Nitric Acid → 4-Methoxy-1-nitroacridine

HRID 617437Notes

Reaction equation

HRID 617437 reaction equation
[CH3:1][O:2][C:3]1[C:16]2[C:7](=[CH:8][C:9]3[C:14]([N:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=1.[N+:17]([O-])([OH:19])=[O:18].S(=O)(=O)(O)O>C(OC(=O)C)(=O)C>[CH3:1][O:2][C:3]1[C:16]2[C:7](=[CH:8][C:9]3[C:14]([N:15]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:6]([N+:17]([O-:19])=[O:18])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 122924034-Methoxyacridine

Product 1

HCID 185050834-Methoxy-1-nitroacridineYield 70%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

4-Methoxyacridine (1.4 g, 6.67 mmole) was dissolved in acetic anhydride (5 ml) and cooled to 0°. Concentrated nitric acid (1 eq, 0.7 ml) was added, followed by concentrated sulphuric acid (1 eq, 0.7 ml). After stirring for 1 hr, the product was filtered and the residue was extracted into methylene chloride and washed with sodium bicarbonate solution. It was then dried and evaporated in vacuo to give 1.2 g (70%) of 4-methoxy-1-nitroacridine. NMR (CDCl3, 90 MHz) δ=4.20, s, 3H; 6.95, d, 9 Hz, 1H; 6.70-8.00, m, 3H; 8.34, d, 9 Hz, 1H; 8.55, d, 9 Hz, 1H; 9.82, s, 1H. The methoxy compound (500 mg) was converted to the 4-hydroxy derivative by heating with KOH (2 ml of an 11M aqueous solution) in DMSO (20 ml). This was tosylated with pyridine and toluenesulfonyl chloride to give the 4-tosyloxy derivative (260 mg, 34%). NMR (CDCl3, 90 MHz) δ 2.2, s, 3H; 7.00, m, 2H, 6.30-6.80, m, 7H; 8.20, d, 9 Hz, 1H; 9.45, s, 1H. The tosyloxy compound (600 mg, 1.5 mmole) was dissolved in acetonitrile (4 ml) and 1,7-diaza-4,10,13-trioxacyclopentadecane (110 mg, 0.5 mmole) were added, followed by 1,8-bis(dimethyl-amino)naphthalene (290 mg, 2 mmole) and the reaction mixture heated under reflux overnight. The reaction mixture was evaporated in vacuo and the residue taken into chloroform and purified by column chromatography (silica gel, ethyl acetate, hexane 1:1) to give the N,N-bis-(1-nitro-4-acridinyl)-diaza[15]-crown-5 as a yellow gum (180 mg, 27%). NMR (CDCl3, 90 MHz) δ 3.40, s, 4H; 3.82, m, 16H; 6.50, d, 9 Hz, 2H; 6.95, d, 9 Hz, 2H; 7.30, t, 9 Hz, 4H; 7.65, d, 9 Hz, 2H; 8.20, d, 9 Hz, 2H; 9.68, s, 2H.

Workup

  1. temperaturecooled to 0°
  2. filtrationthe product was filtered
  3. extractionthe residue was extracted into methylene chloride
  4. washwashed with sodium bicarbonate solution
  5. customIt was then dried
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-fe7670b02d1240588c0d502e3245e542
Source dataset
uspto-grants-1999_09
Patent number
US05948906

Reaction notes

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