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Org. Synth. 1934, 14, 52
DOI: 10.15227/orgsyn.014.0052
2-HYDROXY-3,5-DIIODOBENZOIC ACID
[Salicylic acid, 3,5-diiodo-]
Submitted by G. H. Woollett and W. W. Johnson.
Checked by W. W. Hartman and E. J. Rahrs.
1. Procedure
Twenty-five grams (0.18 mole) of salicylic acid (m.p. 159–160°) is dissolved in 225 cc. of glacial acetic acid in a 2-l. beaker provided with a mechanical stirrer (Note 1). To this is added with stirring a solution of 62 g. (0.38 mole) of iodine monochloride (Note 2) in 165 cc. of glacial acetic acid; then 725 cc. of water is added. A yellow precipitate of diiodosalicylic acid appears. The reaction mixture is gradually heated with stirring on a hot plate to 80° and kept at approximately that temperature for twenty minutes. The entire period of heating should be about forty minutes. Toward the end of the reaction the mixture becomes rather difficult to stir because of the voluminous precipitate. After cooling to room temperature (Note 3), the precipitate is filtered on a Büchner funnel and washed with acetic acid and then with water. When no more water is removed by suction, the solid (75 g.) is dissolved in 100 cc. of warm acetone and filtered by gravity. To the filtrate 400 cc. of water is slowly added with shaking. The fine, flocculent precipitate is filtered by suction, washed with water, and dried. The yield of diiodosalicylic acid melting at 235–236° is 64–64.5 g. (91–92 per cent of the theoretical amount) (Note 4).
2. Notes
1. The amount of glacial acetic acid used may not be sufficient to dissolve the salicylic acid completely. Solution will be completed upon the addition of the iodine chloride solution.
2. Iodine monochloride of sufficient purity for this preparation may be made as follows: Dry chlorine is led in at, or below, the surface of 127 g. (1 mole) of iodine in a 125-cc. distilling flask while the flask is gently shaken. When 34.5 g. (0.97 mole) of chlorine has been introduced, the iodine chloride is distilled in an ordinary distilling apparatus with a filter flask, protected from atmospheric moisture by a calcium chloride tube, as a receiver. The yield of iodine chloride, boiling between 97° and 105°, is 142 g. (87 per cent of the theoretical amount). The product can be preserved in a dry, glass-stoppered bottle. An excess of iodine is essential in this preparation.
3. Free iodine, if present, is removed by the addition of 5 per cent sodium sulfite solution.
4. The checkers found that 4-hydroxy-3,5-diiodobenzoic acid can be made from 4-hydroxybenzoic acid using the above directions with the exception that the product is not recrystallized from acetone, in which it is only slightly soluble. The yield of 4-hydroxy-3,5-diiodobenzoic acid, melting at 278–279° with decomposition, is 59 g. (84 per cent of the theoretical amount).
3. Discussion
The method given is based on that of Cofman.1 Diiodosalicylic acid has been prepared by heating salicylic acid with iodine in alcohol;2 by using the same reagents with the addition of mercuric oxide;3 by treating salicylic acid with iodine in the presence of alkali;3, 4 and by treating salicylic acid with iodine and iodic acid.5 None of these methods, however, appears to give a good yield or a pure product.
This preparation is referenced from:

References and Notes
  1. Cofman, Gazz. chim. ital. 50 (II) 297 (1920).
  2. Lautemann, Ann. 120, 300 (1861).
  3. Weselsky, ibid. 174, 103 (1874).
  4. Kekulé, ibid. 131, 226 (1864).
  5. Liechti, ibid. Spl. 7, 133, 141 (1870).

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

acetic acid (64-19-7)

sodium sulfite (7757-83-7)

salicylic acid

mercuric oxide (21908-53-2)

iodine (7553-56-2)

acetone (67-64-1)

chlorine (7782-50-5)

iodic acid (7782-68-5)

iodine monochloride,
iodine chloride (7790-99-0)

2-Hydroxy-3,5-diiodobenzoic acid,
Salicylic acid, 3,5-diiodo- (133-91-5)

diiodosalicylic acid

4-Hydroxy-3,5-diiodobenzoic acid (618-76-8)

4-hydroxybenzoic acid (99-96-7)