4-(3,4-DICHLORO-PHENYL)-THIAZOL-2-YLAMINE

(1) 2-Amino-4-(3, 4-dichlorophenyl)thiazole. Using 3', 4'-dichloroacetophenone and thiourea as the raw materials, the same operation as the Example 395(1) gave the title compound. Yield: 77.8%. 1H-NMR(DMSO-d6): delta 7.17(2H, s), 7.24(1H, s), 7.62(1H, d, J=8.4Hz), 7.78(1H, dd, J=8.7, 2.7Hz), 8.22(1H, d, J=2.4Hz).General procedure: A mixture of the substrate (i.e. appropriate bromoketone) (1 eq) and thiourea (1.5 eq) in EtOH (3 mL per 1 mmol of bromoketone, unless stated otherwise) was refluxed for 2 h (unless stated otherwise). (0082) Work-up 1: (0083) A saturated aqueous solution of NaHCCE (3 mL per 1 mmol of bromoketone) was added to the mixture, which was then extracted with EtOAc (3 x 5 mL per 1 mmol of bromoketone). The combined organic extracts were washed with brine (3 mL per 1 mmol of bromoketone), dried over MgS04, filtered, and the solvent was evaporated in vacuo. If necessary, the product was purified by column chromatography on silica gel (unless stated otherwise) to provide the desired aminothiazole. (0084) Work-up 2: (0085) The solvent was evaporated in vacuo. The resulting solid was triturated with EtOAc (1 mL per 1 mmol of bromoketone) and the mixture was filtered. The solid residue was dissolved in MeOH (1 mL per 1 mmol of bromoketone). A saturated aqueous solution of NaHCOs (3 mL per 1 mmol of bromoketone) was added and the mixture was extracted with EtOAc (3 x 5 mL per 1 mmol of bromoketone). The combined organic extracts were washed with brine (3 mL per 1 mmol of bromoketone), dried over MgS04, filtered, and the solvent was evaporated in vacuo. The product - the desired aminothiazole - was usually sufficiently pure and was used directly without further purification (unless stated otherwise) in the next step.General procedure: To a mixture of 2-aminothiazole1a'k(1 mmol), ammoniumthiocyanate(1mmol)dissolvedin(10mL)ofPEG400andwatermixture, iodic acid (1 mmol) dissolved in water (1 mL) wasadded with stirring and then the reaction mixture was stirredfor 10'15 min at room temperature. After completion of reaction (As indicated by TLC) the reaction mixture was dilutedwith ice cold water and neutralized with sodium bicarbonate.The solid product was filtered, washed with cold water. Thecrude products were further purified by column chromatography (Petroleum ehter/Ethyl acetate) 20percent. All the remainingderivatives2a'kwere prepared according to the typical procedure given above with more than 90percent yield.

Molecular Weight:245.13
XLogP3:3.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:243.9628748
Monoisotopic Mass:243.9628748
Topological Polar Surface Area:67.2
Heavy Atom Count:14
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes