2-( N -allylsulfamoyl)- N -propylbenzamide

: In this work, a new compound, 2-( N -allylsulfamoyl)- N -propylbenzamide, has been synthesized via a tandem one-pot reaction under sonication. The rotational orientations of the allylsulfamoyl and the amide groups in the title molecule, C 13 H 18 N 2 O 3 S, are partly determined by an intramolecular N—H ··· O hydrogen bond. In the crystal, a layer structure is generated by N—H ··· O and C—H ··· O hydrogen bonds plus C—H ··· π (ring) interactions. A Hirshfeld surface analysis indicates that the most important contributions to crystal packing are from H ··· H (59.2%), H ··· O/O ··· H (23.5%), and H ··· C/C ··· H (14.6%) interactions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G (d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap is 5.3828 eV.


Introduction
Sulfonamides are a very interesting class of drugs because of their many pharmacological properties [1], including their ability to inhibit carbonic anhydrase "CA" and their diuretic [2,3], anticancer [4], hypoglycemic [5], antiviral [6], antibacterial [7], and metalloprotease inhibitory effects [8].Although they were discovered in the 1930s as chemotherapeutic agents for their antibacterial properties, they have recently attracted increasing interest due to the discovery of new pharmacological properties [9].Recent studies have shown that secondary sulfonamides have significant potential, not only for their ability to selectively inhibit "CA" isozymes but also for their beneficial properties in the treatment of cancer and for glutamate carboxypeptidase II inhibition [10].
The reaction that combines amino compounds with sulfonyl chlorides is the most common method for synthesizing secondary sulfonamide derivatives.This method requires difficult synthetic conditions, multiple steps, and long reaction times and results in the production of undesirable chemicals and toxic byproducts [11].Therefore, finding a green and efficient source for the synthesis of secondary sulfonamide derivatives should be a priority.Our research group has recently developed the synthesis of a new series of heterocyclic units bearing secondary sulfonamides using an eco-friendly protocol under ultrasound cavitation [12,13].
Theoretical calculations, besides measuring the activity of molecules, give important information about many properties of these molecules [14].Owing to the wide range of applications mentioned above, the title compound 2-(N-allylsulfamoyl)-N-propylbenzamide Molbank 2023, 2023, M1678 2 of 11 was synthesized and characterized spectroscopically.The three-dimensional structure was determined by a single-crystal X-ray diffraction analysis.The intermolecular interactions and the hydrogen bonds were studied by a Hirshfeld surface analysis and supplemented by density functional theory (DFT) calculations to establish the optimized molecular structural parameters of the compound, HOMO-LUMO energies, and thermodynamic parameters.The chemical properties of the molecule were investigated using Gaussian calculations, applying B3LYP methods with the 6-311 g(d,p) basis set.

Synthesis
We started our one pot three-component tandem reaction with the N-allylation reaction using saccharin 1 (1 equivalent), allyl bromide 2 (1.1 equivalents) and K 2 CO 3 (1.2equivalents) as a base in water as the solvent under ultrasonic cavitation at 25 • C. The reaction was completed in a very short time and monitored by thin-layer chromatography (TLC) to confirm the formation of N-allyl saccharin as the expected intermediate.This compound was then reacted in situ with propylamine 3 (2 equivalents) to give 2-(N-allylsulfamoyl)-N-propylbenzamide 4 by intermolecular N-C-σ-saccharin ring cleavage under ultrasonic cavitation.The reaction exhibited an excellent yield, with 94% of the desired product 4 (Scheme 1).The structure of 4 was fully characterized by IR, 13 C, 1 H NMR, and LCMS spectra, and confirmed by single-crystal X-ray diffraction.Theoretical calculations, besides measuring the activity of molecules, give important information about many properties of these molecules [14].Owing to the wide range of applications mentioned above, the title compound 2-(N-allylsulfamoyl)-N-propylbenzamide was synthesized and characterized spectroscopically.The three-dimensional structure was determined by a single-crystal X-ray diffraction analysis.The intermolecular interactions and the hydrogen bonds were studied by a Hirshfeld surface analysis and supplemented by density functional theory (DFT) calculations to establish the optimized molecular structural parameters of the compound, HOMO-LUMO energies, and thermodynamic parameters.The chemical properties of the molecule were investigated using Gaussian calculations, applying B3LYP methods with the 6-311 g(d,p) basis set.

Synthesis
We started our one pot three-component tandem reaction with the N-allylation reaction using saccharin 1 (1 equivalent), allyl bromide 2 (1.1 equivalents) and K2CO3 (1.2 equivalents) as a base in water as the solvent under ultrasonic cavitation at 25 °C.The reaction was completed in a very short time and monitored by thin-layer chromatography (TLC) to confirm the formation of N-allyl saccharin as the expected intermediate.This compound was then reacted in situ with propylamine 3 (2 equivalents) to give 2-(N-allylsulfamoyl)-N-propylbenzamide 4 by intermolecular N-C-σ-saccharin ring cleavage under ultrasonic cavitation.The reaction exhibited an excellent yield, with 94% of the desired product 4 (Scheme 1).The structure of 4 was fully characterized by IR, 13 C, 1 H NMR, and LCMS spectra, and confirmed by single-crystal X-ray diffraction.

Crystal Structure Determination
The crystal was kept at 150(2) K during data collection which proceeded under control by APEX4 [15] software.The structure was solved with the SHELXT [16] structure solution program using Intrinsic Phasing and refined with the SHELXL [17] refinement package using full-matrix, least-squares methods.2-(N-allylsulfamoyl)-N-propylbenzamide crystallizes in the monoclinic space group P21/c with one molecule in the asymmetric unit (Figure 1).

Crystal Structure Determination
The crystal was kept at 150(2) K during data collection which proceeded under control by APEX4 [15] software.The structure was solved with the SHELXT [16] structure solution program using Intrinsic Phasing and refined with the SHELXL [17] refinement package using full-matrix, least-squares methods.2-(N-allylsulfamoyl)-N-propylbenzamide crystallizes in the monoclinic space group P21/c with one molecule in the asymmetric unit (Figure 1).
Theoretical calculations, besides measuring the activity of molecules, give important information about many properties of these molecules [14].Owing to the wide range of applications mentioned above, the title compound 2-(N-allylsulfamoyl)-N-propylbenzamide was synthesized and characterized spectroscopically.The three-dimensional structure was determined by a single-crystal X-ray diffraction analysis.The intermolecular interactions and the hydrogen bonds were studied by a Hirshfeld surface analysis and supplemented by density functional theory (DFT) calculations to establish the optimized molecular structural parameters of the compound, HOMO-LUMO energies, and thermodynamic parameters.The chemical properties of the molecule were investigated using Gaussian calculations, applying B3LYP methods with the 6-311 g(d,p) basis set.

Synthesis
We started our one pot three-component tandem reaction with the N-allylation reaction using saccharin 1 (1 equivalent), allyl bromide 2 (1.1 equivalents) and K2CO3 (1.2 equivalents) as a base in water as the solvent under ultrasonic cavitation at 25 °C.The reaction was completed in a very short time and monitored by thin-layer chromatography (TLC) to confirm the formation of N-allyl saccharin as the expected intermediate.This compound was then reacted in situ with propylamine 3 (2 equivalents) to give 2-(N-allylsulfamoyl)-N-propylbenzamide 4 by intermolecular N-C-σ-saccharin ring cleavage under ultrasonic cavitation.The reaction exhibited an excellent yield, with 94% of the desired product 4 (Scheme 1).The structure of 4 was fully characterized by IR, 13 C, 1 H NMR, and LCMS spectra, and confirmed by single-crystal X-ray diffraction.

D-H•••A D-H H•••A D•••A D-H•••A
N1-H1 The rotational orientations of the two substituents on the C1•••C6 ring are partly determined by the intramolecular N1---H1•••O3 hydrogen bond (Table 1 and Figure 2).These orientations can be appreciated by the C1---C2---C10---O3 and C2---C1---S1---N1 torsion angles which are, respectively, −56.67 (16) and 72.94 (10)°.The sum of the angles about N2 is 360 (1)°, indicating participation of the lone pair in N-C•••π bonding.This is largely with C10 (N2-C10 = 1.3335(15)Å) because of the presence of the carbonyl group.In the crystal, inversion dimers are generated by N2---H2A•••O2 hydrogen bonds and C12---H12A•••Cg1 interactions (Table 1 and Figure 2).With the major orientation of the disordered allyl group constituting 92% of positions of this group throughout the crystal, the great majority of the packing can be described as the dimers being connected by C9---H9B•••O4 hydrogen bonds (Table 2) to form layers of molecules parallel to (204) (Figure 2).The layers are stacked along the direction of the normal to (204) (Figure 3).To visualize the intermolecular interactions of 2-(N-allylsulfamoyl)-N-propylbenzamide, a Hirshfeld surface (HS) analysis [18,19] was carried out by using Crystal Explorer 17.5 [20].In the HS plotted over d norm (Figure 4a), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colors indicate distances shorter (in close contact) or longer (distant contact) than the van der Waals radii, respectively.The most important red spots and the corresponding interactions are shown in Figure 5.The shape index (Figure 4b) generated in the range of −1 to 1 Å reveals that there are no π-π interactions, normally indicated by adjacent red and blue triangles.The electrostatic potential using the STO-3G basis set at the Hartree-Fock level of theory and mapped on the Hirshfeld surface over the range of ±0.05 a.u.clearly shows the positions of close intermolecular contacts in the compound (Figure 4c).The positive electrostatic potential (blue region) over the surface indicates hydrogen donor potential, whereas the hydrogen bond acceptors are represented by a negative electrostatic potential (red region).To visualize the intermolecular interactions of 2-(N-allylsulfamoyl)-N-propylbenzamide, a Hirshfeld surface (HS) analysis [18,19] was carried out by using Crystal Explorer 17.5 [20].In the HS plotted over dnorm (Figure 4a), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colors indicate distances shorter (in close contact) or longer (distant contact) than the van der Waals radii, respectively.The most important red spots and the corresponding interactions are shown in Figure 5.The shape index (Figure 4b) generated in the range of −1 to 1 Å reveals that there are no π-π interactions, normally indicated by adjacent red and blue triangles.The electrostatic potential using the STO-3G basis set at the Hartree-Fock level of theory and mapped on the Hirshfeld surface over the range of ±0.05 a.u.clearly shows the positions of close intermolecular contacts in the compound (Figure 4c).The positive electrostatic potential (blue region) over the surface indicates hydrogen donor potential, whereas the hydrogen bond acceptors are represented by a negative electrostatic potential (red region).The three-dimensional dnorm surface shows the presence of several bright red spots which correspond to hydrogen bonding interactions, as shown in Figure 5.The three-dimensional d norm surface shows the presence of several bright red spots which correspond to hydrogen bonding interactions, as shown in Figure 5.

D-H•••A D-H H•••A D•••A D-H•••A N1-H1
The overall two-dimensional fingerprint plot [21] is shown in Figure 6a, while those delin- over dnorm in the range of −0.4420 to 1.2928 a.u., (b) mapped over shape index.(c) Electr tential energy in the range of −0.05 to 0.05 a.u., calculated using the STO-3 G basis set at th Fock level of theory.
The three-dimensional dnorm surface shows the presence of several bright which correspond to hydrogen bonding interactions, as shown in Figure 5.

Density Functional Theory Calculations
The structure in the gas phase of 2-(N-allylsulfamoyl)-N-propylbenzamide was optimized by means of density functional theory.The density functional theory calculation was performed by the hybrid B3LYP method and the 6-311 G(d,p) basis set, which is based on Becke's model [22] and considers a mixture of exact (Hartree-Fock) and density functional theory exchange using the B3 functional, together with the LYP correlation functional [23].After obtaining the converged geometry, the harmonic vibrational frequencies were calculated at the same theoretical level to confirm that the number of imaginary frequencies is zero for the stationary point.Both the geometry optimization and harmonic vibrational frequency analysis of the title compound were performed with the GAUSSIAN 09 program [24].As a result of these calculations, many quantum chemical parameters were found.Each parameter describes a different chemical property of a molecule [25].The theoretical and experimental results related to bond lengths and angles are summarized in Table 2. Calculated numerical values for the title compound including electronegativity (χ), hardness (η), ionization potential (I), dipole moment (µ), electron affinity (A), electrophilicity (ω), and softness (σ) are collated in Table 3.Among the calculated parameters of the molecules, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) parameters are more important than the others [26,27].The electron transition from the HOMO to the LUMO energy level is shown in

Materials and Methods
NMR spectra were recorded on a Bruker AC 200 spectrometer (Bruker Biospin, Rheinstetten, Germany) at 200 MHz for 1 H NMR and 50 MHz for 13 C NMR in dry CDCl 3 solvent.Mass spectral analyses (ESI-MS) were recorded on an Agilent Technologies 1260 Infinity II LC/MSD (Agilent Technologies, Santa Clara, CA, USA) and the samples were diluted in acetonitrile.Melting points were determined on a Munz Köfler Bench System.Analytical thin-layer chromatography (TLC) was performed on precoated with silica gel 60 GF254 (Merck, Darmstadt, Germany) and visualization was performed using a UV lamp at 254 and 360 nm.Ultrasound-assisted reactions were performed in a Vibra-Cell™ Model 75022 Ultrasonic Processor (Sonics & Materials Inc., Newtown, CT, USA) using a 4 mm titanium alloy Ti-6Al 4V probe (20 kHz, 130 W) with a 4 mm tip diameter.The reactions were performed at 60% P max using a 10-50 mL pear-shaped flask with the sonotrode immersed in the solution for maximum energy.

Synthesis of Compound 4
In a pear-shaped flask, a mixture of saccharin 1 (1 mmol), allyl bromide 2 (1.1 mmol), and K 2 CO 3 (1.2mmol) in H 2 O (8 mL) was sonicated at 25 • C for 4 min using the ultrasonic probe.After completion of the reaction (monitored by TLC), a propylamine solution (2 mmol) was added.After sonication for 2 min, the crude mixture was filtered and the filtrate was extracted with CH 2 Cl 2 (10 mL × 3).The organic phase was washed with saturated brine solution (10 mL × 2) and water (15 mL), dried over MgSO 4 , and concentrated under vacuum.The Figures S1-S4 containing 1H, 13C NMR, mass, and IR spectra of the synthesized compound 4.

X-ray Data of Crystal Structure
Crystal data, data collection, and structure refinement details are given in Table 4. Refinement of F 2 against ALL reflections.H atoms attached to carbon were placed in calculated positions (C-H = 0.95-0.99Å) and were included as riding contributions with isotropic displacement parameters 1.2-1.5 times those of the attached atoms.Those attached to nitrogen were placed in locations derived from a difference map and refined independently.The allyl group is disordered over two sites in a 0.920 (3)/0.080(3) refined ratio and the components were refined with SAME, SADI, and EADP restraints so that their geometries and displacement parameters would be comparable.

Figure 1 .
Figure 1.The title molecule with labeling scheme and 50% probability ellipsoids.An intramolecular hydrogen bond is depicted by a dashed line.Only the major component of the disorder is shown.

Figure 2 .
Figure 2. A portion of one layer viewed along the c-axis with N-H•••O and C-H•••O hydrogen bonds depicted, respectively, by violet and black dashed lines.The C-H•••π(ring) interactions are depicted by green dashed lines and non-interacting hydrogen atoms are omitted for clarity.

Figure 3 .
Figure 3. Packing viewed along the c-axis with intermolecular interactions depicted as in Figure 2 and non-interacting hydrogen atoms omitted for clarity.

Figure 3 .
Figure 3. Packing viewed along the c-axis with intermolecular interactions depicted as in Figure 2 and non-interacting hydrogen atoms omitted for clarity.

Figure 4 .
Figure 4. View of the Hirshfeld surface of 2-(N-allylsulfamoyl)-N-propylbenzamide.(a) Mapped over dnorm in the range of −0.4420 to 1.2928 a.u., (b) mapped over shape index.(c) Electrostatic potential energy in the range of −0.05 to 0.05 a.u., calculated using the STO-3 G basis set at the Hartree-Fock level of theory.

Figure 4 .
Figure 4. View of the Hirshfeld surface of 2-(N-allylsulfamoyl)-N-propylbenzamide.(a) Mapped over d norm in the range of −0.4420 to 1.2928 a.u., (b) mapped over shape index.(c) Electrostatic potential energy in the range of −0.05 to 0.05 a.u., calculated using the STO-3 G basis set at the Hartree-Fock level of theory.
and S•••H/H•••S contacts are illustrated in Figure 6b-g, respectively, together with their relative contributions to the Hirshfeld surface (HS).The most important interaction is H•••H, contributing 59.2% to the overall crystal packing, which is reflected in Figure 6b as widely scattered points of high density due to the large hydrogen content of the molecule, with the tip at d e = d i = 1.10 Å.In the presence of O-H interactions, the pair of characteristic wings in the fingerprint plot delineated into H•••O/O•••H contacts (23.5% contribution to the HS), Figure 6c, has tips at d e + d i = 2 Å.The pair of scattered points of spikes in the fingerprint plot delineated into C•••H/H•••C, Figure 6d (14.6%), has tips at d e + d i = 2.66 Å.The N•••H/H•••N contacts, Figure 6e (1.6%), have tips at d e + d i = 3.29 Å.The O•••C/C•••O contacts, Figure 6f, contribute 0.6% to the HS and appear as a pair of scattered points of spikes with tips at d e + d i = 3.17 Å.The N•••O/O•••N contacts, Figure 6g, contribute 0.2% to the HS and appear as a pair of scattered points of spikes with tips at d e + d i = 3.34 Å.The O•••O contacts, Figure 6h, contribute 0.2% to the HS and appear as a pair of scattered points of spikes with a tip at d e + d i = 3.26 Å.Finally, the S•••H/H•••S contacts, Figure 6i, make only a 0.1% contribution to the HS and have a low-density distribution of points.

Figure 5 .
Figure 5.The Hirshfeld surface plotted over d norm and the main non-covalent interactions in the crystal packing of 2-(N-allylsulfamoyl)-N-propylbenzamide.

Figure 7 .
The green and brown regions of the figure represent molecular orbitals with completely opposite phases.The positive phase of the molecule is shown in green and the negative phase in brown.The HOMO and LUMO are localized in the plane extending over the whole 2-(Nallylsulfamoyl)-N-propylbenzamide system.The energy band gap [∆E = ELUMO-EHOMO] of the molecule is 5.3828 eV, and the frontier molecular orbital energies, EHOMO and ELUMO, are −6.9656 and −1.5828 eV, respectively.+ di = 2.66 Å.The N•••H/H•••N contacts, Figure 6e (1.6%), have tips at de + di = 3.29 Å.The O•••C/C•••O contacts, Figure 6f, contribute 0.6% to the HS and appear as a pair of scattered points of spikes with tips at de + di = 3.17 Å.The N•••O/O•••N contacts, Figure 6g, contribute 0.2% to the HS and appear as a pair of scattered points of spikes with tips at de + di = 3.34 Å.The O•••O contacts, Figure 6h, contribute 0.2% to the HS and appear as a pair of scattered points of spikes with a tip at de + di = 3.26 Å.Finally, the S•••H/H•••S contacts, Figure 6i, make only a 0.1% contribution to the HS and have a low-density distribution of points.

Table 2 .
Comparison (X-ray and density functional theory) of selected bond lengths and angles (Å, • ).