Synthesis and crystallographic characterization of N-allyl-N-benzyl-4-methylbenzenesulfonamide European Journal of Chemistry 11 (3) (2020) 245-249 European Journal of Chemistry ISSN 2153-2249 (Print) / ISSN 2153-2257 (Online) – Copyright © 2020 The Authors – Atlanta Publishing House LLC – Printed in the USA. This work is published and licensed by Atlanta Publishing House LLC – CC BY NC – Some Rights Reserved. http://dx.doi.org/10.5155/eurjchem.11.3.245-249.2017 European Journal of Chemistry View Journal Online View Article Online Synthesis and crystallographic characterization of N-allyl-N-benzyl-4-methylbenzenesulfonamide Brock Anton Stenfors and Felix Nyuangem Ngassa * Department of Chemistry, Grand Valley State University, 1 Campus Drive, Allendale, MI 49401, USA stenforb@mail.gvsu.edu (B.A.S.), ngassaf@gvsu.edu (F.N.N.) * Corresponding author at: Department of Chemistry, Grand Valley State University, 1 Campus Drive, Allendale, MI 49401, USA. e-mail: ngassaf@gvsu.edu (F.N. Ngassa). 10.5155/eurjchem.11.3.245-249.2017 Received: 05 August 2020 Received in revised form: 21 August 2020 Accepted: 22 August 2020 Published online: 30 September 2020 Printed: 30 September 2020 N-Benzyl-4-methylbenzenesulfonamides were prepared via a two-step synthetic process involving the treatment of 4-methylbenzenesulfonyl chloride with a primary amine to give the corresponding 4-methylbenzenesulfonamide. Benzylation of the sulfonamide affords the substituted N-benzyl-4-methylbenzenesulfonamides. The similarities between the two steps of synthesis lend credence to the development of a one-pot synthesis of substituted N- benzyl-4-methylbenzenesulfonamides from 4-methylbenzenesulfonyl chloride. This method was applied to the synthesis of N-allyl-N-benzyl-4-methylbenzenesulfonamide and characterized through spectroscopic and crystallographic means. The crystal structure of N- allyl-N-benzyl-4-methylbenzenesulfonamide was obtained by single-crystal X-ray diffraction. The crystal structure reveals an orthorhombic Pna21 space group with cell parameters a = 18.6919 (18) Å, b = 10.5612 (10) Å, c = 8.1065 (8) Å, V = 1600.3 (3) Å3 and Z = 4, T = 173.15 K, μ(MoKα) = 0.206 mm-1, Dcalc = 1.251 g/cm3, 14455 reflections measured (4.36° ≤ 2Θ ≤ 54.96°), 3619 unique (Rint = 0.0439, Rsigma = 0.0429) which were used in all calculations. The final R1 was 0.0428 (I > 2σ(I)) and wR2 was 0.1079 (all data). Molecules are linked through C-H···N hydrogen bonds and C-H···π interactions. Sulfa drug Benzylation Amino acids Sulfonamide Environmentally benign Nucleophilic substitution Cite this: Eur. J. Chem. 2020, 11(3), 245-249 Journal website: www.eurjchem.com 1. Introduction The N-benzylbenzenesulfonamide moiety is found in a variety of biologically significant compounds. In particular, 2- (N-benzyl-N-phenylsulfonamido)alkyl amide derivatives (R)-2- [(4-chlorobenzensulfonyl) - (4-methoxybenzyl)amino]-2-hexa nolactam and (R)-2-[(4-chlorobenzensulfonyl)-(4-methoxy benzyl)amino]-4-methylpentanoic acid amide have been reported to exhibit inhibition against γ-secretase (Figure 1) [1]. γ-Secretase is a four-subunit protein responsible for the cleavage of numerous type-1 transmembrane proteins [2]. Inhibition of this protein leads to the decreased production of the amyloid β-peptide (Aβ), whose accumulation within the brain is one of the two pathological hallmarks of patients with Alzheimer’s disease (AD) [3,4]. γ-Secretase inhibition via sulfonamide compounds lends credence to the prevention or treatment of AD. The N-benzylbenzenesulfonamide moiety is also found in novel nonsteroidal glucocorticoid receptor modulators (Figure 2) [5]. The glucocorticoid receptor (GR) is a ligand-activated transcription factor and a component of the nuclear receptor superfamily [6]. GR is activated by endogenous and synthetic glucocorticoids [7]. In recent years, synthetic glucocorticoids are most commonly used as anti-inflammatory agents [8]. SCl O O N NH O O (a) SCl O O N O O NH2 (b) Figure 1. 2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives reported to exhibit inhibition against γ-secretase. The compounds shown are (R)-2-[(4-chlorobenzensulfonyl)-(4-methoxybenzyl)amino]-2-hexa- nolactam (a) and (R)-2-[(4-chlorobenzensulfonyl)-(4-methoxybenzyl) amino]-4-methylpentanoic acid amide (b). A facile synthesis of compounds containing the N- benzylbenzenesulfonamide moiety is necessary to produce novel drugs for therapeutic use. Herein, we report an efficient and environmentally benign synthesis of N-benzyl-4-methyl benzenesulfonamide derivatives as well as the crystallographic characterization of N-allyl-N-benzyl-4-methylbenzenesulfon- amide. ABSTRACT RESEARCH ARTICLE KEYWORDS http://dx.doi.org/10.5155/eurjchem.11.3.245-249.2017 http://www.eurjchem.com/ http://dx.doi.org/10.5155/eurjchem.11.3.245-249.2017 mailto:stenforb@mail.gvsu.edu mailto:ngassaf@gvsu.edu mailto:ngassaf@gvsu.edu http://www.eurjchem.com/ https://crossmark.crossref.org/dialog/?doi=10.5155/eurjchem.11.3.245-249.2017&domain=pdf&date_stamp=2020-09-30 246 Stenfors and Ngassa / European Journal of Chemistry 11 (3) (2020) 245-249 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.3.245-249.2017 S O O N O R 23 4 R = H R = 4-OMe R = 4-Me R = 4-F R = 4-Cl R = 4-OCF3 R = 4-NO2 R = 4-CN R = 4-NH2 R = 4-NHCOMe R = 4-NHCOOMe Figure 2. N-Benzylbenzenesulfonamide compounds exhibiting GR antagonistic activity. 2. Experimental The reagents used in the synthesis of N-benzyl-4- methylbenzenesulfonamide derivatives were obtained from commercial sources and used without further purification. Thin-layer chromatography (TLC) was used to track reaction progress and obtain Rf values for the reactions. 1H NMR spectra (400 MHz) were recorded on a JEOL ECZ400 spectrometer using a chloroform-d solvent. Chemical shifts are reported in parts per million (ppm, δ) relative to the residual solvent peak, and coupling constants (J) are reported in Hertz (Hz). The results were analyzed, and figures were created with the use of MestreNova [9]. 2.1. Synthesis of N-allyl-4-methylbenzenesulfonamide (2a) 4-Methylbenzenesulfonyl chloride (1.002 g, 5.25 mmol) was dissolved in 10 mL of tetrahydrofuran. Allylamine (0.46 mL, 5.90 mmol) was added dropwise to the stirring mixture, followed by the dropwise addition of 0.59 M aqueous potassium carbonate (10 mL, 5.90 mmol). The reaction mixture was stirred at room temperature for 24 hours. After acidification with 5 M HCl and dilution with 15 mL of dichloromethane, the organic layer was washed three times with water and once with brine. The aqueous layers were back extracted with 10 mL of dichloromethane. The combined organic layers were then dried over anhydrous sodium sulfate and evaporated to dryness. The crude product was recrystallized in ethanol to afford clear crystals, dried under vacuum for 24 hours. M.p.: 69-72 °C. Yield: 0.814 g, 73 %. Rf = 0.44 (CH2Cl2). 1H NMR (400 MHz, Chloroform-d, δ, ppm): 7.78-7.70 (m, 2H, Ar-H), 7.30 (d, J = 8.1 Hz, 2H, Ar-H), 5.71 (ddt, J = 17.2, 10.2, 5.8 Hz, 1H, =CH), 5.15 (dq, J = 17.1, 1.5 Hz, 1H, =CHtrans), 5.09 (dq, J = 10.3, 1.3 Hz, 1H, =CHcis), 4.44 (s, 1H, NH), 3.57 (tt, J = 6.0, 1.5 Hz, 2H, NCH2), 2.42 (s, 3H, CH3). 13C NMR (100 MHz, Chloroform-d, δ, ppm): 143.66, 136.98, 133.06, 129.85, 127.25, 117.87, 45.90, 21.65. HRMS (ESI): calcd. for C10H13NNaO2S [M + Na]+ 234.2700; Found 234.2690. 2.2. Synthesis of N-allyl-N-benzyl-4-methylbenzene sulfonamide (3a) N-Allyl-4-methylbenzenesulfonamide (0.905 g, 4.28 mmol) was added dropwise to a stirring solution of benzyl bromide (0.51 mL, 4.29 mmol) in 10 mL of tetrahydrofuran. This was followed by the dropwise addition of 0.535 M sodium hydroxide (10 mL, 5.35 mmol) and the mixture was left to stir for 24 hours at room temperature. After 24 hours, a white precipitate was isolated directly from the reaction mixture via vacuum filtration. The crude product was recrystallized in ethanol to afford white crystals, dried under vacuum for 24 hours. M.p.: 44-47 °C. Yield: 0.819 g, 67 %. Rf = 0.64 (CH2Cl2). 1H NMR (400 MHz, Chloroform-d, δ, ppm): 7.77-7.69 (m, 2H, Ar-H), 7.34-7.20 (m, 7H, Ar-H), 5.45 (ddt, J = 16.8, 10.2, 6.6 Hz, 1H, =CH), 5.05 (dq, J = 10.1, 1.2 Hz, 1H, =CHtrans), 4.98 (dq, J = 17.0, 1.4 Hz, 1H, =CHcis), 4.32 (s, 2H, NCH2), 3.74 (dt, J = 6.5, 1.3 Hz, 2H, NCH2), 2.43 (s, 3H, CH3). 13C NMR (100 MHz, Chloroform-d, δ, ppm): 143.42, 137.60, 136.08, 132.25, 129.86, 128.63, 128.57, 127.81, 127.31, 119.52, 50.24, 49.55, 21.65. HRMS (ESI): calcd. for C17H19NNaO2S [M+Na]+ 324.3800; Found 324.3801. 2.3. Single-crystal X-ray diffraction data collection The data for the crystallographic characterization of N-allyl- N-benzyl-4-methylbenzenesulfonamide was collected through φ and ω scans using a Bruker APEXII CCD diffractometer with MoKα radiation (λ = 0.71073 Å) at 173 K. The following programs were used during the crystallographic charac- terization of N-allyl-N-benzyl-4-methylbenzenesulfonamide: Data collection, APEX2 [10]; cell refinement, SAINT [11]; data reduction, SAINT [11]; program used to solve structure, SHELXT [12]; program used to refine structure, OLEX2 [13,14]; program used to generate figures, Mercury [15-19]; Absorbance correction, SADABS [20]. The crystal data, data collection and refinement details are summarized in Table 1. Hydrogen atoms were placed in calculated positions and refined as riding with Uiso(H) = 1.2Ueq(C) for all methylene groups and aromatic hydrogens (C- H = 0.95-1.00 Å) and Uiso(H) = 1.5Ueq(C) for all methyl groups. 3. Results and discussion 3.1. Synthesis Preliminary experimentation regarding the synthesis of sulfonamides was done via the treatment of 4-methylbenzene sulfonyl chloride with an amine in the presence of dichloro methane and pyridine. This reaction resulted in low yields, long reaction times, and had a moderate environmental impact due to the carcinogenic properties of dichloromethane. Due to the apparent drawbacks of the reaction, novel methods were developed to produce the sulfonamide compounds more efficiently with less environmental impact over the previous method. In doing so, a single-phase two-solvent system was developed using an aqueous ionic base and tetrahydrofuran. As a result, yields were increased drastically while shorter reaction times were observed. Two ionic bases, sodium hydroxide and potassium carbonate, were used. Potassium carbonate gave the highest yielding reactions, while sodium hydroxide gave the shortest reaction times. It was determined that the use of potassium carbonate allows for high yield reactions without a significant sacrifice in reaction time. The relatively mild nature of the base and solvent used decreases the environmental impact of producing sulfonamides. The synthesized primary amine derived from 4-methyl benzenesulfonamides is able to undergo benzylation via nucleophilic substitution by acting as weak nucleophiles. Due to the compound’s weakly nucleophilic nature, a substitution reaction was created using conditions that support SN1-like reactions. Scheme 1 shows the application of this method regarding the synthesis of N-allyl-N-benzyl-4-methylbenzene sulfonamide (3a). Stenfors and Ngassa / European Journal of Chemistry 11 (3) (2020) 245-249 247 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.3.245-249.2017 Table 1. Crystal data, data collection, and refinement details for the crystallographic characterization of N-allyl-N-benzyl-4-methylbenzenesulfonamide. Crystal data C17H19NO2S Dx = 1.251 Mg m-3 Mr = 301.412 Mo Kα radiation, λ = 0.71073 Å Orthorhombic, Pna21 Cell parameters from 5268 reflections a = 18.6919(18) Å θ = 2.2°-27.5° b = 10.5612(10) Å μ = 0.206 mm-1 c = 8.1065(8) Å T = 173 K V = 1600.3(3) Å3 Plate, colorless Z = 4 0.316 × 0.273 × 0.152 mm F(000) = 640.8 Data collection Bruker APEXII CCD diffractometer 14455 measured reflections φ and ω scans 2960 reflections with I > 2σ(I) Absorption correction: multi-scan 3619 independent reflections SADABS-2014/5 was used for absorption correction. wR2(int) was Rint = 0.044 0.0662 before and 0.0575 after correction. The ratio of minimum to θmax = 27.5°, θmin = 2.2° maximum transmission is 0.9025. The λ/2 correction factor is h = −24 → 23 0.00150. k = −13 → 13 Tmin = 0.673, Tmax = 0.746 l = −10 → 10 Refinement Refinement on F2 H atom treatment: constrained Least-squares matrix: full w = 1/[σ2(Fo2) + (0.0564P)2 + 0.1062P], where P = (Fo2 + 2 Fc2)/3 R[F2 > 2σ(F2)] = 0.043 (Δ/σ)max < 0.001 wR(F2) = 0.114 Δρmax = 0.32 e A� -3 S = 1.07 Δρmin = -0.24 e A� -3 3619 reflections Absolute structure: Flack x determined using 2140 quotients 191 parameters [(I+)-(I-)]/[(I+)+(I-)] [21] 1 restraint Absolute structure parameter: 0.03(9) Hydrogen site location: mixed Br S O O NS O O N H S O O Cl NH2 aq. K2CO3, THF, r.t., 24 h aq. NaOH, THF, r.t., 24 h 1a 2a 3a Scheme 1. Synthesis of N-allyl-4-methylbenzenesulfonamide (2a) via the treatment of 4-methylbezenesulfonyl chloride (1a) with allylamine and the benzylation of compound 2a to form N-allyl-N-benzyl-4-methylbenzenesulfonamide (3a). S