4-Chloro-2-iodophenol

Synthesis Example 22 1) Compound) : 4-Chloro-2-iodophenol (Tetrahedron, 1995, 51, 8555) 2-Amino-4-chlorophenol (ex Aldrich) (50g 0. 35mol) was dissolved in 2.5 M hydrochloric acid (500ml), cooled to 0 °C and a solution of sodium nitrite (25.3g, 0. 37mol) in water (50 ml) was slowly added over 20 minutes at 0-5 °C, stirred for 30 minutes, then a solution of potassium iodide (70g, 0.42 mol.) in water (100ml) was added slowly at 0 °C. The reaction mixture was then allowed to warm to 10 °C over 3 hours. The product was then extracted with ethyl acetate (200ml), washed with 10percent sodium bisulphite, water, and was dried over magnesium sulphate and evaporated down to dryness. The product was purified by column chromatography with 5percent ethylacetate in hexane to give an orange solid. wt. 62g. 70percent yield.To a solution of 2-amino-4-chloro-phenol 4a (50 g, 0.35 mol) in HC1 (2.5 mol, 500 mL) was added drop-wise a solution of sodium nitrite (25.25 g, 0.35 mol) in water (50 mL) at 0 °C. The mixture was stirred at this temperature for 30 min. Then a cooled solution of KI (70 g, 0.42 mol) in H2O (100 mL) was slowly added at 0 °C. After addition, the mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was diluted with ethyl acetate (200 mL) and the separated aqueous phase was extracted with ethyl acetate (100 mL x 3). The combined organic fraction was washed with Nac) ETHYL 3- (5-CHLORO-1-BENZOFURAN-2-YL) benzoate A stirring solution of 4-chloro-2-iodoanisole (2.68 g, 10 mmole) in dry DICHLOROMETHANE (60 ML) was treated with boron tribromide (15.0 ml, 1 M solution in DICHLOROMETHANE) at room temperature. The reaction was run overnight before being quenched with 100 ml of water. The resulting mixture was extracted with two portions (250 ML) of dichloromethane, the organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by flash silica gel column chromatography yielded the title compound as a solid (2.5 g, 100percent). A stirring solution of the above 4-chloro-2-iodophenol (0.75 g, 2.96 MMOLE), ethyl 3-ethynylbenzoate (0. 566 g, 3.25 mmole) and triphenylphosphine (59 mg, 0.225 mmole) in 15 ml of dry triethylamine was degassed and treated with Cul (5.7 mg, 0.03 mmole) and Pd (PPh3) 2CI2 (42 mg, 0.06 mmole). The resulting mixture was heated at 90 °C overnight, cooled to RT and concentrated in vacuo. Preparative HPLC (CH3CN 60percent- 98percent over 10 minutes) yielded the title product (0.463 g, 52percent) as a white solid. MS (ES) m/e 301.2 (M+).To 4-Chloro-2-iodo-1-methoxy-benzene (5.00 g, 18.6 mmol) in an ice bath under argon was added dropwise neat BBrGeneral procedure: The general method for ultrasonically assisted brominationreaction is almost similar to conventional reaction as mentionedabove. A centimolar (0.01 mol) organic substrate (phenols, anilines, or acetanilides), 0.001 mol potassium halide(KBr), about 50 mg of dilute KHSO4, and hypervalent Cr(VI) reagent (IQCC or IQDC) were suspended in about30 mL solvent (DCE or ACN) in a previously cleaned roundbottom(R.B) flask placed in a sonicator. The reaction mixtureis sonicated at room temperature about 30–40 min. Progressof the reaction was monitored by TLC technique. Workupprocedure after completion of the reaction mixture is similarto the one described previously.

Molecular Weight:254.45
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:253.89954
Monoisotopic Mass:253.89954
Topological Polar Surface Area:20.2
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes