Peroxide oxidation of an isatin

SyntheticPage 466

DOI:

10.1039/SP466

Submitted: September 3, 2010, published: September 16, 2010

Authors

Christopher Cooksey (rsc@chriscooksey.demon.co.uk)

A contribution from

R J H Clark Group, UCL

Chemicals

6-Bromoisatin page 464

NaOH

H₂O₂

Procedure

6-Bromoisatin (4.8 g, 21 mmol) was dissolved in NaOH solution (2.4 g in 60 cm³) by warming to 50 °C. H₂O₂ (100 vol, 5.5 cm³, about 48 mmol) was added dropwise (exothermic reaction) so that the temperature was maintained between 50 °C and 51 °C. After cooling, the mixture was acidified with HCl (4M) to pH 3 to give a white paste which was filtered and washed with water (30 cm³). The yield was 3.97 g (87%)

Author Comments

On the same scale and 5x the scale, lower yields (79%) were obtained.

940 mg of the product was recrystallised from aqueous ethanol (50 cm³, 1:1) to give long (>1 cm) colourless needles (789 mg), m.p. 227.2 °C (lit: m.p. 230 °C).

The literature yield was 99%; 26 analogous anthranilic acids were described.

Data

δ_H (dmso-d₆) 12.5brs (1H), 7.57d (1H, 8.5), 6.96d (1H, 2.0), 6.62dd (1H, 8.5, 2.0), 5.3brs (2H)

Lead Reference

Holt SJ, Sadler PW, Proc Roy Soc Lond B, 1958, 148(933), 481-494

PMID: 13542639

Get structure file (.cdx)

Keywords

anthranilic acid, carboxylic acids, isatin, oxidation

Comments

modification of 466

An improvement in the yield to 100% was achieved using the conditions suggested for the 5-bromo-7-ethyl analogue (Snieckus VA, Onouchi T, Boekelheide V, J Org Chem 1972 37(18) 2845–2848, DOI: 10.1021/jo00983a011). 6-Bromoisatin (13.4 g) was dissolved as above, cooled to 0 °C, peroxide added and the mixture stood overnight at 20 °C, then proceeding as before.

By Christopher Cooksey on September 25, 2010