1-BROMO-4-IODO-2-(TRIFLUOROMETHYL)BENZENE

A solution prepared by the addition of 4-bromo-3- (trifluoromethyl)aniline (500 mg, 2.08 mmol) to a warmed mixture of concentrated HCharged 35percent aqueous hydrochloric acid solution (47gm., 0.44 moles), water (95gm) and 5-amino-2-bromo-benzotrifluoride (20gm., O.083moles) in the reaction flask. Cooled reaction mass to 5°C and charged chilled 15percent aqueous solution of sodium nitrite (40gm., 0.09moles) in small portions maintaining 0°C. After complete addition of sodium nitrite, stirred the reaction mass at 0°C to 5°C for 1.0 hour to get diazonium salt solution. Then charged an aqueous solution of potassium iodide (14gm., 0.08 moles) and further heated the reaction mixture to reflux point using a reflux condenser until no more gas is evolved then allowed to cool and stand undisturbed until the heavy organic layer has settled. The title compound was isolated. Yield (percent): 75percentA solution prepared by the addition of 4-bromo-3- (trifluoromethyl)aniline (500 mg, 2.08 mmol) to a warmed mixture of concentrated H2SO4 37% w/w (0.51 mL, 4.6 eq) and water (2.3 mL, C=3.4M) was cooled with vigourous stirring to -10C (ice-salt bath). A slurry of the aniline hydrogen sulfate precipitated. Then, a solution of NaNO2 (158 mg, 1.1 eq) in 1.06 mL (C=2.15M) of water was added dropwise. The mixture was stirred for 40 min at -8C before a solution of KI (495 mg, 1.43 eq) in water (0.4 mL, C=8M) and copper powder (4 mg) were added. The brown reaction mixture was allowed to warm to r.t. by removal of the ice bath, stirred for 30 min, and then, the reactants were heated at reflux (102C) for an additional lh. After cooling to r.t. and diluting with water, the aqueous layer was extracted with DCM (3><20mL). Extracts were washed with a saturated Na2S2O3 solution (20mL), with brine (20mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was chromatographed (hexane) to afford theiodinated compound in 93% yield (679 mg) as an orange solid. 1H NMR (300 MHz, CDC13) delta 7.98 (d, J = 2.3 Hz, 1H), 7.69 (dd, J = 8.4, 2.1 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDC13) delta 142.1 (CH), 136.7 (q, J = 5.6 Hz, CH), 136.6 (CH), 132.0 (q, J = 31.7 Hz, C), 121.9 (q, J = 274.2 Hz, C), 120.0 (q, J = 1.7 Hz, C), 91.8 (C)Charged 35% aqueous hydrochloric acid solution (47gm., 0.44 moles), water (95gm) and 5-amino-2-bromo-benzotrifluoride (20gm., O.083moles) in the reaction flask. Cooled reaction mass to 5C and charged chilled 15% aqueous solution of sodium nitrite (40gm., 0.09moles) in small portions maintaining 0C. After complete addition of sodium nitrite, stirred the reaction mass at 0C to 5C for 1.0 hour to get diazonium salt solution. Then charged an aqueous solution of potassium iodide (14gm., 0.08 moles) and further heated the reaction mixture to reflux point using a reflux condenser until no more gas is evolved then allowed to cool and stand undisturbed until the heavy organic layer has settled. The title compound was isolated. Yield (%): 75%A solution prepared by the addition of 4-bromo-3- (trifluoromethyl)aniline (500 mg, 2.08 mmol) to a warmed mixture of concentrated H2SO4 37% w/w (0.51 mL, 4.6 eq) and water (2.3 mL, C=3.4M) was cooled with vigourous stirring to -10C (ice-salt bath). A slurry of the aniline hydrogen sulfate precipitated. Then, a solution of NaNO2 (158 mg, 1.1 eq) in 1.06 mL (C=2.15M) of water was added dropwise. The mixture was stirred for 40 min at -8C before a solution of KI (495 mg, 1.43 eq) in water (0.4 mL, C=8M) and copper powder (4 mg) were added. The brown reaction mixture was allowed to warm to r.t. by removal of the ice bath, stirred for 30 min, and then, the reactants were heated at reflux (102C) for an additional lh. After cooling to r.t. and diluting with water, the aqueous layer was extracted with DCM (3><20mL). Extracts were washed with a saturated Na2S2O3 solution (20mL), with brine (20mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was chromatographed (hexane) to afford theiodinated compound in 93% yield (679 mg) as an orange solid. 1H NMR (300 MHz, CDC13) delta 7.98 (d, J = 2.3 Hz, 1H), 7.69 (dd, J = 8.4, 2.1 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDC13) delta 142.1 (CH), 136.7 (q, J = 5.6 Hz, CH), 136.6 (CH), 132.0 (q, J = 31.7 Hz, C), 121.9 (q, J = 274.2 Hz, C), 120.0 (q, J = 1.7 Hz, C), 91.8 (C)Charged 35% aqueous hydrochloric acid solution (47gm., 0.44 moles), water (95gm) and 5-amino-2-bromo-benzotrifluoride (20gm., O.083moles) in the reaction flask. Cooled reaction mass to 5C and charged chilled 15% aqueous solution of sodium nitrite (40gm., 0.09moles) in small portions maintaining 0C. After complete addition of sodium nitrite, stirred the reaction mass at 0C to 5C for 1.0 hour to get diazonium salt solution. Then charged an aqueous solution of potassium iodide (14gm., 0.08 moles) and further heated the reaction mixture to reflux point using a reflux condenser until no more gas is evolved then allowed to cool and stand undisturbed until the heavy organic layer has settled. The title compound was isolated. Yield (%): 75%

Molecular Weight:350.90
XLogP3:4.1
Hydrogen Bond Acceptor Count:3
Exact Mass:349.84149
Monoisotopic Mass:349.84149
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes