**1. Introduction**

N-substituted triazinanes are interesting molecules that are used as efficient aminomethylation reagents and as formal 1,4- and 1,2-dipolar adducts in annulation reactions [1–10]. Moreover, this type of molecules presents remarkable antimicrobial activity [11]. While the access to symmetric N-substituted triazinanes is simple, there was no convenient method for the synthesis of triazinanes bearing different substituents on nitrogen atoms. Recently, we have described a straightforward approach to *<sup>N</sup>*-alkyl-*N,N"*-substituted triazinanes that is based on a one-pot multi-component reaction of amines, paraformaldehyde and sulfonamides or thioureas [12].

In this manuscript, the synthesis, single crystal X-ray diffraction characterization, Hirshfeld surface analysis and density functional theory (DFT) calculations of four triazinanes (see Scheme 1) are reported. The combination in the same structure of butyl substituents (*n*-Bu or *t*-Bu) with two aromatic rings facilitates the formation of a variety of C–H···<sup>π</sup> interactions in combination with C–H···O/N bonds. These noncovalent interactions have been studied using Hirshfeld surface analysis and DFT calculations. Moreover, they have been rationalized using the quantum theory of atoms in molecules (QTAIM) and molecular electrostatic potential (MEP) surfaces.

**Scheme 1.** Compounds **1**–**4** studied in this work.

## **2. Materials and Methods**

## *2.1. Experimental Details*

As it was mentioned above, the main objects of this work, *N*,*N*-disulfamide substituted triazinanes **1**–**4**, were prepared according to the method described in our preliminary communication [12] using the three-component Mg(ClO4)2 catalyzed condensation of arylsulfonamides with paraformaldehyde and *n*- or *tert*-butyl amine (Scheme 2, see the Supplementary Materials for detail of the experimental procedures and spectral data). The *tert*-butyl- and *n*-butylamines were chosen as the amino-components providing the highest yield of the target triazinanes.

**Scheme 2.** Synthesis of 1,3,5-triazacyclohexanes **1**–**4**.

All obtained triazinanes are well-crystallized solids that allowed the growth of crystals suitable for XRD analysis.

## *2.2. Crystallographic Details*

Single crystal X-ray diffraction experiments were performed at the Center for Shared Use of Physical Methods of Investigation at the Frumkin Institute of Physical Chemistry and Electrochemistry. The single crystal X-ray diffraction data for 1,3,5-triazacyclohexanes (**1**–**4**) were collected on a Bruker Kappa Apex II automatic four-circle diffractometer (Bruker AXS, Madison, WI, USA) equipped with an area detector (Mo-Kα sealed-tube X-ray source, λ = 0.71073 Å, graphite monochromator) at 100 K for all compounds. The principal crystallographic data and structural refinements are summarized in Table 1. Atomic coordinates for compounds **1**–**4**, have been deposited with the CCDC (number 1992667−1992670). The supplementary crystallographic data are available in the ESI section. The comparison of the crystal structure parameters with the analogous compounds were performed

using ConQuest search in Cambridge Structural Database (CSD, Version 5.40). The histograms of angles values were obtained from a graphical search of sulfonamides (C–S(=O)2–NC2) with 3D parameters for angles. More than 7000 hits were analyzed.


**Table 1.** Crystal data and structure refinement for **1**–**4**.

## *2.3. Hirshfeld Surface Calculations*

The Hirshfeld surface (HS) analysis [13–15] and their associated 2D fingerprint plots (full and decomposed) [16] were carried out employing the CrystalExplorer 17 program [17] in order to visualize and quantify various non-covalent interactions that stabilize the crystal packing. The HS was mapped over *d*norm property. The *d*norm property is a symmetric function of distances to the surface from nuclei inside and outside the Hirshfeld surface (*d*i and *d*e, respectively), relative to their respective van der Waals radii. The regions with red and blue color on the *d*norm represent the shorter and longer inter contacts while the white color indicates the contacts around the van der Waals radii. 2D fingerprint plots provide relevant information of intermolecular contacts in the crystal. The *d*norm surface was mapped with the color scale in the range −0.050 au (red) to 0.600 au (blue). 2D fingerprint plots (*d*i vs. *d*e) were displayed using the expanded 0.6–2.8 Å range.

## *2.4. Theoretical Methods*

All DFT calculations were carried out using the Gaussian-16 program [18] at the PBE1PBE-D3/def2-TZVP level of theory and using the crystallographic coordinates. The formation energies of the assemblies were evaluated by calculating the difference between the total energy of the assembly and the sum of the monomers that constitute the assembly, which have been maintained frozen. That is ΔEAB = EAB − EA − EB, where ΔEAB is the interaction energy; EAB is the energy of the dimer and EA and EB are the energy of the monomers. The BSSE has been used to correct the interaction energies by using the counterpoise =2 keyword in the Gaussian-19 program [18]. The molecular electrostatic potential was computed at the same level of theory and plotted onto the 0.001 a.u. isosurface. The Quantum Theory of Atoms-in-Molecules (QTAIM) [19] analysis was carried out at the same level of theory by means of the AIMAll program [20] to obtain the distribution of bond critical points (CPs) and bond paths [21].
