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Bromomethyl to carboxylic acid (and hydroxymethyl) conversion; 1,3,4-Trimethoxy-9,10-dioxo-9,10-dihydro-anthracene-2-carboxylic acid, 2-Hydroxymethyl-1,3,4-trimethoxyanthraquinone

SyntheticPage 457
DOI: 10.1039/SP457
Submitted Aug 03, 2010, published Aug 06, 2010

A contribution from R J H Clark Group, UCL

			Reaction Scheme: Bromomethyl to carboxylic acid (and hydroxymethyl) conversion

Chemicals Used

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

sodium nitrite

acetic acid



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).

Author's Comments

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)

Lead Reference

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

DOI: 10.1021/jo962110n

Other References

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

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Get structure file (.cdx, .sk2, .mol)

Keywords: alcohols, carboxylic acids, hydrolysis, nucleophilic, rearrangement, substitution

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