An unexpected tautomer: synthesis and crystal structure of N-[6-amino-4-(methylsulfanyl)-1,2-dihydro-1,3,5-triazin-2-ylidene]benzenesulfonamide

The title compound, C10H11N5O2S2, consists of an unexpected imino-dihydro-triazine tautomer. Molecules are linked by hydrogen bonds and by Osulfonamide⋯(C—NH—C)triazine contacts.


Chemical context
Sulfonamides constitute a significant category of bioactive molecules with remarkable pharmacological activities (Wan et al., 2021;Elgemeie et al., 2022).They are clinically utilized as anticancer (Owa & Nagasu, 2000), antibacterial, antithyroid, hypoglycaemic and antiviral drugs; among many other effective molecules one may cite the anti-cancer agent indisulam (Supuran, 2003).The presence of a moiety with a triazine core (as an aza-pyrimidine analogue) would represent a new structure of significant importance.Continuing with our project of developing synthetic strategies for the design and synthesis of efficient antimetabolites (Elgemeie & Mohamed-Ezzat, 2022), focussing on derivatives of sulfonamides, we describe here a new approach (Fig. 1) that generates novel substituted triazine sulfonamides starting from the highly reactive compound dimethyl cyanocarboimidodithioate (2), which has shown its effectiveness in synthesizing various heterocycles (Elgemeie & Mohamed, 2014;Mohamed-Ezzat et al., 2021), in particular nucleoside and non-nucleoside pyrimidine analogues (Elgemeie et al., 2015(Elgemeie et al., , 2017(Elgemeie et al., , 2019)).
Thus, the reaction of benzenesulfonylguanidine 1 with the N-cyanodithioiminocarbonate derivative 2 in refluxing dioxane containing potassium hydroxide for 1 h provided an adduct for which two possible tautomeric structures 3a or 3b (derivatives of 1,3,5-triazine, also known as s-triazine, with a benzenesulfonamide substituent) might be assigned (Fig. 1).Investigation by TLC and NMR revealed the presence of only one product in solution.The 1 H NMR spectrum of the product showed three singlet signals at � = 2.29, 7.35 and 11.83 ppm, assigned to SCH 3 , NH 2 and NH protons, in addition to signals from the aromatic protons; it is, however, inconclusive in differentiating between the two tautomers.An X-ray structure determination, described in this paper, indicated unambiguously the formation of the dihydro-1,3,5-triazine-benzenesulfonamide derivative, the title compound 3a, as the isolated product in the solid state.This compound consists of two important substructures (the sulfonamide and the triazine moieties) and this may prove to have a significant impact in developing the medicinal chemistry of sulfonamides.

Structural commentary
The structure of 3a is shown in Fig. 2, with selected molecular dimensions in Table 1.Surprisingly, the alternative tautomer 3b, N-[6-amino-4-(methylsulfanyl)-1,3,5-triazin-2-yl]benzenesulfonamide, in which the hydrogen atom at N1 is shifted to N2 (using the numbering of Fig. 2) was not formed, at least not in significant amounts.It should be stressed that the three hydrogen atoms bonded to nitrogen were identified in a difference synthesis and refined freely.
The interplanar angle between the two rings is 79.56 (5) � ; the phenyl ring, which is almost ideally planar (r.m.s.deviation = 0.0015 A ˚), is oriented such that C13 is approximately synperiplanar to O1, with an O1-S2-C8-C13 torsion angle of 7.00 ( 14) � and a short intramolecular contact O1� � �H13 2.48 A ˚.The modified triazine ring, with formal single bonds at N1 and a formal exocyclic double bond C2 N2, has a higher r.m.s.deviation from planarity of 0.03 A ˚.This is associated with a significant deviation at the nitrogen atom N1, which lies 0.112 (2) A ˚out of the plane of the other five atoms, although it retains its planarity (angle sum of 359.3 � ).Accordingly, the ring torsion angles involving N1 differ appreciably from zero, at ca �10 � .The substituents at the triazine ring are also somewhat displaced from the ring plane, N2 by 0.171 (2), N4 by 0.141 (2) and S1 by À 0.134 (2) A ˚.The NH 2 group is essentially planar (angle sum of 358.2 � ) and almost coplanar with the triazine ring (its hydrogen atoms lie less than 0. The molecule of 3a in the crystal.Ellipsoids represent 50% probability levels.

Supramolecular features
The molecules of 3a are linked by a series of classical hydrogen bonds (Table 2), forming a ribbon structure (Fig. 3).
One set of such ribbons, in the region z ' 0.5, is parallel to [110]; further sets at z ' 0 and 1 are parallel to [110].All three potential donor hydrogen atoms (H01, H04A, H04B) are involved; the respective acceptors are the exocyclic nitrogen atom N2, the ring nitrogen atom N5, and the sulfonyl oxygen O2.The hydrogen-bonded rings all have graph set R 2 2 (8) (Bernstein et al., 1995).In the fused set of three rings, formed via the inversion operator 1 À x, À y, 1 À z, the outer rings are antidromic whereas the central ring is homodromic.The single ring based on the H04A� � �N5 interaction is also formed by inversion (À x, 1 À y, 1 À z) and is homodromic.

Database survey
The search employed the routine ConQuest (Bruno et al., 2002), part of Version 2022.3.0 of the CSD (Groom et al., 2016).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms bonded to nitrogen were refined freely.The methyl group was included as an idealized rigid group allowed to rotate but not tip (command 'AFIX 137').Other hydrogen atoms were included using a riding model starting from calculated positions (C-H = 0.95 A ˚).The U(H) values were fixed at 1.5 � U eq of the parent carbon atoms for the methyl group and 1.2 � U eq for other hydrogens.(Rigaku OD, 2023), SHELXT (Sheldrick, 2015a), SHELXL2019/3 (Sheldrick, 2015b) and XP (Bruker, 1998).

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes. Fractional Figure 2

Figure 1
Figure 1Synthesis of the novel triazine sulfonamide derivative 3a.
wished to determine how unusual the protonation at the s-triazine ring was, in comparison to protonation at an N-research communications 122 Mohamed-Ezzat et al. � C 10 H 11 N 5 O 2 S 2 Acta Cryst.(2024).E80, 120-124

Figure 3
Figure 3 Packing diagram of 3a, viewed perpendicular to (110), showing the formation of a ribbon of molecules linked by classical hydrogen bonds (dashed lines).Labelled atoms indicate the asymmetric unit.Hydrogen atoms not involved in hydrogen bonding are omitted.

Figure 4
Figure 4Formation of chains of molecules 3a parallel to the a axis, showing the short contacts between O1 and the triazine ring of a neighbouring molecule (thick dashed bonds).The view direction is approximately parallel to the b axis, and the a axis runs horizontally.Two such chains, running mutually antiparallel, are connected by the borderline contacts S1� � �C6 (thin dashed lines).Hydrogen atoms are omitted.

Table 3
Experimental details.