O3i0.89 (2)2.36 (2)3.003 (2)129.2 (19)
O2—H2D···O11.17 (3)1.27 (3)2.4349 (16)168 (2)
O1—H2D···O31.27 (3)2.50 (3)3.4435 (18)128.9 (17)
Symmetry code: (i) x+5/2, y+1/2, z1/2.

Experimental details

(3)(4)(5)(6)
Crystal data
Chemical formulaC15H13N2O+·CH3O3SC15H15N2O+·CH3O3SC15H12N2O·C2HF3O2C15H12N2O·C2HF3O2
Mr332.37334.38350.29350.29
Crystal system, space groupMonoclinic, P21/cMonoclinic, P21/cMonoclinic, P21/nMonoclinic, P21/n
Temperature (K)120100100270
a, b, c (Å)5.5673 (7), 15.7196 (19), 18.125 (2)5.4477 (2), 15.7340 (7), 18.5034 (8)14.9968 (12), 5.2660 (3), 20.1911 (12)14.9970 (3), 5.3712 (1), 20.4441 (4)
β (°) 97.641 (4) 96.647 (4) 102.191 (7) 101.529 (2)
V3)1572.1 (3)1575.34 (11)1558.60 (18)1613.58 (5)
Z4444
Radiation typeMo KαMo KαCu KαCu Kα
µ (mm1)0.230.231.101.06
Crystal size (mm)0.35 × 0.18 × 0.100.30 × 0.20 × 0.120.45 × 0.20 × 0.100.45 × 0.25 × 0.18
Data collection
DiffractometerBruker SMART 1K CCD area-detector
diffractometer
Agilent SuperNova (Dual, Cu at zero, Atlas)
diffractometer
SuperNova, Dual, Cu at zero, Atlas
diffractometer
SuperNova, Dual, Cu at zero, Atlas
diffractometer
Absorption correctionMulti-scan
(CrysAlis PRO; Agilent, 2011)
Multi-scan
(CrysAlis PRO; Agilent, 2011)
Multi-scan
(CrysAlis PRO; Agilent, 2011)
Tmin, Tmax0.766, 1.0000.650, 1.0000.738, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections
13272, 3203, 2626 7104, 3215, 2783 7053, 3189, 2937 7096, 3302, 2957
Rint0.0330.0210.0300.021
(sin θ/λ)max1)0.6250.6250.6250.625
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.037, 0.098, 1.00 0.032, 0.090, 1.00 0.047, 0.137, 1.01 0.050, 0.155, 1.00
No. of reflections3203321531893302
No. of parameters221221266267
H-atom treatmentH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinementH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.27, 0.400.38, 0.440.26, 0.290.34, 0.21

Computer programs: SMART (Bruker, 1999), CrysAlis PRO (Agilent, 2011), SMART and SAINT (Bruker, 1999), SAINT (Bruker, 1999) and SHELXTL (Sheldrick, 2008), SHELXTL (Sheldrick, 2008) and Mercury (Macrae et al., 2008).

Hydrogen-bond geometry (Å, º) for (3) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O20.98 (3)1.53 (3)2.5004 (18)171 (3)
N2—H2C···O3i0.85 (3)2.11 (3)2.885 (2)152 (2)
N2—H2B···O40.86 (3)2.11 (3)2.924 (2)159 (2)
Symmetry code: (i) x+2, y+1, z+1.
Hydrogen-bond geometry (Å, º) for (4) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O20.92 (3)1.58 (3)2.4941 (15)168 (2)
N2—H2C···O3i0.830 (19)2.112 (19)2.8830 (17)154.4 (17)
N2—H2B···O40.87 (2)2.02 (2)2.8523 (17)159.5 (17)
Symmetry code: (i) x+2, y+1, z+1.
Hydrogen-bond geometry (Å, º) for (5) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O30.86 (2)2.04 (2)2.8941 (18)169.1 (18)
N2—H2C···O3i0.87 (2)2.31 (2)2.9383 (16)129.1 (16)
O1—H2D···O21.18 (3)1.27 (3)2.4322 (14)168 (2)
O1—H2D···O31.18 (3)2.57 (3)3.4622 (15)130.9 (17)
Symmetry code: (i) x+5/2, y+1/2, z1/2.
Hydrogen-bond geometry (Å, º) for (6) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O30.88 (2)2.03 (2)2.904 (2)169.1 (19)
N2—H2C···O3i0.89 (2)2.36 (2)3.003 (2)129.2 (19)
O2—H2D···O11.17 (3)1.27 (3)2.4349 (16)168 (2)
O1—H2D···O31.27 (3)2.50 (3)3.4435 (18)128.9 (17)
Symmetry code: (i) x+5/2, y+1/2, z1/2.
 

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