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Acta Crystallogr Sect E Struct Rep Online. 2009 November 1; 65(Pt 11): o2851.
Published online 2009 October 28. doi:  10.1107/S1600536809043347
PMCID: PMC2971094

N-(4,6-Dimethyl­pyrimidin-2-yl)-4-(oxolan-2-ylamino)benzene­sulfonamide

Abstract

The title compound, C16H20N4O3S, adopts an l-shaped conformation, as seen by the dihedral angle of 76.93 (7)° formed between the two aromatic rings. The most notable feature of the crystal packing is the formation of N—H(...)O and N—H(...)N hydrogen bonds that lead to supra­molecular chains orientated along the b axis.

Related literature

For background to the co-crystallization of active pharmaceutical agents, see: Shan & Zaworotko (2008 [triangle]). For background to sulfa drugs, see: Caira (2007 [triangle]); Nishimori et al. (2009 [triangle]). For the synthesis, see: Fructos et al. (2006 [triangle]); Kemnitz et al. (1998 [triangle]). For related studies on co-crystal formation, see: Broker & Tiekink (2008 [triangle]); Broker et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2851-scheme1.jpg

Experimental

Crystal data

  • C16H20N4O3S
  • M r = 348.42
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2851-efi1.jpg
  • a = 10.291 (5) Å
  • b = 9.592 (4) Å
  • c = 17.196 (8) Å
  • β = 106.445 (10)°
  • V = 1628.0 (13) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.22 mm−1
  • T = 98 K
  • 0.35 × 0.21 × 0.11 mm

Data collection

  • Rigaku Saturn724 diffractometer
  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995 [triangle]) T min = 0.761, T max = 1.000
  • 11164 measured reflections
  • 3749 independent reflections
  • 3341 reflections with I > 2σ(I)
  • R int = 0.046

Refinement

  • R[F 2 > 2σ(F 2)] = 0.057
  • wR(F 2) = 0.137
  • S = 1.10
  • 3749 reflections
  • 225 parameters
  • 2 restraints
  • H-atom parameters constrained
  • Δρmax = 0.60 e Å−3
  • Δρmin = −0.39 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2005 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: DIAMOND (Brandenburg, 2006 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809043347/hb5159sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809043347/hb5159Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The Queensland Department of Employment, Economic Development and Innovation is thanked for an International Fellowship to DJY.

supplementary crystallographic information

Comment

The co-crystallization of active pharmaceutical ingredients is an active area of contemporary crystal engineering (Shan & Zaworotko, 2008). Sulfonamide drugs, e.g. sulfadimidine and sulfameter, attract significant interest in this regard, especially owing to their propensity to form polymorphs (Caira, 2007). They are also receiving renewed attention as selective inhibitors of carbonic anhydrase isoforms (e.g. Nishimori et al., 2009). As a continuation of studies into the phenomenon of co-crystallization (Broker & Tiekink, 2008; Broker et al., 2008), the co-crystallization of N'-(4,6-dimethyl-2-pyrimidinyl)sulfanilamide (sulfadimidine) and 1,4-C6H4I2 in THF was investigated. Colourless crystals of the title compound (I) were obtained unexpectedly; we are not aware of any precedence for this reaction. The insertion of nitrenes into the α C—H bond of cyclic ethers is known (Fructos et al., 2006) and it is suggested that adventitious I2 in 1,4-C6H4I2 reacts with the aryl amine to give a nitrene stabilized by the para-sulfonamide group (Kemnitz et al., 1998).

The molecule of (I), Fig. 1, is bent at the S atom, N3—S1—C7 = 107.85 (10)°, and adopts an overall `L'-conformation; the dihedral angle between the two six-membered rings is 76.93 (7)°. The five membered ring adopts an envelope configuration at the C16 atom. The crystal packing is dominated by N—H···O and N—H···N hydrogen bonding interactions, Table 1, that co-operate to form a supramolecular chain along the b axis, Fig. 2.

Experimental

Colourless crystals of (I) were isolated from the attempted co-crystallization of N'-(4,6-dimethyl-2-pyrimidinyl)-sulfanilamide and 1,4-di-iodobenzene in THF.

Refinement

Carbon-bound H-atoms were placed in calculated positions (C–H 0.95–1.00 Å) and were included in the refinement in the riding model approximation with Uiso(H) set to 1.2–1.5Ueq(C). The nitrogen-bound H-atoms were located in a difference Fourier map and were refined with a N–H 0.880±0.001 Å restraint, and with Uiso(H) = 1.2Ueq(N).

Figures

Fig. 1.
Molecular structure of (I) showing atom-labelling scheme and displacement ellipsoids at the 50% probability level.
Fig. 2.
Supramolecular chain formation along the b axis in (I) mediated by N—H···N (orange dashed lines) and N—H···N (blue dashed lines) hydrogen bonding.

Crystal data

C16H20N4O3SF(000) = 736
Mr = 348.42Dx = 1.422 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 6601 reflections
a = 10.291 (5) Åθ = 2.5–40.2°
b = 9.592 (4) ŵ = 0.22 mm1
c = 17.196 (8) ÅT = 98 K
β = 106.445 (10)°Block, colourless
V = 1628.0 (13) Å30.35 × 0.21 × 0.11 mm
Z = 4

Data collection

Saturn724 diffractometer3749 independent reflections
Radiation source: sealed tube3341 reflections with I > 2σ(I)
graphiteRint = 0.046
Detector resolution: 28.5714 pixels mm-1θmax = 27.5°, θmin = 2.1°
ω scansh = −12→13
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)k = −12→11
Tmin = 0.761, Tmax = 1.000l = −22→17
11164 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.057Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.137H-atom parameters constrained
S = 1.10w = 1/[σ2(Fo2) + (0.0464P)2 + 1.4631P] where P = (Fo2 + 2Fc2)/3
3749 reflections(Δ/σ)max < 0.001
225 parametersΔρmax = 0.60 e Å3
2 restraintsΔρmin = −0.39 e Å3

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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 (Å2)

xyzUiso*/Ueq
S10.31473 (6)0.75837 (6)0.11287 (3)0.02795 (16)
O10.23391 (18)0.71472 (18)0.03422 (9)0.0357 (4)
O20.45898 (17)0.76422 (18)0.12920 (9)0.0339 (4)
O30.03413 (17)1.4900 (2)0.10040 (10)0.0406 (4)
N10.40297 (19)0.74868 (19)0.29276 (10)0.0271 (4)
N20.27644 (18)0.53811 (19)0.29370 (10)0.0265 (4)
N30.2755 (2)0.6434 (2)0.17341 (10)0.0283 (4)
H3N0.20480.59060.15120.034*
N40.1102 (2)1.3038 (2)0.18799 (14)0.0421 (5)
H4N0.16581.35940.22270.051*
C10.3215 (2)0.6443 (2)0.25786 (12)0.0258 (4)
C20.4447 (2)0.7458 (2)0.37479 (12)0.0283 (5)
C30.4038 (2)0.6408 (2)0.41786 (12)0.0298 (5)
H30.43360.63950.47540.036*
C40.3183 (2)0.5378 (2)0.37529 (12)0.0283 (4)
C50.5376 (3)0.8614 (3)0.41506 (14)0.0378 (5)
H5A0.62800.84550.40850.057*
H5B0.54350.86370.47290.057*
H5C0.50210.95060.39010.057*
C60.2706 (3)0.4199 (3)0.41651 (14)0.0348 (5)
H6A0.17410.40320.39040.052*
H6B0.28400.44320.47370.052*
H6C0.32230.33570.41250.052*
C70.2564 (2)0.9212 (2)0.13414 (12)0.0279 (4)
C80.3417 (2)1.0138 (2)0.18760 (13)0.0291 (5)
H80.43340.98910.21290.035*
C90.2929 (2)1.1411 (2)0.20371 (13)0.0307 (5)
H90.35131.20380.24020.037*
C100.1574 (2)1.1793 (2)0.16669 (13)0.0318 (5)
C110.0733 (2)1.0854 (2)0.11240 (14)0.0344 (5)
H11−0.01811.11000.08620.041*
C120.1224 (2)0.9580 (2)0.09687 (13)0.0322 (5)
H120.06450.89490.06050.039*
C13−0.0074 (3)1.3735 (3)0.14064 (16)0.0384 (6)
H13−0.06241.30770.09910.046*
C14−0.0727 (3)1.5920 (3)0.0855 (2)0.0582 (8)
H14A−0.11411.60350.02650.070*
H14B−0.03601.68320.10850.070*
C15−0.1763 (3)1.5425 (4)0.1246 (2)0.0573 (8)
H15A−0.25341.49710.08480.069*
H15B−0.21051.61990.15130.069*
C16−0.0957 (3)1.4381 (4)0.1863 (2)0.0618 (9)
H16A−0.04151.48510.23620.074*
H16B−0.15571.36810.20070.074*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.0279 (3)0.0329 (3)0.0212 (2)0.0002 (2)0.0038 (2)0.00097 (19)
O10.0393 (9)0.0426 (10)0.0218 (7)−0.0014 (8)0.0032 (7)−0.0022 (6)
O20.0289 (8)0.0431 (9)0.0297 (8)0.0015 (7)0.0085 (7)0.0009 (7)
O30.0274 (8)0.0554 (11)0.0384 (9)0.0039 (8)0.0083 (7)0.0090 (8)
N10.0287 (9)0.0260 (9)0.0242 (8)0.0000 (7)0.0037 (7)−0.0023 (7)
N20.0261 (9)0.0278 (9)0.0245 (8)0.0005 (7)0.0053 (7)0.0001 (7)
N30.0307 (10)0.0284 (9)0.0221 (8)−0.0028 (8)0.0013 (7)−0.0012 (7)
N40.0332 (11)0.0337 (11)0.0476 (12)0.0010 (9)−0.0079 (9)−0.0087 (9)
C10.0250 (10)0.0260 (10)0.0246 (9)0.0039 (8)0.0042 (8)−0.0011 (8)
C20.0297 (11)0.0273 (10)0.0251 (10)0.0030 (9)0.0031 (8)−0.0039 (8)
C30.0329 (11)0.0349 (12)0.0198 (9)0.0012 (9)0.0044 (8)−0.0017 (8)
C40.0277 (11)0.0310 (11)0.0265 (10)0.0024 (9)0.0080 (8)0.0005 (8)
C50.0430 (14)0.0333 (12)0.0319 (11)−0.0059 (11)0.0020 (10)−0.0070 (9)
C60.0336 (12)0.0388 (13)0.0311 (11)−0.0018 (10)0.0075 (10)0.0042 (9)
C70.0262 (11)0.0297 (11)0.0253 (10)−0.0007 (9)0.0032 (8)0.0046 (8)
C80.0238 (10)0.0311 (11)0.0286 (10)−0.0031 (9)0.0015 (8)0.0048 (8)
C90.0264 (11)0.0318 (11)0.0290 (10)−0.0064 (9)−0.0001 (9)0.0012 (8)
C100.0286 (11)0.0305 (11)0.0309 (11)−0.0021 (9)−0.0001 (9)0.0012 (9)
C110.0268 (11)0.0338 (12)0.0355 (11)−0.0005 (9)−0.0025 (9)0.0001 (9)
C120.0291 (11)0.0341 (12)0.0279 (10)−0.0030 (9)−0.0011 (9)0.0000 (9)
C130.0300 (12)0.0293 (12)0.0472 (13)−0.0007 (10)−0.0031 (10)−0.0046 (10)
C140.0399 (16)0.0565 (19)0.077 (2)0.0120 (14)0.0149 (15)0.0303 (16)
C150.0522 (18)0.063 (2)0.0633 (18)0.0242 (15)0.0275 (15)0.0178 (15)
C160.0483 (18)0.073 (2)0.074 (2)0.0206 (16)0.0344 (16)0.0345 (18)

Geometric parameters (Å, °)

S1—O21.4316 (18)C6—H6A0.9800
S1—O11.4351 (17)C6—H6B0.9800
S1—N31.644 (2)C6—H6C0.9800
S1—C71.748 (2)C7—C121.392 (3)
O3—C141.439 (3)C7—C81.396 (3)
O3—C131.442 (3)C8—C91.379 (3)
N1—C11.334 (3)C8—H80.9500
N1—C21.353 (3)C9—C101.407 (3)
N2—C11.340 (3)C9—H90.9500
N2—C41.346 (3)C10—C111.405 (3)
N3—C11.394 (3)C11—C121.377 (3)
N3—H3N0.8800C11—H110.9500
N4—C101.377 (3)C12—H120.9500
N4—C131.420 (3)C13—C161.494 (4)
N4—H4N0.8800C13—H131.0000
C2—C31.384 (3)C14—C151.488 (4)
C2—C51.500 (3)C14—H14A0.9900
C3—C41.386 (3)C14—H14B0.9900
C3—H30.9500C15—C161.523 (4)
C4—C61.490 (3)C15—H15A0.9900
C5—H5A0.9800C15—H15B0.9900
C5—H5B0.9800C16—H16A0.9900
C5—H5C0.9800C16—H16B0.9900
O2—S1—O1119.23 (10)C8—C7—S1121.15 (17)
O2—S1—N3109.23 (10)C9—C8—C7120.0 (2)
O1—S1—N3102.72 (10)C9—C8—H8120.0
O2—S1—C7108.79 (11)C7—C8—H8120.0
O1—S1—C7108.43 (10)C8—C9—C10120.7 (2)
N3—S1—C7107.85 (10)C8—C9—H9119.6
C14—O3—C13107.26 (19)C10—C9—H9119.6
C1—N1—C2115.27 (19)N4—C10—C11122.3 (2)
C1—N2—C4115.51 (18)N4—C10—C9118.9 (2)
C1—N3—S1125.67 (16)C11—C10—C9118.6 (2)
C1—N3—H3N116.9C12—C11—C10120.4 (2)
S1—N3—H3N115.6C12—C11—H11119.8
C10—N4—C13124.3 (2)C10—C11—H11119.8
C10—N4—H4N119.7C11—C12—C7120.4 (2)
C13—N4—H4N112.9C11—C12—H12119.8
N1—C1—N2128.24 (19)C7—C12—H12119.8
N1—C1—N3117.29 (19)N4—C13—O3108.7 (2)
N2—C1—N3114.47 (18)N4—C13—C16116.1 (2)
N1—C2—C3121.2 (2)O3—C13—C16103.8 (2)
N1—C2—C5116.0 (2)N4—C13—H13109.3
C3—C2—C5122.79 (19)O3—C13—H13109.3
C2—C3—C4118.66 (19)C16—C13—H13109.3
C2—C3—H3120.7O3—C14—C15108.2 (2)
C4—C3—H3120.7O3—C14—H14A110.1
N2—C4—C3121.1 (2)C15—C14—H14A110.1
N2—C4—C6116.5 (2)O3—C14—H14B110.1
C3—C4—C6122.36 (19)C15—C14—H14B110.1
C2—C5—H5A109.5H14A—C14—H14B108.4
C2—C5—H5B109.5C14—C15—C16101.9 (2)
H5A—C5—H5B109.5C14—C15—H15A111.4
C2—C5—H5C109.5C16—C15—H15A111.4
H5A—C5—H5C109.5C14—C15—H15B111.4
H5B—C5—H5C109.5C16—C15—H15B111.4
C4—C6—H6A109.5H15A—C15—H15B109.3
C4—C6—H6B109.5C13—C16—C15101.4 (2)
H6A—C6—H6B109.5C13—C16—H16A111.5
C4—C6—H6C109.5C15—C16—H16A111.5
H6A—C6—H6C109.5C13—C16—H16B111.5
H6B—C6—H6C109.5C15—C16—H16B111.5
C12—C7—C8119.9 (2)H16A—C16—H16B109.3
C12—C7—S1118.99 (17)
O2—S1—N3—C156.4 (2)N3—S1—C7—C895.14 (19)
O1—S1—N3—C1−176.07 (18)C12—C7—C8—C90.4 (3)
C7—S1—N3—C1−61.7 (2)S1—C7—C8—C9−179.57 (16)
C2—N1—C1—N20.0 (3)C7—C8—C9—C10−0.1 (3)
C2—N1—C1—N3179.72 (19)C13—N4—C10—C11−22.4 (4)
C4—N2—C1—N10.5 (3)C13—N4—C10—C9161.0 (2)
C4—N2—C1—N3−179.25 (19)C8—C9—C10—N4176.2 (2)
S1—N3—C1—N11.0 (3)C8—C9—C10—C11−0.6 (3)
S1—N3—C1—N2−179.18 (16)N4—C10—C11—C12−175.7 (2)
C1—N1—C2—C3−0.2 (3)C9—C10—C11—C120.9 (4)
C1—N1—C2—C5179.3 (2)C10—C11—C12—C7−0.6 (4)
N1—C2—C3—C4−0.1 (3)C8—C7—C12—C110.0 (3)
C5—C2—C3—C4−179.6 (2)S1—C7—C12—C11179.91 (18)
C1—N2—C4—C3−0.8 (3)C10—N4—C13—O3−104.0 (3)
C1—N2—C4—C6−179.43 (19)C10—N4—C13—C16139.5 (3)
C2—C3—C4—N20.6 (3)C14—O3—C13—N4−153.7 (2)
C2—C3—C4—C6179.2 (2)C14—O3—C13—C16−29.5 (3)
O2—S1—C7—C12156.85 (17)C13—O3—C14—C155.4 (3)
O1—S1—C7—C1225.8 (2)O3—C14—C15—C1620.2 (4)
N3—S1—C7—C12−84.79 (19)N4—C13—C16—C15160.5 (3)
O2—S1—C7—C8−23.2 (2)O3—C13—C16—C1541.3 (3)
O1—S1—C7—C8−154.31 (18)C14—C15—C16—C13−37.0 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N3—H3n···O3i0.881.982.854 (3)174
N4—H4n···N2ii0.882.223.086 (3)167

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HB5159).

References

  • Brandenburg, K. (2006). DIAMOND Crystal Impact GbR, Bonn, Germany.
  • Broker, G. A., Bettens, R. P. A. & Tiekink, E. R. T. (2008). CrystEngComm, 10, 879–887.
  • Broker, G. A. & Tiekink, E. R. T. (2008). CrystEngComm, 9, 1096–1109.
  • Caira, M. R. (2007). Mol. Pharm.4, 310–316. [PubMed]
  • Fructos, M. R., Trofimenko, S., Mar Díaz-Requejo, M. & Pérez, P. J. (2006). J. Am. Chem. Soc.128, 11784–11791. [PubMed]
  • Higashi, T. (1995). ABSCOR Rigaku Corporation, Tokyo, Japan.
  • Kemnitz, C. R., Karney, W. L. & Borden, W. T. (1998). J. Am. Chem. Soc.120, 3499–3503.
  • Nishimori, I., Minakuchi, T., Vullo, D., Scozzafava, A., Innocenti, A. & Supuran, C. T. (2009). J. Med. Chem.52, 3116–3120. [PubMed]
  • Rigaku/MSC (2005). CrystalClear Rigaku/MSC Inc. The Woodlands, Texas, USA.
  • Shan, N. & Zaworotko, M. J. (2008). Drug Discovery Today, 13, 440–446. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography