1,4-Benzodioxan-6-carboxaldehyde

Yellowish-beige powder and chunks

2,3-dihydro-1,4-benzodioxine-6-carbaldehyde is a heteroarenecarbaldehyde in which a formyl group is located at position 6 of 2,3-dihydro-1,4-benzodioxine. It is a heteroarenecarbaldehyde and a benzodioxine.

preparation of 5-f f2, 3-dihydro-f .41-benzodioxin)-6-vimethvf)amino}-N- (2-r2-dimethvlamino )ethvll-1 H-benzordelisoguinolin-1, 3(2H)-dione; The synthetic route of this compound proceeds in a series of steps schematically shown in attached figure 2 and is described in more details as follows; a); in a first step, 500 mg 3, 4-dihydroxybenzaldehyde, 2.6 g cesium carbonate (2 equivalents), 1.4 g 1, 2-dibromoethane (2 equivalents) and 5 mL anhy-drous DMF were stirred at 70°C for 16 hours. After cooling, the solvent was evaporated under reduced pressure and the residue was submitted to a flash chromatography (Si02, eluent : CH2CI2), thus resulting in 575.3 mg (yield : 97 percent) of the intermediate shown as product A in figure 2 ;To a solution of 3, 4-dihydroxybenzaldehyde (20, 10 g, 72.40 mmol) in acetone (100 mL) was added K138 mg of 3, 4-dihydroxybenzaldehyde was dissolved in 5 ml of N, N-dimethylformamide.Add 100 mg of 1, 2-dibromoethane and 300 mg of potassium carbonate, 60-90°C reaction for 8 hours. After the reaction is over, the system is quenched with water.Extract three times with 30 ml of ethyl acetate and wash with saturated saline.Dry over anhydrous magnesium sulfate, filter, and concentrate to obtain intermediate 120 mg1, 4-benzodioxane-7-carbaldehyde, yield 74percent, untreated, Used directly for the next reaction.SYNTHETIC PREPARATION 5Anhydrous potassium carbonate (21 g) was added in portions to a stirred solution of 27.6 g of 3, 4-dihydroxy benzaldehyde in 100 ml of dry acetone followed by the dropwise addition of 4.3 ml of ethylene dibromide. Another 21 g of potassium carbonate and 4.3 ml of ethylene dibromide were added similarly and this was repeated twice more using a total of 84 g of potassium carbonate and 17.2 g of ethylene dibromide. Stirring and refluxing was continued for another 25 h. The reaction mixture was then filtered by sintered glass funnel and the solid residue was washed several times with acetone. The combined filtrate was concentrated to about 25 ml and the residue was poured onto crushed ice, asolid was separated which was filtered, dried and crystallized with methanol to give a low melting solid; mp 35-37 °C; 67percent yield; General procedure: 43.80 g potassium carbonate (0.32 mol) and 15.1 cm3 1, 2-dibromoethane (32.90 g, 0.18 mol) were added to a solutionof 22.00 g 13 (0.16 mol) or 26.70 g 15 (0.16 mol) in250 cm3 DMF. The reaction mixture was stirred at100–110 C for 4–8 h. After cooling to rt, the precipitatedinorganic salts were filtered and the reaction mixture wasevaporated to 80 cm3 in vacuo. The residue was pouredinto 670 cm3 water. The product was isolated as specified.2, 3-Dihydrobenzo[b][1, 4]dioxine-6-carbaldehyde (16) Theaqueous phase was extracted with ethyl acetate(4 9 200 cm3), and the combined organic layer waswashed with brine and dried over Na2SO4. The crudeproduct was purified by distillation in vacuo to afford 16.Yield: 63percent; white solid; m.p.: 48–49 C (Ref. [63] 49.5–50.5 C); b.p.: 105–108 C (0.3 mbar); 1H NMR(300 MHz, CDCl3): d = 9.82 (s, 1H, CHO), 7.42–7.38 (m, 2H, 5-HAr and 7-HAr), 6.98 (d, J = 8.7 Hz, 1H, 8-HAr), 4.35–4.28 (m, 4H, OCH2CH2O) ppm; 13C NMR (75 MHz, CDCl3): d = 64.0 (OCH2CH2O), 64.7 (OCH2CH2O), 117.8(5-CAr or 8-CAr), 118.4 (5-CAr or 8-CAr), 124.2 (7-CAr), 130.7 (6-CAr), 143.9 (4a-CAr), 149.1 (8a-CAr), 190.7(CHO) ppm; IR (KBr): m = 3001, 2883, 1687, 1581, 1506, 1458, 1394, 1291, 1156, 1062, 887, 777 cm-1.In this step, 3, 4-dihydroxybenzaldehyde was used as a starting material, And 1, 2-dibromoethane in the alkaline environment for the reduction reaction, the synthesis of intermediate 2, 3-dihydro-1, 4-benzodioxane-6-carbaldehyde. The base used in the present reaction includes: potassium hydroxide, The condensing agent is an ammonium bromide compound such as tetrabutylammonium bromide; The molar ratio used was 3, 4-dihydroxybenzaldehyde: 1, 2-dibromoethane = 1: 5; The use of sodium hydroxide in excess of 5 times, under strong alkaline conditions for testing. The temperature used was the reflux temperature.

1,4-Benzodioxane-6-carboxaldehyde was screened as a fragment for inhibitors of PDEA using enthalpy arrays and X-ray crystallography. 1,4-Benzodioxane-6-carboxaldehyde have also been used as an intermediate in the synthesis of a new class of Dopamine D3 and D4 receptor antagonists.

Molecular Weight:164.16
XLogP3:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:164.047344113
Monoisotopic Mass:164.047344113
Topological Polar Surface Area:35.5
Heavy Atom Count:12
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes