K.S. Etsè, G. Zaragoza and K.D. Etsè
Journal of Molecular Structure 1238 (2021) 130435
mercial product. The 1H NMR spectra recorded in DMSO–d6 high-
˚
(2.93017(12) A). The respective donor-H-acceptor angles are 163.6
(17) ° and 170.0(15) ° (See Table S1). These intermolecular interac-
tions extend as an infinite chain along crystallographic b axis di-
lights two broad peaks at 7.20 and 5.83 ppm attributed to Carm
–
NH2 and SO2–NH2 protons respectively confirming the formation
of the sulfonamide.
To obtain the desired benzothiadiazine dioxide 10, the experi-
mental conditions developed by Kumar et al. [30] were tried. In-
deed, compound 9 was first allowed to react with 1.1 equivalent
of acetone in the presence of 1.5 equivalents of magnesium sul-
fate and polyphosphoric acid anhydride in toluene at 100 °C. Using
such procedure, the reaction didn’t lead to the product. This re-
sult is probably due to the low boiling point of acetone. We then
performed the reaction at room temperature during one night. Pu-
rification of the reaction mixture highlighted various byproducts
associated to the expected benzothiadiazine dioxide in less than
20% yield. Realizing the reaction without polyphosphoric acid an-
hydride provided an increase of the yield (35%). Finally, the simple
reaction of the sulfonamide 9 with acetone used as reactant and
solvent in a close flask at room temperature during 48 h was found
to be the best conditions with a very good yield of 93% (Fig. 2).
The proton nuclear magnetic resonance spectrum of compound
10 confirms the formation of the desired product. Indeed, the two
methyl groups signals appear at 1.48 ppm as a singlet for the six
protons. The benzothiazine heterocycle resulting from the ring clo-
sure reaction comprises two different N–H bonds. The SO2–NH
proton is observed at 7.57 ppm and the second Carm–NH proton
is localized at 7.03 ppm. The chemical shifts for aromatic ring pro-
tons were found to be around 6.5–7.5 ppm as a set of doublets and
triplets.
3.2.2. Hirshfeld surface analysis of compound 9
The interactions stabilizing the crystal packing of compound 9
can be also described by analyzing the mapping of various con-
tact descriptors mapped on the Hirshfeld surface using CrystalEx-
plorer17 program [33]. The donors, the acceptors, the withdrawing
groups, the hydrogen bonds and π-π interactions could be visual-
ized and identified on the different surfaces. This strategy is there-
fore employed to complete all the contacts described earlier. The
maps of dnorm, di and de on molecular Hirshfeld surfaces of com-
pound 9 are shown in Fig. 4. A front and back view are present to
allow best visualization of the different contacts. The red spots on
the surfaces mapped over dnorm depicted hydrogen bonding and re-
veals that the sum of di and de is shorter than the sum of the Van
In 2-aminobenzenesulfonamide 9, the surface mapped over di
shows red spots around N1H1 and N1H2 atoms revealing that they
are the nearest internal nuclei from the point of the surface. In
the other hand, the red spots on the de surface show that O1 and
O2 atoms of the sulfonamide group are the nearest external nu-
clei from the point of the surface behaving like acceptor groups in
–
the intermolecular N H···O interactions in 9. Hence, the normal-
ized dnorm mapped on the Hirshfeld surface confirmed the pres-
ence of the two intermolecular N1—H1N···O1i and N1—H2N···O2ii
hydrogen bonds involved in the crystal structure as red spots on
the surface. The nearest molecules in the crystal packing impli-
cated in these contacts are shown and the interaction are high-
lighted as dashed yellow lines on Fig. 4. Finally, the Hirshfeld sur-
face was also mapped with Shape-index. Convex blue regions rep-
resent hydrogen donor groups and concave red regions represent
acceptor groups. The donor as well as acceptor properties of N1H
hydrogens and SO oxygens are confirmed by blue and red spots re-
spectively on the Shape-index surface located around these atoms.
CrystalExplorer software allows characterization of the molec-
ular structure of compound in the crystallographic environment
encompassing all the close contacts by the means of plotting
the two-dimensional Fingerprint histogram [35,36]. The fingerprint
plot indicates the contributions of interatomic contacts to the Hir-
shfeld surfaces in the crystal packing [37]. The 2D fingerprint plot
of 2-aminobenzenesulfonamide and the percentage of contribution
of each interaction are presented in Fig. 4(a-j). Decomposed finger-
print of compound 9 reveals that the most important contributions
come from O···H (34.6%), H···H (34.2%) and H···C (19.9%) interac-
tions. The percentage of O···H contribution in the fingerprint could
be explained by the presence of hydrogen bonds. Other interac-
tions percentages are shown in Fig. 4(e-j).
3.2. Molecular structures description
In view to complete the compounds characterization, we at-
tempted to obtain monocrystals of 9 and 10 suitable for X-ray
diffraction analysis. Fortunately, crystals of these compounds were
obtained by slow evaporation of their solution in a mixture of ace-
tone/dichloromethane (2/5) and were further analyzed. The molec-
ular structures of the two compounds were then confirmed unam-
biguously from the single X-ray diffraction results and the experi-
mental data are reported in Table 1. Other structural and interac-
tions descriptors like NCI plot and Hirshfeld surface were further
used to describe the structures.
3.2.1. X-ray structural description of compound 9
The sulfonamide 9 crystallizes in monoclinic P21/c space group
and the molecular structure is shown in Fig. 3a. The aniline C6—N2
and the sulfonamide C1—S1, S1—N1, S—O bonds length of 1.3745
˚
(12), 1.7559 (9), 1.6052 (9) and ~1.44 A respectively, are typical
of the distances observed in aniline and sulfonamide compounds
[31,32]. The dihedral angle N2-C6-C1-S1 value of 3.27 ° revealed
that the aniline and the sulfone bonds are almost coplanar with
the aromatic ring. The amine H atoms are implicated on intra and
intermolecular interactions. These interactions were therefore ana-
lyzed and reported in Fig. 3b. The oxygen O1 linked to the sulfur
atom is implicated in one intramolecular hydrogen bond with the
H4N hydrogen of the aniline. This interaction is characterized by
In view to assess the weight on the interactions energies sta-
bilizing the crystal packing, the various intermolecular interactions
energies were calculated using CE-B3LYP/6–31G(d,p) energy model
available in CrystalExplorer [38,39]. The resulting interaction ener-
gies frameworks are represented graphically as energy diagrams in
Fig. 5. A view along the crystallographic a, b and c axes are shown
to allow better description. The radii of the corresponding cylin-
ders are proportional to the magnitude of interaction energy. The
molecules surrounding the original one indicated in black are color
coded according to their interaction energy within a cluster of ra-
˚
a N2···O1 distance 2.9517(13) A and a N2—H4N···O1 angle of 130.9
(16) °.
The analysis of the crystal packing shows that the molecular
structure is stabilized by the presence of short intermolecular in-
teractions (Fig. 3b). Each molecule is linked to one another via hy-
drogen bonds that stabilize the crystal packing of this aminoben-
zenesulfonamide.
˚
dius of 3.8 A in the three dimensions. The total intermolecular en-
ergy Etot (kJ/mol) relative to the reference molecule (in black) is
obtained by summing the energies of four main components, com-
prising electrostatic (Eele), polarization (Epol), dispersion (Edis) and
exchange-repulsion (Erep) [38] with scale factors of 1.057, 0.740,
0.871and 0.618, respectively [40,41].
The sulfonamide group is implicated in two different hydrogen
bonds: N1—H2N···O2ii (−x, y + 1/2, −z + 1/2) and N1—H2N···O1i
(x, −y + 1/2, z + 1/2). These interactions are characterized by
i
a N1···O2ii distance of 2.9684 (12) A, similar to N1···O1 distance
˚
4