DIRECT IODINATION OF ANISOLE, DIPHENYL ETHER, AND PHENYLACETIC ACID

V. T. SLYUSARCHUK, A. N. NOVIKOV

(Presented by the scientific seminar of the departments and laboratories of organic synthesis of the KhTF)

Previously, one of us described the direct iodination of certain aromatic hydrocarbons, their halogen-substituted derivatives, and aromatic acids and aldehydes [1, 2] with elemental iodine in the presence of a sulfuric–nitric acid mixture. This reaction had not been investigated for aromatic simple ethers and fatty-aromatic acids. The present work is intended to fill this gap. For this purpose, the direct iodination of anisole, diphenyl oxide, and phenylacetic acid in an acetic acid medium was studied. As a result, 4-iodophenylacetic acid, 4-iodo-2,4-diiodoanisoles, and 4-iodo- and 4,4′-diiododiphenyl oxides were obtained.

The literature describes methods for obtaining the listed substances based on the classical method of introducing iodine into the benzene ring through a nitro-amino-diazonium compound, and also proposes methods for their direct preparation by interaction of the starting substances with iodine in the presence of fuming nitric acid or iodic acid [3, 4, 5, 6, 7].

The main drawback of the first method is the multistage nature of the process. The consequence of this is the considerable duration of the synthesis and the low yield of the final compound. Direct iodination in the presence of fuming nitric acid is accompanied by oxidation and nitration, which complicates purification of the reaction product and lowers its yield. The use of iodic acid is uneconomical because of significant losses of iodine. The listed disadvantages can be avoided by the method of direct iodination in the presence of a sulfuric–nitric acid mixture composed of nitric acid, specific gravity 1.39–1.40, and sulfuric acid, specific gravity 1.83–1.84.

Experimental Part

Iodination was carried out in a round-bottom flask equipped with a reflux condenser, dropping funnel, and stirrer. To a mixture of the starting compound, acetic acid, finely powdered iodine, and carbon tetrachloride (added in cases where the reaction proceeded at a temperature above 40°C), the sulfuric–nitric acid mixture was added gradually dropwise with vigorous mechanical stirring.

After completion of the synthesis, water was added to the flask; the precipitate that formed was filtered off, washed with water to a neutral reaction, then with sodium sulfite solution to remove residual iodine, again with water, and recrystallized from the appropriate solvent until the melting point of the substance remained constant.

Iodination of Phenylacetic Acid

Phenylacetic acid 34.0 g, iodine 32.0 g, glacial acetic acid 80.0 ml, carbon tetrachloride 5 ml. The reaction temperature was 50°C (inside the bath); the sulfuric–nitric acid mixture, consisting of 28.0 ml of sulfuric acid and 7.5 ml of nitric acid, was added over the course of one hour. Synthesis time: 2 hours. The crude p-iodophenylacetic acid was first crystallized from dilute ethanol, then from water. Yield 30–35%, melting point 134–135°C (literature 134–135°C). Found, %: C 36.5; H 2.72; I 48.21. C₈H₇O₂I. Calculated, %: C 36.66; H 2.69; I 48.42.

Iodination of Anisole

5.4 ml of anisole, 6.35 g of iodine, 50.0 ml of glacial acetic acid. The reaction temperature was 10°C (inside the bath). A sulfuric–nitric acid mixture of 2 ml of sulfuric acid and 1 ml of nitric acid was added over 40 min. Duration of the experiment: 2 hours. p-Iodoanisole was crystallized from methanol. Yield 20–25%, melting point 52°C (literature 52°C).

To obtain diiodoanisole, 5.4 ml of anisole, 12.7 g of iodine, and 50 ml of acetic acid were taken. The synthesis temperature was 18–20°C (room temperature). A mixture of acids consisting of 4 ml of nitric acid and 12 ml of sulfuric acid was added over 30 min. Reaction time: 2 hours. 2,4-Diiodoanisole was purified by crystallization from methanol. Yield 45–50%, melting point 68–69°C (literature 68–69°C).

Iodination of Diphenyl Ether

17 g of diphenyl oxide, 12.7 g of iodine, 30.0 ml of glacial acetic acid, and 5.0 ml of sulfuric acid. The reaction was carried out at room temperature. 2.0 ml of nitric acid was added over the course of 1 hour. Duration of synthesis: 1.5 hours. Crystallization from methanol gave 25% of 4-iododiphenyl ether with melting point 43–44°C (literature 43–44°C) and 50–55% of 4,4′-diiododiphenyl ether with melting point 140–141°C (literature 140–141°C). When the reaction temperature was raised and the ratio of the reagents taken was changed, only diiododiphenyl oxide was obtained. Found, %: I 42.50; C₁₂H₉OI. Calculated, %: I 42.0. Found, %: I 59.57; C₁₂H₈OI₂. Calculated, %: I 60.01.

Conclusions

1. By direct iodination with elemental iodine in the presence of a sulfuric–nitric acid mixture composed of sulfuric acid, \(d = 1.83–1.84\), and nitric acid, \(d = 1.39–1.40\), the following were obtained: 4-iodoanisole, 2,4-diiodoanisole, 4-iododiphenyl oxide, 4,4′-diiododiphenyl oxide, and 4-phenylacetic acid.

2. Activity in the direct iodination reaction in the presence of the sulfuric–nitric acid mixture decreases in the following order:

anisole > diphenyl oxide > phenylacetic acid.

LITERATURE

1. B. V. Tronov, A. N. Novikov. Izv. VSh, 3, 872, (1960).
2. A. N. Novikov, T. A. Khalimova. Author’s Certificate 162519, Byull. izobr. No. 10, (1964).
3. M. Ciannini, M. Fedi, Boll. chim. farmac. 97, No. 10, 602, (1958).
4. French Patent 1190174, 9.10.59. RZhKh, Ref. 97615 P, (1960).
5. Beilst. 6, main volume, 208, (1923).
6. H. O. Wirth, O. Königstein, W. Kern, Ann. 634, No. 1–3, 84, (1960).
7. Beilst. 6, 1st Suppl., 109, (1931).