[Journal logo]

Volume 68 
Part 3 
Pages o99-o103  
March 2012  

Received 25 November 2011
Accepted 14 January 2012
Online 4 February 2012

Planarity of heteroaryl­dithio­carbazic acid derivatives showing tuberculostatic activity. IV. Diesters of benzoyl­carbonohydrazonodithioic acid1

aInstitute of General and Ecological Chemistry, Technical University of Lódz, Poland, and bDepartment of Organic Chemistry, Medical University of Gdansk, Poland
Correspondence e-mail: marek.glowka@p.lodz.pl

Dimethyl (3,4-dichloro­benzo­yl)carbonohydrazonodithio­ate, C10H10Cl2N2OS2, (D1), dibenzyl (3,4-dichloro­benzo­yl)car­bono­hydrazonodithio­ate, C22H18Cl2N2OS2, (D2), dimethyl (3,4-dichloro­benzo­yl)-1-methyl­carbonohydrazonodithio­ate, C11H12Cl2N2OS2, (D3), 3,4-dichloro-N'-(1,3-dithio­lan-2-yl­idene)-N-methyl­benzohydrazide, C11H10Cl2N2OS2, (D4), were synthesized as potential tuberculostatics. Compound (D1) (with two molecules in the asymmetric unit) was the only one showing tuberculostatic activity of the same range as the common drugs isoniazid and pyrazinamide. The mol­ecular structures of the studied compounds depend on the substitution at the N atom adjacent to the carbonyl group. In the case of the unsubstituted derivatives (D1) and (D2), their central frames are generally planar with a twist of the 3,4-dichloro­phenyl ring by 30-40°. Until now, coplanarity of the aromatic ring with the (methyl­ene)carbonohydrazone fragment has been considered a prerequisite for tuberculostatic activity. The N-methyl­ated derivatives (D3) and (D4) show an additional twist along the N-C(=O) bond by 20-30° due to the spatial repulsion introduced by the methyl substituent.

1. Comment

Because of the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis in developed countries, significant efforts have been put into a search for new lead tuberculostatics. Among others, Foks and coworkers have synthesized hundreds of compounds, many of which showed reasonable activity against tuberculosis (Pancechowska-Ksepko et al., 1993[Pancechowska-Ksepko, D., Foks, H., Janowiec, M. & Zwolska-Kwiek, Z. (1993). Acta Pol. Pharm. Drug Res. 50, 259-267.]; Milczarska et al., 1998[Milczarska, B., Foks, H., Trapkowski, Z., Milzynska-Kolaczek, A., Janowiec, M., Zwolska, Z. & Andrzejczyk, Z. (1998). Acta Pol. Pharm. Drug Res. 55, 289-295.], 1999[Milczarska, B., Foks, H., Sokolowska, J., Janowiec, M., Zwolska, Z. & Andrzejczyk, Z. (1999). Acta Pol. Pharm. Drug Res. 56, 121-126.]; Foks et al., 2002[Foks, H., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2002). Ann. Acad. Med. Gedanensis, 32, 301-307.]; Gobis et al., 2011[Gobis, K., Foks, H., Zwolska, Z., Augustynowicz-Kopec, E., Glówka, M. L., Olczak, A. & Sabisz, M. (2011). Monatsh. Chem. 142, 1137-1142.]).

Several crystal structures of selected representatives of these compounds were determined by our group in a search for relationships between activity and mol­ecular structure (Glówka et al., 2005[Glówka, M. L., Martynowski, D., Olczak, A., Orlewska, C., Foks, H., Bojarska, J., Szczesio, M. & Golka, J. (2005). J. Chem. Crystallogr. 35, 477-480.]; Olczak et al., 2007[Olczak, A., Glówka, M. L., Golka, J., Szczesio, M., Bojarska, J., Kozlowska, K., Foks, H. & Orlewska, C. (2007). J. Mol. Struct. 830, 171-175.], 2011[Olczak, A., Szczesio, M., Golka, J., Orlewska, C., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o37-o42.]; Szczesio et al., 2011[Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.]). The main working hypothesis tested in these studies was that planarity of a mol­ecule is a prerequisite for tuberculostatic activity (Olczak et al., 2007[Olczak, A., Glówka, M. L., Golka, J., Szczesio, M., Bojarska, J., Kozlowska, K., Foks, H. & Orlewska, C. (2007). J. Mol. Struct. 830, 171-175.]). The hypothesis was based on an observation from our very first study on the mol­ecular structure of 2-[amino­(pyridine-2-yl)methyl­ene]hydrazinecarbodithioic acid methyl ester in the crystalline state (Glówka et al., 2005[Glówka, M. L., Martynowski, D., Olczak, A., Orlewska, C., Foks, H., Bojarska, J., Szczesio, M. & Golka, J. (2005). J. Chem. Crystallogr. 35, 477-480.]). This active compound in the crystal state exists in the zwitterionic form (formula A in Scheme 1) and it is planar (except for the terminal ester group) due to conjugations and intra­molecular hydrogen bonds (Glówka et al., 2005[Glówka, M. L., Martynowski, D., Olczak, A., Orlewska, C., Foks, H., Bojarska, J., Szczesio, M. & Golka, J. (2005). J. Chem. Crystallogr. 35, 477-480.]; Olczak et al., 2007[Olczak, A., Glówka, M. L., Golka, J., Szczesio, M., Bojarska, J., Kozlowska, K., Foks, H. & Orlewska, C. (2007). J. Mol. Struct. 830, 171-175.]; Orlewska et al., 2001[Orlewska, C., Foks, H., Sowinski, P., Martynowski, D., Olczak, A. & Glówka, M. L. (2001). Pol. J. Chem. 75, 1237-1245.]). Surprisingly, overall planarity was also observed in the crystals of [amino­(pyrazin-2-yl)methyl­ene]carbonohydrazonodithioic acid diesters showing tuberculostatic activity (formula B in Scheme 1) (Olczak et al., 2011[Olczak, A., Szczesio, M., Golka, J., Orlewska, C., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o37-o42.]). Owing to the lack of an H atom at N3, the same intra­molecular hydrogen-bond contacts as those observed in all type A (Scheme 1) structures could not be formed. Instead, another intra­molecular hydrogen contact was observed, i.e. that between the amine group as a donor and the N atom at the ortho position of the pyrazine ring as an acceptor, similar to that observed in all pyrazin­amide structures [Cambridge Structural Database (CSD), Version 5.32; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]]. In the case of type B compounds (Scheme 1), planarity of the central structure frame (as evidenced by the torsion angle at the N-N bond) was secured by the conjugation alone (Olczak et al., 2011[Olczak, A., Szczesio, M., Golka, J., Orlewska, C., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o37-o42.]).

[Scheme 1]

Next, the amine function in compounds of the types A and B has been replaced by a carbonyl group (compounds type C in Scheme 1), with some of the resulting structures also showing promising activity (Foks et al., 2004[Foks, H., Trapkowska, I., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2004). Khim. Geterotsikl. Soedin. pp. 1368-1376.]; Sitarz et al., 2005[Sitarz, M., Foks, H., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2005). Chem. Heterocycl. Compd, 41, 200-207.]). This was in accord with our hypothesis as the compounds could form similar intra­molecular hydrogen bonds as in compounds of type A. The overall planarity of the mol­ecules was confirmed in our studies on their crystal structures (Szczesio et al., 2011[Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.]).

Our earlier observation that the conjugation in type B compounds was sufficient to secure planarity of the central mol­ecular chain prompted us to synthesize the respective analogues D (Scheme 1), in which we have removed the final possibility of keeping the aromatic ring coplanar with the hydrazide fragment due to the intra­molecular N5-H...N(ring) hydrogen bond (formula D in Scheme 1). We were encouraged by the structural characteristics of the well known agent isoniazid, in which this intra­molecular hydrogen bond could also not be formed (Scheme 1). Most of the type B compounds show weak tuberculostatic activity [minimum inhibitory concentration (MIC) about 50 mg ml-1] but for some the values are 20 times lower (Foks et al., 1992[Foks, H., Orlewska, C. & Janowiec, M. (1992). Acta Pol. Pharm. Drug Res. 49, 47-50.]; Orlewska et al., 1995[Orlewska, C., Foks, H., Janowiec, M. & Zwolska-Kwiek, Z. (1995). Pharmazie, 50, 265-266.]).

We report here a study on the crystal structures of four type D compounds, (D1)-(D4) (Figs. 1[link]-4[link][link][link]), which differ in the ester groups (methyl, benzyl or cyclic) or in the substitution by the methyl group at the N3 atom (see Scheme 2). There are seven diesters of benzoyl­carbonohydrazonodithioic acid (CSD, Version 5.32; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]). All are unsubstituted at the N3 atom. However, no mention has been made of their tuberculostatic activity in the literature.

[Scheme 2]

In accord with our expecta­tion, replacement of the aromatic ring containing an N atom in the ortho position by a phenyl ring resulted in its significant twist of 30-40° in comparison with planar 2-pyrazine or 2-pyrazine derivatives studied earlier. Similar values are observed in 19 benzamide structures found in the CSD, with an average of 22° (CSD, Version 5.32; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]).

The other significant difference in the mol­ecular structures of the D type and the formerly studied C type (Szczesio et al., 2011[Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.]) compounds is the conformation around the N2-N3 bond. The absolute values of the respective C1=N2-N3-C4 torsion angles are close to 177° in two planar diesters of (pyrazine-2-carbon­yl)carbonohydrazonodithioic acid (type C) (Szczesio et al., 2011[Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.]) as compared with values of 166.39 (15)° in (D2), -139.31 (18) and -150.87 (17)° in (D1), 131.65 (16)° in (D3) and 126.49 (17)° in (D4) (Table 1[link]). The lack of an H atom at the N3 atom in (D3) and (D4) also results in their very different conformation around their N3-C4 bonds in com­parison with N3-unsubstituted aroylcarbonohydrazono­di­thioic acid esters (Table 1[link]). The crucial N2-N3-C4-C41 torsion angle is about 180° in (D1) and (D2) and only 21-31° in (D3) and (D4), due to spatial repulsion introduced by the methyl group in the latter structures. A similar difference is seen in the related N2-N3-C4=O5 torsion angle, being about 4° in (D1) and (D2), and about 155° in (D3) and (D4) (Table 1[link]).

The question arises whether the observed differences in the mol­ecular structures may be related to low tuberculostatic activity of the N3-substituted compounds. The fact is that only N3-unsubstituted derivatives show higher activity, especially (D1) (Gobis et al., 2011[Gobis, K., Foks, H., Zwolska, Z., Augustynowicz-Kopec, E., Glówka, M. L., Olczak, A. & Sabisz, M. (2011). Monatsh. Chem. 142, 1137-1142.]).

The differences in conformations along the main chain correlate with differences in the respective bond lengths (Table 1[link]) indicating the change in conjugations. The largest difference is found for the N2-N3 bond length, which is 1.435 (2) Å (torsion about 130°) in (D3), 1.433 (2) Å (torsion about 125°) in (D4), 1.416 (2) and 1.402 (2) Å (torsion about -140 and -150°) in (D1) and 1.3703 (18) Å (torsion about 166°) in (D2) due to increasing (in the listed order) p(N3)-p(N2=C1) conjugation for the anti­periplanar (torsion about 180°) conformation.

Another inter­esting issue concerns the intra­molecular N3-H...S hydrogen-bond contact possible in (D1) and (D2). Although the H...S distances of 2.49 and 2.52 Å in (D1) and 2.59 Å in (D2) are significantly shorter than the sum of their van der Waals radii (2.89 Å), the angles at the H atom are only 104, 99 and 108°, respectively. So, despite the H...S distances indicating hydrogen bonds, there is some doubt in the literature concerning contribution of the contacts to the stabilization energy of the crystals, especially because of the low values of the N3-H...S angles (Wood et al., 2009[Wood, P. A., Allen, F. H. & Pidcock, E. (2009). CrystEngComm, 11, 1563-1571.]; Galek et al., 2010[Galek, P. T. A., Fábián, L. & Allen, F. H. (2010). Acta Cryst. B66, 237-252.]; Bilton et al., 2000[Bilton, C., Allen, F. H., Shields, G. P. & Howard, J. A. K. (2000). Acta Cryst. B56, 849-856.]). Our view on the subject has been presented in Szczesio et al. (2011[Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.]).

In the studied crystals there are several inter­mol­ecular hydrogen bonds, some of which are quite strong and important for crystal packing (Figs. 5[link]-7[link][link]). In (D1), the two independent mol­ecules form an infinite C22(8) chain [according to the graph-set definition of Bernstein et al. (1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.])] parallel to the [100] direction through two inter­molecular hydrogen bonds, viz. N3-H...O5A and N3A-H...O5(x - 1, y, z). In addition, in (D1), there exists a C21-H...Cl4A(x + 1, y, z + 1) contact taking part in the formation of two additional chains, viz. C22(14) parallel to the [101] direction with an N3-H...O5A hydrogen bond and C22(16) parallel to the [001] direction with an N3A-H...O5(x - 1, y, z) hydrogen bond. At the third level of the graph-set theory, the R66(38) ring formed by N3-H...O5A, N3A-H...O5(x - 1, y, z) and C21-H...Cl4A(x + 1, y, z + 1) can be identified (Fig. 5[link]). In (D2), there is only one weak hydrogen bond, C16-H...O5(x, -y, z - [{1\over 2}]), forming a C(11) chain parallel to the [001] direction (Fig. 6[link]). In (D3), there is also one weak hydrogen bond, C11-H...O5(x, y + 1, z), forming a C(8) chain parallel to the [010] direction (Fig. 7[link]). No significant inter­molecular contacts were observed in (D4).

[Figure 1]
Figure 1
The mol­ecular structure of the two independent molecules of (D1), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 2]
Figure 2
The mol­ecular structure of (D2), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 3]
Figure 3
The mol­ecular structure of (D3), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 4]
Figure 4
The mol­ecular structure of (D4), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
[Figure 5]
Figure 5
The inter­molecular hydrogen bonds of (D1) determining the packing of mol­ecules in the crystal. [Symmetry codes: (i) x + 1, y, z + 1; (ii) x - 1, y, z.]
[Figure 6]
Figure 6
The inter­molecular hydrogen bonds of (D2) determining the packing of mol­ecules in the crystal. [Symmetry code: (i) x, -y, z - [{1\over 2}].]
[Figure 7]
Figure 7
The inter­molecular hydrogen bonds of (D3) determining the packing of mol­ecules in the crystal. [Symmetry code: (i) x, y + 1, z.]

2. Experimental

The synthesis of (D1) was described previously by Gobis et al. (2011[Gobis, K., Foks, H., Zwolska, Z., Augustynowicz-Kopec, E., Glówka, M. L., Olczak, A. & Sabisz, M. (2011). Monatsh. Chem. 142, 1137-1142.]). The other compounds were obtained from 3,4-dichloro­ben­zo­hy­dra­zide [for (D2)] or 3,4-dichloro-N-methyl­hydrazide [for (D3) and (D4)] according to the same method. Benzohydrazides were dissolved in a methanol solution of triethyl­amine and treated with carbon disulfide and the respective halide, viz. methyl iodide for (D3), benzyl chloride for (D2) or ethyl­ene bromide for (D4). Single crystals of (D1), (D2), (D3) and (D4) suitable for X-ray diffraction were obtained from ethanol solutions by slow evaporation of the solvents at room temperature.

2.1. Compound (D1)[link]

2.1.1. Crystal data
  • C10H10Cl2N2OS2

  • Mr = 309.22

  • Monoclinic, P 21

  • a = 9.2225 (4) Å

  • b = 11.2741 (5) Å

  • c = 13.0892 (5) Å

  • [beta] = 95.367 (1)°

  • V = 1354.99 (10) Å3

  • Z = 4

  • Mo K[alpha] radiation

  • [mu] = 0.77 mm-1

  • T = 296 K

  • 0.3 × 0.3 × 0.1 mm

2.1.2. Data collection
  • Bruker SMART APEXII CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003[Sheldrick, G. M. (2003). SADABS. University of Göttingen, Germany.]) Tmin = 0.914, Tmax = 1.000

  • 33334 measured reflections

  • 7766 independent reflections

  • 7138 reflections with I > 2[sigma](I)

  • Rint = 0.021

2.1.3. Refinement
  • R[F2 > 2[sigma](F2)] = 0.033

  • wR(F2) = 0.092

  • S = 1.08

  • 7766 reflections

  • 312 parameters

  • 1 restraint

  • H-atom parameters constrained

  • [Delta][rho]max = 0.79 e Å-3

  • [Delta][rho]min = -0.31 e Å-3

  • Absolute structure: Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 3697 Friedel pairs

  • Flack parameter: -0.02 (4)

Table 2
Hydrogen-bond geometry (Å, °) for (D1)[link]

D-H...A D-H H...A D...A D-H...A
C21-H21E...Cl4Ai 0.96 2.75 3.565 (3) 144
N3A-H3A...O5ii 0.86 2.10 2.8434 (18) 144
N3-H3...O5A 0.86 2.06 2.834 (2) 149
N3-H3...S1 0.86 2.52 2.7810 (17) 99
N3A-H3A...S1A 0.86 2.49 2.8216 (16) 104
Symmetry codes: (i) x+1, y, z+1; (ii) x-1, y, z.

2.2. Compound (D2)[link]

2.2.1. Crystal data
  • C22H18Cl2N2OS2

  • Mr = 461.40

  • Monoclinic, C 2/c

  • a = 28.6760 (11) Å

  • b = 10.3705 (3) Å

  • c = 14.7176 (6) Å

  • [beta] = 90.900 (4)°

  • V = 4376.2 (3) Å3

  • Z = 8

  • Mo K[alpha] radiation

  • [mu] = 0.50 mm-1

  • T = 292 K

  • 0.55 × 0.4 × 0.3 mm

2.2.2. Data collection
  • Kuma KM-4 CCD diffractometer

  • Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008[Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]) Tmin = 0.942, Tmax = 1.000

  • 17461 measured reflections

  • 3868 independent reflections

  • 3021 reflections with I > 2[sigma](I)

  • Rint = 0.022

2.2.3. Refinement
  • R[F2 > 2[sigma](F2)] = 0.030

  • wR(F2) = 0.084

  • S = 0.94

  • 3868 reflections

  • 262 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.22 e Å-3

  • [Delta][rho]min = -0.29 e Å-3

Table 3
Hydrogen-bond geometry (Å, °) for (D2)[link]

D-H...A D-H H...A D...A D-H...A
N3-H3...S1 0.86 2.59 2.9751 (14) 108
C16-H16...O5i 0.93 2.44 3.294 (3) 153
Symmetry code: (i) [x, -y, z-{\script{1\over 2}}].

2.3. Compound (D3)[link]

2.3.1. Crystal data
  • C11H12Cl2N2OS2

  • Mr = 323.25

  • Triclinic, [P \overline 1]

  • a = 8.9307 (4) Å

  • b = 9.0858 (7) Å

  • c = 10.3873 (5) Å

  • [alpha] = 65.039 (6)°

  • [beta] = 69.172 (4)°

  • [gamma] = 74.892 (5)°

  • V = 708.08 (7) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 0.74 mm-1

  • T = 291 K

  • 0.5 × 0.35 × 0.2 mm

2.3.2. Data collection
  • Kuma KM-4 CCD diffractometer

  • Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2008[Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]) Tmin = 0.447, Tmax = 1.000

  • 10270 measured reflections

  • 2494 independent reflections

  • 2181 reflections with I > 2[sigma](I)

  • Rint = 0.034

2.3.3. Refinement
  • R[F2 > 2[sigma](F2)] = 0.033

  • wR(F2) = 0.097

  • S = 1.15

  • 2494 reflections

  • 166 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.24 e Å-3

  • [Delta][rho]min = -0.42 e Å-3

Table 4
Hydrogen-bond geometry (Å, °) for (D3)[link]

D-H...A D-H H...A D...A D-H...A
C11-H11B...O5i 0.96 2.49 3.200 (2) 131
Symmetry code: (i) x, y+1, z.

2.4. Compound (D4)[link]

2.4.1. Crystal data
  • C11H10Cl2N2OS2

  • Mr = 321.23

  • Monoclinic, P 21 /c

  • a = 13.3680 (2) Å

  • b = 8.1817 (1) Å

  • c = 13.5158 (2) Å

  • [beta] = 105.415 (1)°

  • V = 1425.08 (3) Å3

  • Z = 4

  • Cu K[alpha] radiation

  • [mu] = 6.76 mm-1

  • T = 296 K

  • 0.3 × 0.2 × 0.05 mm

2.4.2. Data collection
  • Bruker SMART APEXII CCD diffractometer

  • Absorption correction: multi-scan (SADABS; Sheldrick, 2003[Sheldrick, G. M. (2003). SADABS. University of Göttingen, Germany.]) Tmin = 0.423, Tmax = 0.753

  • 15835 measured reflections

  • 2643 independent reflections

  • 2589 reflections with I > 2[sigma](I)

  • Rint = 0.034

2.4.3. Refinement
  • R[F2 > 2[sigma](F2)] = 0.034

  • wR(F2) = 0.100

  • S = 1.06

  • 2643 reflections

  • 165 parameters

  • H-atom parameters constrained

  • [Delta][rho]max = 0.48 e Å-3

  • [Delta][rho]min = -0.36 e Å-3

Table 1
Selected bond lengths (Å) and torsion angles (°) for the title compounds

  C1-N2-N3-C4 N2-N3-C4-C41 N2-N3-C4-O5 N2-N3
(D1) -139.31 (18) -177.95 (16) 4.0 (3) 1.416 (2)
  -150.87 (17) -178.19 (15) 3.1 (3) 1.402 (2)
(D2) 166.39 (15) 177.63 (13) -4.1 (2) 1.3703 (18)
(D3) 131.65 (16) -31.2 (2) 152.86 (16) 1.435 (2)
(D4) 126.49 (17) -21.1 (2) 159.99 (18) 1.433 (2)

H atoms were located in difference Fourier maps and subsequently geometrically optimized and allowed for as riding atoms, with C-H = 0.93 Å for aromatic CH groups, 0.97 Å for secondary CH2 groups and 0.96 Å for methyl groups, N-H = 0.86 Å and Uiso(H) = 1.5Ueq(C) for methyl groups or 1.2Ueq(C,N) otherwise.

Data collection: APEX2 (Bruker, 2005[Bruker (2005). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.]) for (D1) and (D4); CrysAlis CCD (Oxford Diffraction, 2008[Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]) for (D2) and (D3). Cell refinement: SAINT-Plus (Bruker, 2008[Bruker (2008). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.]) for (D1) and (D4); CrysAlis RED (Oxford Diffraction, 2008[Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.]) for (D2) and (D3). Data reduction: SAINT-Plus for (D1) and (D4); CrysAlis RED for (D2) and (D3). For all compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]) and Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]); software used to prepare material for publication: PLATON.


Supplementary data for this paper are available from the IUCr electronic archives (Reference: WQ3009 ). Services for accessing these data are described at the back of the journal.


Acknowledgements

The present study was supported by the Ministry of Science and Higher Education under project No. N204 111735.

References

Allen, F. H. (2002). Acta Cryst. B58, 380-388.  [Web of Science] [CrossRef] [IUCr Journals]
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.  [CrossRef] [ChemPort] [Web of Science]
Bilton, C., Allen, F. H., Shields, G. P. & Howard, J. A. K. (2000). Acta Cryst. B56, 849-856.  [CrossRef] [IUCr Journals]
Bruker (2005). APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.
Bruker (2008). SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA.
Flack, H. D. (1983). Acta Cryst. A39, 876-881.  [CrossRef] [IUCr Journals]
Foks, H., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2002). Ann. Acad. Med. Gedanensis, 32, 301-307.  [ChemPort]
Foks, H., Orlewska, C. & Janowiec, M. (1992). Acta Pol. Pharm. Drug Res. 49, 47-50.  [ChemPort]
Foks, H., Trapkowska, I., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2004). Khim. Geterotsikl. Soedin. pp. 1368-1376.
Galek, P. T. A., Fábián, L. & Allen, F. H. (2010). Acta Cryst. B66, 237-252.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Glówka, M. L., Martynowski, D., Olczak, A., Orlewska, C., Foks, H., Bojarska, J., Szczesio, M. & Golka, J. (2005). J. Chem. Crystallogr. 35, 477-480.
Gobis, K., Foks, H., Zwolska, Z., Augustynowicz-Kopec, E., Glówka, M. L., Olczak, A. & Sabisz, M. (2011). Monatsh. Chem. 142, 1137-1142.  [CrossRef] [ChemPort]
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Milczarska, B., Foks, H., Sokolowska, J., Janowiec, M., Zwolska, Z. & Andrzejczyk, Z. (1999). Acta Pol. Pharm. Drug Res. 56, 121-126.  [ChemPort]
Milczarska, B., Foks, H., Trapkowski, Z., Milzynska-Kolaczek, A., Janowiec, M., Zwolska, Z. & Andrzejczyk, Z. (1998). Acta Pol. Pharm. Drug Res. 55, 289-295.  [ChemPort]
Olczak, A., Glówka, M. L., Golka, J., Szczesio, M., Bojarska, J., Kozlowska, K., Foks, H. & Orlewska, C. (2007). J. Mol. Struct. 830, 171-175.  [Web of Science] [CSD] [CrossRef] [ChemPort]
Olczak, A., Szczesio, M., Golka, J., Orlewska, C., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o37-o42.  [CSD] [CrossRef] [IUCr Journals]
Orlewska, C., Foks, H., Janowiec, M. & Zwolska-Kwiek, Z. (1995). Pharmazie, 50, 265-266.
Orlewska, C., Foks, H., Sowinski, P., Martynowski, D., Olczak, A. & Glówka, M. L. (2001). Pol. J. Chem. 75, 1237-1245.  [ChemPort]
Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, Oxfordshire, England.
Pancechowska-Ksepko, D., Foks, H., Janowiec, M. & Zwolska-Kwiek, Z. (1993). Acta Pol. Pharm. Drug Res. 50, 259-267.  [ChemPort]
Sheldrick, G. M. (2003). SADABS. University of Göttingen, Germany.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [ChemPort] [IUCr Journals]
Sitarz, M., Foks, H., Janowiec, M., Zwolska, Z. & Augustynowicz-Kopec, E. (2005). Chem. Heterocycl. Compd, 41, 200-207.  [CrossRef] [ChemPort]
Spek, A. L. (2009). Acta Cryst. D65, 148-155.  [Web of Science] [CrossRef] [ChemPort] [IUCr Journals]
Szczesio, M., Olczak, A., Golka, J., Gobis, K., Foks, H. & Glówka, M. L. (2011). Acta Cryst. C67, o235-o240.  [CSD] [CrossRef] [ChemPort] [IUCr Journals]
Wood, P. A., Allen, F. H. & Pidcock, E. (2009). CrystEngComm, 11, 1563-1571.  [Web of Science] [CrossRef] [ChemPort]


Acta Cryst (2012). C68, o99-o103   [ doi:10.1107/S0108270112001734 ]