4-Methyl-N-(1-benzyl)-N’-(1-benzylidene)benzenesulfonohydrazide

Abstract

4-Methyl-N-(1-benzyl)-N’-(1-benzylidene)benzenesulfonohydrazide is formed through a direct, solventless reaction between benzaldehyde tosylhydrazone and potassium carbonate, which is carried out using an eco-friendly grinding method. The NMR spectra of the compound are here described. The structure was unequivocally determined by X-ray analysis. As suggested by Hirshfeld surface analysis, the predominant intermolecular H-O interactions in this molecule are involved in crystal packing.

1. Introduction

Initially considered as side products of the Bamford–Stevens reaction, N-alkyl-N’-alkylidene sulfonohydrazides are interesting but elusive compounds derived from carbene insertions of aryl p-toluenesulfonyl hydrazones [1,2,3]. These compounds are proposed as intermediates in the formation of azines and other similar products during the base-mediated fragmentation of tosylhydrazones [4,5]. In addition, alkylidene sulfonohydrazides are recognized as starting materials in diverse, three-component reactions used for the preparation of isoquinolines [6,7]. Because of this, structural studies on this kind of compound are crucial for understanding how these processes take place.

Some time ago, we described the formation of the N-alkyl-N’-alkylidene sulfonohydrazide derived from acetophenone tosylhydrazone [4]. As a continuation of this study, we investigated other p-tolunesufonyl hydrazones under different conditions. In this report, we disclose the crystal structure and other structural details that we observed in N-alkyl-N’-alkylidene sulfonohydrazide derived from benzaldehyde tosylhydrazone, which was obtained using a mechanochemical synthetic approach.

2. Results and Discussion

The first experiments were designed based on previous reports [1,2,3,4] and focused on the role of the solvent. These experiments revealed the possibility of avoiding solvents during this acid-base process. Thus, the straightforward, solventless treatment of benzaldehyde p-toluenesulfonyl hydrazone 1 with potassium carbonate showed promise. In an optimized procedure, the grinding of a mixture of tosylhydrazone 1 with excess potassium carbonate, followed by slight warming (40 °C), afforded 4-methyl-N-(1-benzyl)-N’-(1-benzylidene)benzenesulfonohydrazide 2 in a 91% yield (see Scheme 1).

The spectroscopic analysis of molecule 2 corroborated the proposed structure, which was similar to that described in previous reports [8], highlighting a singlet signal at δ 4.84 ppm, which was observed in the ¹H NMR spectrum and assigned to the methylene group belonging to the benzyl moiety formed during this process (Figure 1); the presence of a signal at 52.3 ppm in the ¹³C NMR spectrum (see Figure 2) associated with the methylene group was also evidence that confirmed the formation of sulfohydrazide 2.

Sulfonohydrazide 2 was obtained as a crystalline solid from an AcOEt solution through slow evaporation over several days. Single-crystal X-ray crystallography was used to study it, allowing this compound to be unequivocally identified. Crystallographic data and structural refinement parameters of 2 are summarized in

Table 1. Crystallographic data for the structural analysis of compound 2.

Crystal Data	2
Empirical formula	C21H20N2O2S
Formula weight	364.45
Temperature (K)	100(2)
Radiation type	Mo Kα
Crystal system	Monoclinic
Space group	P21/c
Unit cell dimensions (Å, °)
a	6.9754(2)
b	26.3865(7)
c	10.7776(3)
α	90
β	107.2028(8)
γ	90
Volume (Å3)	1894.94(9)
Z	4
Density (calculated, Mg/m3)	1.277
Absorption coefficient μ (mm−1)	0.188
F(000)	768
Crystal size (mm3)	0.298 × 0.284 × 0.136
Θ range (deg)	2.123 to 27.445
Index ranges	−9 ≤ h ≤ 9, −34 ≤ k ≤ 34, −13 ≤ l ≤ 13
Reflections collected	51,884
Independent reflections	4312 [R(int) = 0.0398]
Data/restraints/parameters	4312/312/282
Goodness of fit on F2	1.085
Final R indices [I > 2sigma(I)]	R1 = 0.0372, wR2 = 0.0953
R indices (all data)	R1 = 0.0391, wR2 = 0.0966
Largest diff. peak and hole (e Å−3)	0.387, −0.392

and an ORTEP representation of the structure of compound 2 is shown in Figure 3.

Compound 2 crystallized in the monoclinic centrosymmetric P2₁/c space group, with four molecules in the asymmetric unit. The characteristic C=N bond angles were present in this molecule, displaying angles N(2)-C(8)-H(8) and N(2)-C(8)-C(9) of 120.3° and 119.43(12)°, respectively (see

Table 2. Selected bond distances (Å) and bond angles (deg) for compound 2.

Bond	Distance (Å)	Bond	Angle (°)
N(1)-N(2)	1.3863(15)	N(2)-C(8)-H(8)	120.3
N(1)-C(1)	1.4707(16)	N(2)-C(8)-C(9)	119.43(12)
N(2)-C(8)	1.2783(19)	C(8)-N(2)-N(1)	118.81(11)
S(1)-N(1)	1.6616(12)	N(2)-N(1)-C(1)	122.74(11)
S(1)-C(15)	1.7551(13)	N(2)-N(1)-S(1)	110.55(8)
S(1)-O(2)	1.4308(10)	C(1)-N(1)-S(1)	120.86(9)
S(1)-O(1)	1.4347(10)	O(2)-S(1)-O(1)	119.50(6)
C(8)-H(8)	0.9500	O(2)-S(1)-N(1)	107.08(6)
C(8)-C(9)	1.4721(18)	O(2)-S(1)-C(15)	108.29(6)

). Furthermore, the N(1)-N(2) bond distance (1.3863(15) Å) aligned with that reported for other hydrazides in the literature [9,10].

The C-H···O interactions present in sulfonohydrazide 2 were particularly noteworthy. These interactions are listed below: C8-H···O2 = 2.585 Å, C14-H···O2 = 2.618 Å, C12-H···O2 = 2.626 Å, C16-H···O1 = 2.606 Å, C7-H···O1 = 2.637 Å, and C1-H1B···O1 = 2.464 Å. Moreover, some π-like interactions were distinguished in compound 2. For example, importantly, the distance from the hydrogen atom H21A to the computed Cg1 centroid of the C16–C20 phenyl ring appended to the sulfonyl group was 2.562 Å. Similarly, the distance between the hydrogen atom H11 and the computed Cg2 centroid of the C5–C7 phenyl ring from the benzyl moiety was 3.580 Å. The crystal packing depicted in Figure 4 was defined by the combination of these intermolecular interactions.

A visualization of the previously mentioned intermolecular interactions was achieved through the use of Hirshfeld surface analysis, a method that has gained popularity as a quick, visually appealing instrument to detect interactions caused by intermolecular contacts in a crystal [11]. Figure 5 shows a general view of the Hirshfeld surfaces for sulfonohydrazide 2, mapped over d_norm, d_i, d_e, shape index, and curvedness.

As expected, the C-H···O intermolecular interactions in compound 2 were clearly visible as red spots in the d_norm chart, denoting high-intensity contacts and the closest interactions (see Figure 6). On the other hand, the large green regions recognized in the curvedness plot of sulfonohydrazide 2 suggested relatively planar surface areas due to π-π stacking interactions.

Other pivotal elements offered by the Hirshfeld surfaces analysis were the fingerprint plots, which were used to examine the chemical composition of a surface. In the case of compound 2 (see Figure 7), the largest contribution to the overall crystal packing was from H···H interactions, 50.7%. Other important contributions to the Hirshfeld surface were C···H/H···C (28.2%) and O···H/H···O (15.4%) interactions, underlining the importance of these last interactions in the crystal structure. Minor contributions were provided by C···C (3.5%) and N···H/H···N (2.0%) interactions. These features complemented the observations made above.

Worthy of mention is the use of solvent-free milling conditions, through a mechanochemical approach, in the preparation of sulfonohydrazide 2 as a synthetic alternative for the preparation of these compounds, which, together with the results described herein, will help to elucidate the structural arrangement of sulfonohydrazides.

3. Materials and Methods

The starting materials were purchased from Aldrich Chemical Co. (Milwakee, WI, USA) and were used without further purification. The solvents were distilled before use. Silica plates of 0.20 mm thickness were used for thin layer chromatography. Melting points were determined with a Krüss Optronic melting point apparatus (Hamburg, Germany) and were uncorrected. ¹H and ¹³C NMR spectra were recorded using a Bruker Avance 300-MHz (Billerica, MA, USA); the chemical shifts (δ) were given in ppm relative to TMS as an internal standard (0.00). For analytical purposes, the mass spectra were recorded on a Shimadzu GCMS-QP2010 Plus (Kyoto, Japan) device in the EI mode with 70 eV and 200 _C via a direct inlet probe. Only the molecular and parent ions (m/z) were reported. IR spectra were recorded on a Bruker Tensor 27 (Billerica, MA, USA). (Compounds spectroscopic data are in Supplementary Materials).

For the X-ray diffraction studies, crystals of compound 2 were obtained by the slow evaporation of a dilute hexane solution, and the reflections were acquired with a Bruker APEX DUO (Billerica, MA, USA) diffractometer equipped with an Apex II CCD detector, with Mo Kα radiation (λ = 0.71073 Å) at 100 K. Frames were collected using omega scans and integrated with SAINT, and multi-scan absorption correction (SADABS) was applied [12]. The structure was solved by direct methods (SHELXS-97) [13]; missing atoms were found by difference-Fourier synthesis and refined on F2 by a full-matrix least-squares procedure using anisotropic displacement parameters using SHELXL [14] and the ShelXle GUI [15]. The hydrogen atoms of the C–H bonds were placed in idealized positions. The molecular graphics were prepared using Mercury [16] and POV-Ray [17]. Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre, CCDC no. 2456252 for compound 2. Copies of available materials can be obtained free of charge on application to the Director, CCDC, 12 Union Road, Cambridge CB2 IEZ, UK (facsimile: (44) 01223 336033); e-mail: deposit@ccdc.ac.uk).

The Hirshfeld surface mapped with d_norm and fingerprint plots was visualized with the Crystal Explorer 21.5 program [18]. The 2-D fingerprint plots were used for visualizing, exploring, and quantifying intermolecular interactions.

Synthesis of 4-Methyl-N-(1-benzyl)-N’-(1-benzylidene)benzenesulfonohydrazide 2

A mortar was charged with K₂CO₃ (0.414 g, 3 mmol) and benzaldehyde p-toluenesulfonyl hydrazone (0.274 g, 1 mmol) and vigorously ground with a pestle for 15 min. The mortar with the reaction mixture was placed in an oven and warmed for an additional 2 h. The mixture was cooled to room temperature and extracted with AcOEt (3× 10 mL), the organic layers were joined and dried over Na₂SO₄, the solvent was removed under reduced pressure, and the product was purified by column chromatography (SiO₂, hexane/AcOEt 80:20), affording 4-methyl-N-(1-benzyl)-N’-(1-benzylidene)benzenesulfonohydrazide 2 as a white solid (0.165 g, 0.43 mmol, 91%), m.p. 110 °C (lit. 109–110 °C) [8]. ¹H NMR (300 MHz, DMSO-d₆) δ 7.87 (d, 8.4 Hz, 2H), 7.70 (s, 2H), 7.61 (d, 8.0 Hz, 2H), 7.50 (m, 8H), 4.85 (s, 2H), 2.42 (s, 3H); ¹³C NMR (75 MHz, DMSO-d₆) δ 146.90, 144.04, 135.77, 134.45, 133.76, 130.04, 129.85, 128.79, 128.74, 127.74, 127.47, 126.91, 126.81, 52.3, 21.8; IR (ATR, cm⁻¹): 2921, 2854, 1598, 1355, 1167; MS [EI+] m/z (%): 364 [M]⁺, (40), 209 [M-C₇H₇O₂S]⁺ (10), 182 [C₇H₆N₂O₂S]⁺ (90), 166 [C₇H₄NO₂S]⁺ (85), 90 [C₇H₆]⁺ (100); Anal. Calcd. for C₂₁H₂₀N₂O₂S (%): C, 69.20; H, 5.53; N, 7.69; found: C, 69.29; H, 5.57; N, 7.68.

4. Conclusions

In summary, sulfonohydrazide 2 was obtained from a novel approach that involved the solventless grinding of reactants through a simple, environmentally friendly method. A structural analysis of this molecule revealed that intermolecular H···O interactions were predominant and involved in crystal packing, as suggested by the corresponding Hirshfeld surface analysis. These characteristics suggest that this procedure will enjoy widespread application.