Copper-Catalyzed Tandem Reaction of 2-Haloaniline Derivatives with Tetraalkylthiuram Disulfides: Selective Synthesis of 2-Aminobenzothiazoles

Abstract

A simple and efficient protocol for the synthesis of 2-aminobenzothiazoles by copper-catalyzed tandem reaction has been developed. In the presence of CuBr and Cs₂CO₃, a variety of 2-haloanilines underwent the reaction with tetramethylthiuram di­sulfide (TMTD) efficiently to afford the corresponding 2-aminobenzothiazoles in moderate to excellent yields. The present process allows the construction of 2-aminobenzothiazoles from a wide range of 2-haloaniline derivatives, including 2-iodoanilines, 2-bromoanilines, and 2-chloroanilines.

copper - tandem reaction - 2-haloanilimine - tetraalkyl­thiuram disulfides - 2-aminobenzothiazoles

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General Procedure for the Copper-Catalyzed Tandem Reaction of 2-Haloanilimine Derivatives with Tetraalkylthiuram Disulfides A flame-dried Schlenk tube with a magnetic stirring bar was charged with 2-haloanilimine derivative 1 (0.2 mmol), tetraalkylthiuram disulfide (0.15 mmol), CuBr (1.4 mg, 0.01 mmol), Cs₂CO₃ (196 mg, 0.6 mmol), and DMSO (1 mL). The reaction mixture was stirred at 80 ˚C for the indicated time (Tables  [¹] and  [²] ) until complete consumption of starting material as monitored by TLC and GC-MS analysis. After the reaction was finished, the mixture was poured into EtOAc, washed with brine (3 × 10 mL), and extracted with EtOAc. The combined organic layers were dried over anhyd Na₂SO₄ and evaporated under vacuum. The residue was purified by flash column chromatography (hexane-EtOAc) to afford the desired product.
N , N -Dimethy-6-(trifluoromethyl)benzo[ d ]thiazol-2-amine (4)
Mp 98.5-101.1 ˚C(uncorrected). ^¹H NMR (300 MHz, CDCl₃): δ = 7.84 (s, 1 H), 7.58 (d, J = 8.5 Hz, 1 H), 7.52 (d, J = 8.5 Hz, 1 H), 3.22 (s, 6 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 170.3, 155.8, 131.2, 124.6 (q, J _C-F = 269.9 Hz, 1 C), 123.4, 122.8 (d, J _C-F = 32.2 Hz, 1 C), 122.1, 118.0, 40.2. ^¹9F NMR (283 MHz, CDCl₃): δ = -60.79. IR (KBr): 2913, 1616, 1573, 1337, 1145, 1099 cm^-¹. LRMS (EI, 70 eV): m/z (%) = 246 (93) [M⁺], 217 (100). ESI-HRMS: m/z calcd for C₁₀H₁₀F₃N₂S⁺ [M + H]⁺: 247.0511; found: 247.0503.