A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1956, 36, 46
DOI: 10.15227/orgsyn.036.0046
[Veratrole, 4-iodo-]
Submitted by Donald E. Janssen and C. V. Wilson1.
Checked by Max Tishler and George Purdue.
1. Procedure
A. Silver trifluoroacetate. To a suspension of 187 g. (0.81 mole) of silver oxide (Note 1) in 200 ml. of water is added 177 g. (1.55 moles) of trifluoroacetic acid (Note 2). The resulting solution is filtered, and the filtrate is evaporated to dryness under reduced pressure. The dry silver trifluoroacetate thus obtained is purified by placing it in a Soxhlet thimble and extracting with ether, or by dissolving the salt in 1.2 l. of ether, filtering through a thin layer of activated carbon, and evaporating the filtered ether solution to dryness. The yield of colorless crystalline salt obtained after removal of the ether is 300 g. (88%).
B. 4-Iodoveratrole. In a 3-l. three-necked round-bottomed flask, fitted with a sealed stirrer, a dropping funnel, and a reflux condenser protected with a drying tube, is placed 110 g. (0.5 mole) of dry silver trifluoroacetate (Note 3). The flask is flamed to remove all moisture, and 69 g. (0.5 mole) of dry veratrole is added (Note 2). To the stirred suspension a solution of 127 g. (0.5 mole) of iodine in 1.6 l. of chloroform is added through the dropping funnel over a period of 2 hours. After stirring an additional hour, the mixture is filtered and the precipitated silver iodide is washed with 100 ml. of chloroform. The solvent is removed from the filtrate and washings under vacuum, and the residue is distilled through an 8-in. Vigreux column. The fraction boiling at 152–155°/15 mm. weighs 112–120 g. and constitutes a yield of 85–91% (Note 4) and (Note 5).
2. Notes
1. The silver oxide was prepared by adding, with manual stirring, 66 g. of 98% sodium hydroxide (1.62 moles) in 2 l. of water to a solution of 274 g. (1.62 moles) of silver nitrate in 500 ml. of water. The precipitate was collected by filtration and washed with water until free from alkali. The wet cake can be dried or preferably used moist for reaction with trifluoroacetic acid.
2. The trifluoroacetic acid and veratrole used were Eastman Kodak Company white label grade.
3. Commercially available silver acetate may be used in place of the silver trifluoroacetate, but the yield is somewhat lower (75–80%).
4. The product, nD25 1.612, solidifies on chilling. Recrystallization from ethanol gives solid of melting point 34–35°.
5. Iodination in the presence of mercuric oxide2,3,4,5,6 gives yields of about 40–55%, and even after careful distillation the product is contaminated with mercury salts.
3. Discussion
4-Iodoveratrole has been prepared by iodination of veratrole in the presence of mercuric oxide2,3,4,5,6 and by methylation of 4-iodoguaiacol with methyl iodide in alcoholic sodium ethoxide solution.7
This preparation is referenced from:

References and Notes
  1. Eastman Kodak Company, Rochester 17, New York.
  2. Ritchie, J. Proc. Roy. Soc. N. S. Wales, 78, 134 (1945) [C. A., 40, 876 (1946)].
  3. Jurd, Australian J. Sci. Research, 2A, 246 (1949) [C. A., 45, 2887 (1951)].
  4. Seer and Karl, Monatsh., 34, 647 (1913).
  5. Bruce and Sutcliffe, J. Chem. Soc., 1955, 4435.
  6. Gutzke, Fox, Ciereszko, and Wender, J. Org. Chem., 22, 1271 (1957).
  7. Tassilly and Leroide, Compt. rend., 144, 757 (1907); Bull. soc. chim. France, [4] 1, 932 (1907) [C. A., 1, 1848 (1907)].

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

ethanol (64-17-5)

ether (60-29-7)

sodium hydroxide (1310-73-2)

chloroform (67-66-3)

silver oxide (20667-12-3)

silver nitrate (7761-88-8)

mercuric oxide (21908-53-2)

iodine (7553-56-2)

activated carbon (7782-42-5)

sodium ethoxide (141-52-6)

Methyl iodide (74-88-4)

silver acetate (563-63-3)

veratrole (91-16-7)

silver iodide (7783-96-2)

Veratrole, 4-iodo- (5460-32-2)

trifluoroacetic acid (76-05-1)

silver trifluoroacetate (2966-50-9)