True symmetry or pseudosymmetry: 5-amino-1-(4-methyl­phenyl­sulfonyl)-4-pyrazolin-3-one and a comparison with its 1-phenyl­sulfonyl analogue

The title compound, C₁₀H₁₁N₃O₃S, (I), crystallizes as the NH tautomer. The two rings subtend an inter­planar angle of 72.54 (4)°. An intra­molecular hydrogen bond is formed from the NH₂ group to a sulfonyl O atom. The mol­ecular packing involves layers of mol­ecules parallel to the bc plane at x ≃ 0, 1 etc., with two classical linear hydrogen bonds (amino–sulfonyl and pyrazoline–carbonyl N—H...O) and a further inter­action (amino–sulfonyl N—H...O) completing a three-centre system with the intra­molecular contact. The analogous phenyl derivative, (II) [Elgemeie, Hanfy, Hopf & Jones (1998). Acta Cryst. C54, 136–138], crystallizes with essentially the same unit cell and packing pattern, but with two independent mol­ecules that differ significantly in the orientation of the phenyl groups. The space group is P2₁/c for (I) but P2₁ for (II), which is thus a pseudosymmetric counterpart of (I).

S1. Comment

Recent reports from our laboratory have demonstrated the effectiveness of a variety of N-sulfonylated heterocycles and other antimetabolites as antiplastic agents in a number of experimental murine tumour systems (Elgemeie & Sood, 2006; Elgemeie et al., 2009). These compounds have been shown to cause inhibition of thymidine and uridine incorporation into DNA and RNA, and appear to constitute a new class of antimetabolites (Elgemeie et al., 2007). It was of interest to study their stereostructure and evaluate the effects of various structural modifications on their biological activity. Recently, some of our synthesized N-sulfonylated pyrazoles proved to be inhibitors of the enzyme cathepsin B (Myers et al., 2007). Members of this class, along with functional group analogues, were synthesized in an effort to define the structural requirements for activity. We report here the synthesis and structure of 5-amino-1-(4-methylphenylsulfonyl)-4-pyrazolin-3-one, (I), an N-sulfonated pyrazole obtained by intramolecular cyclization of cyanoaceto-N-tolylsulfonylhydrazide. Some time ago, we reported the structure of the corresponding 1-phenyl derivative, (II) (Elgemeie et al., 1998).

Compound (I) can potentially exist in a different tautomeric (hydroxy) form. However, spectroscopic studies indicated the presence of the NH tautomer in solution (e.g. the ¹³C NMR signal at 172.65 p.p.m. indicates a carbonyl C atom rather than a C—OH group). X-ray analysis (Fig. 1) establishes the exclusive presence of the ketonic form in the solid state; all H atoms could be located unambiguously, and bond lengths are also consistent with the NH form. Molecular dimensions (Table 1) may be regarded as normal. Atoms N2 and N3 are pyramidally coordinated; they lie 0.31 (1) and 0.21 (1) Å, respectively, out of the plane of their three substituents. The pyrazoline ring is reasonably planar (r.m.s. deviation = 0.04 Å), although its largest absolute torsion angle is N1—N2—C3—C4 = -10.30 (11)°. The two rings subtend an interplanar angle of 72.54 (4)°, and their orientation is further described by the torsion angles C12—C11—S1—O2 = -0.31 (11)° and N2—N1—S1—O3 = -179.59 (7)°. In other words, C12—C11 is synperiplanar to S1—O2, and N1—N2 is antiperiplanar to S1—O3. An intramolecular N3—H03A···O3 hydrogen bond is observed, albeit with a narrow angle of 116.6 (14)° at the H atom; at N3, atoms H03A and H03B lie out of the plane (of the pyrazoline ring plus N3) by 0.28 (2) and 0.25 (2) Å, respectively, both in the opposite direction to atom O3.

The molecular packing of (I) involves thick layers of molecules parallel to the bc plane at x ≈ 0, 1 etc. (Fig. 2); the tolyl groups project into the space between the layers (Fig. 3). In the order shown in Table 2, hydrogen bond 1 forms eight-membered rings of the common graph set R₂²(8) (Bernstein et al., 1995) over an inversion centre, hydrogen bonds 2 and 3 form a three-centre system (2 is the intramolecular hydrogen bond mentioned above), and hydrogen bond 4 connects the R₂²(8) rings in the direction of the diagonals [011] and [011]. We note that the H03B···O2ⁱⁱ contact of 2.76 (2) Å would complete a bifurcated hydrogen-bond system with hydrogen bond 3, but we regard it as too long.

Several years ago, we published the structure of the phenyl analogue, (II), of (I) (Elgemeie et al., 1998). The unit cells are strikingly similar, except that the a axis of (II) is around 1.2 Å shorter [for (II): a = 10.7794 (19), b = 7.8301 (8) and c = 11.8317 (12) Å, and β = 97.505 (8)°, at 173 K]. The space group of (II) was originally thought to be P2₁/c, but a more detailed analysis showed that the true space group was P2₁. The packing diagram of (II) is shown in Fig. 4. The two independent molecules in the asymmetric unit, which are related to each other by a local inversion centre, differ significantly in the orientation of the phenyl rings (Fig. 5), with torsion angles N1—S1—C11—C12 = 109.5 (3) and -73.0 (3)°. The two independent molecules of (II) form an exactly equivalent set of hydrogen bonds to each other and to (I), so that the packing pattern is topologically the same in both structures. Compound (II) is thus a pseudosymmetric counterpart of (I). The absence of the methyl group leads to the shorter a axis in (II).

Related literature

For related literature, see: Bernstein et al. (1995); Elgemeie & Sood (2006); Elgemeie et al. (1998, 2007, 2009); Myers et al. (2007).

S2. Experimental

Compound (I) was obtained by refluxing an ethanolic solution [Volume?] of cyanoaceto-N-tolylsulfonylhydrazide [Quantity?] containing a few drops of piperidine for 1 h. After cooling, the precipitate, (I), was filtered off and recrystallized from ethanol (yield 87%; m.p. 500 K). Spectroscopic analysis: IR (KBr, ν, cm^-1): 3550, 3500, 3420 (NH₂, NH), 1630 (C═O, s); ¹H NMR (DMSO, δ, p.p.m.): 2.34 (s, 3H, CH₃), 4.48 (s, 1H, CH), 6.88 (s, br, 2H, NH₂), 7.41–7.92 (m, 4H, C₆H₄); MS, m/z = 253. Elemental analysis, calculated for C₁₀H₁₁N₃O₃S: C 47.42, H 4.37, N 16.59, O 18.95, S 12.66%; found: C 47.66, H 4.47, N 16.62, O 19.18, S 12.71%.

S3. Refinement

The N-bound H atoms were refined freely. The methyl group was refined as an idealized rigid group [C—H = 0.98 Å and H—C—H = 109.5°; U_iso(H) = 1.5U_eq(C)] allowed to rotate but not tip; slow convergence of this group may indicate some degree of rotational disorder. Other H atoms were included using a riding model starting from calculated positions [C—H = 0.95 Å, and U_iso(H) = 1.2U_eq(C)]. [Please check added text]

Computing details

Data collection: CrysAlis PRO (Oxford Diffraction, 2011); cell refinement: CrysAlis PRO (Oxford Diffraction, 2011); data reduction: CrysAlis PRO (Oxford Diffraction, 2011); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

Fig. 1. The molecular structure of (I), with the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The dashed line indicates the intramolecular N—H···O hydrogen bond.

Fig. 2. A packing diagram for (I), viewed parallel to the a axis. For clarity, the tolyl rings are reduced to the ipso-C atom, and all H atoms not involved in hydrogen bonding have also been omitted. Hydrogen bonds are indicated by thick dashed lines (two-centre) or thin dashed lines (three-centre) and are numbered according to their order in Table 2.

Fig. 3. A packing diagram for (I), viewed parallel to the b axis. Dashed lines indicate hydrogen bonds.

Fig. 4. A packing diagram for (II) (Elgemeie et al., 1998), viewed parallel to the a axis. The first independent molecule is drawn with full bonds and the second with open bonds. For clarity, phenyl rings are reduced to the ipso-C atom, and all H atoms not involved in hydrogen bonding have also been omitted. Hydrogen bonds are indicated by thick dashed lines (two-centre) or thin dashed lines (three-centre) and are numbered analogously to those of (I) in Table 2, with an additional `a' for those with the donor in molecule 1 and `b' for those with the donor in molecule 2. The origin has been shifted along the b axis to be consistent with Fig. 2, but not along the c axis, where it would be shifted by 1/4 with respect to (I).

Fig. 5. A least-squares fit of the two molecules of (II). The r.m.s. deviation for all atoms except the non-ipso atoms of the phenyl ring is 0.06 Å. Molecule 1 (unprimed atoms) was inverted and is shown with dashed bonds.

5-Amino-1-(4-methylphenylsulfonyl)-4-pyrazolin-3-one

Crystal data

C10H11N3O3S	F(000) = 528
Mr = 253.28	Dx = 1.523 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.9857 (2) Å	Cell parameters from 20410 reflections
b = 7.9094 (2) Å	θ = 2.4–30.8°
c = 11.6777 (2) Å	µ = 0.29 mm^−1
β = 93.778 (2)°	T = 100 K
V = 1104.63 (4) Å^3	Tablet, colourless
Z = 4	0.35 × 0.30 × 0.10 mm

Data collection

Oxford Xcalibur Eos diffractometer	3349 independent reflections
Radiation source: Enhance (Mo) X-ray Source	3081 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
Detector resolution: 16.1419 pixels mm^-1	θmax = 30.9°, θmin = 3.1°
ω scans	h = −17→17
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2011)	k = −11→11
Tmin = 0.962, Tmax = 1.000	l = −16→16
55463 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.031	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.083	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0375P)^2 + 0.8152P] where P = (Fo^2 + 2Fc^2)/3
3349 reflections	(Δ/σ)max = 0.008
167 parameters	Δρmax = 0.44 e Å^−3
0 restraints	Δρmin = −0.44 e Å^−3

Special details

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

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.82267 (2)	0.20196 (3)	0.22306 (2)	0.00923 (7)
O1	0.92704 (7)	0.70212 (10)	0.02289 (7)	0.01415 (16)
O2	0.86903 (7)	0.08937 (10)	0.14307 (7)	0.01331 (16)
O3	0.82447 (7)	0.15888 (11)	0.34220 (7)	0.01446 (16)
N1	0.89922 (7)	0.38073 (11)	0.21784 (7)	0.00910 (16)
N2	0.90457 (8)	0.44047 (12)	0.10377 (8)	0.01045 (17)
H02	0.9571 (15)	0.390 (2)	0.0653 (14)	0.021 (4)*
N3	0.86198 (8)	0.50217 (13)	0.39905 (8)	0.01302 (18)
H03A	0.8868 (14)	0.410 (2)	0.4299 (14)	0.020 (4)*
H03B	0.8723 (14)	0.591 (2)	0.4407 (14)	0.019 (4)*
C3	0.90350 (8)	0.61599 (14)	0.10757 (9)	0.01048 (19)
C4	0.87726 (9)	0.66602 (14)	0.22022 (9)	0.01122 (19)
H4	0.8622	0.7779	0.2446	0.013*
C5	0.87772 (8)	0.52327 (13)	0.28673 (9)	0.00963 (18)
C11	0.68587 (9)	0.25427 (14)	0.17167 (9)	0.01096 (19)
C12	0.64353 (10)	0.18606 (16)	0.06803 (10)	0.0170 (2)
H12	0.6889	0.1166	0.0237	0.020*
C13	0.53346 (10)	0.22144 (17)	0.03042 (11)	0.0198 (2)
H13	0.5036	0.1741	−0.0398	0.024*
C14	0.46595 (9)	0.32476 (16)	0.09343 (10)	0.0162 (2)
C15	0.51177 (10)	0.39525 (17)	0.19568 (11)	0.0191 (2)
H15	0.4674	0.4684	0.2385	0.023*
C16	0.62106 (10)	0.36036 (16)	0.23585 (10)	0.0167 (2)
H16	0.6512	0.4080	0.3059	0.020*
C17	0.34648 (10)	0.35846 (19)	0.05166 (12)	0.0237 (3)
H17A	0.2962	0.2995	0.1011	0.036*
H17B	0.3337	0.3176	−0.0273	0.036*
H17C	0.3318	0.4803	0.0540	0.036*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.01033 (12)	0.00810 (12)	0.00918 (12)	−0.00069 (8)	−0.00006 (8)	0.00048 (8)
O1	0.0163 (4)	0.0134 (4)	0.0132 (4)	0.0029 (3)	0.0043 (3)	0.0053 (3)
O2	0.0140 (4)	0.0107 (4)	0.0152 (4)	0.0018 (3)	0.0001 (3)	−0.0032 (3)
O3	0.0184 (4)	0.0140 (4)	0.0108 (3)	−0.0033 (3)	−0.0003 (3)	0.0039 (3)
N1	0.0113 (4)	0.0090 (4)	0.0071 (4)	−0.0012 (3)	0.0013 (3)	0.0004 (3)
N2	0.0140 (4)	0.0103 (4)	0.0073 (4)	0.0001 (3)	0.0028 (3)	0.0019 (3)
N3	0.0189 (5)	0.0118 (4)	0.0084 (4)	−0.0025 (3)	0.0011 (3)	−0.0014 (3)
C3	0.0089 (4)	0.0109 (4)	0.0117 (4)	0.0012 (3)	0.0007 (3)	0.0015 (4)
C4	0.0123 (4)	0.0096 (4)	0.0119 (4)	0.0000 (3)	0.0022 (4)	0.0002 (4)
C5	0.0086 (4)	0.0102 (4)	0.0101 (4)	−0.0009 (3)	0.0003 (3)	−0.0014 (3)
C11	0.0098 (4)	0.0117 (4)	0.0113 (4)	−0.0009 (4)	0.0009 (3)	0.0000 (4)
C12	0.0136 (5)	0.0218 (6)	0.0155 (5)	0.0030 (4)	−0.0008 (4)	−0.0068 (4)
C13	0.0146 (5)	0.0271 (6)	0.0172 (5)	0.0020 (4)	−0.0036 (4)	−0.0074 (5)
C14	0.0113 (5)	0.0183 (5)	0.0188 (5)	0.0002 (4)	0.0003 (4)	0.0006 (4)
C15	0.0141 (5)	0.0235 (6)	0.0199 (5)	0.0039 (4)	0.0027 (4)	−0.0057 (5)
C16	0.0144 (5)	0.0213 (6)	0.0144 (5)	0.0012 (4)	0.0006 (4)	−0.0061 (4)
C17	0.0119 (5)	0.0298 (7)	0.0288 (6)	0.0034 (5)	−0.0024 (4)	−0.0018 (5)

Geometric parameters (Å, º)

S1—O2	1.4293 (8)	C14—C15	1.3970 (17)
S1—O3	1.4313 (8)	C14—C17	1.5057 (16)
S1—N1	1.6889 (9)	C15—C16	1.3897 (16)
S1—C11	1.7578 (11)	N2—H02	0.891 (17)
O1—C3	1.2483 (13)	N3—H03A	0.859 (18)
N1—C5	1.4184 (13)	N3—H03B	0.859 (18)
N1—N2	1.4188 (12)	C4—H4	0.9500
N2—C3	1.3891 (14)	C12—H12	0.9500
N3—C5	1.3478 (13)	C13—H13	0.9500
C3—C4	1.4284 (14)	C15—H15	0.9500
C4—C5	1.3702 (14)	C16—H16	0.9500
C11—C12	1.3901 (15)	C17—H17A	0.9800
C11—C16	1.3950 (15)	C17—H17B	0.9800
C12—C13	1.3911 (16)	C17—H17C	0.9800
C13—C14	1.3938 (17)
O2—S1—O3	120.36 (5)	C15—C14—C17	121.21 (11)
O2—S1—N1	105.22 (5)	C16—C15—C14	121.20 (11)
O3—S1—N1	105.12 (5)	C15—C16—C11	118.95 (10)
O2—S1—C11	108.52 (5)	C3—N2—H02	118.2 (11)
O3—S1—C11	109.99 (5)	N1—N2—H02	113.6 (11)
N1—S1—C11	106.70 (5)	C5—N3—H03A	116.5 (11)
C5—N1—N2	106.79 (8)	C5—N3—H03B	115.2 (11)
C5—N1—S1	121.71 (7)	H03A—N3—H03B	115.2 (15)
N2—N1—S1	111.77 (7)	C5—C4—H4	126.2
C3—N2—N1	107.56 (8)	C3—C4—H4	126.2
O1—C3—N2	121.13 (10)	C11—C12—H12	120.6
O1—C3—C4	130.79 (10)	C13—C12—H12	120.6
N2—C3—C4	108.02 (9)	C12—C13—H13	119.2
C5—C4—C3	107.51 (9)	C14—C13—H13	119.2
N3—C5—C4	131.15 (10)	C16—C15—H15	119.4
N3—C5—N1	119.73 (9)	C14—C15—H15	119.4
C4—C5—N1	109.12 (9)	C15—C16—H16	120.5
C12—C11—C16	121.13 (10)	C11—C16—H16	120.5
C12—C11—S1	118.99 (8)	C14—C17—H17A	109.5
C16—C11—S1	119.87 (8)	C14—C17—H17B	109.5
C11—C12—C13	118.75 (11)	H17A—C17—H17B	109.5
C12—C13—C14	121.52 (11)	C14—C17—H17C	109.5
C13—C14—C15	118.42 (11)	H17A—C17—H17C	109.5
C13—C14—C17	120.37 (11)	H17B—C17—H17C	109.5
O2—S1—N1—C5	−179.86 (8)	S1—N1—C5—C4	−133.79 (8)
O3—S1—N1—C5	−51.83 (9)	O2—S1—C11—C12	−0.31 (11)
C11—S1—N1—C5	64.97 (9)	O3—S1—C11—C12	−133.86 (10)
O2—S1—N1—N2	52.38 (8)	N1—S1—C11—C12	112.62 (10)
O3—S1—N1—N2	−179.59 (7)	O2—S1—C11—C16	178.57 (9)
C11—S1—N1—N2	−62.80 (8)	O3—S1—C11—C16	45.01 (11)
C5—N1—N2—C3	8.76 (11)	N1—S1—C11—C16	−68.50 (10)
S1—N1—N2—C3	144.13 (7)	C16—C11—C12—C13	−1.86 (18)
N1—N2—C3—O1	167.27 (9)	S1—C11—C12—C13	177.00 (10)
N1—N2—C3—C4	−10.30 (11)	C11—C12—C13—C14	0.8 (2)
O1—C3—C4—C5	−169.30 (11)	C12—C13—C14—C15	0.9 (2)
N2—C3—C4—C5	7.95 (12)	C12—C13—C14—C17	−178.94 (12)
C3—C4—C5—N3	177.50 (11)	C13—C14—C15—C16	−1.67 (19)
C3—C4—C5—N1	−2.41 (12)	C17—C14—C15—C16	178.19 (12)
N2—N1—C5—N3	176.21 (9)	C14—C15—C16—C11	0.67 (19)
S1—N1—C5—N3	46.28 (13)	C12—C11—C16—C15	1.14 (18)
N2—N1—C5—C4	−3.86 (11)	S1—C11—C16—C15	−177.71 (10)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H02···O1^i	0.891 (17)	1.926 (18)	2.8153 (12)	175.4 (16)
N3—H03A···O3	0.859 (18)	2.333 (17)	2.8241 (13)	116.6 (14)
N3—H03A···O2^ii	0.859 (18)	2.512 (17)	2.9359 (12)	111.3 (13)
N3—H03B···O1^iii	0.859 (18)	1.986 (18)	2.8322 (12)	168.0 (16)

Symmetry codes: (i) −x+2, −y+1, −z; (ii) x, −y+1/2, z+1/2; (iii) x, −y+3/2, z+1/2.