2,5-DIMETHOXYTEREPHTHALALDEHYDE

To a solution of 1, 4-dimethoxybenzene (1) (10.0 g, 72.3 mmol) in 1, 4-dioxane (30 mL), HCHO solution (38percent inwater, 5 mL) and paraformaldehyde (3.0 g, 99.0 mmol) wereadded in turn [27]. The resulting mixture was heated to90 °C, concentrated HCl (2×5 mL) was added during 30 minintervals. Heating continued for 1 h and a further 30 mL ofconcentrated HCl was added. The reaction mixture wascooled to room temperature to afford a white precipitate, which was obtained by filtration and dried under vacuum.The crude product was recrystallized with acetone to giveproduct 1 (4.5 g, 26percent) as a white precipitate. A solution ofproduct 1 (15.0 g, 63.8 mmol) and hexamethylenetetramine(18.0 g, 127.6 mmol) in chloroform (50 mL) was stirred atreflux for 24 h. After cooling to r.t., the pale yellow precipitatewas collected by filtration and redissolved in water(30 mL). The aqueous solution was acidified withCH3COOH (10 mL) and stirred at 90 °C for 24 h. The mixturewas cooled to r.t. and extracted with DCM (200 mL).The organic phase was washed three times with H2O(200 mL) and dried over anhydrous Na2SO4. After solventevaporation, the residue was recrystallized from CH3CH2OHto yield DMA (5.5 g, 45percent) as a bright yellow solid. 1H NMR(300 MHz, CDCl3) δ 10.50 (s, 2H), 7.26 (s, 2H), 3.95 (s, 6H).13C NMR (101 MHz, CDCl3) δ 189.19, 155.73, 129.15, 110.92, 77.33, 77.01, 76.70, 56.23. FTMS for C10H10O4:calcd, m/z 195.1 [M+1]+; Anal. Calcd. (194.1).This precursor center was prepared in three synthetic steps, from a procedure involving small modifications of the method already reported [33] . Initially, we dissolved 24.1 g (0.10 mol) of I and 30.0 g (0.21 mol) of urotropine (hexamethylenetetramine) in 200 mL of chloroform. The mixture was refluxed overnight. At the end of this first stage, after leaving the mixture cool to room temperature, the solvent was removed under reduced pressure and the solid residue obtained was dissolved in 320 mL of a 50percent acetic acid aqueous solution, being refluxed subsequently for 12 h. In the last part of the process, 25 mL of concentrated HCl was dropwise added to the solution, which was then refluxed for 8 h. After cooling, we observed the formation of a yellow precipitate, which was filtered off, washed with cold water and ethanol and dried under vacuum. Yield: 2.1 g (∼10percent), m.p. 207 °C (literature m.p.: 207 °C). From the filtrate, anadditional 0.8 g of the product could be obtained; its m.p. was 200 °C. Thesubstance was used in the next step without further purification. Elemental analysis - Percentages found: C, 61.9; H, 5.2. Calcd. for CA three-necked reactor equipped with a thermometer was charged with 7.0 g (50.67 mmol) of 1, 4-dimethoxybenzene, 29.44 g (253.33 mmol) of N, N, N′, N′-tetramethylethylenediamine, and 280 ml of diethyl ether under a nitrogen stream to prepare a homogeneous solution. After cooling the solution to 0° C., 97.4 ml (253.33 mmol) of 2.6 M n-butyllithium (n-hexane solution) was added dropwise to the solution over 30 minutes. After the dropwise addition, the reaction mixture was reacted for 5 hours under reflux, and then cooled to −78° C. After the addition of 18.52 g (253.33 mmol) of N, N-dimethylformamide, the mixture was stirred at −78° C. for 1 hour. After the addition of 350 ml of a 3 N hydrochloric acid aqueous solution to the reaction mixture at −78° C., the mixture was heated to 25° C., and 300 ml of distilled water and 200 ml of a saturated sodium chloride solution were added to the mixture, followed by extraction with 700 ml of chloroform. The chloroform layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. The solvent was evaporated from the filtrate under reduced pressure using a rotary evaporator. The resulting solid was added to 100 ml of toluene. After stirring the mixture for 5 minutes, the resulting crystals were filtered off to obtain 6.1 g of an intermediate A as yellow crystals (yield: 62percent). (0225) The structure of the target product was identified by 1, 4-Dibromo-2, 5-dimethoxybenzene (2.0 g, 6.76 mmol) was added dissolved in THF 35 mL, it was added dropwise a 1.6 M BuLi slowly at -78 . After stirring the reaction solution for 2 hours at -78 , it was added dropwise to DMF (2.8 mL, 33.7 mmol). The reaction solution is stirred at room temperature for 15 hours (20 ). 2 N HCl in a 20 mL reaction mixture was stirred slowly dropping off. The resulting solid was then filtered under reduced pressure, dried to obtain a 2, 5-dimethoxyterephthalaldehyde 267 mg (30percent).2, 5-Dimethoxy-1, 4-benzenedicarboxaldehyde (2) To a solution of 1-1 1 , 4-dimethoxybenzene (11.5 g, 83.26 mmol, 1 eq) in distilled Et20(276 mL) was added TMEDA (37, 4 mL, 249.78 mmol, 3 eq). At 000, nBuLi at 2.5 M inhexane (100 mL, 249.78 mmol, 3 eq) was added dropwise. The mixture was stirred atreflux overnight under inert atmosphere. At 000, 1-formylpiperidine (27.74 mL, 249.78mmol, 3 eq). was added dropwise. The mixture was stirred at room temperature for 1 h.Following the addition of distilled water (300 mL) and HCI 3 M (57.5 mL), the mixture was extracted with hot CHCI3 (300 mLx4). The organic phase was dried over an hydrous Na2SO4 and filtered. After removing the solvent, the remaining residue was purified by recrystallization in CHCI3 to give an orange solid (9.51 g, 51 percent).1H NMR (300 MHz, ODd3) 6 ppm = 10.51 (s, 2 H, CHO), 7.46 (s, 2 H, Ar), 3.95 (s, 6 H, OH3) data matched with literature reference

Molecular Weight:194.18
XLogP3:0.8
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:194.05790880
Monoisotopic Mass:194.05790880
Topological Polar Surface Area:52.6
Heavy Atom Count:14
Complexity:182
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes