-1,2,4-triazol-3-yl] thio}-1-phenyl-1-ethanol H -1,2,4-triazol-3-yl] thio}-1-phenyl-1-ethanol

: 4-(4-Methoxyphenyl)-5-phenyl–4 H -1,2,4-triazole-3-thiol ( 4 ) was alkylated to 2-{[4-(-4-methoxyphenyl)-5-phenyl-4 H -1,2,4-triazol-3-yl]thio}-1-phenylethan-1-one ( 5 ) in alkaline conditions using 2-bromo-1-phenylethanone. The alkylated compound ( 5 ) was reduced at the carbonyl group to the corresponding racemic secondary alcohol with an asymmetric carbon, ( R , S )-2-{[4-(4-methoxyphenyl)-5-phenyl-4 H -1,2,4-triazol-3-yl]thio}-1-phenyl-1-ethanol ( 6 ). Both synthesized compounds, ketone ( 5 ) and secondary alcohol ( 6 ), are new and have not been reported yet in the literature. All the synthesized compounds were characterized by IR, 1D and 2D NMR 1 H- 1 H, 1 H- 13 C and 1 H- 15 N-NMR spectroscopy and by elemental analysis. Abstract: 4-(4-Methoxyphenyl)-5-phenyl--4 H -1,2,4-triazole-3-thiol ( 4 ) was alkylated to 2-{[4-(-4-methoxyphenyl)-5-phenyl-4 H -1,2,4-triazol-3-yl]thio}-1-phenylethan-1-one ( 5 ) in alkaline conditions using 2-bromo-1-phenylethanone. The alkylated compound ( 5 ) was reduced at the carbonyl group to the corresponding racemic secondary alcohol with an asymmetric carbon, ( R , S )-2-{[4-(4-methox-yphenyl)-5-phenyl-4 H -1,2,4-triazol-3-yl]thio}-1-phenyl-1-ethanol ( 6 ). Both synthesized compounds, ketone ( 5 ) and secondary alcohol ( 6 ), are new and have not been reported yet in the literature. All the synthesized compounds were characterized by IR, 1D and 2D NMR 1 H- 1 H, 1 H- 13 C and 1 H- 15 N-NMR spectroscopy and by elemental analysis.


Introduction
The recent literature reveals that the mercapto-and thione-substituted 1,2,4-triazole moieties should be an important structural feature of a wide range of synthetic medicines [1]. A variety of medicinal actions have been reported, ranging from anti-tubercular action [2] to protein inhibitory action involved in the mechanism of diseases such as diabetes, obesity and cancer [3]. Other S-alkylated compounds derived from 4H-1,2,4-triazole-3-thiol 4,5-disubstituted show proven antifungal [4], antimicrobial and antibiotic activity [5] (Scheme 1).

Results and Discussion
3-Mercaptotriazole (4) can theoretically have two tautomeric forms: the thiol form (4a) and the thione form (4b). As a result, alkylation in a basic medium can theoretically occur as S-alkylation at the tautomeric form (4a) or as N-alkylation at the tautomeric form (4b) (Scheme 3). From the 1 H and 13 C-NMR spectra, it is confirmed that the tautomeric equilibrium is completely shifted to the tautomeric form (4b) in Py-d5. This shift of equilibrium is confirmed by the deshielded signal of the 2-N-H proton at 16.00 ppm, as well as by the deshielded signal of the 3-C carbon atom at 171.7 ppm, corresponding to a C=S thionic carbon atom.
Following alkylation using cesium carbonate as a base in N,N-dimethylformamide, it has been observed that the alkylation occurs exclusively at the thiol group as S-alkylation. This is observed from 2D NMR spectroscopic analysis by analyzing the couplings over two to three bonds in the HMBC spectrum as well as by the shifting of the signal of the triazolic carbon 3-C atom to a lower δ value at 151.7 ppm, corresponding to a thiol

Results and Discussion
3-Mercaptotriazole (4) can theoretically have two tautomeric forms: the thiol form (4a) and the thione form (4b). As a result, alkylation in a basic medium can theoretically occur as S-alkylation at the tautomeric form (4a) or as N-alkylation at the tautomeric form (4b) (Scheme 3).
Molbank 2021, 2021, x 2 of 6 ketone group to the corresponding secondary alcohol was carried out with sodium borohydride [13].

Results and Discussion
3-Mercaptotriazole (4) can theoretically have two tautomeric forms: the thiol form (4a) and the thione form (4b). As a result, alkylation in a basic medium can theoretically occur as S-alkylation at the tautomeric form (4a) or as N-alkylation at the tautomeric form (4b) (Scheme 3). From the 1 H and 13 C-NMR spectra, it is confirmed that the tautomeric equilibrium is completely shifted to the tautomeric form (4b) in Py-d5. This shift of equilibrium is confirmed by the deshielded signal of the 2-N-H proton at 16.00 ppm, as well as by the deshielded signal of the 3-C carbon atom at 171.7 ppm, corresponding to a C=S thionic carbon atom.
Following alkylation using cesium carbonate as a base in N,N-dimethylformamide, it has been observed that the alkylation occurs exclusively at the thiol group as S-alkylation. This is observed from 2D NMR spectroscopic analysis by analyzing the couplings over two to three bonds in the HMBC spectrum as well as by the shifting of the signal of the triazolic carbon 3-C atom to a lower δ value at 151.7 ppm, corresponding to a thiol From the 1 H and 13 C-NMR spectra, it is confirmed that the tautomeric equilibrium is completely shifted to the tautomeric form (4b) in Py-d5. This shift of equilibrium is confirmed by the deshielded signal of the 2-N-H proton at 16.00 ppm, as well as by the deshielded signal of the 3-C carbon atom at 171.7 ppm, corresponding to a C=S thionic carbon atom.
The methylene protons in the obtained secondary alcohol (5) are diastereotopic and appear in the 1 H-NMR spectrum at different δ values as two distinct doublets of doublets. This is specific for a methylene group attached to an asymmetric carbon atom. From the 1 H-13 C HMBC spectrum, the long-range coupling over three bonds of the methylene diastereotopic protons with the 3-C triazole carbon atom is observed, thus further confirming the S-alkylation.

Materials and Methods
The chemical reagents were purchased from commercial sources and used in syntheses with no further purification. Melting points were determined on a Böetius PHMK (Veb type carbon atom. S-Alkylation of 4-(4-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3thiol (4) was carried out using 2-bromo-1-phenylethanone in DMF in the presence of Cs2CO3 at room temperature. 2-{[4-(-4-Methoxyphenyl)-5-phenyl-4H-1,2,4-triazol-3yl]thio}-1-phenylethan-1-one (5) resulting from S-alkylation was obtained in a yield of 79% after recrystallization from ethanol (Scheme 4).  From the correlative 1 H-15 N HMBC spectra, the signal for the 4-N nitrogen atom in all the synthesized compounds could be identified by its coupling over three bonds with hydrogen atoms in the ortho positions of the phenyl ring attached to this atom. This longrange coupling was very useful in the assignment of the corresponding 1 H-NMR signals for the ortho protons on the phenyl ring bound to the 4-N nitrogen atom.
The methylene protons in the obtained secondary alcohol (5) are diastereotopic and appear in the 1 H-NMR spectrum at different δ values as two distinct doublets of doublets. This is specific for a methylene group attached to an asymmetric carbon atom. From the 1 H-13 C HMBC spectrum, the long-range coupling over three bonds of the methylene diastereotopic protons with the 3-C triazole carbon atom is observed, thus further confirming the S-alkylation.

Materials and Methods
The chemical reagents were purchased from commercial sources and used in syntheses with no further purification. Melting points were determined on a Böetius PHMK (Veb From the correlative 1 H-15 N HMBC spectra, the signal for the 4-N nitrogen atom in all the synthesized compounds could be identified by its coupling over three bonds with hydrogen atoms in the ortho positions of the phenyl ring attached to this atom. This long-range coupling was very useful in the assignment of the corresponding 1 H-NMR signals for the ortho protons on the phenyl ring bound to the 4-N nitrogen atom. The methylene protons in the obtained secondary alcohol (5) are diastereotopic and appear in the 1 H-NMR spectrum at different δ values as two distinct doublets of doublets. This is specific for a methylene group attached to an asymmetric carbon atom. From the 1 H-13 C HMBC spectrum, the long-range coupling over three bonds of the methylene diastereotopic protons with the 3-C triazole carbon atom is observed, thus further confirming the S-alkylation.