Synthesis of 4-( 2 H-[ 1 , 2 , 4 ]-Triazol-5-ylsulfanyl )-1 , 2-dihydropyrazol-3-one via Ring-Switching Hydrazinolysis of 5-Ethoxymethylidenethiazolo [ 3 , 2-b ] [ 1 , 2 , 4 ] triazol-6-one

4-(1H-[1,2,4]-Triazol-5-ylsulfanyl)-1,2-dihydropyrazol-3-one (4) was synthesized with a yield of 55% via ring-switching hydrazinolysis of 5-ethoxymethylidenethiazolo[3,2-b][1,2,4] triazol-6-one (3) in ethanol medium. The initial 1H-[1,2,4]-triazole-3-thiol (1) was modified via a two-step reaction: S-alkylation with chloroacetic acid under Williamson reaction conditions, and further one-pot cyclization–condensation with triethylorthoformate in the acetic anhydride medium, yielding compound 3. The structures of compounds 3 and 4 were confirmed by LC-MS, NMR spectra and a single X-ray diffraction analysis (for compound 4).

The structure and purity of compounds 3 and 4 were confirmed by LC-MS, 1 H and 13 C NMR spectra (copies of spectra are presented in Supplementary).In the 1 H NMR spectra of compounds 3 and 4, protons of the triazol ring appeared as singlets at 8.50 (C-3) and 8.26 ppm (C-2), respectively.A chemical shift in the methylidene group of compound 3 has been assigned in a weak magnetic field at 8.41 ppm.A signal of the pyrazole ring proton at C-5 of compound 4 was observed as a singlet at 7.71 ppm.
The structure and purity of compounds 3 and 4 were confirmed by LC-MS, 1 H and 13 C NMR spectra (copies of spectra are presented in Supplementary).In the 1 H NMR spectra of compounds 3 and 4, protons of the triazol ring appeared as singlets at 8.50 (C-3) and 8.26 ppm (C-2), respectively.A chemical shift in the methylidene group of compound 3 has been assigned in a weak magnetic field at 8.41 ppm.A signal of the pyrazole ring proton at C-5 of compound 4 was observed as a singlet at 7.71 ppm.

X-ray Crystallographic Analysis of the Compound 4
X-ray analysis was used for the structure determination of compound 4. The ORTEP drawing and atomic numbering are shown in Figure 1.The performed X-ray studies revealed that the 1,2,4-triazole system in the molecule of compound 4 undergoes a tautomeric transition in a solution.The crystals 4(A) (lath shape) and 4(B) (prism shape), obtained simultaneously from the same solution of CH 3 OH and H 2 O mixed at a 1:1 ratio, prove this conclusion.The lath-shaped crystals, 4(A), have the tautomeric hydrogen atoms at N2 while the prism-shaped ones, 4(B), have these hydrogen atoms located at N1 (Figure 1).
X-ray analysis was used for the structure determination of compound 4. The ORTEP drawing atomic numbering are shown in Figure 1.The performed X-ray studies revealed that the 1,2,4-triazole system in the molecule of compound 4 undergoes a tautomeric transition in a solution.The crystals 4(A) (lath shape) and 4(B) (prism shape), obtained simultaneously from the same solution of CH3OH and H2O mixed at a 1:1 ratio, prove this conclusion.The lath-shaped crystals, 4(A), have the tautomeric hydrogen atoms at N2′ while the prism-shaped ones, 4(B), have these hydrogen atoms located at N1 (Figure 1).The X-ray studies has shown that proton tautomerism is observed in the 1,2,4-triazole system.In the first case (crystal 4(A)), the 1,2,4-triazole system has a tautomeric structure with hydrogen located at N1A and 4-sulfanyl-1,2-dihydro-3H-pyrazol-3-one moiety located at the C5 atom (form A) while in the other one (crystal 4(B)), the hydrogen atom is located at N1A and the 4-sulfanyl-1,2-dihydro-3H-pyrazol-3-one moiety at the C3 atom (form B) (Scheme 2).The positions of protons connected to N atoms in both heterocyclic systems of molecules in crystals 4(A) and 4(B), i.e., 1,2-dihydro-3H-pyrazol-3-one and 1,2,4-triazole systems, were obtained from the difference Fourier maps and were refined freely.The presence of the H atom in the 1,3,4-triazole system at N1A (the molecules in the crystal 4(A)) and at N1A (the molecules in the crystal 4(B)) is supported by intermolecular hydrogen bonds N1A-H1A•••O1 ii (Table 1, Figure 2) and N1A-H1A•••O1 ii (Table 1, Figure 3).In the mentioned bonds, the oxygen atom from the carbonyl group (O1) acts as a proton acceptor.

Materials and Methods
Melting points were measured in open capillary tubes on a B ŰCHI B-545 melting point apparatus (BÜCHI Labortechnik AG, Flawil, Switzerland) and are uncorrected.The elemental analyses (C, H, N) were performed using the Perkin-Elmer 2400 CHN analyzer (PerkinElmer, Waltham, MA, USA) and were within ±0.4% of the theoretical values.The 1 H and 13 C NMR spectra were recorded on a Varian Gemini spectrometer (Agilent, Santa Clara, CA, USA) at 400 and 100 MHz, respectively, using DMSO-d 6 as a solvent and TMS as an internal standard.Chemical shift values are reported in ppm units with use of δ scale.LC-MS spectra were obtained on a Finnigan MAT INCOS-50 (Thermo Finnigan LLC, San Jose, CA, USA).Solvents and reagents that are commercially available were used without further purification.Compound 3 (CAS 2111914-32-8) is also commercially available from Ambinter [10]; Aurora Fine Chemicals [11]; Zerenex Molecular Ltd. [12] and compound 4 (CAS 2176338-67-1) is also commercially available from Aurora Fine Chemicals [11] although it is rather expensive.A mixture of (2H- [1,2,4]triazol-3-yflsulfanyl)-acetic acid (2) (10.0 mmol) and triethylorthoformate (12.5 mmol) refluxed for 2 h in the 10 mL of acetic anhydride.Reaction mixture was cooled to the room temperature and light brown precipitate was filtered off, washed with small portion of cold water and recrystallized from ethanol.
Structure solution and refinement.The structure was solved by a dual-space algorithm (SHELXT) [14], and refined against F 2 for all data (SHELXL-97) [15].The positions of all H atoms were obtained from the difference Fourier maps and were refined freely.Final refinement converged with R = 0.029 (for 1392 data with F 2 > 4σ(F 2 )), wR = 0.078 (on F 2 for all data), and S = 1.048 (on F 2 for all data).The largest difference peak and hole was 0.325 and −0.325 eÅ 3 .The molecular illustrations were drawn using ORTEP-3 for Windows [16].
The crystallographic data in the CIF form are available as Electronic Supplementary data from the Cambridge Crystallographic Data Centre, deposition number CCDC-1859739; http://www.ccdc.cam.

Figure 1 .
Figure 1.The molecular structures of compound 4 in the crystals 4(A) and 4(B).

Figure 2 .
Figure 2. Part of the molecular packing in the crystal 4(A), showing (a) molecules linked by N-H•••N, N-H•••O hydrogen bonds and (b) the hydrogen bonded (C-H•••O) sheets parallel to the (10-1) plane.The H atoms not involved in hydrogen bonds have been omitted for clarity.

Figure 2 .
Figure 2. Part of the molecular packing in the crystal 4(A), showing (a) molecules linked by N-H•••N, N-H•••O hydrogen bonds and (b) the hydrogen bonded (C-H•••O) sheets parallel to the (10-1) plane.The H atoms not involved in hydrogen bonds have been omitted for clarity.
crystal 4(A), the molecules are connected by N1-H1•••N4A i and N2-H2•••O1 iii hydrogen bonds into columns extending along the [101] direction.The columns are further connected by N1A-H1A•••O1 ii hydrogen bonds into layers parallel to (101 ) plane.The layers linked with C3A-H3A•••O1 iv hydrogen bonds form three-dimensional network (Table 1, Figure 2a,b).Crystal 4(B) has a form of a hydrate.The asymmetric unit contains one solute molecule (host) and one water molecule (guest).In the crystal solute, molecules are connected by N1-H1•••N4A i and N1A-H1A•••O1 ii hydrogen bonds into columns as in crystal 4(A), but in this case, they extend along the c axis.Water molecules are also involved in the hydrogen bond formation.They act as a proton donor twice and as a proton acceptor once.Taking part in N2-H2•••O2 iii , O2-H21•••N2A and O2-H22•••O1 iv hydrogen bonds, water molecules are a link connecting the mentioned columns into a three-dimensional network (Table

Figure 3 .
Figure 3.The hydrogen bonding in the crystal 4(B).The H atoms not involved in hydrogen bonds have been omitted for clarity.In crystal 4(A), the molecules are connected by N1-H1•••N4A i and N2-H2•••O1 iii hydrogen bonds into columns extending along the [101] direction.The columns are further connected by N1A-H1A•••O1 ii hydrogen bonds into layers parallel to (101) plane.The layers linked with C3A-H3A•••O1 iv hydrogen bonds form three-dimensional network (Table 1, Figure 2a,b).Crystal 4(B) has a form of a hydrate.The asymmetric unit contains one solute molecule (host) and one water molecule (guest).In the crystal solute, molecules are connected by N1-H1•••N4A i and N1A-H1A•••O1 ii hydrogen bonds into columns as in crystal 4(A), but in this case, they extend along the c axis.Water molecules are also involved in the hydrogen bond formation.They act as a proton donor twice and as a proton acceptor once.Taking part in N2-H2•••O2 iii , O2-H21•••N2A and O2-H22•••O1 iv hydrogen bonds, water molecules are a link connecting the mentioned columns into a three-dimensional network (Table1, Figure3).