CoII-catalysed synthesis of N-(4-methoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine hemihydrochloride monohydrate

The CoII-catalysed synthesis and crystal structure is reported for the title compound, which features a symmetric N⋯H+⋯N unit.


Chemical context
1,3,4-Oxadiazole derivatives have been studied in recent years for their diverse biological activities (Gond et al., 2023;Abd-Ellah et al., 2017;Bitla et al., 2020).As a result of their electron-accepting properties, high quantum yield, and good thermal and chemical stabilities, they have also been used in electroluminescent, optical and electron-transporting materials and chelating agents (Najare et al., 2020;Wu et al., 2012).Several methods for the synthesis of 1,3,4-oxadiazoles from acyclic precursors are available, which include oxidative cyclization of acylhydrazones (Jedlovska ´& Les ˇko, 1994) and acylthiosemicarbazides (Omar et al., 1996, Paswan et al., 2015).In the presence of a strong acid, an N-acylhydrazine carbodithioate is converted into a thiadiazole whereas in the presence of a weak acid or base or on complexation they can be cyclized into oxadiazole (Reid & Heindel, 1976;Jasinski et al., 2011).
We have previously reported the cyclo-desulfurization of several N-acylhydrazine carbodithioates into the corresponding 1,3,4-oxadiazole in the presence of manganese(II) acetate via the loss of H 2 S where the Mn II ion presumably behaves as a weak Lewis acid (Paswan et al., 2015(Paswan et al., , 2016;;Gond et al., 2022).In the present work, a similar reaction is reported in presence of Co II chloride.Similar Co II -assisted cyclization reactions are also reported in the literature (Li et al., 2021(Li et al., , 2023;;Bharty et al., 2012).

Supramolecular features
In the extended structure, two organic molecules are linked through their pyridine nitrogen atoms via the proton of the hydrochloric acid, which lies on a crystallographic twofold axis.This strong, symmetrical, almost linear N4� � �H4N� � �N4 hydrogen bond (Table 1) leads to a rod-like dimeric structure.These units form a layer-like structure when viewed along b axis of the unit cell (Fig. 3).The water molecules and chloride ions (site symmetry 2) are embedded in the space between the chains and are connected to them via N-H� � �O and O-H� � �Cl hydrogen bonds, thereby generating [001] chains.Weak C-H� � �Cl interactions are also observed (Table 1; Fig. 2).

Hirshfeld Surface Analysis
To gain further insight into the intermolecular interactions, a Hirshfeld surface analysis was performed using Crystal The molecular structure of the title compound showing 30% probability displacement ellipsoids with hydrogen bonds indicated by dashed lines.

Figure 2
The packing of the title compound viewed along the a-axis direction.

Figure 3
The packing of title compound viewed along the b-axis direction.
Explorer 17.5 (Spackman et al., 2021).Fig. 4a,b shows the Hirshfeld surface mapped over d norm .The red spots show the various hydrogen bonds noted above.

Synthesis and crystallization
2-Isonicotinoyl-N-(4-methoxyphenyl)hydrazine-1-carbothioamide was prepared by adding 1.652 g (10.00 mmol) of 4methoxy phenyl isothiocyanate in ethanol solution to 1.370 g (10.00 mmol) of isonicotinohydrazide and the reaction mixture was refluxed for 6 h at 333 K. Upon cooling, a white precipitate of 2-isonicotinoyl-N-(4-methoxyphenyl)hydrazine-1-carbothioamide was obtained (Fig. 5), which was filtered off and washed with a 50:50 v/v mixture of water and ether.Then, 1.00 mmol of 2-isonicotinoyl-N-(4-methoxyphenyl)hydrazine- The IR spectrum (KBr disc) shows an absorption band at 3280 cm À 1 due to the NH group.The C O band is absent and a new band is observed at 1623 cm À 1 corresponding to the C N bond.In addition, a blue shift is observed for the N N band at 1179 cm À 1 compared to the single bond in the thiosemicarbazide intermediate (Fig. 1 in the supporting information).All these data indicate that the carbothioamide moiety has been transformed into the corresponding oxadiazole (Chandra et al., 2022;Jaiswal et al., 2023ab).
The 1 H NMR spectrum of the title compound in DMSO-d6 displays peaks at � 10.69 ppm due to the NH proton, at � 8.91 and 7.90 ppm due to the pyridyl ring protons and at � 7.55 and 6.98 ppm due to phenyl ring protons.The methoxy protons appear at � 3.74 ppm.(Fig. 2 in the supporting information).In the 13 C NMR spectrum, peaks at � 156.9 and 155.2 ppm arise from oxadiazole ring carbon atoms, the methoxy C atom appears at 55.7 ppm and the phenyl and pyridyl carbon atoms are observed in the range � 114.8-132.4ppm (Fig. 3 in the supporting information).An absorption at 338 nm in the electronic spectrum of the title compound can be attributed to its �-�* transition (Fig. 4 in the supporting information).It displays fluorescence at 418 nm upon excitation at 338 nm (Fig. 5 in the supporting information) when dissolved in 10 À 5 M DMSO solution.

Figure 5
Synthesis scheme for the title compound.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Atom H4N was freely refined.Other H atoms were placed in idealized locations (N-H = 0.86 A ˚, C-H = 0.93-0.96 A ˚) and refined using a riding model with U iso (H) =1.2U eq (C,N) or 1.5U eq (C-methyl).Asymmetric N-H� � �N/N� � �H-N refinements with the H atom displaced towards one of the N atoms were inconclusive and atom H4N was placed on the twofold axis.

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.

Figure 1
Figure 1 1-carbothioamide was dissolved in a 50:50 v/v mixture of methanol and chloroform, and a methanolic solution of 0.5 mmol of CoCl 2 •6H 2 O was added and stirred for 2 h, during which time the smell of H 2 S was noted.The clear solution obtained was kept for crystallization and after 15 days, palepink blocks of the title compound were grown.Yield: 60.6%; m.p. 495-498 K. Analysis calculated for C 14 H 12 N 4 O 2. 0.5 HCl•H 2 O: C, 55.21; H, 4.79; N, 18.39%; found: C, 55.25; H, 4.50; N, 18.55%.

Table 2
Experimental details.