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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296
Volume 60| Part 4| April 2004| Pages o226-o228
doi:10.1107/S0108270104003026

The imide tautomer of sulfasalazine

CROSSMARK_Color_square_no_text.svg
Alexander J. Blake,a Xiang Lin,a Martin Schröder,a Claire Wilsona and Rong-Xin Yuana,b*

aSchool of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, England, and bDepartment of Chemistry, Changshu College, Changshu 215500, People's Republic of China
*Correspondence e-mail: a.j.blake@nottingham.ac.uk

(Received 5 February 2004; accepted 9 February 2004; online 11 March 2004)

The title compound, 5-{4-[(2-pyridyl­idene­amino)­sulfonyl]­phenyl­diazenyl}salicylic acid, C18H14N4O5S, crystallizes as the imide tautomer in the monoclinic space group P21/c. In addition to an intramolecular O—H⋯O hydrogen bond, intermolecular O—H⋯O interactions link adjacent mol­ecules into helices, which are connected by pairwise N—H⋯N interactions into two-dimensional hydrogen-bonded layers. Both the molecular conformation and the packing differ from those seen in the triclinic amide form [Filip et al. (2001[Filip, L. A., Caira, M. R., Farcas, S. I. & Bojita, M. T. (2001). Acta Cryst. C57, 435-436.]). Acta Cryst. C57, 435–436].

Comment

Crystal engineering of pharmaceutical solids represents a fertile emerging area of research (Walsh et al., 2003[Walsh, B. R. D., Bradner, M. W., Fleischman, S., Morales, L. A., Moulton, B., Rodriguez-Hornedo, N. & Zaworotko, M. J. (2003). Chem. Commun. pp. 186-187.]; Oswald et al., 2002[Oswald, I. D. H., Allan, D. R., McGregor, P. A., Motherwell, W. D. S., Parsons, S. & Pulham, C. R. (2002). Acta Cryst. B58, 1057-1066.]). The impetus for discovery of diverse crystal forms of drugs stems from the critical need to balance stability, bio­availability and other performance characteristics, and also to provide valuable intellectual property protection. Sulfa­salazine (synonyms: salazo­pyridine and salazosulfa­pyridine; abbreviated herein as SSZ) is a conjugate of 5-amino­salicylic acid and sulfa­pyridine possessing antimicrobial properties, and is used as a drug for treating inflammatory bowel disorders (Svartz, 1942[Svartz, N. (1942). Acta Med. Scand. 110, 577-598.]; Das & Rubin, 1976[Das, K. M. & Rubin, R. (1976). Clin. Pharmacokin. 1, 406-425.]) and rheumatoid arthritis (Pullar, 1989[Pullar, T. (1989). Pharmacol. Ther. 42, 459-468.]). It is also a known inhibitor of α-, μ- and π-class gluta­thione S-transferases, with concentrations of 28 µM or less required to inhibit 50% of enzymatic activity (Ahmad et al., 1992[Ahmad, H., Singhal, S. S. & Awasthi, S. (1992). Biochem. Arch. 8, 335-361.]). We are investigating the interaction of this drug with metal ions, with a view to obtaining complexes with useful medicinal properties. In this paper, we report the crystal structure of the monoclinic form, (I[link]), of SSZ and compare the hydrogen-bonding interactions observed in the two forms of SSZ, the structure of the triclinic amide form having been reported by Filip et al. (2001[Filip, L. A., Caira, M. R., Farcas, S. I. & Bojita, M. T. (2001). Acta Cryst. C57, 435-436.]).

In the title phase, (I[link]) (Fig. 1[link]), both the C5—N2 [1.348 (4) Å] and the S1—N2 [1.586 (3) Å] bond lengths are much shorter than those observed in the triclinic amide form [1.425 (2) and 1.6539 (16) Å, respectively], indicating conjugation between the pyridine ring and the side chain. These bond lengths and the orange colour of the crystals of (I[link]) identify the imide tautomeric form observed previously as a di­methyl­form­amide–water mixed solvate by van der Sluis & Spek (1990[Sluis, P. van der & Spek, A. L. (1990). Acta Cryst. C46, 883-886.]) [C—N = 1.348 (7) and N—S = 1.600 (4) Å], rather than the triclinic amide phase reported by Filip et al. (2001[Filip, L. A., Caira, M. R., Farcas, S. I. & Bojita, M. T. (2001). Acta Cryst. C57, 435-436.]). This conclusion was supported by competitive refinement of the occupancies of possible H-atom positions on N1 and N2, which clearly locates the H atom on the former. Other molecular geometry parameters are comparable with those found for the amide form.

[Scheme 1]

The molecular conformation of (I[link]) (Fig. 1[link]) is different from that of the triclinic form. Although the aromatic rings linked by the –N=N– bridge are essentially coplanar in both forms, the relative orientations of the (2-pyridyl­amino)­sulfonyl group differ markedly. In the triclinic form, the N—S—C—C torsion angles lie near 87°, while in the title phase, these torsions are about 44° (Table 1[link]). In both forms, the bulk of the mol­ecule (including the S atom, the phenyl ring, the azo bridge and the salicylic acid segment) is almost planar, as a result of exten­sive electron delocalization, with an intramolecular O3—H3O⋯O4 hydrogen bond (Table 2[link]) directing the orientation of the carboxylic acid group; atom H3O lies within 0.075 (5) Å of the least-squares mean plane through the other atoms (O4/C12/C13/C14/O3) of the six-membered ring. The overall conformation is similar to that of one of the two independent mol­ecules in the asymmetric unit of the solvate (Van der Sluis & Spek, 1990[Sluis, P. van der & Spek, A. L. (1990). Acta Cryst. C46, 883-886.]).

Analysis of the crystal packing of (I[link]) shows the presence of intermolecular O—H⋯O and N—H⋯N hydrogen bonds in the structure (Table 2[link]). The H atom of a carboxyl group forms an O5—H5O⋯O2ii interaction with an O atom of a sulfonyl group [symmetry code: (ii) 1 − x, y − [{1 \over 2}], [{1 \over 2}] − z]. These hydrogen bonds connect adjacent mol­ecules into helices running along the b axis, with a pitch [6.0911 (11) Å] equal to its length (Fig. 2[link]). Meanwhile, N1—H1N⋯N2i inter­actions (Fig. 3[link]) between pyridyl­amine moieties generate R22(8) rings (Etter, 1990[Etter, M. C. (1990). Acc. Chem. Res. 23, 120-126.]; Etter et al., 1990[Etter, M. C., MacDonald, J. C. & Bernstein, J. (1990). Acta Cryst. B46, 256-262.]) and link the helices to form two-dimensional hydrogen-bonded sheets (Fig. 4[link]) [symmetry code: (i) 2 − x, 2 − y, 1 − z]. This packing contrasts with that of the amide tautomer (Filip et al., 2001[Filip, L. A., Caira, M. R., Farcas, S. I. & Bojita, M. T. (2001). Acta Cryst. C57, 435-436.]), which is characterized by a repeating unit consisting of a centrosymmetric dimer assembled through N—H⋯O hydrogen bonds between the pyridyl­amine and carboxylic acid moieties, and which exhibits aromatic π–π stacking between adjacent mol­ecules.

We note that reaction under the same conditions but in the absence of the ZnII ions, or under ambient conditions, did not result in the formation of (I[link]), suggesting that the presence of these ions is important in obtaining the structure. As we have also obtained the same crystals in the presence of Cu(ClO4)2, Zn(ClO4)2 and Cd(ClO4)2, and the amide form was isolated from a reaction between SSZ and CuCl2 (Filip et al., 2001[Filip, L. A., Caira, M. R., Farcas, S. I. & Bojita, M. T. (2001). Acta Cryst. C57, 435-436.]), it seems that the ions present play a structure-directing role in the system, although the origin of this effect remains unclear.

[Figure 1]
Figure 1
A view of (I[link]) showing the atom-numbering scheme, with displacement ellipsoids drawn at the 50% probability level and H atoms shown as small spheres of arbitrary radii. The dashed line identifies the intramolecular O3—H3O⋯O4 hydrogen bond.
[Figure 2]
Figure 2
A side view of a helix formed in (I[link]) via O5—H5O⋯O2 hydrogen bonds. The helix runs parallel to the b axis. Atoms are shown as plain for C, dotted for N, lined for O and cross-hatched for S.
[Figure 3]
Figure 3
A view of representative parts of three helices in (I[link]), showing the intermolecular N1—H1N⋯N2 interactions which link them. Atom shading is as in Fig. 2[link] [symmetry code: (i) 2-x,1-y,1-z].
[Figure 4]
Figure 4
An overall view of the crystal packing in (I[link]) along the b axis, showing a side view of the two-dimensional layers. Atom shading is as in Fig. 2[link].

Experimental

A mixture of Zn(ClO4)2·6H2O (0.074 g, 0.2 mmol), SSZ (0.080 g, 0.2 mmol), ethanol (8 ml) and distilled water (2 ml) was sealed in a Teflon-lined stainless steel autoclave and heated at 393 K for 48 h under autogenous pressure and then cooled to room temperature. Orange lozenge-like crystals of (I[link]) were obtained. Analysis calculated: C 54.3, H 3.5, N 14.1%; found: C 54.3, H 3.6, N 13.8%. Spectroscopic analysis, IR (KBr, ν, cm−1): 3125 (s), 3059 (s), 3026 (s), 1677 (m), 1635 (m), 1617 (m), 1586 (m), 1393 (m), 1358 (m), 1270 (m), 1269 (m), 1199 (m), 1172 (m), 1127 (m), 1085 (m), 800 (m), 790 (m), 768 (m), 613 (m), 574 (m).

Crystal data

  • C18H14N4O5S

  • Mr = 398.39

  • Monoclinic, P21/c

  • a = 19.308 (3) Å

  • b = 6.0911 (11) Å

  • c = 16.109 (3) Å

  • β = 113.405 (3)°

  • V = 1738.7 (5) Å3

  • Z = 4

  • Dx = 1.522 Mg m−3

  • Mo Kα radiation

  • Cell parameters from 2040 reflections

  • θ = 2.5–27.4°

  • μ = 0.23 mm−1

  • T = 150 (2) K

  • Column, orange

  • 0.49 × 0.14 × 0.09 mm
Data collection

  • Bruker SMART APEX CCD area-detector diffractometer

  • ω scans

  • Absorption correction: multi-scan (SADABS; Bruker, 2001[Bruker (2001). SMART (Version 5.625), SADABS (Version 2.03a) and SHELXTL (Version 6.12). Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.711, Tmax = 1.000

  • 10 720 measured reflections

  • 3950 independent reflections

  • 2603 reflections with I > 2σ(I)

  • Rint = 0.038

  • θmax = 27.4°

  • h = −25 → 24

  • k = −7 → 4

  • l = −20 → 20
Refinement

  • Refinement on F2

  • R[F2 > 2σ(F2)] = 0.067

  • wR(F2) = 0.195

  • S = 1.04

  • 3950 reflections

  • 262 parameters

  • H atoms treated by a mixture of independent and constrained refinement

  • w = 1/[σ2(Fo2) + (0.109P)2 + 1.095P] where P = (Fo2 + 2Fc2)/3

  • (Δ/σ)max < 0.001

  • Δρmax = 1.02 e Å−3

  • Δρmin = −0.44 e Å−3

Table 1
Selected geometric parameters (Å, °)

S1—O1 1.431 (3)
S1—O2 1.439 (3)
S1—N2 1.586 (3)
C5—N2 1.348 (4)
C12—O4 1.235 (4)
C12—O5 1.316 (5)
C14—O3 1.358 (4)
N3—N4 1.242 (4)
O1—S1—O2 116.79 (15)
O1—S1—N2 113.77 (15)
O2—S1—N2 104.12 (14)
O1—S1—C6 106.96 (15)
O2—S1—C6 107.00 (15)
N2—S1—C6 107.73 (14)
C1—N1—C5 124.3 (3)
C5—N2—S1 120.2 (2)
N4—N3—C9 113.5 (3)
N3—N4—C17 114.6 (3)
N2—S1—C6—C11 43.9 (3)
N2—S1—C6—C7 −137.3 (3)
O4—C12—C13—C18 177.8 (3)
C12—C13—C14—O3 1.7 (5)
N1—C5—N2—S1 164.7 (2)
C4—C5—N2—S1 −15.8 (5)
C10—C9—N3—N4 −179.6 (3)
C8—C9—N3—N4 −2.1 (5)
C9—N3—N4—C17 178.6 (3)
C18—C17—N4—N3 −176.8 (3)
C16—C17—N4—N3 3.2 (5)

Table 2
Hydrogen-bonding geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
O3—H3O⋯O4 0.91 (3) 1.75 (3) 2.612 (4) 157 (4)
N1—H1N⋯N2i 0.90 (3) 1.98 (3) 2.878 (4) 173 (3)
O5—H5O⋯O2ii 0.91 (3) 1.77 (3) 2.636 (4) 159 (4)
Symmetry codes: (i) 2-x,1-y,1-z; (ii) [1-x,y-{\script{1\over 2}},{\script{1\over 2}}-z].

The highest difference electron-density peak (1.02 e Å−3) lies 0.85 Å from atom S1. H atoms of the O—H and N—H groups were located from difference Fourier syntheses and thereafter refined with distance restraints of 0.90 (1) Å. C-bound H atoms were included at geometrically calculated positions and constrained to ride at distances of 0.93 Å from their parent atoms. For all H atoms, Uiso(H) = 1.2Ueq(C). The location of an H atom on N1 rather than on N2 was established by competitive refinement of the occupancies of the two possible H-atom positions.

Data collection: SMART (Bruker, 2001[Bruker (2001). SMART (Version 5.625), SADABS (Version 2.03a) and SHELXTL (Version 6.12). Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT (Bruker, 2002[Bruker (2002). SAINT. Version 6.36a. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT and SHELXTL (Bruker, 2001[Bruker (2001). SMART (Version 5.625), SADABS (Version 2.03a) and SHELXTL (Version 6.12). Bruker AXS Inc., Madison, Wisconsin, USA.]); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany.]); molecular graphics: SHELXTL; software used to prepare material for publication: enCIFer (CCDC, 2003[CCDC (2003). enCIFer. Version 1.0. Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, England.]) and PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S0108270104003026/sk1702sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S0108270104003026/sk1702Isup2.hkl


Comment top

Crystal engineering of pharmaceutical solids represents a fertile emerging area of research (Walsh et al., 2003; Oswald et al., 2002). The impetus for discovery of diverse crystal forms of drugs stems from the critical need to balance stability, bioavailability and other performance characteristics, and also to provide valuable intellectual property protection. Sulfasalazine (synonyms salazopyridine and salazosulfapyridine, abbreviated herein as SSZ) is a conjugate of 5-aminosalicylic acid and sulfapyridine possessing antimicrobial properties, and is used as a drug for treating inflammatory bowel disorders (Svartz, 1942; Das & Rubin, 1976) and rheumatoid arthritis (Pullar, 1989). It is also a known inhibitor of α, µ and π class glutathione S-transferases, with concentrations of 28µM or less required to inhibit 50% of enzymatic activity (Ahmad et al., 1992). We are investigating the interaction of this drug with metal ions, with a view to obtaining complexes with useful medicinal properties. In this paper, we report the crystal structure of the monoclinic form, (I), of SSZ and compare the hydrogen-bonding interactions observed in the two forms of SSZ, the structure of the triclinic amide form having been reported by Filip et al. (2001). \sch

In the title phase, (I) (Fig. 1), both the C5—N2 [1.342 (4) Å] and the N2—S1 [1.584 (3) Å] bond lengths are much shorter than those observed in the triclinic amide form [1.425 (2) and 1.6539 (16) Å, respectively], indicating conjugation between the pyridine ring and the side chain. These bond lengths and the orange colour of the crystals of (I) identify the imide tautomeric form previously observed as a dimethylfomamide-water mixed solvate by Van der Sluis & Spek (1990) [C—N 1.348 (7) and N—S 1.600 (4) Å], rather than the triclinic amide phase reported by Filip et al. (2001). This conclusion was supported by competitive refinement of the occupancies of possible H-atom positions on N1 and N2, which clearly locates the H atom on the former. Other molecular geometry parameters are comparable with those found for the amide form.

The molecular conformation of (I) (Fig. 1) is different from that of the triclinic form. Although the aromatic rings linked by the —N═N— bridge are essentially coplanar in both forms, the relative orientations of the (2-pyridylamino)sulfonyl group differ markedly. In the triclinic form, the N—S—C—C torsion angles lie near 87°, while in the title phase, these torsions are about 44° (Table 1). In both forms, the bulk of the molecule (including the S atom, the phenyl ring, the azo bridge and the salicylic acid segment) is almost planar, as a result of extensive electron delocalization, with the intramolecular O3—H3O···O4 hydrogen bond (Table 2) directing the orientation of the carboxylic acid group: atom H3O lies within 0.075 (5) Å of the least-squares mean plane through the other atoms (O4/C12/C13/C14/O3) of the six-membered ring. The overall conformation is similar to that of one of the two independent molecules in the asymmetric unit of the solvate (Van der Sluis & Spek, 1990).

Analysis of the crystal packing of (I) shows the presence of intermolecular O—H···O and N—H···N hydrogen bonds in the structure (Table 2). The H atom of a carboxyl group forms an O5—H5O···O2ii interaction with one O atom of a sulfonyl group [symmetry code: (ii) 1 − x, y − 1/2, 1/2 − z]. These hydrogen bonds connect adjacent molecules into helices running along the b axis and with a pitch [6.0911 (11) Å] equal to its length (Fig. 2). Meanwhile, N1—H1N···N2i interactions (Fig. 3) between pyridylamino moieties generate R22(8) rings (Etter, 1990; Etter et al., 1990) and link the helices to form two-dimensional hydrogen-bonded sheets (Fig. 4) [symmetry code: (i) 2 − x, 2 − y, 1 − z]. This packing contrasts with that of the amide tautomer (Filip et al., 2001), which is characterized by a repeating unit consisting of a centrosymmetric dimer assembled through N—H···O hydrogen bonds between the pyridylamino and carboxylic acid moieties, and which exhibits aromatic π–π stacking between adjacent molecules.

We note that reaction under the same conditions but in the absence of the ZnII ions, or under ambient conditions, did not result in the formation of (I), suggesting that the presence of these ions is important in obtaining the structure. As we have also obtained the same crystals in the presence of Cu(ClO4)2, Zn(ClO4)2 and Cd(ClO4)2, and the amide form was isolated from a reaction between SSZ and CuIICl2 (Filip et al., 2001), it therefore seems that the ions present play a structure-directing role in the system, although the origin of this effect remains unclear.

Experimental top

A mixture of Zn(ClO4)2·6H2O (0.074 g, 0.2 mmol), SSZ (0.080 g, 0.2 mmol), ethanol (8 ml) and distilled water (2 ml) was sealed in a Teflon-lined stainless steel autoclave and heated at 393 K for 48 h under autogenous pressure and then cooled to room temperature. Orange lozenge-like crystals of (I) were obtained. Analysis, calculated: C 54.3, H 3.5, N 14.1%; found: C 54.3, H 3.6, N 13.8%. Spectroscopic analysis: IR (KBr, ν, cm−1): 3125 (s), 3059 (s), 3026 (s), 1677 (m), 1635 (m), 1617 (m), 1586 (m), 1393 (m), 1358 (m), 1270 (m), 1269 (m), 1199 (m), 1172 (m), 1127 (m), 1085 (m), 800 (m), 790 (m), 768 (m), 613 (m), 574 (m).

Refinement top

The highest difference electron-density peak (1.02 e Å−3) lies 0.85 Å from atom S1. H atoms of O—H and N—H groups were located from difference Fourier syntheses and thereafter refined with distance restraints of 0.90 (1) Å. C-bound H atoms were included at geometrically calculated positions and constrained to ride 0.93 Å from their parent atoms. For all H atoms, Uiso(H) = 1.2Ueq(C). The location of an H atom on N1 rather than on N2 was established by competitive refinement of the occupancies of the two possible H-atom positions.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT and SHELXTL (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: enCIFer (CCDC, 2003) and PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. A view of (I) showing the atom-numbering scheme, with displacement ellipsoids drawn at the 50% probability level and H atoms shown as small spheres of arbitrary radii. The dashed line identifies the intramolecular O3—H3O···O4 hydrogen bond.
[Figure 2] Fig. 2. A side view of a helix formed in (I) via O5—H5O···O2 hydrogen bonds. The helix runs parallel to the b axis. Atoms are shown as plain for C, dotted for N, right-hashed for O and cross-hatched for S.
[Figure 3] Fig. 3. A view of representative parts of three helices in (I), showing the intermolecular N1—H1N···N2 interactions which link them. Atom shading is as in Fig. 2.
[Figure 4] Fig. 4. An overall view of the crystal packing in (I) along the b axis, showing a side view of the two-dimensional layers. Atom shading is as in Fig. 2.
5-{4-[(2-pyridylideneamino)sulfonyl]phenyldiazenyl}salicylic acid top
Crystal data top
C18H14N4O5SF(000) = 824
Mr = 398.39Dx = 1.522 Mg m−3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 2040 reflections
a = 19.308 (3) Åθ = 2.5–27.4°
b = 6.0911 (11) ŵ = 0.23 mm−1
c = 16.109 (3) ÅT = 150 K
β = 113.405 (3)°Column, orange
V = 1738.7 (5) Å30.49 × 0.14 × 0.09 mm
Z = 4
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		3950 independent reflections
Radiation source: normal-focus sealed tube2603 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.038
ω scansθmax = 27.4°, θmin = 2.5°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		h = −25→24
Tmin = 0.711, Tmax = 1.000k = −7→4
10720 measured reflectionsl = −20→20
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)] = 0.067Hydrogen site location: see text
wR(F2) = 0.195H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.109P)2 + 1.095P]
where P = (Fo2 + 2Fc2)/3
3950 reflections(Δ/σ)max < 0.001
262 parametersΔρmax = 1.02 e Å−3
3 restraintsΔρmin = −0.44 e Å−3
Crystal data top
C18H14N4O5SV = 1738.7 (5) Å3
Mr = 398.39Z = 4
Monoclinic, P21/cMo Kα radiation
a = 19.308 (3) ŵ = 0.23 mm−1
b = 6.0911 (11) ÅT = 150 K
c = 16.109 (3) Å0.49 × 0.14 × 0.09 mm
β = 113.405 (3)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		3950 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		2603 reflections with I > 2σ(I)
Tmin = 0.711, Tmax = 1.000Rint = 0.038
10720 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0673 restraints
wR(F2) = 0.195H atoms treated by a mixture of independent and constrained refinement
S = 1.04Δρmax = 1.02 e Å−3
3950 reflectionsΔρmin = −0.44 e Å−3
262 parameters
Special details top

Geometry. Least-squares plane (x,y,z in crystal coordinates) through heavy atoms of the six-membered hydrogen bonded ring, and deviations from this plane (* indicates atom used to define plane)

0.1703 (0.0311) x − 2.5541 (0.0071) y + 13.3640 (0.0147) z = 3.7006 (0.0076)

* 0.0134 (0.0017) O4 * −0.0198 (0.0024) C12 * 0.0119 (0.0022) C13 * 0.0005 (0.0023) C14 * −0.0060 (0.0016) O3 − 0.0753 (0.0499) H3O

Rms deviation of fitted atoms = 0.0122

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.84229 (4)0.31088 (14)0.35744 (6)0.0306 (3)
C11.03415 (19)0.1557 (6)0.6604 (2)0.0350 (8)
H11.08310.18700.70090.042*
C20.9951 (2)−0.0084 (7)0.6784 (3)0.0451 (9)
H21.0171−0.09450.72990.054*
C30.9215 (2)−0.0451 (6)0.6182 (3)0.0463 (10)
H30.8930−0.15280.63110.056*
C40.89000 (19)0.0738 (6)0.5405 (3)0.0371 (8)
H40.84060.04620.50070.045*
C50.93222 (17)0.2388 (5)0.5205 (2)0.0272 (7)
C60.76057 (16)0.4047 (6)0.3706 (2)0.0290 (7)
C70.69737 (18)0.2689 (6)0.3419 (2)0.0363 (8)
H70.69900.13020.31860.044*
C80.63203 (18)0.3434 (6)0.3486 (2)0.0396 (9)
H80.58910.25570.32890.048*
C90.63090 (17)0.5500 (6)0.3848 (2)0.0316 (7)
C100.6941 (2)0.6799 (6)0.4137 (3)0.0386 (8)
H100.69290.81730.43830.046*
C110.75952 (19)0.6089 (6)0.4069 (2)0.0378 (8)
H11B0.80220.69760.42640.045*
C120.25593 (19)0.3793 (7)0.3446 (2)0.0399 (9)
C130.32173 (18)0.5223 (6)0.3735 (2)0.0334 (8)
C140.32089 (18)0.7265 (6)0.4117 (2)0.0355 (8)
C150.38208 (19)0.8644 (7)0.4354 (3)0.0421 (9)
H150.38081.00080.46070.051*
C160.44526 (19)0.8016 (7)0.4220 (2)0.0410 (9)
H160.48620.89630.43720.049*
C170.44786 (17)0.5955 (6)0.3854 (2)0.0349 (8)
C180.38714 (17)0.4589 (6)0.3610 (2)0.0346 (8)
H180.38880.32260.33590.042*
N11.00235 (14)0.2740 (5)0.58389 (18)0.0287 (6)
H1N1.0288 (17)0.379 (4)0.570 (2)0.034*
N20.91305 (13)0.3695 (5)0.44721 (18)0.0292 (6)
N30.56743 (15)0.6376 (5)0.39784 (19)0.0366 (7)
N40.51169 (15)0.5139 (5)0.37114 (19)0.0363 (7)
O10.83263 (12)0.0804 (4)0.33919 (17)0.0395 (6)
O20.85146 (12)0.4462 (4)0.28928 (15)0.0391 (6)
O30.25995 (14)0.7990 (5)0.42586 (18)0.0444 (7)
H3O0.2268 (19)0.688 (5)0.400 (3)0.053*
O40.19811 (13)0.4243 (5)0.35643 (17)0.0457 (7)
O50.26400 (15)0.1993 (5)0.3041 (2)0.0495 (7)
H5O0.2179 (13)0.134 (7)0.278 (3)0.059*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.0191 (4)0.0406 (5)0.0327 (4)−0.0020 (3)0.0111 (3)−0.0096 (4)
C10.0311 (17)0.041 (2)0.0356 (18)0.0057 (14)0.0157 (15)0.0025 (16)
C20.050 (2)0.045 (2)0.047 (2)0.0059 (18)0.0257 (19)0.0130 (18)
C30.054 (2)0.039 (2)0.057 (2)−0.0074 (18)0.034 (2)0.0069 (19)
C40.0295 (17)0.038 (2)0.048 (2)−0.0086 (15)0.0196 (16)−0.0072 (17)
C50.0237 (15)0.0279 (17)0.0348 (18)0.0001 (12)0.0167 (13)−0.0080 (14)
C60.0204 (14)0.0400 (19)0.0275 (16)−0.0015 (13)0.0104 (12)−0.0056 (14)
C70.0245 (16)0.047 (2)0.0384 (19)−0.0070 (14)0.0137 (14)−0.0174 (16)
C80.0209 (15)0.056 (2)0.042 (2)−0.0078 (15)0.0125 (14)−0.0132 (18)
C90.0266 (16)0.040 (2)0.0300 (17)0.0060 (14)0.0135 (13)−0.0011 (15)
C100.0368 (19)0.034 (2)0.050 (2)−0.0018 (15)0.0231 (17)−0.0093 (17)
C110.0297 (17)0.036 (2)0.051 (2)−0.0074 (15)0.0195 (16)−0.0114 (17)
C120.0327 (18)0.051 (2)0.0373 (19)0.0043 (16)0.0150 (15)0.0075 (17)
C130.0256 (16)0.047 (2)0.0268 (16)0.0056 (14)0.0097 (13)0.0080 (15)
C140.0260 (16)0.052 (2)0.0287 (17)0.0075 (15)0.0109 (14)0.0045 (16)
C150.0307 (18)0.048 (2)0.047 (2)0.0045 (16)0.0148 (16)−0.0072 (18)
C160.0249 (16)0.052 (2)0.045 (2)−0.0018 (15)0.0122 (15)−0.0079 (18)
C170.0246 (16)0.049 (2)0.0306 (17)0.0040 (15)0.0105 (13)0.0004 (16)
C180.0275 (16)0.043 (2)0.0307 (18)0.0008 (14)0.0086 (14)0.0032 (15)
N10.0244 (13)0.0311 (15)0.0348 (15)−0.0022 (11)0.0162 (12)−0.0025 (12)
N20.0179 (12)0.0335 (15)0.0352 (15)−0.0028 (11)0.0095 (11)−0.0021 (12)
N30.0253 (14)0.0487 (19)0.0382 (16)0.0022 (13)0.0151 (12)−0.0008 (14)
N40.0248 (14)0.0508 (19)0.0336 (15)0.0017 (13)0.0120 (12)−0.0017 (14)
O10.0281 (12)0.0407 (15)0.0488 (15)−0.0011 (10)0.0143 (11)−0.0175 (12)
O20.0240 (11)0.0605 (17)0.0311 (12)0.0035 (11)0.0091 (10)−0.0012 (12)
O30.0293 (13)0.0609 (19)0.0488 (16)0.0042 (12)0.0217 (12)−0.0028 (13)
O40.0324 (13)0.0668 (19)0.0420 (14)−0.0011 (12)0.0190 (11)0.0038 (13)
O50.0338 (14)0.0503 (17)0.0626 (18)−0.0025 (12)0.0173 (13)−0.0058 (14)
Geometric parameters (Å, º) top
S1—O11.431 (3)C9—N31.427 (4)
S1—O21.439 (3)C10—C111.380 (5)
S1—N21.586 (3)C10—H100.9300
S1—C61.768 (3)C11—H11B0.9300
C1—N11.346 (4)C12—O41.235 (4)
C1—C21.351 (5)C12—O51.316 (5)
C1—H10.9300C12—C131.456 (5)
C2—C31.384 (6)C13—C141.390 (5)
C2—H20.9300C13—C181.410 (5)
C3—C41.363 (5)C14—O31.358 (4)
C3—H30.9300C14—C151.374 (5)
C4—C51.410 (5)C15—C161.376 (5)
C4—H40.9300C15—H150.9300
C5—N21.348 (4)C16—C171.396 (5)
C5—N11.351 (4)C16—H160.9300
C6—C111.378 (5)C17—C181.362 (5)
C6—C71.392 (5)C17—N41.430 (4)
C7—C81.385 (4)C18—H180.9300
C7—H70.9300N1—H1N0.90 (3)
C8—C91.391 (5)N3—N41.242 (4)
C8—H80.9300O3—H3O0.91 (3)
C9—C101.372 (5)O5—H5O0.91 (3)
O1—S1—O2116.79 (15)C9—C10—H10119.6
O1—S1—N2113.77 (15)C11—C10—H10119.6
O2—S1—N2104.12 (14)C6—C11—C10119.0 (3)
O1—S1—C6106.96 (15)C6—C11—H11B120.5
O2—S1—C6107.00 (15)C10—C11—H11B120.5
N2—S1—C6107.73 (14)O4—C12—O5123.6 (4)
N1—C1—C2120.1 (3)O4—C12—C13123.0 (4)
N1—C1—H1119.9O5—C12—C13113.4 (3)
C2—C1—H1119.9C14—C13—C18118.5 (3)
C1—C2—C3118.4 (4)C14—C13—C12121.0 (3)
C1—C2—H2120.8C18—C13—C12120.5 (3)
C3—C2—H2120.8O3—C14—C15117.4 (3)
C4—C3—C2121.1 (3)O3—C14—C13121.9 (3)
C4—C3—H3119.5C15—C14—C13120.7 (3)
C2—C3—H3119.5C14—C15—C16120.3 (4)
C3—C4—C5120.1 (3)C14—C15—H15119.9
C3—C4—H4119.9C16—C15—H15119.9
C5—C4—H4119.9C15—C16—C17120.0 (3)
N2—C5—N1114.4 (3)C15—C16—H16120.0
N2—C5—C4129.7 (3)C17—C16—H16120.0
N1—C5—C4115.9 (3)C18—C17—C16120.0 (3)
C11—C6—C7121.2 (3)C18—C17—N4116.1 (3)
C11—C6—S1120.4 (2)C16—C17—N4123.9 (3)
C7—C6—S1118.3 (3)C17—C18—C13120.6 (3)
C8—C7—C6119.0 (3)C17—C18—H18119.7
C8—C7—H7120.5C13—C18—H18119.7
C6—C7—H7120.5C1—N1—C5124.3 (3)
C7—C8—C9119.7 (3)C1—N1—H1N121 (2)
C7—C8—H8120.1C5—N1—H1N115 (2)
C9—C8—H8120.1C5—N2—S1120.2 (2)
C10—C9—C8120.3 (3)N4—N3—C9113.5 (3)
C10—C9—N3115.8 (3)N3—N4—C17114.6 (3)
C8—C9—N3123.9 (3)C14—O3—H3O100 (3)
C9—C10—C11120.7 (3)C12—O5—H5O108 (3)
N1—C1—C2—C3−2.4 (5)C12—C13—C14—O31.7 (5)
C1—C2—C3—C43.1 (6)C18—C13—C14—C151.0 (5)
C2—C3—C4—C5−0.6 (6)C12—C13—C14—C15−177.3 (3)
C3—C4—C5—N2177.9 (3)O3—C14—C15—C16−179.3 (3)
C3—C4—C5—N1−2.6 (5)C13—C14—C15—C16−0.3 (6)
O1—S1—C6—C11166.6 (3)C14—C15—C16—C17−1.0 (6)
O2—S1—C6—C11−67.6 (3)C15—C16—C17—C181.7 (5)
N2—S1—C6—C1143.9 (3)C15—C16—C17—N4−178.4 (3)
O1—S1—C6—C7−14.6 (3)C16—C17—C18—C13−1.0 (5)
O2—S1—C6—C7111.3 (3)N4—C17—C18—C13179.1 (3)
N2—S1—C6—C7−137.3 (3)C14—C13—C18—C17−0.4 (5)
C11—C6—C7—C81.2 (5)C12—C13—C18—C17178.0 (3)
S1—C6—C7—C8−177.6 (3)C2—C1—N1—C5−1.0 (5)
C6—C7—C8—C9−0.9 (6)N2—C5—N1—C1−177.0 (3)
C7—C8—C9—C100.0 (6)C4—C5—N1—C13.4 (4)
C7—C8—C9—N3−177.4 (3)N1—C5—N2—S1164.7 (2)
C8—C9—C10—C110.5 (6)C4—C5—N2—S1−15.8 (5)
N3—C9—C10—C11178.1 (3)O1—S1—N2—C5−36.7 (3)
C7—C6—C11—C10−0.6 (6)O2—S1—N2—C5−164.9 (2)
S1—C6—C11—C10178.1 (3)C6—S1—N2—C581.7 (3)
C9—C10—C11—C6−0.2 (6)C10—C9—N3—N4−179.6 (3)
O4—C12—C13—C14−3.9 (5)C8—C9—N3—N4−2.1 (5)
O5—C12—C13—C14175.4 (3)C9—N3—N4—C17178.6 (3)
O4—C12—C13—C18177.8 (3)C18—C17—N4—N3−176.8 (3)
O5—C12—C13—C18−2.8 (5)C16—C17—N4—N33.2 (5)
C18—C13—C14—O3180.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3O···O40.91 (3)1.75 (3)2.612 (4)157 (4)
N1—H1N···N2i0.90 (3)1.98 (3)2.878 (4)173 (3)
O5—H5O···O2ii0.91 (3)1.77 (3)2.636 (4)159 (4)
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, y−1/2, −z+1/2.

Experimental details

Crystal data
Chemical formulaC18H14N4O5S
Mr398.39
Crystal system, space groupMonoclinic, P21/c
Temperature (K)150
a, b, c (Å)19.308 (3), 6.0911 (11), 16.109 (3)
β (°) 113.405 (3)
V (Å3)1738.7 (5)
Z4
Radiation typeMo Kα
µ (mm−1)0.23
Crystal size (mm)0.49 × 0.14 × 0.09
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2001)
Tmin, Tmax0.711, 1.000
No. of measured, independent and
observed [I > 2σ(I)] reflections		10720, 3950, 2603
Rint0.038
(sin θ/λ)max (Å−1)0.647
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.067, 0.195, 1.04
No. of reflections3950
No. of parameters262
No. of restraints3
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)1.02, −0.44

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2002), SAINT and SHELXTL (Bruker, 2001), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL, enCIFer (CCDC, 2003) and PLATON (Spek, 2003).

Selected geometric parameters (Å, º) top
S1—O11.431 (3)C12—O41.235 (4)
S1—O21.439 (3)C12—O51.316 (5)
S1—N21.586 (3)C14—O31.358 (4)
C5—N21.348 (4)N3—N41.242 (4)
O1—S1—O2116.79 (15)N2—S1—C6107.73 (14)
O1—S1—N2113.77 (15)C1—N1—C5124.3 (3)
O2—S1—N2104.12 (14)C5—N2—S1120.2 (2)
O1—S1—C6106.96 (15)N4—N3—C9113.5 (3)
O2—S1—C6107.00 (15)N3—N4—C17114.6 (3)
N2—S1—C6—C1143.9 (3)C10—C9—N3—N4−179.6 (3)
N2—S1—C6—C7−137.3 (3)C8—C9—N3—N4−2.1 (5)
O4—C12—C13—C18177.8 (3)C9—N3—N4—C17178.6 (3)
C12—C13—C14—O31.7 (5)C18—C17—N4—N3−176.8 (3)
N1—C5—N2—S1164.7 (2)C16—C17—N4—N33.2 (5)
C4—C5—N2—S1−15.8 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O3—H3O···O40.91 (3)1.75 (3)2.612 (4)157 (4)
N1—H1N···N2i0.90 (3)1.98 (3)2.878 (4)173 (3)
O5—H5O···O2ii0.91 (3)1.77 (3)2.636 (4)159 (4)
Symmetry codes: (i) −x+2, −y+1, −z+1; (ii) −x+1, y−1/2, −z+1/2.
 

Acknowledgements

The authors gratefully acknowledge the Royal Society (K. C. Wong Fellowship to RXY). RXY also thanks the Natural Science Foundation of Jiangsu Education Government, China. The authors thank the EPSRC, England, for provision of a diffractometer.

References

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Journal logoSTRUCTURAL
CHEMISTRY
ISSN: 2053-2296
Volume 60| Part 4| April 2004| Pages o226-o228
doi:10.1107/S0108270104003026
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