O O N R H Br Benzylic carbocation S O O N R H NaOH S O O N RSN1 1b 2b 3b Scheme 2. A proposed SN1-like mechanism for the benzylation of primary amine derived from 4-methylbenzenesulfonamides. The benzylation of primary amine derived from 4- methylbenzenesulfonamides most likely follows an SN1-like mechanism (Scheme 2). The use of benzyl bromide (1b) adequately generates the highly stable benzylic carbocation which readily reacts with the weakly nucleophilic sulfonamide (2b). The benzylated sulfonamide product (3b) is formed following proton transfer. Though further experimentation is necessary to reach a conclusion, the results lend credence to the possibility of a one- pot synthesis of benzylated primary amine derived 4- methylbenzenesulfonamides from 4-methylbenzenesulfonyl chloride. 3.2. Crystallographic characterization The crystallographic characterization of N-allyl-N-benzyl- 4-methylbenzenesulfonamide was carried out through the use of single-crystal X-ray diffraction. Pertinent data such as fractional atomic coordinates, equivalent displacement para- meters, and anisotropic displacement parameters can be found in the supporting information. The selected bond lengths (Å), bond angles (°), and torsion angles (°) for the crystal structure of N-allyl-N-benzyl-4-methylbenzenesulfonamide can be found in Tables 2, 3, and 4, respectively. The asymmetric unit of N- allyl-N-benzyl-4-methylbenzenesulfonamide (3b) is shown in Figure 3. The crystal structure of N-allyl-N-benzyl-4-methylbenzene sulfonamide (3b) exhibits a two-fold screw axis (-x, -y, 1/2+z) and two glide plane (1/2-x, 1/2+y, 1/2+z and 1/2+x, 1/2-y, z) geometries which result from efficient packing. The structure reveals an orthorhombic system, Pna21 space group. According to the τ4 descriptor for four-fold coordination, the sulfur atom, S1, has a slightly distorted tetrahedron geometry [22]. The bond lengths of the carbonyls S1=O1 and S1=O2 are 1.4290 (18) and 1.4342 (18) Å, respectively. These values are in agreement with known values. The aryl groups of the structure are oriented gauche about the S1-N1 bond with a C1-S1-N1-C11 torsion angle of 84.2 (2)°. The N1-C11, N1-C8, S1-C1, and N1-S1 bond lengths were 1.466 (3), 1.471 (3), 1.763 (2) and 1.636 (2) Å, respectively. The N1-S1-O1 bond angle was 107.46 (10)°. The molecules are linked through C-H···N hydrogen bonds and C- H···π interactions. Table 5 summarizes the hydrogen bond contacts present in the structure of N-allyl-N-benzyl-4- methylbenzenesulfonamide. A depiction of these can be found in Figure 4. 248 Stenfors and Ngassa / European Journal of Chemistry 11 (3) (2020) 245-249 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.3.245-249.2017 Table 2. Bond distances (Å) for N-allyl-N-benzyl-4-methylbenzenesulfonamide. Atoms labels follow the atom numbering scheme in Figure 3. Bond Distance (Å) Bond Distance (Å) S1-O1 1.4290(18) C4-C7 1.518(4) S1-O2 1.4342(18) C5-C6 1.382(3) S1-N1 1.636(2) C8-C9 1.500(4) S1-C1 1.763(2) C9-C10 1.302(4) N1-C8 1.471(3) C11-C12 1.519(3) N1-C11 1.466(3) C12-C13 1.385(4) C1-C2 1.394(3) C12-C17 1.378(3) C1-C6 1.392(3) C13-C14 1.390(4) C2-C3 1.381(4) C14-C15 1.380(4) C3-C4 1.390(4) C15-C16 1.367(4) C4-C5 1.380(4) C16-C17 1.393(4) Table 3. Bond angles (°) for N-allyl-N-benzyl-4-methylbenzenesulfonamide. Atoms labels follow the atom numbering scheme in Figure 3. Bond Angle (°) Bond Angle (°) O2-S1-O1 119.78(12) C7-C4-C3 120.9(3) N1-S1-O1 107.46(10) C7-C4-C5 120.9(3) N1-S1-O2 106.77(10) C6-C5-C4 121.8(2) C1-S1-O1 107.00(11) C5-C6-C1 119.1(2) C1-S1-O2 108.12(11) C9-C8-N1 113.8(2) C1-S1-N1 107.11(13) C10-C9-C8 125.3(3) C8-N1-S1 117.88(15) C12-C11-N1 110.3(2) C11-N1-S1 119.73(16) C13-C12-C11 119.6(2) C11-N1-C8 116.10(19) C17-C12-C11 121.1(2) C2-C1-S1 119.71(18) C17-C12-C13 119.3(3) C6-C1-S1 119.86(17) C14-C13-C12 120.2(2) C6-C1-C2 120.1(2) C15-C14-C13 120.0(3) C3-C2-C1 119.2(2) C16-C15-C14 120.1(3) C4-C3-C2 121.5(3) C17-C16-C15 120.1(3) C5-C4-C3 118.2(2) C16-C17-C12 120.4(3) Table 4. Torsion angles (°) for N-allyl-N-benzyl-4-methylbenzenesulfonamide. Atoms labels follow the atom numbering scheme in Figure 3. Torsion Angle (°) Torsion Angle (°) O1-S1-N1-C8 47.8(2) C2-C3-C4-C7 -178.5(3) O1-S1-N1-C11 -161.1(2) C3-C4-C5-C6 -1.2(4) O2-S1-N1-C8 177.5(2) S1-C1-C2-C3 173.3(2) O2-S1-N1-C11 -31.4(2) C6-C1-C2-C3 -0.0(4) C1-S1-N1-C8 -66.9(2) S1-C1-C6-C5 -174.0(2) C1-S1-N1-C11 84.2(2) C2-C1-C6-C5 -0.7(4) O1-S1-C1-C2 169.8(2) C4-C5-C6-C1 1.3(4) O1-S1-C1-C6 -16.9(2) N1-C8-C9-C10 117.4(3) O2-S1-C1-C2 39.6(2) N1-C11-C12-C13 -70.0(3) O2-S1-C1-C6 -147.1(2) N1-C11-C12-C17 110.4(3) N1-S1-C1-C2 -75.2(2) C11-C12-C13-C14 179.9(2) N1-S1-C1-C6 98.1(2) C17-C12-C13-C14 -0.5(4) S1-N1-C8-C9 93.1(2) C11-C12-C17-C16 179.0(2) C11-N1-C8-C9 -59.0(3) C13-C12-C17-C16 -0.6(4) S1-N1-C11-C12 138.4(2) C12-C13-C14-C15 0.9(4) C8-N1-C11-C12 -70.0(2) C13-C14-C15-C16 -0.3(5) C1-C2-C3-C4 0.2(5) C14-C15-C16-C17 -0.9(5) C2-C3-C4-C5 0.4(5) C15-C16-C17-C12 1.3(5) Table 5. Length of hydrogen bond contacts (A� ) and corresponding symmetry codes for N-Allyl-N-benzyl-4-methylbenzenesulfonamide. Atom labels follow the atom numbering scheme in Figure 3. Bond Distance (Å) Symmetry codes H8a-O2 2.639 x, y, z 1.5-x, -1/2+y, -1/2+z H10a-O1 2.652 x, y, z 1.5-x, -1/2+y, -1/2+z H17-O2 2.669 x, y, z 1.5-x, -1/2+y, 1/2+z Figure 3. The molecular structure of N-allyl-N-benzyl-4-methylbenzenesulfonamide (3b) with atom labeling scheme. Displacements of ellipsoids are shown at the 50% probability level. Hydrogen atoms have been omitted for clarity. Stenfors and Ngassa / European Journal of Chemistry 11 (3) (2020) 245-249 249 2020 – European Journal of Chemistry – CC BY NC – DOI: 10.5155/eurjchem.11.3.245-249.2017 Figure 4. A depiction of the intermolecular hydrogen bonds in the crystal structure of N-allyl-N-benzyl-4-methylbenzenesulfonamide shown as capped sticks with standard CPK colors. Hydrogen bond contacts are depicted with cyan dashed lines. Atom labels follow the atom numbering scheme in Figure 3. 4. Conclusion The tosylation of allylamine resulted in the formation of N- allyl-4-methylbenzenesulfonamide. The treatment of N-allyl-4- methylbenzenesulfonamide with benzyl bromide afforded the desired product, N-allyl-N-benzyl-4-methylbenzenesulfon amide, as white crystals. The similarity in conditions between the two synthetic steps lends credence to the possibility of a one-pot synthesis. Additionally, the synthetic method is environmentally benign and produces the desired product in good purity and yield. The synthesized product