Benzothiazole,4-chloro-(7CI,8CI,9CI)

General procedure: To a solution of benzothiazoles or benzoxazoles (1, 1 mmol) in DMSO (3 mL), was added KOH (280 mg, 5 equiv) and 1, 3-propanedithiol (207 muL, 2 mmol). The reaction mixture was heated under argon at 130 C for 12 h. After cooling to room temperature, water (10 mL) was added. The pH of the reaction mixture was adjusted to 3-4 using 5% HCl. The resulting mixture was extracted with ethyl acetate (15 mL ×2). The organic layer was washed with water and brine, dried over anhydrous MgSO4 and concentrated using rotary evaporator. The crude product was purified by silica gel column chromatography using ethyl acetate/n-hexane as eluent to afford the corresponding heteroaryl thiols 3.Thiazoles (1b-f, j) were prepared from 2-aminothiazoles according to the reported procedure with slight modifications. 24 To a mechanically-stirred solution of 2-amino-6-chlorobenzothiazole (4 g, 21.7 mmol, 1.0 equiv) in 84% aq phosphoric acid (80 mL) was added a solution of sodium nitrite (9.0 g, 13 mmol, 6.0 equiv) in water (28 mL) dropwise below the surface at -10 C. After stirring at -10 C for another 2 h, a 50% aq solution of hypophosphorous acid (60 mL) was added dropwise to the resulting thick syrup mixture at -5 C. The reaction mixture was warmed to room temperature, stirred overnight, and then diluted with water (300 mL). Na2CO3 was added portionwise to adjust to pH=8 and extracted with DCM. The organic phase was dried over Na2SO4, concentrated under vacuum, and purified over column chromatography (petroleum ether/EtOAc=100:1) to give 6-chlorobenzothiazole as white solid (2.2 g, 59% yield).General procedure: The following provide the typical experimental procedure for the direct C-H thiolation ofbenzothiazole with thiophenol. To the 5 mL of test tube containing a magnetic stirrer bar was placed(IPr)CuI (29 mg, 0.05 mmol) and K2CO3 (69mg, 0.50 mmol)and subsequently added benzothiazole(mg, 0.25 mmol)thiophenol (mg, 0.50 mmol) in DMF (1.5 mL). The resulting mixture was heated at140 C for 3h. After the mixture was allowed to cool to room temperature, water (1 mL) was addedand the solution was extracted with three portions of 10 mL ethyl acetate. GC/MS analysis revealedthe presence of 2-phenylthiobenzothiazole. The organic layer was dried (MgSO4), filtered, and thesolvent was removed by rotary evaporator in vacuo. The residue was subjected to preparative TLC(hexane/ethyl acetate = 5/1) to give the pure productGeneral procedure: A flame-dried 25-mL Schlenk flask equipped with a magnetic stir bar was charged with Pd(OAc)2 (11.2 mg, 0.05 mmol, 10 mol %), copper(II) pivalate (400 mg, 1.5 mmol, 3.0 equiv), Cs2CO3 (163 mg, 0.5 mmol, 1.0 equiv), pyridine N-oxide (190 mg, 2.0 mmol, 4.0 equiv), and CuBr (7 mg, 0.05 mmol, 10 mol %). The flask was fitted with a rubber septum, evacuated, and refilled with argon (repeating three times). Dioxane/DMSO (19:1, 4.0 mL) and benzothiazole (67.3 mg, 0.5 mmol, 1.0 equiv) were added via syringes under an atmosphere of N2. The septum was then replaced by a Teflon-coated screw cap under N2. The reaction mixture was stirred at room temperature for 15 min and then in a preheated oil bath (at 110 C) for 12 h, cooled down to room temperature, diluted with DCM (15 mL) and filtered through a Celite pad. The filtrate was then washed twice with 10-20 mL of DCM. The combined organic extracts were washed with 5 mL of saturated NH4Cl aq solution (containing 1% v/v ammonium hydroxide) to remove the residual copper(II). The blue aqueous phase was extracted with DCM (15 mL×3). The combined organic phase was dried over Na2SO4, concentrated under vacuum, and purified by column chromatography on silica gel (eluent: DCM/acetone=20:1) to provide the desired product 3a as a pale yellow solid (75 mg, 67% yield).

Molecular Weight:169.63
XLogP3:3
Hydrogen Bond Acceptor Count:2
Exact Mass:168.9752980
Monoisotopic Mass:168.9752980
Topological Polar Surface Area:41.1
Heavy Atom Count:10
Complexity:131
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes