9-Chloroacridine

Green to brown solid

A magnetically stirred solution of 9-acridanone (4.01 g, 21 mmol) in phosphorus oxychloride (105 mL, 1.13 mol) was brought to reflux for 12 h. The solution was cooled to rt, added slowly to cracked ice (650 g), and made slightly alkaline with concentrated ammoniumhydroxide. A light tan solid was collected by filtration, washed with water, and air dried for 24 h. Flash chromatography (silica gel/75percent hexane, 20percent THF, 5percent triethylamine) afforded 3.97 g (89percent yield)of 10 as fine yellow needles which was identical to material prepared by method A as judged by TLC, mp, and spectral data.Add 3 mmol of acridone to a two-necked flask equipped with a condenser and a stir bar, fill with N2, add 6 ml of P0C13 in a nitrogen atmosphere, and reflux at 105 ° C for 3 h. After the reaction is completed, cool to room temperature. The reaction solution was slowly dropped into ice water while stirring, and a mixture of ice, concentrated aqueous ammonia and chloroform (volume ratio 1:1:1) was added to the above liquid, and the chloroform layer was separated and dried (anhydrous magnesium sulfate). Filtration gave a pale yellow liquid, which was purified by column chromatography using ethyl acetate: petroleum ether.White needle crystals were obtained with strong fluorescence. Intermediate Compound 1, yield 86percent.A mixture of 50 g (0.25 mol) of intermediate (d) and 35 g of thionyl chloride and 200 g of N, N-dimethylformamide, After completion of the reaction, the reaction mixture was poured into ice water, filtered and dried to obtain 47 g of a yellow solid powdery intermediate ()A magnetically stirred solution of N-phenylanthranilic acid (5.45 g, 26 mmol) in phosphorus oxychloride (100 mL, 1.07 mol) was treated with concentrated sulfuric acid (0.5mL), then brought to reflux for 12 h. The solution was cooled to rt, added slowly to cracked ice (650 g), and made slightly alkaline with concentrated ammonium hydroxide. A light tan solid was collected by filtration, washed with water, and air dried for 24 h. Flash chromatography (silica gel/75percent hexane, 20percentTHF, 5percent triethylamine) afforded 4.67 g (84percent yield) of 10 as fine yellow needles having one medium RGeneral procedure: The phenyl amino benzoic acid derivatives (47 mmol) (2a–c) were cyclized intra molecularly to 9-chloroacridine derivatives(3a–c) by refluxing them in 60 mL of POCl3 for 4 h and the reaction was monitored by TLC. After completion, the excess POCl3 was removed by rota evaporator under reduced pressure to the crude reaction mass crushed ice was added, pH was adjusted 7 by adding saturated bicarbonate solution. The solid separated was filtered, dried and purified by flash column chromatography using 5–10percent ethyl acetate: hexane as eluent in 60–120 mesh silica gelto get the corresponding 9-chloroacridine derivatives in good yield. These intermediates were confirmed by mass analysis (ESI mode) and proceed to next step.In a 100ml eggplant type bottle, N-phenylanthranilic acid (5.0 g, 23.5 mmol) was added, Phosphorus oxychloride (50 ml, 537 mmol). Put it in a 110°C oil bath and stir for 3 hours.TLC (developer: dichloromethane/methanol=20/1) detects complete disappearance of compound III-14.Withdraw from the oil bath and naturally cool to room temperature.The reaction mixture was slowly added to 150 g of ice and stirred vigorously. After the heat is released, The pH was adjusted with saturated sodium bicarbonate solution until bubbles ceased to form.After filtration, the filter cake is washed with water 2 or 3 times and drained.This gave the solid, 9-chlorohydrazine, 2.8 g (brown solid, yield 56percent).

Molecular Weight:213.66
XLogP3:4.2
Hydrogen Bond Acceptor Count:1
Exact Mass:213.0345270
Monoisotopic Mass:213.0345270
Topological Polar Surface Area:12.9
Heavy Atom Count:15
Complexity:209
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes