Hexahydro-1H-isoindole-1,3(2H)-dione

white crystalline powder

REFERENCE EXAMPLE 4 A mixture of 1, 2-cyclohexanedicarboxylic anhydride (3 g; 19.5 mmol) and 29% aqueous ammonia (3.4 g) was heated and kept at an inner temperature of 180-190 C. for 2 hours to give cyclohexane-1, 2-dicarboximide. M.P. 132-136 C.General procedure: a) for compounds of formula (V) with G moiety, wherein L represents C=0, E, if present, is different from O, NH or N-(d-C3)alkyl (imide derivatives) To the appropriate dicarboxylic acid (Via) or acid anhydride (VIb) (0.05 mol) 25% aqueous ammonia (equivalent to 0.05 mol ammonia) and distilled water (10 ml) were added. The mixture was placed in a sand bath and heated until the water evaporates, and then it was heated for 1 hour at 180C. Crude products were purified by crystallization from methanol or 2-propanol.General procedure: DES ChCl/urea was synthesized as described in literature(Abbott et al. 2004). Briefly, choline chloride and urea with the molar ratio of 1:2 were stirred at 80 C for 1 h until a clear and transparent solution was formed (Fig. 1). The obtained DES was used without additional purification. Into a 25-mL round-bottom flask were added ChCl/urea (5.19 g, 20 mmol), phthalic anhydride (1.48 g, 10 mmol) and urea (0.60 g, 10 mmol) in successive, then the mixture was heated at 140 C for 1 h under vigorous stirring. The reaction progress was monitored by GC analysis. After reaction, the reaction mixture was cooled to room temperature, followed by addition of 2 mL of water. The DES was dissolved and the product was precipitated. The solid was collected by filtration and washed thoroughly with water. The white solid was dried thoroughly to afford the product in a yield of 84%. The DES was recovered by evaporation of water under vacuum, and subjected to next run. The product was received in a yield of yield of 95% in the second run.General procedure: To a solution of N-arylglycine esters 1 (0.3 mmol) in MeCN(2 mL) were added imides or amides 2 (0.2 mmol) and CuCl(2.0 mg, 0.02 mmol). Then, the reaction mixture was stirred at60 C under air atmosphere until the reaction was completed.Then, the resulting mixture was concentrated under vacuum, and the residue was purified by column chromatography (silicagel, petroleum ether/EtOAc as an eluent) to afford the correspondingproducts 3.(10)N-4-methylphenylglycine ethyl ester (0.3 mmol) under air atmosphere, A phthalimide compound (0.2 mmol) and cuprous chloride (0.02 mmol) were placed in a dry reaction tube with stirring magnets.Then, an acetonitrile solvent (2 mL) was added to the test tube, and the reaction tube was reacted in an air atmosphere at 60 C for 24 hours.After the reaction was completed, it was cooled to room temperature, and the solvent was distilled off under reduced pressure using a rotary evaporator.The residue is purified by column chromatography to give a pure pale yellow solid 3o.The yield was 96%.General procedure: To a suspension of corresponding cyclic imide 1a-1k (4mmol), potassium carbonate (4.4mmol) in DMF (5mL), 1-bromo-4-chlorobutane (1, 2-dibromoethane (5 eq) for 2l, 1-bromo-3-chloropropane for 2m, 1-bromo-5-chloropentane for 2n) (4.4mmol) was added dropwise at 0C. The mixture was stirred at room temperature overnight and then partitioned between ethyl acetate (EA, 20mL) and water (30mL). The organic layer was washed successively with water (3×30mL), saturated brine, and dried over anhydrous Na2SO4. The solvent was evaporated under vacuum and the residue was purified by column chromatography using petroleum ether(PE): EA (8:1) as eluent to give 2a-2n.General procedure: The reaction conditions and results are shown in Tables 1-4. A typical procedure isgiven for the reaction of 2-fluorocinnamyl acetate (1a), succinimide (2a), and phenol(3a) (Table 1, Entry 7). To a solution of [Pd(pi-allyl)Cl]2 (2.4 mg, 0.0065 mmol), DPPF (7.2 mg, 0.013 mmol), succinimide (2a) (58 mg, 0.59 mmol), phenol (3a) (49 mg0.52 mmol), and Cs2CO3 (169 mg, 0.52 mmol) in Toluene (0.8 mL) was added(Z)-2-fluoro-3-phenylallyl acetate (1a) (25 mg, 0.13 mmol) at room temperature, thenstirred at 80 C for 16 h. The reaction mixture was quenched with H2O, and extractedwith diethyl ether (3 x 2 mL). The combined organic layers were dried over MgSO4and concentrated in vacuo. The residue was chromatographed on silica gel(hexane/EtOAc = 60/40) to give 34 mg (84%) of 4aa as a mixture of two stereoisomers.The pure major stereoisomer (Z-isomer) was obtained after recrystallization fromCH2Cl2/hexane (1/5) at room temperature.REFERENCE EXAMPLE 5 To a solution of cyclohexane-1, 2-dicarboximide (10 g; 65.3 mmol) in anhydrous dimethylformamide (50 ml), there was added 60% sodium hydride (2.6 g; 68.5 mmol) under nitrogen at room temperature, and the resultant mixture was stirred at the same temperature for 3 hours. Tetramethylene bromide (70.5 g; 0.327 mol) was added thereto, and the mixture was stirred for 3 hours. After completion of the reaction, the resultant mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water twice and with a saturated sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent and excessive tetramethylene bromide were removed by evaporation to give N-(4-bromobutyl)cyclohexane-1, 2-dicarboximide. IR numaxFilm (cm-1): 1770, 1700.

Molecular Weight:153.18
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:153.078978594
Monoisotopic Mass:153.078978594
Topological Polar Surface Area:46.2
Heavy Atom Count:11
Complexity:190
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes