exo-5,6-Dehydronorcantharidin

white crystalline powder or chunks

In a 250-mL three-necked round-bottom flask under argonatmosphere, maleic anhydride (5.0 g, 50.99 mmol) andfuran (5.2 g, 76.5 mmol) were dissolved in 30 mL oftoluene. The mixture was stirred for 24 h of heating underreflux. A white precipitate formed during this time. Thesolid was collected by filtration and washed two times withcold diethyl ether. The filtrate was reduced by rotary evaporationand crystallized from MeOH/diethyl ether. Yield:colorless crystals, 8.22 g (97percent).1H NMR (400 MHz, CDCl3, 25 °C) δ = 6.57 (s, 2H, H5, H6), 5.45 (s, 2H, H4, H7), 3.18 (s, 2H, H3a, H7a). 13C NMR(100 MHz, CDCl3, 25 °C) δ = 170.1 (2C=O), 137.2 (C5, C6), 82.4 (C4, C7), 48.9 (C3a, C7a).Furan (45ml, 600mmol) and maleic anhydride (3g, 200mmol) were stirred together in ether (150ml), and themixture was refluxed at 38 °C for 48 h. The white precipitatewas collected and dried under suction. Yield 32.6 g, 96.3percent.mp 118-120 °C (117-119 °CMaleic anhydride (13.43 g, 136.9 mmol) was dissolved in furan (50 mL) at room temperature. This reaction was stirred at the same temperature for 3 h. A pure sample of exo-isomer 7 was obtained as a white solid after evaporating excess furan (21.6 g, 95percent) (m.p.= 112-113 °C). A solution of furan (40 mL, 550 mmol)and maleic anhydride (10 g, 102 mmol) were stirred together in ether (100 mL) at room temperature for 48 h, after which the white precipitate was collected to give 5 as a colorless solid, yield 93.3percent, mp 121–122 °C. Furancarboxylic (40 ml, 550mmol) and maleic anhydride (10g, 102mmol) soln., ether (100 ml) in, at room temperature, the reaction to 48 hours, after recovering a white precipitate, dried, colorless solid, yield 93.3percent, mp121-122 °C as compd. 5 is produced.Mixing furan in ether (furan) (40 ml, 550 mmol) and maleic anhydride (10 g, 102 mmol) and reacted at room temperature for about 48 hours. The precipitate was then collected and dried to give a colorless solid of compound 5(Yield: 93.3percent) having a melting point of about 121-122 °C, And its structure was identified by 1H-NMR and 13C-NMR. The spectral data were as followsSynthesis of Monomer 3: (1) A 250 mL round bottom flask was charged with a solution mixture of furan (10 g, 146 mmol), maleic anhydride (13 g, 100 mmol) and 100 mL toluene. This solution was left for two days at room temperature after which the precipitated product, exo-7-oxabicyclo[2.2.1]hept-5-ene-2, 3-dicarboxylic anhydride, was filtered and washed with cold toluene. Yield=90percent. A certain amount of maleic anhydride 1 was removed from the reagent bottle, Placed in a dry grinding research in the study, And then take electronic balance weighing small maleic anhydride 12, 021 g, Placed in a dry three-necked flask, plug the plug, add ether stirring, in the amount of 90mL ether when maleic anhydride completely dissolved.After the maleic anhydride was completely dissolved, 13 mL of furan was slowly added over a period of 13 minutes using a dropping funnel. Control the reaction at 38 ° C.A white solid appeared after 1 hour of reaction, and the longer the white solid was, the more the solid was.After 24 hours, the reaction mixture was suction-filtered to give compound 2 as a white solid, i.e., 5, 6-didehydro-norcantharidin.Dry weighing 17.459g, yield 85. 75percentTaken out from the reagent bottle was a certain amount of maleic anhydride. Place in a grinder to grind into fine particles. Then, use electronic balance for weighing comminuted maleic anhydride 12.021g. Place in a dry three-mouthed flask. Plug the mouths. Then add diethyl ether and stir. When diethyl ether quantity is 90 ml, maleic anhydride is completely dissolved. After maleic anhydride is completely dissolved, slowly add by dropping funnel 13 ml furan. Used time is 13 min. Control temperature at 38 °C to start reaction. After reacting for 1h, solid white precipitate out of solution, the longer the time the more white solid. After reacting for 24h, filtration, the white solid obtained compound 1, in other words 5-ene norcantharidin. Drying weighing to 17.46g, yield of 85.8percent.Remove a certain amount of maleic anhydride from the reagent bottle, place it in a dry study, and use an electronic balanceWeighed 12.021g of maleic anhydride, placed in a dry three-necked flask, plug the stopper, add ether stirring, in the ether amount of 90mL when the maleic anhydride completely dissolved. After the maleic anhydride was completely dissolved, add 13 mL of furan slowly with a dropping funnel for 13 min. The temperature was controlled at 38 ° C. After 1 h of reaction, the solution appeared white solid, and the longer the time, the more white solid. The reaction was carried out after 24 hours to obtain compound A as a white solid. Dry weighing 17.46g, the yield of 85.8percent.Is removed from reagent bottle amount of maleic anhydride, a dry finely in a mortar, and then weighed electronic balance finely divided maleic anhydride 12.021g, placed in a dry three-necked flask, stuffed plugs, plus diethyl ether was stirred, 90 mL of diethyl ether in an amount of maleic anhydride was completely dissolved. After the maleic anhydride was completely dissolved, the dropping funnel was slowly added 13 mL furyl, when 13 minutes (min, also abbreviated min). Controlling the temperature of the reaction was started at 38 . Solution occurred after 1 hour a white solid (hour, also abbreviated to H), and the more the longer a white solid. After 24h the reaction to suction filtration to give compound 1 as a white solid, i.e., 5, 6-didehydro to cantharidin. Drying weighed 17.459 g, 85.75percent yieldRemove a certain amount of maleic anhydride from the reagent bottle and place it in a dry study.And then the electronic balance weighed into a small amount of maleic anhydride 12.021g, Placed in a dry three-necked flask, plug the plug, add ether stirring, When the amount of ether is 90 mL, the maleic anhydride is completely dissolved. After the maleic anhydride is completely dissolved, Add 13 mL of furan slowly with a dropping funnel for 13 min. The temperature was controlled at 38 ° C.After 1 h reaction, the solution appeared as a white solid, And the longer the timeThe more white solids.The reaction was carried out after 24 hours to obtain compound A as a white solid.Dry weighing 17.46g, the yield of 85.8percent.Remove a certain amount of maleic anhydride from the reagent bottle, place it in a dry grinding solution and grind it finely, and then weigh 12, 021g of finely divided maleic anhydride on an electronic balance and place it in a dry three-necked flask, Plug, add ethyl ether stirring, the maleic anhydride completely dissolved in the amount of ether 90mL.After maleic anhydride is completely dissolved, slowly add 13 mL of furan with a dropping funnel for 13 min.The reaction temperature was controlled at 38 ° C.The solution appeared white solid after reaction for 1h, and the longer the white solid, the more solid.The reaction was filtered with suction until 24h to give Intermediate A, 5, 6-dihydro norcantharidin, as a white solid.Dry weighing 17.459g, yield 85.75percent.Melting point: 122-123 ° C, Rf: 0.52 (developing solvent: petroleum ether: ethyl acetate = 3: 1);Remove a certain amount of maleic anhydride from the reagent bottle, placed in a dry research in the fine grinding, and then weighed on a electronic balance fine maleic anhydride 12.021g, Placed in a dry three-necked flask, Plug the stopper, plus ether stirring, the amount of maleic anhydride in the ether is completely dissolved 90mL.After maleic anhydride is completely dissolved, slowly add 13 mL of furan with a dropping funnel for 13 min.The reaction temperature was controlled at 38 ° C.The solution appeared white solid after reaction for 1h, and the longer the white solid, the more solid.The reaction was filtered with suction until 24h to give Intermediate A, 5, 6-dihydro norcantharidin, as a white solid.Dry weighing 17.459g, yield 85.75percent. Melting point: 122-123 ° C, Rf: 0.52 (developing solvent: petroleum ether: ethyl acetate = 3: 1); 1HNMR (CDCl3) δ: 3.18 (s, 2H), 5.47 (s, 2H).The organic solvent used to dissolve the maleic anhydride in the above can also be used in addition to diethyl ether, and N, N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, acetonitrile and tetrahydrofuran A substitution; the reaction temperature may be between 35 ~ 45 .Dimethoxyl furan (4.67 g, 36.4 mmol) and diethyl fumarate (6.0 mL, 36.6 mmol) were in ethyl acetate (10 mL). The reaction mixture was stirred overnight at room temperature. Solvent was removed in vacuo and the residue was purified by column chromatography on silica gel (EtOAc/hexane 1:5) to yield 9.0 g of 2-1 (30.0 mmol, 83percent); RMaleic anhydride (20 g, 204 mmol), benzene (100 mL) and furan (15 mL, 205 mmol) are put into a 250 mL round-bottom flask in the presence of argon atmosphere one after another, which then are stirred at a room temperature for 24 hours. It is possible at this point to check that over the course of the reaction, products are precipitated in crystallization to form white slurry. The white slurry is filtered, washed with ether and vacuum dried to obtain FDA-anhydride (27.0 g, 160 mmol, 77percent of yield) in the form of white crystallized powder. The data of Maleic anhydride 12-9 (10 g, 0.102 mol) and furan 12-10 (7.0 g, 7.5 mL, 0.103 mol) were dissolved in toluene (50 mL) as described in Macromolecules 2008, 41, 719-726 and stirred for 20 h at RT. The formed crystalline Diels-Alder (D-A) adduct was filtered and washed with diethyl ether. Yield (7.55 g, 45 percent).