Effect of Pyridine on the Iodination of Phenols

L. A. Pershina, I. M. Borodina

(Presented by Professor, Doctor of Chemical Sciences B. V. Tronov)

It is known that bromination of benzene can be carried out not only in the presence of such catalysts, customary for reactions of this type, as the halides of iron, aluminum, zinc [1], etc., but also with pyridine. The reason for the accelerating action of pyridine in this reaction is, it must be supposed [2], that pyridine forms a complex with bromine in which one halogen atom is part of the cation. This leads to activation of the bromine. The complex cation also adds as a complex to a carbon atom of benzene; then the hydrogen of the same ring and bromine exchange places. As a result, bromobenzene and the pyridinium cation are formed.

Iodine is less active than bromine, and activation of iodine by pyridine, as experiment has shown, does not lead to iodination of benzene. However, if a more reactive aromatic compound is taken, namely phenol, then although by itself in benzene solution it did not react with iodine, it did react with it upon addition of pyridine [3]. Obviously, here iodination also occurred owing to formation of a complex having iodine in the cation. A pyridine complex of iodine chloride should be still more active, since the latter is itself polar, with iodine bearing a positive charge.

In the present work we studied the action on phenol and resorcinol of iodine and iodine chloride in the free state (in ether solution, where complexes also arise, but only slightly dissociated) and in the presence of pyridine.

Experiments with phenol showed that free iodine in ether gives no positive results. The use of pyridine, as well as iodination with iodine chloride, led to the formation of a mixture of mono-, di-, and triiodo derivatives, from which p-iodophenol and 2,4,6-triiodophenol were isolated in insignificant yield.

On iodination of resorcinol with free iodine in ether, and also in the presence of pyridine, a mixture of monoiodo derivatives was obtained with a small amount (10–11%) of 2,4,6-triiodoresorcinol. Experiments with iodine chloride led to the formation of 2,4,6-triiodoresorcinol.

The best iodinating agent proved to be iodine chloride with pyridine. Under these conditions, a good yield (60%) of 2,4,6-triiodophenol was obtained from phenol. The yield of 2,4,6-triiodoresorcinol with this method of iodination rises to 70%.

Experimental Part

Iodination with free iodine

A solution of iodine in ether was added to phenol and resorcinol. The ratio of starting materials to iodine was 1:1 and 1:3. After heating for 30 min in a water bath, the reaction mixtures were washed with soda solution and dried with fused potash.

In the iodination of phenol, the oil remaining after evaporation of the ether was unreacted phenol.

In the iodination of resorcinol, in the case of a 1:1 ratio of starting materials, after the usual treatment and evaporation of the ether an oil was obtained, which slowly crystallized over the course of a week. The crystals had

melting point of 63°, which corresponds to the monohydrate of 4-iodoresorcinol. Yield 15%.

With a ratio of the starting materials of 1:3, 2,4,6-triiodoresorcinol was obtained, with a melting point of 144–145°. Yield 10%.

Iodination with a complex of iodine with pyridine

A mixture of pyridine with iodine was added to ethereal solutions of phenol and resorcinol. After 30 min of heating, the reaction mixtures were treated first with dilute hydrochloric acid (1:3) to destroy the complex formed by pyridine with phenol and with the products of its iodination, and then in the usual way.

The yield of the phenol iodination products is 17%. Among them are monoiodophenols and diiodophenols. Triiodophenol was not detected.

With a ratio of the starting substances of 1:1, the iodination product of resorcinol is the monohydrate of 4-iodoresorcinol. Yield 50%. With a ratio of the starting substances of 1:3, 2,4,6-triiodoresorcinol was obtained. Yield 20%.

Iodination with iodine chloride

Into round-bottom flasks containing ethereal solutions of phenol and resorcinol, freshly distilled iodine chloride [4] was added through a reflux condenser. The reaction mixtures were heated for 30 min on a water bath.

In the iodination of phenol (ratio of starting substances 1:3), fractional recrystallization from water gave 16% monoiodophenols; recrystallization from alcohol gave 13% 2,4,6-triiodophenol with a melting point of 156°.

The products of iodination of resorcinol, with a ratio of the starting substances of 1:1, are the monohydrate of 4-iodoresorcinol, in 41% yield, and 2,4,6-triiodoresorcinol, 6.4%.

With a ratio of the starting substances of 1:3, 2,4,6-triiodoresorcinol was obtained in 50% yield.

Iodination with iodine chloride in the presence of pyridine

Pyridine forms complexes with one and with two molecules of iodine chloride.

In our work we used the first complex, without isolating it in the free state, but obtaining it immediately before the reaction by adding pyridine to iodine chloride.

14.7 g of iodine chloride was mixed with 7.2 g of pyridine. To a solution containing 3 g of phenol in 30 ml of ether, pyridine with iodine chloride was gradually added. The mixture was heated on a water bath for 30 min.

After the usual work-up and recrystallization from aqueous alcohol, 2,4,6-triiodophenol was obtained, with a melting point of 156°. Yield 60%. Iodine analysis—80.6%; calculated 80.7%. 10.45 g of iodine chloride was mixed with 5.4 ml of pyridine. To an ethereal solution of 2.45 g of resorcinol, pyridine with iodine chloride was gradually added. After heating and the usual work-up, 7.5 g (70%) of 2,4,6-triiodoresorcinol was obtained, with a melting point of 144°. Iodine analysis: 77.8%; calculated 78%.

With a ratio of resorcinol to iodine chloride with pyridine of 1:1, 13% of 2,4,6-triiodoresorcinol was obtained.

Conclusions

1. The action of iodine and iodine chloride in ethereal solution and in the presence of pyridine on phenol and resorcinol has been studied.

2. It has been shown that the iodination reaction of phenols is significantly accelerated by pyridine.

1. Iodination with iodine chloride in the presence of pyridine may be recommended as a preparative method for the synthesis of 2,4,6-triiodophenol and 2,4,6-triiodoresorcinol.

REFERENCES

1. Tronov B. V., Pershina L. A. ZhOKh, 24, 1608, 1954.
2. Tronov B. V. Izv. TPI, 83, 64, 1956.
3. Tronov B. V., Kolesnikova S. F. Communications of the Mendeleev All-Union Chemical Society, 1, 46, 1953.
4. Koryakin Yu. V., Angelov N. I. Pure Chemical Reagents. Goskhimizdat, p. 158, 1955.
5. Fialkov Ya. A., Muzyka I. D. ZhOKh, 18, 1205, 1948.