STUDY OF THE DIRECT IODINATION REACTION OF FLUORENE IN THE PRESENCE OF A SULFURIC–NITRIC ACID MIXTURE

A. N. Novikov, V. G. Slyusarchuk, T. S. Pigareva

(Presented by the scientific-methodological seminar of the Chemical-Technological Faculty)

This article presents the results of an experiment that is part of the studies being conducted at the department on the reaction of direct iodination in the presence of a sulfuric–nitric acid mixture.

In choosing objects for iodination, we drew attention to the fact that recently there has been interest in the chemistry of fluorene. On the basis of this structure, biologically active substances and intermediates have been synthesized for obtaining other practically useful compounds: medicinal substances, pesticides, and dyes [1—6].

It is known that the introduction of iodine into the structure of medicinal preparations and pesticides increases their activity [7], while iodine imparts purity and brightness of color to dyes [8]. From this point of view, iodination of fluorene is of definite practical interest.

The literature describes a laborious multistage method for obtaining iodine derivatives of fluorene, based on nitration, reduction, and diazotization reactions with subsequent replacement of the diazo group by iodine [9]. The yield of the final product is insignificant.

The method of direct iodination of aromatic compounds in the presence of a sulfuric–nitric acid mixture, previously proposed at our department by B. V. Tronov and A. N. Novikov [10—11], makes it possible simply, cheaply, and in one stage to carry out the synthesis of 2-iodo- and 2,7-diiodofluorenes [12—13]. The yield of these products depends on a number of factors.

In the present work, experimental data are presented on the dependence of the yield of 2,7-diiodofluorene on the reaction temperature and on the amount of sulfuric and nitric acids. We have carried out certain kinetic studies for the purpose of quantitatively characterizing the reaction underlying the synthesis. This article gives the determination of the numerical values of the reaction order, the rate constant with respect to iodine, and the activation energy. Previously, the kinetics of fluorene iodination had not been studied by anyone.

Experimental Part

Into a round-bottom flask equipped with a reflux condenser, a dropping funnel, and a stirrer, containing 0.02 mole of fluorene, 0.02 mole of finely powdered iodine, and 150 ml of glacial acetic acid, with vigorous stirring, a mixture composed of 4 ml of sulfuric acid, \(d\) 1.83, and 0.8 ml of nitric acid, \(d\) 1.4, was gradually added dropwise.

The reaction time was 1.5 hours. The experiments were carried out at the following temperatures in °C: 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80. The solid precipitate

filtered off, washed with water to a neutral medium, and recrystallized twice from acetic acid to a constant melting point. The experimental data are presented graphically in Fig. 1.

Fig. 1. Dependence of the yield of 2,7-diiodofluorene: 1—from the reaction temperature; 2—from the amount of nitric acid; 3—from the amount of sulfuric acid.

It is seen from the graph that the increase in the yield of 2,7-diiodofluorene occurs up to 70°C. Then the product yield decreases, which can apparently be explained by the occurrence of side oxidation and nitration processes.

To clarify the dependence of the yield of 2,7-diiodofluorene on the amount of nitric acid, experiments were carried out at (in moles): 0.0075, 0.012, 0.015, 0.018, 0.022, 0.027. The amount of sulfuric acid was constant—0.06 mole. The reaction time was 1.5 h, the temperature 70°C. The experimental results are presented graphically in Fig. 1. With an increase in the amount of nitric acid in the mixture up to 0.015 mole, the yield of 2,7-diiodofluorene increases, then decreases, and the technical product contains nitrogen.

With an increase in the concentration of nitric acid in the mixture, from a certain point nitration begins to proceed along with iodination, and the reaction product is 2-iodo-7-nitrofluorene.

To clarify the influence of the concentration of sulfuric acid on the yield of 2,7-diiodofluorene, experiments were carried out at amounts of sulfuric acid (in moles): 0.0018, 0.009, 0.018, 0.07, 0.09, 0.1. The amount of nitric acid was constant—0.015 mole. The reaction temperature was 70°C, the time 1.5 h. The technical product from all experiments contained no nitrogen. The results are presented graphically in Fig. 1. The yield of 2,7-diiodofluorene increases with an increase in the concentration of sulfuric acid in the mixture up to 0.018 mole, and then changes almost not at all.

Kinetic experiments were carried out according to the following procedure developed by us: 50 ml of a 0.1 mol/l acetic-acid solution of iodine, 50 ml of a 0.1 mol/l acetic-acid solution of fluorene, 0.018 mole of sulfuric acid, and 0.006 mole of nitric acid were kept for 30 min in a thermostat until its temperature was reached, and then combined. The thermostating accuracy was 0.1°C. The reaction was carried out at 30°C and 40°C. Samples of 10 ml were taken at 30°C after 20 min, and at 40°C after 10 min. The reaction in the sample was stopped by dilution with water by a factor of three. Control experiments showed that under these conditions the reaction ceased completely. Nitrogen was absent from the technical product; consequently, the nitration reaction did not proceed. Iodine was extracted from the sample by extraction with carbon tetrachloride. The concentration of iodine in \( \mathrm{CCl}_4 \) was determined from the measured value of the optical density using a calibration curve constructed from a series of standard solutions on an FEK-M photoelectric colorimeter.

The partial order with respect to iodine was determined by the method of selecting equations. The data, averaged from three well-concordant experiments, correspond to a second-order kinetic equation. In Fig. 2 the dependence

\[ \frac{x}{a(a-x)} \]

on \( t \) is presented graphically (1). The numerical value of \(K_j\) was determined from equation (1). \(K_j = 2.5 \cdot 10^{-6}\ \text{sec}^{-1}\ \text{l/mol}\). At different time points the value of \(K_j\) is well maintained.

Fig. 2. Plot of the dependence of

\[ \frac{x}{a(a-x)} \]

on \(t\).

The activation energy was calculated from two values of the rate constants at 303°K and 313°K using the Arrhenius equation. \(E = 11.2\) kcal/mol. The accuracy of determination of the activation energy is 2%.

Conclusions

1. The effect of the reaction temperature and of the amounts of sulfuric and nitric acids on the yield of 2,7-diiodofluorene was studied.
2. The order of the reaction studied with respect to iodine is second.
3. The rate constant with respect to iodine \((K_j)\) and the activation energy of the reaction were calculated.

REFERENCES

1. G. Ya. Urutskaya, M. Ya. Kraft. ZhORKh, 1, 6, 1074–1076, 1965; ZhOKh, 33, 9, 3053–3056, 1963.
2. Pan-Hsi-Lung, J. Med. Chem., 8, 4, 491–97, 1965; 7, 1, 31–38, 1964.
3. French patent, cl. 61 K, 1345419, 18.01.63; English patent, cl. 960758, 21.12.62.
4. V. I. Khmelevskii. ZhORKh, 1, 2, 262, 1965.
5. B. M. Krasovitskii, A. I. Nazarenko. Ukr. khim. zh., 31, 9, 942–947, 1965.
6. Schneider, Flemming, RZhKh, 12, N626, 1967.
7. M. Ya. Kraft, ZhVKhO im. Mendeleeva, 10, 6, 632, 1965.
8. F. David, Bank, Chem. Rev., 66, No. 3, 1906.
9. S. Varma, J. Indian. Chem. Soc., 15, 72, 1938.
10. B. V. Tronov, A. N. Novikov. Izv. VSh, Khim. i khim. tekhnol., 3, 872, 1960.
11. A. N. Novikov, T. A. Khalimova. Inventor’s certificate No. 159496, No. 162218, Bull. izobr. No. 10, 1964.
12. V. T. Slyusarchuk, A. N. Novikov, ZhORKh, 3, 7, 1323, 1967.
13. A. N. Novikov, V. T. Slyusarchuk. Inventor’s certificate No. 197545, Bull. izobr. No. 13, 1967.