Synthesis and acidic properties of novel 3-methyl-4-[(2-amino-1,3,4-thiadiazol-5-il)-thioacetylamino]-4,5-dihydro-1H-1,2,4-triazol-5-one

A number of studies involving the determination of pK_a values of some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous solvents has been revealed [1,2,3]. 3-Methyl-4-[(2-amino-1,3,4-thiadiazol-5-il)-thioacetylamino]-4,5-dihydro-1H-1,2,4-triazol-5-one 3 was synthesized from the reaction of 3-methyl-4-chloroacetylamino-4,5-dihydro-1H-1,2,4-triazol-5-one 1 with 2-amino-5-mercapto-1,3,4-thiadiazole 2. Moreover, the synthesized compound 3 was titrated potentiometrically with tetrabutylammonium hydroxide (TBAH) in three non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide to determine pK_a values. For compound 3, the half-neutralization potentials (HNP) and the corresponding pK_a values were determined in the three non-aqueous solvents mentioned above. The starting compound 1 was prepared according to literature [2,4].　

3-Methyl-4-chloroacetylamino-4,5-dihydro-1H-1,2,4-triazol-5-one 1 (1.91 g, 0.01 mol) and 2-amino-5-mercapto-1,3,4-thiadiazole 2 (1.33 g, 0.01 mol) in n-butyl acetate (30 mL) was refluxed for five hours and then evaporated at 50-55 °C in vacuo. Several recrystallizations of the residue from ethanol gave pure compound 3 (1.32 g, 45.99 %).

Melting point: 151-152 °C (EtOH, uncorrected).

UV (λ_max nm; EtOH) / ε (dm³.mol^-1.cm^-1): 282 (5980), 203 (9150).

IR (KBr, cm^-1): 3400, 3250, 3100 (NH₂, NH); 1750 (C=O); 1605 (C=N).

¹H-NMR (200 MHz, DMSO-d₆): δ= 2.09 (3H, s, CH₃); 4.14 (2H, s, CH₂); 6.40 (2H, br, NH₂); 11.40 (1H, s, NH); 11.64 (1H, s, NH).

¹³C-NMR (50 MHz, DMSO-d₆): δ= 10.45 (CH₃); 34.75 (CH₂); 144.70, 151.76, 152.21, 166.86 (heterocyclic carbons); 169.89 (C=O).

The potentiometric titration curves of 0.001 M compound 3 solutions titrated with 0.05 N TBAH in isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide are presented in Figure 1.

The HNP values and the corresponding pK_a values of compound 3 are presented

Table 1:. HNP values and the corresponding pK_a values of compound 3

Solvent	HNP1 (mV)	pKa1	HNP2 (mV)	pKa2
Isopropyl alcohol	291	2.06	-221	10.64
tert-butyl alcohol	287	2.16	-269	11.61
N,N-dimethylformamide	218	3.36	-342	12.68

.

As seen Figure 1 and Table 1, compound 3 give two end points as well as two half-neutralization potential values. The potentiometric titration curves of compound 3 resemble the titration curves of diprotic acids.