(±)-2-{[4-(4-Bromophenyl)-5-phenyl-4H-1,2,4-triazol-3-yl]sulfanyl}-1-phenyl-1-ethanol

: The novel racemic secondary alcohol ( ± )-2-{[4-(4-bromophenyl)-5-phenyl-4 H -1,2,4-triazol-3-yl]sulfanyl}-1-phenyl-1-ethanol ( 12 ) has been successfully synthesized through S -alkylation of 4-(4-bromophenyl)-5-phenyl-4 H -1,2,4-triazole-3-thiol ( 10 ) in alkaline medium with 2-bromo-1-phenylethanone followed by reduction of the corresponding ketone 11 . All the synthesized compounds were char-acterized by IR, 1D ( 1 H, 13 C, DEPT135) and 2D ( 1 H- 1 H, 1 H- 13 C and 1 H- 15 N) NMR spectroscopy, elemental and HRMS spectrometry.

Theoretically 4-(4-bromophenyl)-5-phenyl-4H-1,2,4-triazole-3-thiol (10) can have two tautomeric forms: the thiol form 10a and the thione form 10b. As a result, alkylation in a basic medium can occur in fact as S-alkylation at the tautomeric form 10a or as N-alkylation at the tautomeric form 10b (Scheme 3). The corresponding 1 H NMR and 13 C NMR spectra confirmed that the tautomeric equilibri is confirmed by the deshielded signals of the 2-N-H proton at 14.11 ppm and of the 3-C carbon atom at 168.9 ppm which corresponds to a thione-type (C=S) 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 [22] (Scheme 4). This is observed from 2D NMR spectroscopic analysis by analyzing the couplings over two or three bonds in the HMBC spectrum, as well as by the shift of the signal of the triazole carbon 3-C atom to a lower δ value at 152.0 ppm, corresponding to a thiol (C-SH)-type carbon atom. The alkylation is proved by the existence of a 1 H NMR signal at 4.98 ppm corresponding to the methylene proton (S-CH 2 ) and the 13 C NMR signal at 193.0 ppm corresponding to the carbonyl carbon atom (C=O) from the ketone (11). The 2D 1 H-15 N HMBC spectrum does not show the cross-peak over two bonds between the 2-N carbon atom and the methylene protons (-CH 2 ) that could have been observed in the case of N-alkylation, which confirms that S-alkylation has occurred. In the case of S-alkylation the long-range coupling over 4 bonds between the 2-N atom and the methylene protons is not observable.
Reduction of the carbonyl group to the secondary alcohol group was accomplished with sodium borohydride in ethanol. Secondary alcohol 12 was obtained in a yield of 57.0% after recrystallization from ethanol (Scheme 5).
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 reduction of ketone 11 to secondary alcohol 12 is evidenced from the 1 H NMR spectrum by the doublet at 4.94 ppm attributed to the hydroxyl proton (OH), the multiplet at 5.20-5.18 ppm attributed to the methine proton (CH) and the doublets of doublets at 3.47 and 3.62 respectively attributed to the two diastereotopic protons of the methylene group (S-CH2). The 13 C NMR spectrum shows the disappearance of the deshielding signal at 193.0 ppm corresponding to the carbonyl carbon atom and the appearance of the signal at 73.3 ppm attributed to the methine carbon atom (CH-O).
The secondary alcohol 12 has two diastereotopic protons at the methylene group which 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.