4-BROMOISATIN

4-Bromoisatin is a member of indoles. It has a role as an anticoronaviral agent.

Preparation of A33; Synthesis of 4-Bromoisatin (K-98) and 6-Bromoisatin (K-99); To a solution chloral hydride (50.0 g, 0.247 mol) in water (237mL) were successively added Na3-bromoaniline 10.00 g (58.13 mmol)Placed in a 1000 mL round bottom flask, Add 500mL of water, To the mixture was added 64.41 g (453.43 mmol) of anhydrous sodium sulfate, And hydroxylamine hydrochloride (13.33 g, 191.84 mmol)Then add 2mol / L hydrochloric acid solution 10mL, Stirred at room temperature for 5 min, Finally, 10.58 g (63.95 mmol) of chloral hydrate was added.The reaction mixture was stirred at room temperature for 15 min, And then heated under reflux at 90 ° C for 2 h.TLC detection of raw materials disappeared, Then cooled to room temperature, Filter, Vacuum drying, A pale yellow solid of 12.90 g was obtained. 40 mL of concentrated sulfuric acid was added to a 100 mL round bottom flask, 12.90 g of a yellow solid was slowly added to concentrated sulfuric acid at 50 ° C, After the addition of the reaction at 65 ° C for 30 min.After completion of the reaction, the mixture was cooled to room temperature, The reaction mixture was then poured into an ice-water mixture, Stirring for 30min, Filter the red solid, Vacuum drying oven, Petroleum ether: ethyl acetate = 5: 1, 200 mesh silica gel column chromatography, 4-bromoindole diketone 7.42 g, yield 51percent.3-bromoaniline 10.00g (58.13mmol) was put into a 1000 ml round bottom flask. Add 500 ml water. Under stirring condition, add anhydrous sodium sulfate 64.41g (453.43mmol) and hydroxylamine hydrochloride 13.33g (191.84mmol), then add 2 mol/L hydrochloric acid solution 10 ml, stir at room temperature 5min, finally adding chloral hydrate 10.58g (63.95mmol). The reaction mixture stirring at the room temperature 15min, then 90 °C heating under reflux 2h. TLC detection raw material disappears, then cooling to room temperature, filtered, vacuum drying, to obtain light yellow solid 12.90g.General procedure: To a solution of 120mL water, chloral hydrate (8.93g, 0.054mol), anhydrous sodium sulfate (130g, 0.40mol), aniline or substituted aniline 5 (0.05mol), hydroxylammonium chloride (10.98g, 0.158mol) and concentrated hydrochloric acid (43mL) were added respectively. Subsequently, the resulting suspension was heated to 90°C for 5min and cooled to room temperature. After filtration and washing with water (2×20mL), the crude material was obtained. The crude was added in batches to a 250mL, three mouth flask filled with concentrated sulfuric acid (32.6mL) at the temperature of 65°C and then heated up to 80°C for 20min. The reaction solution was cooled to room temperature and poured onto 500g of ice water and stirred vigorously for 4h. Intermediates 6a–i were isolated by filtration, washing with water, and recrystallization from ethanol with yields from 25.7percent to 73.2percent.General procedure: Indoles 1 (0.5 mmol), DMSO (3mL) and ISulfuric acid (1 L) was heated in a 3 L beaker on a hot plate to 60 °C and then removed. The dry isonitrosoacetanilide 2a-f was added in portion with stirring over 30 min so that the temperature did not exceed 65 °C. The mixture was then heated to 80 °C for 15 min, allowed to cool to 70 °C and cooled on ice. The solution was poured onto crushed ice (5 L) and left to stand for 1 h before filtering the orange-red precipitate. The product was washed by stirring with water (400 mL) and filtered to give a mixture of 3a-f and 4a-f. The crude product was dissolved in a solution of NaOH (20 g) in water (200 mL) at 60 °C, and then acidified with acetic acid (60 mL). After standing 0.5 h and cooling to 35 °C, the 4a-4f precipitate was filtered and washed with water (50 mL). The combined filtrate and washings were acidified with conc. HCL (60mL) and, after standing for 2 h at 5 °C, the 3a-f precipitate was filtered off and washed with water (50 mL). Yields: 3a: 27percent, 3b: 14percent, 3c : 29percent, 3d: 22percent, 3e: 33percent, 3f : 31percent, 4a: 56percent, 4b: 64percent, 4c: 53percent, 4d: 59percent, 4e: 49percent, 4f : 51percent.Take 40mL concentrated sulfuric acid was added to a 100mL round bottom flask, 12.90 g of a yellow solid was slowly added to concentrated sulfuric acid at 50 ° C, After completely adding 65 reaction 30min. After the reaction was cooled to room temperature, The reaction mixture was then poured into an ice-water mixture, stirred for 30 min, and filtered with suction to give a red solid.Dried under vacuum oven, petroleum ether: ethyl acetate = 5: 1, 200 mesh silica gel column chromatography, 4 - Bromoindole dione7.42 g, yield 51percent.

Molecular Weight:226.03
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:224.94254
Monoisotopic Mass:224.94254
Topological Polar Surface Area:46.2
Heavy Atom Count:12
Complexity:241
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes