Crystal structure of N-allyl-4-methyl­benzene­sulfonamide

Patel, Z.S.; Stevens, A.C.; Bookout, E.C.; Staples, R.J.; Biros, S.M.; Ngassa, F.N.

doi:10.1107/S2056989018010290

research communications

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ISSN: 2056-9890

Volume 74| Part 8| August 2018| Pages 1126-1129

https://doi.org/10.1107/S2056989018010290

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Crystal structure of N-allyl-4-methylbenzenesulfonamide

Zeel S. Patel,^a Amanda C. Stevens,^a Erin C. Bookout,^a Richard J. Staples,^b Shannon M. Biros ^a and Felix N. Ngassa ^a ^*

^aDepartment of Chemistry, Grand Valley State University, 1 Campus Dr., Allendale, MI 49401, USA, and ^bCenter for Crystallographic Research, Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
^*Correspondence e-mail: ngassaf@gvsu.edu

Edited by M. Weil, Vienna University of Technology, Austria (Received 6 July 2018; accepted 16 July 2018; online 20 July 2018)

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.

Keywords: crystal structure; aryl sulfonamide; hydrogen bond; offset π–π interaction.

CCDC reference: 1856234

1. 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.

2. Structural commentary

The molecular structure of compound (I), which was solved in the triclinic space group P $[\overline{1}]$ , 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.

3. 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⋯Cgⁱⁱ 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].

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) -x, -y, -z+1.

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.]

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).

4. 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.

5. 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).

6. 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: Csp³—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 $[\overline{1}]$
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[F² > 2σ(F²)], wR(F²), 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
Δρ_max, Δρ_min (e Å⁻³)	0.60, −0.26
Computer programs: APEX2 and SAINT (Bruker, 2013 ), SHELXS (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015), OLEX2 (Dolomanov et al., 2009 ; Bourhis et al., 2015 ) and CrystalMaker (Palmer, 2007 ).

Supporting information

CCDC reference: 1856234

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989018010290/wm5455sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989018010290/wm5455Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989018010290/wm5455Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: OLEX2 (Dolomanov et al., 2009; Bourhis et al., 2015); software used to prepare material for publication: CrystalMaker (Palmer, 2007).

N-Allyl-4-methylbenzenesulfonamide top

Crystal data top

C₁₀H₁₃NO₂S	Z = 2
M_r = 211.27	F(000) = 224
Triclinic, P1	D_x = 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 top

Bruker APEXII CCD diffractometer	1564 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.036
Absorption correction: multi-scan (SADABS; Bruker, 2014)	θ_max = 25.4°, θ_min = 2.2°
T_min = 0.672, T_max = 0.745	h = −9→9
6472 measured reflections	k = −9→9
1963 independent reflections	l = −11→11

Refinement top

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(F_o²) + (0.0902P)² + 0.112P] where P = (F_o² + 2F_c²)/3
S = 1.09	(Δ/σ)_max < 0.001
1963 reflections	Δρ_max = 0.60 e Å⁻³
132 parameters	Δρ_min = −0.26 e Å⁻³
1 restraint

Special details top

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) top

	x	y	z	U_iso*/U_eq
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) top

	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) top

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) top

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.

Acknowledgements

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.

Funding information

Funding for this research was provided by: National Science Foundation (grant No. CCLI CHE-0087655; grant No. MRI CHE-1725699); GVSU Chemistry Department's Weldon Fund.

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