Anthranilic Acid

[118-92-3]  · C7H7NO2  · Anthranilic Acid  · (MW 137.14)

(useful benzyne precursor1; building block for the synthesis of heterocyclic compounds2-7)

Physical Data: mp 144-148 °C; d 1.412 g cm-3.

Solubility: sol EtOH, AcOEt; partially sol water; insol petroleum ether.

Form Supplied in: yellow powder; widely available.

Benzyne Precursor.

Anthranilic acid can be diazotized to benzenediazonium-2-carboxylate, which is a very useful benzyne precursor. This transformation is usually accomplished under aprotic conditions with Isopentyl Nitrite (caution: isopentyl nitrite is a heart stimulant) (eq 1).1

Synthesis of Heterocycles.

Anthranilic acid reacts with Phosgene (eq 2)2 or Ethyl 4-Chloroacetoacetate3 to afford isatoic anhydride.2

Benzoxazines have been obtained by treatment of a mixture of anthranilic acid and a substituted benzoic acid with Phosphorus Oxychloride (eq 3).4

Reaction of anthranilic acid with methazonic acid under acid conditions, followed by treatment with sodium acetate/acetic anhydride, leads, in moderate yield, to 3-nitroquinol-4-one (eq 4).5

Acridones can be obtained, by means of the Niementowski modification of the Friedländer synthesis, by heating a mixture of anthranilic acid and a ketone (eq 5).6

Condensation with formanilide yields a benzo-1,3-diazine (eq 6).7

The following interesting reaction between anthranilic acid and a cyclopropylphosphonium salt has also been reported (eq 7).8

1. Logullo, F. M.; Seitz, A. H.; Friedman, L. OS, 1968, 48, 12.
2. Erdmann, E. CB 1899, 32, 2159. Wagner, E. C.; Fegley, M. F. OS 1947, 27, 45.
3. Niementowski, St.; Rozánski, Br. CB 1889, 22, 1673.
4. Rose, U. JHC 1991, 28, 2005.
5. Bachman, G. B.; Welton, D. E.; Jenkins, G. L.; Christian, J. E. JACS 1947, 69, 365.
6. Tiedtke, H. CB 1909, 42, 621.
7. Koelsch, C. F. JACS 1945, 67, 1718.
8. Dauben, W. G.; Hart, D. J. TL 1975, 4353.

Luis Castedo & Enrique Guitián

CSIC & University of Santiago, Spain

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.