underwent a single-crystal X-ray diffraction process to reveal an ortho- rhombic system (Pna21 space group) with screw axis and glide plane geometries. The values for S=O bond length align with known values. A slightly distorted tetrahedron geometry was observed from the four-fold coordination about the S1 atom. The crystallographic results support the successful formation of N-allyl-N-benzyl-4-methylbenzenesulfonamide. Acknowledgements The authors thank Pfizer Inc. for the donation of a Varian INOVA 400 FT-NMR spectrometer. The CCD-based X-ray diffractometers at Michigan State University were upgraded and/or replaced by departmental funds. The authors also thank Dr. Richard Staples and Dr. Shannon Biros for help with providing access to the X-ray diffractometer at Michigan State University Supporting information CCDC-2022196 contains the supplementary crystallo- graphic data for this paper. These data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/, or by e- mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033. Disclosure statement Conflict of interests: The authors declare that they have no conflict of interest. Author contributions: All authors contributed equally to this work. Ethical approval: All ethical guidelines have been adhered. Sample availability: Samples of the compounds are available from the author. Funding Funding for this research was provided by: National Science Foundation, Directorate for Mathematical and Physical Sciences (grant No. MRI CHE-1725699; grant No. MRI CHE-1919817); GVSU Chemistry Department’s Weldon Fund. ORCID Brock Anton Stenfors http://orcid.org/0000-0001-8760-5878 Felix Nyuangem Ngassa http://orcid.org/0000-0001-8246-3639 References [1]. Parker, M. F.; Barten, D. M.; Bergstrom, C. P.; Bronson, J. J.; Corsa, J. A.; Dee, M. F.; Gai, Y.; Guss, V. L.; Higgins, M. A.; Keavy, D. J.; Loo, A.; Mate, R. A.; Marcin, L. R.; McElhone, K. E.; Polson, C. T.; Roberts, S. B.; Macor, J. E. Bioorg. Med. Chem. Lett. 2012, 22, 6828-6831. [2]. Hebert, S. S.; Serneels, L.; Dejaegere, T.; Horre, K; Dabrowski, M.; Baert, V.; Annaert, W.; Hartmann, D.; Strooper, B. D. Neurobiol. Dis. 2004, 17, 260-272. [3]. O’Brien, R. J.; Wong, P. C. Annu. Rev. Neurosci. 2011, 34, 185-204. [4]. Herrup, K. J. 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P. Dalton Trans. 2007, 9, 955-956. Copyright © 2020 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry). https://www.ccdc.cam.ac.uk/structures/ mailto:data_request@ccdc.cam.ac.uk http://orcid.org/0000-0001-8760-5878 http://orcid.org/0000-0001-8246-3639 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms http://creativecommons.org/licenses/by-nc/4.0 http://www.eurjchem.com/index.php/eurjchem/pages/view/terms 1. Introduction 2. Experimental 2.1. Synthesis of N-allyl-4-methylbenzenesulfonamide (2a) 2.2. Synthesis of N-allyl-N-benzyl-4-methylbenzene sulfonamide (3a) 2.3. Single-crystal X-ray diffraction data collection 3. Results and discussion 3.1. Synthesis 3.2. Crystallographic characterization 4. Conclusion Acknowledgements Supporting information Disclosure statement Funding ORCID References PrintField10: PrintField11: PrintField12: PrintField13: PrintField14: PrintField20: PrintField21: PrintField22: PrintField23: PrintField24: