2-bromomethyl-1,3,4-trimethoxyanthraquinone Page 454

sodium nitrite

acetic acid

DMSO

2-Bromomethyl-1,3,4-trimethoxyanthraquinone (4.929 g, 12.6 mmol) was stirred in dimethyl sulfoxide and NaNO₂ (3.8 g, 55 mmol) added. The bromo compound dissolved after a few seconds. After standing overnight, acetic acid (7.2 g, 12 mmol) was added and the mixture stirred at 35 °C for 6 h. HCl (10 cm³, 5M) was added and stirring continued for 1 h. The product was diluted with diethyl ether (100 cm³) and HCl (100 cm³, 1M). The phases were separated and the aqueous phase extracted again with ether (3 x 100 cm³). The combined organic phases were washed with saturated NaCl solution (50 cm³) then extracted with portions of NaOH solution (1M, a total of 200 cm³). The aqueous extract was acidified (conc. HCl, 20 cm³) and allowed to stand overnight at 5 °C to give orange-brown needles of 1,3,4-trimethoxy-9,10-dioxo-9,10-dihydro-anthracene-2-carboxylic acid (2.13 g, 62% yield).

 

The ether solution of NaOH-insolubles was evaporated to give a yellow solid (1.80 g) which was extracted with boiling cyclohexane (200 cm³) to give yellow needles of 2-hydroxymethyl-1,3,4-trimethoxyanthraquinone (1.39 g, 34% yield).

Benzylic bromides react with NaNO₂/CH₃CO₂H/DMSO:

-CH₂Br → -CH₂NO₂ + -CH₂ONO;   

-CH₂NO2 rearranges via the nitrolic acid to the  hydroxamic acid which is hydrolysed to –COOH.  

-CH₂ONO is hydrolysed to –CH₂OH.   (C Matt, et al 1997).  

The application of this procedure to 2-bromomethyl-1,3,4-trimethoxyanthraquinone gave modest amounts (27%, 33%) of the corresponding carboxylic acid. The yield of the required carboxylic acid could be increased to 62% by using more NaNO2 and adding the acetic acid later. The 2-hydroxymethyl-1,3,4-trimethoxyanthraquinone (34%) is easily oxidised to give the corresponding carboxylic acid with KMnO₄.

1,3,4-Trimethoxy-9,10-dioxo-9,10-dihydro-anthracene-2-carboxylic acid:

δH (CDCl₃) 8.21m (2H), 7.78m (2H), 4.13s (3H), 4.06s (3H), 4.03s (3H)

EI-MS m/z (%), 342 (97), 312 (41), 310 (11), 309 (50), 298 (17), 297 (98)

2-Hydroxymethyl-1,3,4-trimethoxyanthraquinone, pale yellow needles, mp 127-128 °C,  lit: Hirose Y, 1960, mp. 131-132 ºC (petrol)

δH (CDCl₃) 8.19m (2H), 7.75m (2H), 4.84s (2H), 4.10s (3H), 4.02s (3H), 4.00s (3H), 2.58brs (1H)

EI m/z (%), 328 (100), 313 (64), 295 (27)

C Matt, A Wagner, C Mioskowski, J Org Chem, 1997, 62(2), 234-235

DOI: 10.1021/jo962110n

Hirose Y, Chem Pharm Bull, 1960, 8(5), 417-426