The ligand exchange reaction is a typical reaction of ferrocenes. This reaction proceeds via the abstraction of a cyclopentadienyl ring by a Lewis acid followed by coordination of an aromatic compound to the resulting species. This reaction with conventional heating requires a long reaction time. Furthermore, the reactions with heterocycles are lower than those with the corresponding hydrocarbons, and do not produce any products in some cases. In this paper, the ligand exchange reaction of ferrocene and a heterocyclic aromatic compound during microwave irradiation and its effect are discussed. As a result, for some heterocycles, the decrease in the reaction time was confirmed. Furthermore, under the microwave irradiation conditions, the tendency in which the difference in their reactivities became low was confirmed.
Ferrocene has an aromaticity, and undergoes a great variety of reactions. One of them is the ligand exchange reaction with aromatic compounds. This reaction easily proceeds when ferrocene and arenes are heated with aluminum chloride in suitable solvents [
On the other hand, it is known that various kinds of organic reactions are accelerated by microwave irradiation [
Scheme 1. Reaction mechanism of ligand exchange reaction between ferrocene and benzene.
reactions with ferrocene and substituted benzenes [
Ferrocene (4.0 mmol) and the heterocycles (4.0 mmol) were dissolved in 1, 2-dichloroethane (40 cm3) in a small vessel. Anhydrous aluminum (III) chloride (8.0 mmol) was then added to the solution. The vessel was placed in a microwave reactor or in an oil bath. For the microwave irradiation, a multi-mode microwave reactor, a Shikoku Keisoku μ-reactor, was used. The irradiation was carried out by a cycle of a 2 minutes irradiation and a 0.5 minute interval. The used heterocycles are shown in Scheme 2.
The products were analyzed by 1H-NMR and HPLC, and the yields were determined by the weight measurement of the PF6 salts [
The 1H-NMR spectra were measured at room temperature using a JEOL A-400. The data are listed in Reference 4.
HPLC was obtained using a Shimadzu LC-10A system. The used column was Nacalai Tesque Cosmosil 5C18-II (150 mm × 4.6 mm Φ), and the eluent was methanol.
As mentioned in a previous paper [
Under conventional heating conditions, the reaction with benzothiophene pro- ceeds, but the reactions with the other bicyclic heterocycles do not proceeds [
The reactions with the tricyclic heterocycles produced the products (
Scheme 2. The heterocycles used in this study.
Conditions | Reaction time/min | Yield/% | |||
---|---|---|---|---|---|
Indol | Benzofuran | Benzotiophene | Indene | ||
Microwave | 5 | 0 | 0 | 10.0 | 29.8 |
10 | 0 | 0 | - | - | |
Conventional | 120 | 0 | 0 | 9.6 | 31.5 |
a. solvent: 1, 2-dichloroethane, b. temperature: 80˚C, c. Fc: arene: AlCl3 = 1:1:2.
Conditions | Reaction time/min | Yield/% | ||
---|---|---|---|---|
Quinoline | Isoquinoline | Naphthalene | ||
Microwave | 5 | 0 | 0 | 20.9 |
Conventional | 120 | 0 | 0 | 31.8 |
a. solvent: 1, 2-dichloroethane, b. temperature: 80˚C, c. Fc: arene: AlCl3 = 1:1:2.
Conditions | Reaction time/min | Yield/% | ||
---|---|---|---|---|
Carbazole | Dibenzofuran | Benzothiophene | ||
Microwave | 4 | 26.4 | 27.7 | 30.4 |
10 | 32.9 | 34.3 | 32.9 | |
Conventional | 120 | 36.9 | 37.6 | 38.5 |
a. solvent: 1, 2-dichloroethane, b. temperature: 80˚C, c. Fc: arene: AlCl3 = 1:1:2.
Furthermore, for these tricyclic heterocycles, shorting of the reaction time was possible by the microwave accelerating effect just like for carbocycles. Namely, for the arenes, which do not react under conventional heating conditions, the reaction also did not occur under the microwave irradiation conditions, while for the arenes, which produce the exchange products, the same products were obtained, and the accelerating effect was recognized. Furthermore, a significant increase in the temperature of the reaction solution was observed as well as in the case of the carbocycles. This means that the ferrocene-AlCl3 adduct would efficiently absorb the microwaves.
As mentioned in the introduction, the ligand exchange reaction of ferrocene proceeds via two steps [
For the reaction using microwaves with carbazole, dibenzofuran, dibenzothiophene, which are tricyclic heterocycles, the same products as those under conventional heating conditions were obtained, and it was confirmed that the reaction time was sharply reduced. Furthermore, from the experiments in which the two tricyclic heterocycles were placed in the same reaction vessel, the order of reactivity was carbazole > dibenzothiophene > dibenzofuran, the same as under the conventional heating conditions. However, under the microwave irradiation conditions, the difference in their reactivity became negligible (
The ligand exchange reaction of ferrocene is a reaction consisting of the two following steps: 1) extraction of the Cp ring by AlCl3, and 2) coordination of the arene to the intermediate [Cp-Fe]+. The microwaves are efficiently absorbed by the ferrocene-AlCl3 adduct or the [Cp-Fe]+. Therefore, it is considered that the first step, including the adduct, received a remarkable accelerating effect as in the case of the carbocycles. In the second step, the difference in reactivity depending on the type of heterocycles would be reduced, because the intermediate, [Cp-Fe]+, which absorbed the microwaves, has a high energy.
Okada, Y., Niou, A. and Nakano, S. (2017) Microwave Irradiation Effect on the Ligand Exchange Reaction between Ferrocene and Heterocycles. Green and Sustainable Chemistry, 7, 95-100. https://doi.org/10.4236/gsc.2017.72008