5-Bromoisatoicanhydride

Off-white to salmon powder

5-bromoisatin (II) (20.0 g, 88.49 mmol) was dispersed in dichloromethane (300 mL)At room temperature in batches to join betweenChloroperoxybenzoic acid (22.91 g, 132.73 mmol) and reacted at room temperature2h, TLC detection, the reaction is completed. After cooling to 10 ° C and stirring continued, the sodium bisulfite was added dropwise Solution until the starch test paper does not change color, spin to dichloromethane, add 50mL water and residual mixture of mixed Stir, and add saturated saturated sodium bicarbonate solution to no bubbles, filter, a small amount of water to wash, Dried at 50 ° C to obtain 20.99 g of 5-bromoisoin anhydride (III) in a yield of 98percent.Compound 1 ((500 mg, 2 . 2mmol) was suspended in 10 ml of dry methylene chloride, at zero-degree celsius added meta-chloroperoxybenzoic acid (0.76g, 4 . 4mmol, 85percent). Stirred under room temperature for 2 hours. TLC (CH a) Preparation of 6-bromo-1H-benzo[d][1, 3]oxazine-2, 4-dione A solution of 2-amino-5-bromo-benzoic acid (280 g, 1.3 mol) in acetonitrile (1.3 l) was warmed up to 50-55° C. Pyridine (206 g, 2.61 mol) and a solution of triphosgene (128.8 g, 0.43 mol) in dichloromethane (720 ml) were simultaneously added dropwise. After completion of the addition, the mixture was stirred at 50-55° C. for an additional 2 h. The solvent was removed under reduced pressure and water was added. The precipitate was collected by filtration, successively washed with water and chilled dichloromethane, and then dried under vacuum to afford the desired product 6-bromo-1H-benzo[d][1, 3]oxazine-2, 4-dione (304 g, 98percent). This material was used in the next step without further purification.To a solution of 25 g (116 mmol) of 2-amino-5-bromobenzoic acid (3a) in 350 mL of THF was added 24.4 g (82 mmol) of bis(trichloromethyl) carbonate was added, and the resulting suspension was stirred at reflux temperature for 4 h. The reaction mixture was poured onto ice, and the precipitate was collected by filtration, washed with methanol and dried to afford 27.1 g (96percent) of 6-bromo-2H-3, 1-benzoxazine-2, 4(1H)-dione as a white powder. The 2-amino-5-bromobenzoic acid (10.00g, 46 . 29mmol) dissolved in tetrahydrofuran (100 ml) and triphosgene was also added (9.80g, 33 . 00mmol) under nitrogen atmosphere which is heated to 80 °C stirring 4 hours. Cooling to room temperature, the reaction solution the ice water (120 ml) in, filtering, the filter cake are sequentially water, ether washing, drying, get white solid (10.6g, 94.6percent).b) A 500 mL single neck round-bottomed flask equipped with a football-shaped PTFE stirring bar (16 mm × 37 mm) was chargedwith 2-amino-5-bromobenzoic acid (10.0 g, 46.3 mmol, 1.0 equiv) followed by the addition of tetrahydrofuran (230 mL, 0.2 molar) and solid triphosgene (13.7 g, 46.3 mmol, 1.0 equiv)resulting in a suspension. The reaction vessel was placed into afitted metal heating mantle and the neck was equipped with a24/40 Liebig condenser. The suspension was stirred (500 rpm)and the heating mantle set to 70 °C. The suspension becamehomogenous before a white solid precipitated out after about30 minutes at 70 °C. The heterogeneous reaction mixture wasaged for 12 hours then cooled to room temperature (25 °C). Theslurry was poured into a 600 mL beaker equipped with overheadmechanical stirrer (PTFE 75 mm paddle) containing250 mL of deionized water. With vigorous stirring, the mixturebecame homogenous followed by precipitation of a pale whitesolid. The solid was collected by vacuum filtration on aBüchner funnel (7.6 cm diameter) with Whatman 1 filter paper(70 mm) and air pulled through for 5 minutes. The material was transferred to a 250 mL Erlenmeyer flask equipped with cylindricalstir bar and 50 mL of methanol was added. The slurrywas stirred for 10 minutes and then collected by vacuum filtration.The filter cake was dried under vacuum (0.1 mmHg at 25 °C) for 12 hours to afford 9b as a white powder (90percent yield).Physical characteristics of 9b: white powder with 95.4percent purityas determined by quantitative 1H NMR using maleic acid as theinternal standard; mp > 270 °C; IR (solid) cm−1: 3170, 1751;1H NMR (DMSO-d6, 400 MHz) δ 11.86 (s, 1H, N-H), 7.98 (d, J = 2.3 Hz, 1H, Ce-H), 7.88 (dd, J = 8.7, 2.3 Hz, 1H, Cd-H), 7.19 (d, J = 8.7 Hz, 1H, Cf-H); 13C NMR (DMSO-d6, 100 MHz) δ 158.8 (s, Ca), 146.7 (s, Cb), 140.6 (s, Cc), 139.3(d, Cd), 130.5 (d, Ce), 117.6 (d, Cf), 114.5 (s, Cg), 112.4 (s, Ch); HRMS (ESI): calcd for [C8H4BrNO3 + Na]+ 263.926677;found: 263.926475; anal. calcd for C8H4BrNO3: C, 50.34; H, 3.90; found: C, 49.98; H, 3.80.To a dry, 4-L round bottom flask was added [175] g [(810 MMOL) OF 2-AMINO-5-] bromobenzoic acid (19), triphosgene (83 g, 278 [MMOL), ] and dioxane (3 L). The suspension was stirred under N2 and heated to reflux. The reaction was found to be complete by TLC and NMR after stirring at reflux for 3 h, but did not become homogenous at any time. After cooling to room temperature, the reaction was filtered and the precipitate washed with ether. The solid was dried in the vacuum oven at 40 [°C] to afford 5-bromoisatoic anhydride (20, 151. 1 g, 72percent) as a white solid [:APOS;H NMR] [(DMSO-D6) 8] 7.29 (d, J= 8.7, [1H), ] 7.91 (dd, [J = 2.] 5, 8. 7, [1H), ] 8.09 (d, J= 2.3, 1H).The reaction was carried out in a round-bottom flask fittedwith a magnetic stirrer bar and a rubber septum with aneedle as vent. To a solution of 1.00 g isatin (3, 6.8 mmol)in 95 cm3 acetonitrile, a solution of 6.05 g NBS (34 mmol)in 40 cm3 acetonitrile was added at temperature 0 C. Nextreaction was continued for 22 days at ambient temperature, with access to air. The separated solid was collected byfiltration and washed with acetonitrile (2 9 10 cm3). Thepure product was obtained as a yellow solid in 77 percent yield.A. Bromine (35 mL, 660 mmol) was added dropwise to a suspension of isatoicanhydride (100 g, 610 mmol) in 1.6 L water at 50 °C. This temperature was maintained for an additional 2 hours. After cooling the solution to room temperature, the solid was filtered and washed twice with water and twice with acetone, yielding 125.6 g (85percent) 6-hromo-lH-benzo[d][l, 3]oxazine-2, 4-dione as a pink solid.

Molecular Weight:242.03
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:240.93746
Monoisotopic Mass:240.93746
Topological Polar Surface Area:55.4
Heavy Atom Count:13
Complexity:256
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes