In the crystal structure of the title sulfonamide, intermolecular N—H⋯O hydrogen bonds are present between sulfonamide groups, as well as offset π–π interactions.
Keywords: crystal structure, aryl sulfonamide, hydrogen bond, offset π–π interaction
Abstract
The title compound, C10H13NO2S, was synthesized by a nucleophilic substitution reaction between allyl amine and p-toluenesulfonyl chloride. The sulfonate S—O bond lengths are 1.4282 (17) and 1.4353 (17) Å, and the C—N—S—C torsion angle involving the sulfonamide moiety is −61.0 (2)°. In the crystal, centrosymmetric dimers of the title compound are present via intermolecular N—H⋯O hydrogen bonds between sulfonamide groups. These dimers are linked into ribbons along the c-axis direction through offset π–π interactions.
Chemical context
The sulfonamide moiety has been widely studied and its application in drug design has been reported (Qadir et al., 2015 ▸; Rehman et al., 2017 ▸; Gul et al., 2018 ▸). Sulfa drugs, which incorporate the sulfonamide moiety, have found applications as antibacterial, anticancer, antifungal, anti-inflammatory, and antiviral agents (Alaoui et al., 2017 ▸).
The synthesis of sulfonamides generally relies on the use of sulfonyl chlorides as electrophilic partners that react with nucleophilic amines. According to the current state of knowledge in the field, the use of sulfonyl chlorides as electrophilic substrates in the synthesis of sulfonamides suffers from some drawbacks. One such drawback is the difficulty in handling and storage (Caddick et al., 2004 ▸). Other alternatives to sulfonyl chlorides have been reported (Parumala & Peddinti, 2016 ▸; Yang & Tian, 2017 ▸). Nucleophilic acyl substitution is the mechanism that describes the reaction between a carboxylic acid derivative such as acid chloride with an amine to form the corresponding amide. The mechanism of the reaction between sulfonyl chlorides and amines is analogous to nucleophilic acyl substitution, except that it occurs at the sulfonyl group and not the carbonyl group (Um et al., 2013 ▸).
Recently, we have been particularly interested in the structural motif of sulfonamide compounds that are known to modulate 5-HT6 receptor activity and are used for the treatment of CNS diseases and disorders (Blass, 2016 ▸). We are also interested in the therapeutic application of sulfonamide molecules used for chondrogenic differentiation (Choi et al., 2016 ▸), and for the treatment of cancer (Gul et al., 2018 ▸). Fig. 1 ▸ shows the structure of Sulefonur, which has been reported as a potent anticancer sulfonamide drug candidate and is under anticancer clinical trials (Gul et al., 2018 ▸). As part of our ongoing effort to synthesize small sulfonamide molecules that mimic the structural motifs of known sulfonamide drug candidates, we synthesized the title compound, C10H13NO2S, (I) and determined its crystal structure from single crystal X-ray diffraction data.
Figure 1.
The structure of Sulefonur.
Structural commentary
The molecular structure of compound (I), which was solved in the triclinic space group P
, is shown in Fig. 2 ▸. The S—O bond lengths of 1.4282 (17) and 1.4353 (17) Å and the O1—S1—O2 bond angle of 118.87 (11)° are typical for sulfonamide moieties. The S1—N1 bond length is 1.617 (2) Å, and the C1—N1—S1—C4 torsion angle is −61.0 (2)°.
Figure 2.
The molecular structure of the title compound, showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level.
Supramolecular features
Molecules of the title compound are linked to one another via hydrogen bonds and π–π interactions. Centrosymmetric dimers of compound (I) are formed through intermolecular hydrogen bonds between the sulfonamide N—H group and an O atom of a neighbouring sulfonamide group (Fig. 3 ▸). The N1⋯O2i distance of 2.900 (3) Å suggests interactions of medium strength with a nearly linear N—H⋯O hydrogen bond of 174 (3)° (Table 1 ▸). These dimers are then linked through offset π–π interactions into ribbons that lie along the c axis (Figs. 3 ▸, 4 ▸). The intercentroid distance Cg⋯Cg ii is 3.8340 (17) Å, with a slippage of 1.320 Å and a plane-to-plane distance between phenyl rings of 3.600 Å [symmetry code (ii) = −x, −y, −z].
Figure 3.
A depiction of the intermolecular hydrogen bonds and offset π–π interactions present in the crystal, viewed down the a axis, using a ball and stick model with standard CPK colors. [Symmetry codes: (i) −x, −y, −z + 1; (ii) −x, −y, −z.]
Table 1. Hydrogen-bond geometry (Å, °).
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| N1—H1⋯O2i | 0.83 (1) | 2.07 (1) | 2.900 (3) | 174 (3) |
Symmetry code: (i) 
.
Figure 4.
A view along the a axis of the title compound showing the supramolecular ribbons assembled via N—H⋯O hydrogen bonds (blue, dashed lines) and π–π interactions (red, dotted lines).
Database survey
The Cambridge Structural Database (CSD, Version 5.39, February 2018; Groom et al., 2016 ▸) contains 17 structures of p-tolylsulfonamides where there is a –CH2—C=C group bonded to the sulfonamide-N atom. The alkene group in these structures is a part of, for example, furan rings (DERTIE and DERTOK, Hashmi et al., 2006 ▸), an allene (XUDNEP, Lan & Hammond, 2002 ▸), and various acyclic systems (BUXYUQ, Kiyokawa et al., 2015 ▸; KIHMIY, Lee et al., 2007 ▸). While all of the structures listed here display intermolecular hydrogen bonds between sulfonamide groups, none of them display π–π interactions between the p-tolylsulfonamide rings as seen in the title compound.
Synthesis and crystallization
Allylamine (1.31 ml, 18 mmol) was added in 20 ml of degassed dichloromethane. This was followed by the addition of pyridine (1.42 ml, 18 mmol). The resulting solution was stirred under an atmosphere of N2, followed by the portion-wise addition of p-toluenesulfonyl chloride (3.05 g, 16 mmol). The mixture was stirred at room temperature for 24 h. Reaction completion was verified by using TLC analysis. The mixture was acidified to pH 2–3 using concentrated HCl. After dilution with 20 ml of CH2Cl2, the organic phase was washed with H2O (3 × 20 ml) and the aqueous layer was back-extracted with CH2Cl2 (20 ml). The combined organic extracts were dried over anhydrous Na2SO4. After solvent evaporation, the residue was obtained as a yellow solid which was recrystallized in cold ethanol to afford pale-yellow crystals (56%; m.p. 332–333 K).
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All hydrogen atoms bonded to carbon atoms were placed in calculated positions and refined as riding: Csp 3—H = 0.95–1.00 Å with U iso(H) = 1.2U eq(C) for methine and methylene groups, and U iso(H) = 1.5U eq(C) for methyl groups. The hydrogen atom bonded to the nitrogen atom (H1) was located using electron-density difference maps, and the N—H bond length was restrained to 0.84±0.01 Å using the DFIX command as executed in SHELXL (Sheldrick, 2015 ▸).
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C10H13NO2S |
| M r | 211.27 |
| Crystal system, space group | Triclinic, P
|
| Temperature (K) | 173 |
| a, b, c (Å) | 7.5538 (10), 8.2591 (11), 9.7145 (13) |
| α, β, γ (°) | 85.9415 (16), 72.9167 (16), 67.6989 (15) |
| V (Å3) | 535.42 (12) |
| Z | 2 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.28 |
| Crystal size (mm) | 0.28 × 0.25 × 0.20 |
| Data collection | |
| Diffractometer | Bruker APEXII CCD |
| Absorption correction | Multi-scan (SADABS; Bruker, 2014 ▸) |
| T min, T max | 0.672, 0.745 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 6472, 1963, 1564 |
| R int | 0.036 |
| (sin θ/λ)max (Å−1) | 0.604 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.053, 0.156, 1.09 |
| No. of reflections | 1963 |
| No. of parameters | 132 |
| No. of restraints | 1 |
| H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
| Δρmax, Δρmin (e Å−3) | 0.60, −0.26 |
Supplementary Material
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989018010290/wm5455sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018010290/wm5455Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989018010290/wm5455Isup3.cml
CCDC reference: 1856234
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
The authors thank Pfizer, Inc. for the donation of a Varian INOVA 400 FT NMR. The CCD-based X-ray diffractometers at Michigan State University were upgraded and/or replaced by departmental funds.
supplementary crystallographic information
Crystal data
| C10H13NO2S | Z = 2 |
| Mr = 211.27 | F(000) = 224 |
| Triclinic, P1 | Dx = 1.310 Mg m−3 |
| a = 7.5538 (10) Å | Mo Kα radiation, λ = 0.71073 Å |
| b = 8.2591 (11) Å | Cell parameters from 2805 reflections |
| c = 9.7145 (13) Å | θ = 2.2–25.3° |
| α = 85.9415 (16)° | µ = 0.28 mm−1 |
| β = 72.9167 (16)° | T = 173 K |
| γ = 67.6989 (15)° | Chunk, pale yellow |
| V = 535.42 (12) Å3 | 0.28 × 0.25 × 0.20 mm |
Data collection
| Bruker APEXII CCD diffractometer | 1564 reflections with I > 2σ(I) |
| φ and ω scans | Rint = 0.036 |
| Absorption correction: multi-scan (SADABS; Bruker, 2014) | θmax = 25.4°, θmin = 2.2° |
| Tmin = 0.672, Tmax = 0.745 | h = −9→9 |
| 6472 measured reflections | k = −9→9 |
| 1963 independent reflections | l = −11→11 |
Refinement
| Refinement on F2 | Primary atom site location: structure-invariant direct methods |
| Least-squares matrix: full | Hydrogen site location: mixed |
| R[F2 > 2σ(F2)] = 0.053 | H atoms treated by a mixture of independent and constrained refinement |
| wR(F2) = 0.156 | w = 1/[σ2(Fo2) + (0.0902P)2 + 0.112P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.09 | (Δ/σ)max < 0.001 |
| 1963 reflections | Δρmax = 0.60 e Å−3 |
| 132 parameters | Δρmin = −0.26 e Å−3 |
| 1 restraint |
Special details
| Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| S1 | 0.23035 (9) | −0.06592 (8) | 0.28093 (6) | 0.0355 (3) | |
| O1 | 0.4258 (2) | −0.1649 (2) | 0.19086 (19) | 0.0423 (5) | |
| O2 | 0.1100 (3) | −0.1576 (2) | 0.36436 (18) | 0.0407 (5) | |
| N1 | 0.2532 (3) | 0.0508 (3) | 0.3966 (2) | 0.0352 (5) | |
| H1 | 0.153 (3) | 0.085 (4) | 0.468 (2) | 0.048 (8)* | |
| C1 | 0.3608 (4) | 0.1687 (4) | 0.3441 (3) | 0.0436 (7) | |
| H1A | 0.2923 | 0.2565 | 0.2830 | 0.052* | |
| H1B | 0.4984 | 0.1006 | 0.2847 | 0.052* | |
| C2 | 0.3677 (4) | 0.2590 (4) | 0.4684 (3) | 0.0483 (7) | |
| H2 | 0.4323 | 0.1874 | 0.5339 | 0.058* | |
| C3 | 0.2948 (6) | 0.4239 (5) | 0.4948 (4) | 0.0705 (10) | |
| H3A | 0.2289 | 0.5005 | 0.4322 | 0.085* | |
| H3B | 0.3063 | 0.4703 | 0.5770 | 0.085* | |
| C4 | 0.0966 (3) | 0.0803 (3) | 0.1729 (3) | 0.0318 (6) | |
| C5 | −0.1007 (4) | 0.1904 (3) | 0.2347 (3) | 0.0390 (6) | |
| H5 | −0.1655 | 0.1827 | 0.3334 | 0.047* | |
| C6 | −0.2011 (4) | 0.3105 (4) | 0.1516 (3) | 0.0424 (7) | |
| H6 | −0.3363 | 0.3849 | 0.1937 | 0.051* | |
| C7 | −0.1092 (4) | 0.3257 (3) | 0.0072 (3) | 0.0397 (6) | |
| C8 | 0.0869 (4) | 0.2125 (4) | −0.0528 (3) | 0.0423 (7) | |
| H8 | 0.1509 | 0.2187 | −0.1520 | 0.051* | |
| C9 | 0.1909 (4) | 0.0909 (4) | 0.0291 (3) | 0.0380 (6) | |
| H9 | 0.3258 | 0.0156 | −0.0130 | 0.046* | |
| C10 | −0.2180 (5) | 0.4608 (4) | −0.0817 (3) | 0.0506 (7) | |
| H10A | −0.1212 | 0.4891 | −0.1614 | 0.076* | |
| H10B | −0.3076 | 0.5669 | −0.0212 | 0.076* | |
| H10C | −0.2964 | 0.4147 | −0.1205 | 0.076* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| S1 | 0.0316 (4) | 0.0323 (4) | 0.0372 (4) | −0.0107 (3) | −0.0031 (3) | −0.0010 (3) |
| O1 | 0.0323 (10) | 0.0378 (10) | 0.0444 (10) | −0.0067 (8) | −0.0007 (8) | −0.0047 (8) |
| O2 | 0.0425 (10) | 0.0322 (10) | 0.0428 (10) | −0.0158 (9) | −0.0034 (8) | 0.0010 (8) |
| N1 | 0.0325 (11) | 0.0363 (12) | 0.0333 (11) | −0.0124 (10) | −0.0049 (9) | 0.0010 (9) |
| C1 | 0.0464 (16) | 0.0444 (16) | 0.0430 (15) | −0.0237 (13) | −0.0087 (12) | 0.0036 (12) |
| C2 | 0.0484 (17) | 0.0476 (18) | 0.0550 (17) | −0.0218 (14) | −0.0196 (14) | 0.0063 (14) |
| C3 | 0.084 (3) | 0.056 (2) | 0.073 (2) | −0.0282 (19) | −0.020 (2) | −0.0084 (18) |
| C4 | 0.0280 (12) | 0.0331 (13) | 0.0346 (13) | −0.0140 (11) | −0.0058 (10) | −0.0009 (10) |
| C5 | 0.0337 (14) | 0.0439 (16) | 0.0344 (13) | −0.0135 (12) | −0.0032 (11) | −0.0019 (12) |
| C6 | 0.0334 (14) | 0.0474 (17) | 0.0421 (15) | −0.0113 (12) | −0.0086 (12) | −0.0027 (13) |
| C7 | 0.0431 (15) | 0.0423 (16) | 0.0433 (15) | −0.0228 (13) | −0.0173 (12) | 0.0013 (12) |
| C8 | 0.0415 (15) | 0.0546 (17) | 0.0312 (13) | −0.0227 (14) | −0.0045 (11) | 0.0008 (12) |
| C9 | 0.0339 (14) | 0.0442 (15) | 0.0337 (13) | −0.0169 (12) | −0.0022 (11) | −0.0038 (11) |
| C10 | 0.0553 (18) | 0.0505 (18) | 0.0528 (17) | −0.0216 (15) | −0.0242 (14) | 0.0076 (14) |
Geometric parameters (Å, º)
| S1—O1 | 1.4282 (17) | C4—C9 | 1.383 (3) |
| S1—O2 | 1.4353 (17) | C5—H5 | 0.9500 |
| S1—N1 | 1.617 (2) | C5—C6 | 1.373 (4) |
| S1—C4 | 1.760 (3) | C6—H6 | 0.9500 |
| N1—H1 | 0.831 (10) | C6—C7 | 1.390 (4) |
| N1—C1 | 1.468 (3) | C7—C8 | 1.388 (3) |
| C1—H1A | 0.9900 | C7—C10 | 1.501 (4) |
| C1—H1B | 0.9900 | C8—H8 | 0.9500 |
| C1—C2 | 1.487 (4) | C8—C9 | 1.383 (4) |
| C2—H2 | 0.9500 | C9—H9 | 0.9500 |
| C2—C3 | 1.273 (4) | C10—H10A | 0.9800 |
| C3—H3A | 0.9500 | C10—H10B | 0.9800 |
| C3—H3B | 0.9500 | C10—H10C | 0.9800 |
| C4—C5 | 1.390 (3) | ||
| O1—S1—O2 | 118.87 (11) | C9—C4—C5 | 120.4 (2) |
| O1—S1—N1 | 107.94 (11) | C4—C5—H5 | 120.3 |
| O1—S1—C4 | 108.08 (11) | C6—C5—C4 | 119.3 (2) |
| O2—S1—N1 | 105.56 (11) | C6—C5—H5 | 120.3 |
| O2—S1—C4 | 108.64 (11) | C5—C6—H6 | 119.3 |
| N1—S1—C4 | 107.21 (11) | C5—C6—C7 | 121.5 (2) |
| S1—N1—H1 | 112 (2) | C7—C6—H6 | 119.3 |
| C1—N1—S1 | 119.02 (17) | C6—C7—C10 | 121.1 (3) |
| C1—N1—H1 | 118 (2) | C8—C7—C6 | 118.2 (2) |
| N1—C1—H1A | 109.7 | C8—C7—C10 | 120.7 (2) |
| N1—C1—H1B | 109.7 | C7—C8—H8 | 119.4 |
| N1—C1—C2 | 109.8 (2) | C9—C8—C7 | 121.2 (2) |
| H1A—C1—H1B | 108.2 | C9—C8—H8 | 119.4 |
| C2—C1—H1A | 109.7 | C4—C9—C8 | 119.3 (2) |
| C2—C1—H1B | 109.7 | C4—C9—H9 | 120.3 |
| C1—C2—H2 | 117.1 | C8—C9—H9 | 120.3 |
| C3—C2—C1 | 125.7 (3) | C7—C10—H10A | 109.5 |
| C3—C2—H2 | 117.1 | C7—C10—H10B | 109.5 |
| C2—C3—H3A | 120.0 | C7—C10—H10C | 109.5 |
| C2—C3—H3B | 120.0 | H10A—C10—H10B | 109.5 |
| H3A—C3—H3B | 120.0 | H10A—C10—H10C | 109.5 |
| C5—C4—S1 | 119.60 (19) | H10B—C10—H10C | 109.5 |
| C9—C4—S1 | 119.9 (2) |
Hydrogen-bond geometry (Å, º)
| D—H···A | D—H | H···A | D···A | D—H···A |
| N1—H1···O2i | 0.83 (1) | 2.07 (1) | 2.900 (3) | 174 (3) |
Symmetry code: (i) −x, −y, −z+1.
Funding Statement
This work was funded by National Science Foundation grants CCLI CHE-0087655 and MRI CHE-1725699. GVSU Chemistry Department’s Weldon Fund grant .
References
- Alaoui, S., Dufies, M., Driowya, M., Demange, L., Bougrin, K., Robert, G., Auberger, P., Pagès, G. & Benhida, R. (2017). Bioorg. Med. Chem. Lett. 27, 1989–1992. [DOI] [PubMed]
- Blass, B. (2016). ACS Med. Chem. Lett. 7, 12–14. [DOI] [PMC free article] [PubMed]
- Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59–75. [DOI] [PMC free article] [PubMed]
- Bruker (2013). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.
- Bruker (2014). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.
- Caddick, S., Wilden, J. D. & Judd, D. B. (2004). J. Am. Chem. Soc. 126, 1024–1025. [DOI] [PubMed]
- Choi, E., Lee, J., Lee, S., Song, B. W., Seo, H. H., Cha, M. J., Lim, S., Lee, C., Song, S. W., Han, G. & Hwang, K. C. (2016). Bioorg. Med. Chem. Lett. 26, 5098–5102. [DOI] [PubMed]
- Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.
- Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. [DOI] [PMC free article] [PubMed]
- Gul, H. I., Yamali, C., Sakagami, H., Angeli, A., Leitans, J., Kazaks, A., Tars, K., Ozgun, D. O. & Supuran, C. T. (2018). Bioorg. Chem. 77, 411–419. [DOI] [PubMed]
- Hashmi, A. S. K., Weyrauch, J. P., Kurpejović, E., Frost, T. M., Miehlich, B., Frey, W. & Bats, J. W. (2006). Chem. Eur. J. 12, 5806–5814. [DOI] [PubMed]
- Kiyokawa, K., Kojima, T., Hishikawa, Y. & Minakata, S. (2015). Chem. Eur. J. 21, 15548–15552. [DOI] [PubMed]
- Lan, Y. & Hammond, G. B. (2002). Org. Lett. 4, 2437–2439. [DOI] [PubMed]
- Lee, Y. T., Choi, S. Y. & Chung, Y. K. (2007). Tetrahedron Lett. 48, 5673–5677.
- Palmer, D. (2007). CrystalMaker. CrystalMaker, Bicester, England.
- Parumala, S. K. R. & Peddinti, R. K. (2016). Tetrahedron Lett. 57, 1232–1235.
- Qadir, M. A., Ahmed, M. & Khaleeq, A. (2015). Lat. Am. J. Pharm. 34, 719–724.
- Rehman, H., Qadir, M. A., Shad, H. A. & Khan, Z. I. (2017). Med. Chem. (Los Angeles) 7, 252–256.
- Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [DOI] [PubMed]
- Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8.
- Um, I. H., Kang, J. S., Shin, Y. H. & Buncel, E. (2013). J. Org. Chem. 78, 490–497. [DOI] [PubMed]
- Yang, F.-L. & Tian, S.-K. (2017). Tetrahedron Lett. 58, 487–504.
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989018010290/wm5455sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989018010290/wm5455Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989018010290/wm5455Isup3.cml
CCDC reference: 1856234
Additional supporting information: crystallographic information; 3D view; checkCIF report