2-Chloro-5-iodobenzoic acid

white to light yellow crystal powder

123 g of 2-chloro-5-aminobenzoic acid was added to 2000 g of a 20percent aqueous solution of sulfuric acid, and the temperature was maintained at 0 to 10 ° C. An aqueous solution of sodium nitrite (51 g of sodium nitrite dissolved in 200 g of water) was added dropwise, The reaction solution was solid, TLC (PE / EA: 1/3). After the reaction was completed, 1.2 g of urea was added, cooled to 0 ° C with stirring, and potassium iodide solution (130 g of KI dissolved in 500 g of water) was rapidly added, Stir until no bubbles continue to stir for 30min, filter, 200g washed to get brown solid;The solid was dissolved in 400 g of ethyl acetate, washed with 300 ml of 1N hydrochloric acid, 300 ml of 10percent sodium hydrogen sulfate, 400 ml of saturated brine, dried over magnesium sulfate, dried at 50 ° C under reduced pressure to obtain a crude product, and 400 ml of toluene was added at 80 ° C for 1 h, Cooling 0 ~ 5° C crystallization 1h, pumping 50° C under reduced pressure drying, To give a pale yellow solid2-chloro-5-iodobenzoic acid 191 g was 99.6percent pure and the yield was 93.7percent.1. Synthetic routeamong them, the condition (a) is LiTMP, THF, -78 to -60 C, 2 to 3 h / CO 2 , -60 to -50 C, 2 to 3 h.2, the synthesis step (1) After the reaction vessel is washed and dried, High-purity ultra-dry nitrogen is used as the reaction shielding gas. Pay attention to removing the air in the reaction vessel and protect the nitrogen ball. (2) Add 60 mL of ultra-dry tetrahydrofuran (THF) containing molecular sieve under nitrogen protection, then anhydrous diisopropylamine (30 mmol, 8.41 mL) was taken under nitrogen. Magnetically stir and put in a Dewar Add 300 ± 5 mL of ethyl acetate to the Dewar, slowly add crushed dry ice to lower the reaction temperature below -20 C. Stir at low temperature for 10 min; (3) Under the protection of nitrogen, add n-butyl lithium (2.5 M, 30 mmol, 12 mL) to the reaction vessel. Stirring at a low temperature of -20 C for 30 min; (4) Immediately after the addition of crushed dry ice in the ethyl acetate solvent of the Dewar, the cooling temperature is lowered to -78 to -60 C. Adding substituted iodobenzene A with different halogen structures (eg 2, 4-dichloro-1-iodobenzene, 2-trifluoromethyliodobenzene or 4-chloroiodobenzene, added in an amount of 2.72 mL, 2.9 mL or 2.4 mL, respectively), 20 mmol, the reaction was stirred at a low temperature of -78 C for 2 h. Excess milled dry ice is then added to the reaction vessel under nitrogen protection.The reaction is carried out at a low temperature of -50 C or lower for 2 to 3 hours. Remove the Dewar bottle until the temperature of the reaction vessel rises to room temperature; The reaction endpoint was detected by TLC [developing agent: V (petroleum ether) / V (ethyl acetate) = 1 / 1]; (5) After the reaction is completed, tetrahydrofuran and other volatile solvents are removed under reduced pressure at 45 C. Slowly add 50mL of deionized water. Slowly add 4M HCl solution under magnetic stirring to adjust the pH of the system to 1~2. Extracted three times with ethyl acetate, drying through anhydrous MgSO4, and the mixture was filtered and evaporated to give a crude brown solid. Purified by silica gel column chromatography [eluent: V ( petroleum ether) / V (ethyl acetate) = 16 / 1] obtaining the compound intermediate B (B1, B2, B3), white or light gray solids with yields of 91%, 14% and 45%, respectively.To a solution of In the l00mL hydrothermal synthesis reactor, Add sodium hydroxide (3 mmol), water (5 mL), stir and dissolve, Add General procedure: To a stirred suspension of General procedure: To a stirred suspension of

Molecular Weight:282.46
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:281.89445
Monoisotopic Mass:281.89445
Topological Polar Surface Area:37.3
Heavy Atom Count:11
Complexity:163
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes