Benzarone

Pale Yellow Solid

Benzarone is a member of 1-benzofurans.|Benzbromarone is a nonpurine xanthine oxidase inhibitor used for the treatment of gout, but never approved for use in the United States because of concerns over reports of acute liver injury and deaths with its use.

In a RBF/SB (50 mL), benzofuran (12; 1.00 g; 3.57 mmol) was diluted with DMF (18 mL) and NaSEt (455 mg) was added. The mixture was heated (125-130 °C; 1.0 h). Next, the mixture was quenched (2 vol NH4CI aq) and extracted with EtOAc (4 x 75 mL). The organic phase was washed with HEthanethiol (8 mL) was added dropwise to a suspension of sodium hydride (640 mg, 16.0 mmol) in dry THF (15 mL) under ice-water bath. Stir for 5 minutes. A large number of solid precipitation. The solvent was distilled off under reduced pressure. DMF (20 mL) was then added to the residue. The reaction solution A was obtained. A solution of compound 2 (3.0 g, 10.7 mmol) in DMF (20 mL) was added dropwise to reaction solution A. Followed by stirring at 110°C for 3 hours. Cooled to room temperature. Water (120 mL) was added. Extraction with ethyl acetate (60 mL x 3). The combined organic phases were washed with saturated brine (30 mL x 2). Dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The product was purified by column chromatography (200-300 mesh silica gel, ethyl acetate: petroleum ether = 1:50 to 1: 6) to obtain (2-ethylbenzofuran-3-yl)(4-hydroxyphenyl)methanone (3) (2.2 g). The yield was 77.2percent.(1) To a 500 mL reaction vessel, 112 g of chloroform, 36 g of 2-ethylbenzofuran, and 72 g of p-methoxybenzoyl chloride were added, and then a feed tube was washed by further adding 50 g of chloroform. When cooling to 10-30 ° C, then the first addition of Lewis acid 17g; cooling to the last temperature range for the second time plus Lewis acid 17g; cooling to the last temperature range for the third time to add Lewis acid 17g, a total of 51g of Lewis acid was added, and the temperature was kept constant at 15-30 ° C for 4 h;(2) After the completion of the heat preservation reaction, tap water is quenched; acidified with 110 g of dilute hydrochloric acid (10percent).Then, the heating is started to 65-70 ° C, and the stirring is kept for 0.5 hour; the stirring is stopped for 0.5 hours, and then the liquid is separated, and the material in the reactor is washed twice with hot water of about 70 ° C.The washed material is sucked into the reactor for distillation under reduced pressure; after the distillation is completed, it is slightly lowered.The temperature was about 65 ° C, and 35 g of methanol was further added thereto, and the mixture was cooled, cooled, and crystallized by freezing, filtered, and dried to obtain 60 g of a benzalkonone intermediate (white solid).(3) Add 140g of chloroform, benzalkonone intermediate dry product 60g, add 30g of chloroform rinse feed pipe to the clean 500ml reactor; pass the cooling water to reduce the temperature inside the reactor, when the temperature is stable at 15-30 At a temperature of °C, 43g of Lewis acid was added at a time, and stirred under the action of cooling water for 0.5 hours; after the completion of the stirring, the temperature was raised to 90-95 ° C, and the heat preservation was started.Should be 2-3h; after the reaction is completed, pass the cooling water and start to cool down to 20-30 °C;(4) After cooling for 3 hours, add water to quench; add 130 g of dilute hydrochloric acid (10percent) to acidify, stir for half an hour, then warm to 90-95 ° C, stir for half an hour to separate the liquid; after the liquid separation, use 70 ° C or so Washed twice, will wash the finished materialDistillation was carried out, acetonitrile and petroleum ether were added to cool and crystallize, and after filtration, it was rinsed with an appropriate amount of solvent to obtain a crude benzalkonium. Then, 40 g of the obtained benzalkonone crude product and 70 g of acetonitrile and petroleum ether were charged into the reactor, activated carbon was added, and the temperature was immediately maintained by heating and refluxing for 0.5 hour.It was filtered with a precision filter under air pressure, cooled, crystallized, filtered, and dried to obtain 35 g of benzalkonone, and the yield of the final product was 68.2percent.(b) Complexes of aluminium chloride with 2-ethyl-3-(4-methoxy- and 4-hydroxybenzoyl)benzofurans Into a first reactor, 280.3 g (1 mol) of crystallized 2-ethyl-3-(4-methoxybenzoyl)benzofuran and 588 g of toluene were introduced. The solid was dissolved by heating, with stirring, the reactants were dried azeotropically and the solution obtained was cooled to 10° C. Into a second perfectly dry reactor, 253 g of anhydrous toluene were introduced followed, with cooling, by 241 g (1.8 mol) of anhydrous aluminium chloride. The temperature of the mass was adjusted to 0°+- 5° C. and the toluene solution of 2-ethyl-3-(4-methoxybezoyl)benzofuran prepared in the first reactor was added. The addition took approximately 90 minutes, with external cooling so as not to exceed 15° C. The solution produced in this manner, containing the 1:1 complex of aluminium chloride with 2-ethyl-3-(4-methoxybenzoyl)benzofuran was then kept at a temperature below or equal to 15° C. Into the first reactor 356 g of anhydrous toluene were introduced and then stirred and placed under a residual pressure of 300-350 mm Hg, before the toluene was heated to reflux (mass temperature:84°+- 1° C.). The vacuum and the temperature were stabilized, the system was set for distillation and then a gradual addition of the solution in the second reactor, containing the complex, was started (total addition time of complex:4 to 5 h; toluene-containing distillate:about 1400 g). The second reactor was rinsed with 48 g of anhydrous toluene and the mass was heated to 100° C. while the reduced pressure in the reactor was gradually lowered (toluene-containing distillate: approximately 105 g), which provoked the formation of the 2:1 complex of aluminium chloride with 2-ethyl-3-(4-hydroxybenzoyl)benzofuran. In this manner, a toluene solution of a molecular complex of aluminium chloride with 2-ethyl-3-(4-hydroxybenzoyl)benzofuran was obtained.In this manner, 233 g of crude 2-ethyl-3-(4-hydroxybenzoyl) benzofuran, or benzarone, were obtained. Yield:83+- 3percent [based on 2-ethyl-3-(4-methoxybenzoyl)benzofuran].(1) To a 500 mL reaction vessel, 112 g of chloroform, 36 g of 2-ethylbenzofuran, and 72 g of p-methoxybenzoyl chloride were added, and then a feed tube was washed by further adding 50 g of chloroform. When cooling to 10-30 ° C, then the first addition of Lewis acid 17g; cooling to the last temperature range for the second time plus Lewis acid 17g; cooling to the last temperature range for the third time to add Lewis acid 17g, a total of 51g of Lewis acid was added, and the temperature was kept constant at 15-30 ° C for 4 h;(2) After the completion of the heat preservation reaction, tap water is quenched; acidified with 110 g of dilute hydrochloric acid (10percent).Then, the heating is started to 65-70 ° C, and the stirring is kept for 0.5 hour; the stirring is stopped for 0.5 hours, and then the liquid is separated, and the material in the reactor is washed twice with hot water of about 70 ° C.The washed material is sucked into the reactor for distillation under reduced pressure; after the distillation is completed, it is slightly lowered.The temperature was about 65 ° C, and 35 g of methanol was further added thereto, and the mixture was cooled, cooled, and crystallized by freezing, filtered, and dried to obtain 60 g of a

Benzarone is an EYA (Eyes Absents), multifunctional protein involved in organogenesis, inhibitor which makes it a potent anticancer agent. EYA~"s are over expressed in ovarian and breast cancers. As well it is involved in the synthesis of Human Uric Acid Transporter 1 inhibitors which may be used to treat kidney diseases.

Molecular Weight:266.29
XLogP3:4.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:266.094294304
Monoisotopic Mass:266.094294304
Topological Polar Surface Area:50.4
Heavy Atom Count:20
Complexity:346
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes