Related Products of 4179-19-5,Some common heterocyclic compound, 4179-19-5, name is 3,5-Dimethoxytoluene, molecular formula is C9H12O2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
A 3-necked round bottom flask was added 3,5-dimethoxytoluene (6.088g, 40mmol) and cyclohexane(28mL) under nitrogen.Was added dimethyl carbonate (30.3g,336mmol), at 60 deg.] Cand the reaction mixture was heated. After 15 minutes was added an excess of chlorosulfonic acid. By inserting the tubeof solid sodium hydroxide to remove HCl gas release. After the addition wascomplete, the reaction mixture was heated at 70-72 for one hour, then cooled toroom temperature. The solid was filtered off, washed with dimethyl carbonate /cyclohexane (1:1,20mL)and washed. The solid was dried under vacuum to give pure material (6.13g, 66%). To sulfonic acid (product fromthe above, 4.65g, 20mmol) and triethylamine(2.03g, 2.79mL) was added 2,4,6-trichloro-1,3,5triazine (cyanuric chloride, 3.69g, 20mmol)in (40 mL) in amixture of acetone-.The reaction mixture was heated at reflux for 20 hours, then cooled to room temperature. Thesolution was passed through a pad of Celite, and evaporated in vacuo to leave asolid, which was filtered off, washed with hexane. The product of cyanuric acidand hydroxides (cyanuric hydroxide) in a mixture of salt and triethylamine (was7.58 g) used in the next step without further purification. Fitted to acondenser (acetone – cooled with dry ice), 3-neck round bottom flask was addedthe mixture from step (was 7.58 g) and acetone (100mL). Thereaction mixture was cooled to -78 , ammonia gas intothe solution for 0.5hours. The reaction mixture was allowed to stand overnight, so that theammonia was slowlyevaporated, and then the solvent was evaporated. Water was added, the productwas extracted with DCM. The solvent was dried and evaporated to a mixture ofthe remaining solid and thick liquids. The solid was filtered off, washed withhexane, the remaining pure sulfonamide (3.23g,70%). To a round bottomflask was added 3,5-dimethyl-4-hydroxybenzoicacid (2.99g, 18mmol). Was added anhydrous DMF (20mL), and sodium hydride (1.8g, 45mmol). The reaction mixturewas stirred at roomtemperature for 1hour. Was added p-methoxybenzyl chloride (6.20g,39.6mmol), and the mixture was stirred at room temperature overnight (20 hours). Thereaction mixture was poured into water, acidified with 1N HCl and stirred for 1hour. The precipitated solid was filtered off, washed with water and hexane togive the pure B- cyclic structural unit (6.93g, 95%). The structural unitof the B- ring (6.93g, 17.1mmol) was dissolvedin a mixture of methanol(50mL) and tetrahydrofuran(50 mL) of. Waterwas added (20 mL) of potassium hydroxide (1.25g,22.2mmol). At 70 deg.] Cand the reaction mixture was refluxed for 24 hours. The solvent was evaporated in vacuo.Water was added, the reaction mixture was acidified with 1N HCl (pH4-5). Thesolid was filtered off, washed with water and hexanes. The yield was 4.61g (94%). Under nitrogen,above product (1.932g, 6.75mmol), and sulfonamidefrom above (1.04g, 4.5mmol) was added to a 3-neck round bottom flask. Dichloromethane was addedunder stirring (100mL). To this stirred mixture was addedN-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDCI.HCl, 1.36g, 7.09mmol), followed by addition of N, N- dimethylaminopyridine(2.06g, 16.9mmol). At roomtemperature the reaction mixture was stirred for 24 hours, then washed with 1N HCI, 2.5%NaOH and saturated sodium bicarbonate solution. The organic layer was dried andevaporated in vacuo to leave a residue, which was purified by silica gel (100g)column chromatography using 20-50% hexane in ethyl acetate in methylenechloride and methanol as the eluting 5% purification agent. Fractions 30-66afforded pure material (1.35g, 60%). Under nitrogen,compounds from the previous step(0.105g, 0.21mmol) was dissolved in tetrahydrofuran, cooled to -78 . N-butyllithium was added, and the reaction mixture wasslowly warmed to roomtemperature and stirredovernight (~ 14 hours).TLC showed incomplete conversion. The reaction mixture was quenched withsaturated ammonium chloride solution, extracted with ethyl acetate. The solventwas evaporated in vacuo, the remaining residue, which was purified by silicagel (15g) column chromatography adopt in 20-50% ethyl acetate in hexanes aseluent. Product was not pure enough, thus making use of another pillar, the useof hexane in 0.5% methanol as eluent. Finally, the material was purified bypreparative TLC. Under nitrogen compounds from the previous step(0.277 g of) was dissolved in trifluoroacetic acid (10mL), and the reaction mixture was refluxed (bath temperature 80 ) 4 days. The solvent wasevaporated in vacuo, the residue was dissolvedin 0.25N NaOH (20mL), and acidified with acetic acid. At this time, the solidhas precipitated. The solid was filtered off, washed with water, washed withhexane, and dried. 0.005g of pure substances isolated from the batch. 0.060gcompound isolated from another batch, which is not enough pure. The compoundwas further purified by preparative HPLC, to give pure 6,8-dimethoxy-3-(4-hydroxy-3,5-dimethylphenyl) -2H-1,2- benzothiazine 1,1-…
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3,5-Dimethoxytoluene, its application will become more common.
Reference:
Patent; RESVERLOGIX CORP; HANSEN, H; (62 pag.)CN103319408; (2016); B;,
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