Preparation method of 1,2-methylenedioxy-4-nitrobenzene_Kain Industrial Additive

Background and overview^[1]

1,2-Methylenedioxy-4-nitrobenzene is an aromatic nitro compound. Aromatic nitro compounds are widely used in production and life. In addition to its traditional applications in explosives, spices and dyes, it is also an important functional group in many medicines and pesticides. In addition, because the nitro group in nitro compounds is a very active leading group and can be easily converted into other functional groups, complex target molecules can be synthesized through it. Therefore, it is the most important type of chemical raw materials and synthetic intermediates.

Preparation^[1-3]

Report 1,

In the air, add compounds benzo[d][1,3]dioxolane 1a (0.5mmol, 61mg), I₂ in sequence to a 10mL sealed pressure tube. O₅(2.5mmol,835mg), NaNO₂(2.5mmol,173mg), 2mL CH₃NO₂And 0.1mL water. React for 2 h under vigorous magnetic stirring at 15°C. TLC followed the reaction. When the reaction is completed, add anhydrous Na₂SO₃ to quench the reaction. First add 15 mL of saturated Na₂S₂O₃ to the reaction solution, and use CH₂Cl₂(15mL×3) Wash the aqueous phase, combine the organic phases, dry with anhydrous Na₂SO₄, filter, evaporate the solvent of the filtrate under reduced pressure, and column layer After analysis (ethyl acetate: petroleum ether = 1:5), 70 mg of 1,2-methylenedioxy-4-nitrobenzene was isolated as a light yellow solid, with a yield of 84%, m.p. 145~147°C; ¹ H NMR (300MHz, CDCl₃) δ: 7.90 (dd, J＝8.6, 2.3Hz, 1H), 7.67 (d, J＝2.3Hz, 1H), 6.87 (d ,J＝8.6Hz,1H),6.15(s,2H); MS(EI)m/z: Calcd for C7H5NO4[M]+168.03, found 168.00.

Report 2,

Add 1 mmol pepper ring into the reaction flask and dissolve it in 2 mL acetonitrile. Add 145 uL tert-butyl nitrite, stir at room temperature, and react for 1 hour. After the reaction is completed, use a rotary evaporator to remove the organic solvent and column layer The product nitro product was obtained by precipitation, and the reaction yield was 71%.

Report 3,

Dissolve benzo[1,3]dioxolane (40g, 0.327mol) in DCM (2.44L) and glacial acetic acid (2.277L), cool to 15°C, and add concentrated HNO_{3 dropwise} (325.2mL), keep the temperature below 40℃, after the dropwise addition, raise to room temperature and stir for 30 minutes, cool to 0-5℃, add fuming concentrated HNO₃(813mL) dropwise ), after the dropwise addition is completed, the reaction mixture is raised to room temperature and stirred overnight.

Add 9.6L ice water to the reaction solution and stir for 10 minutes, let stand and separate into layers. Extract the water phase once with 800mL DCM and 800mL EA in turn. Combine the organic phases and wash twice with 640mL water and 640mL saturated NaHCO₃ Wash twice, dry over anhydrous sodium sulfate, filter, and spin dry to obtain 24 g of crude product, with a yield of 34.7%.

References

[1] [Chinese invention] CN201910259994.1 A nitration electron-rich aromatic compound using I₂O₅/NaNO₂ method

[2] [Chinese invention] CN201810602331.0 A direct nitrification method of electron-rich aromatics

[3] [Invented in China, authorized by China] CN201780000221.0 A class of macrocyclic heterocyclic compounds that inhibit hepatitis C virus and their preparation and use