1,2-Benzenediol,4-(5-amino-1,3,4-thiadiazol-2-yl)-(9CI) synthesis

Yield:134952-04-8 68%

Reaction Conditions:

Stage #1: 3,4-Dihydroxybenzoic acidwith trichlorophosphate at 20; for 0.333333 h;
Stage #2: thiosemicarbazide for 1 h;Reflux;

Steps:

Procedure for the synthesis of 2 and 2'.

General procedure: A mixture of 3,4-dihydroxybenzoic acid, 1 or 2,3-dihydroxybenzoic acid, 1' (0.308 g, 2.00 mmol) and POCl₃ (1.0 mL) was stirred for 20 minutes at the room temperature. Then, thiosemicarbazide (2.50 mmol, 0.228 g) was added and the resulting suspension was refluxed for 1 hour. After cooling the flask in an ice bath, 3.0 ml of distilled water was added carefully, and reflux was continued for 1 hour. The mixture was then cooled to the room temperature, saturated aqueous solution of NaOH was added until pH 8.5 was reached and the suspension was stirred for 1 hour at the room temperature. The formed precipitate of the corresponding 1,3,4-thiadiazole derivative (2 and 2') was then filtrated, dried over CaCl₂ and recrystallized from hot 50 % aqueous EtOH.4-(5-Amino-1,3,4-thiadiazol-2-yl)benzene-1,2-diol x H₂O (2): Beige powder; yield: 0.31 g (68%); mp: > 250 C; ¹H NMR (200 MHz, DMSO-d₆): 6.77, (d, 1H, J = 8.2 Hz, Ar-H); 6.98, (dd, 1H, J = 8.2 and 2.0 Hz, Ar-H); 7.18, (d, 1H, J = 2.0 Hz, Ar-H); 7.20, (s, 2H, NH₂); 9.30, (s, 1H, OH); 9.38, (s, 1H, OH); ¹³C NMR (50 MHz, DMSO-d₆): 113.36, 116.03, 118.47, 122.56, 145.69, 147.25, 157.04, 167.49; IR (KBr, cm^-1): 3430, 3318, 2926, 1625, 1605, 1509, 1444, 1297, 1260, 764; Anal. Calcd. For C₈H₇N₃O₂SxH₂O (227.24 g/mol): C, 42.28; H, 3.99; N, 18.49; S, 14.11; Found: C, 42.35; H, 3.98; N, 18.55; S, 14.06.

References:

Jakovljevi?, Katarina;Mati?, Ivana Z.;Stanojkovi?, Tatjana;Krivoku?a, Ana;Markovi?, Violeta;Joksovi?, Milan D.;Mihailovi?, Nevena;Ni?iforovi?, Marija;Joksovi?, Ljubinka [Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,# 16,p. 3709 - 3715] Location in patent:supporting information