The Claisen rearrangement is a [3,3]-sigmatropic rearrangement which is an important method for new C-C bond formation in organic synthesis. This reaction is a typical thermal reaction that requires a high temperature and long reaction time. In this paper, the acceleration effects of the iron (III) chloride (FeCl 3) catalyst and microwave irradiation during the Claisen rearrangement reaction of allyloxyarene derivatives are reported. The FeCl 3 catalyst was able to initiate the reaction at low temperature and induced the subsequent cyclization reaction. The moderation of excellent yields was obtained in a short reaction time. The formation of complex ferric-arenes under microwave irradiation conditions to efficiently absorb the microwaves was expected and confirmed.
Presently, several environmental problems such as global warming and pollution caused by an industrial process become the world concern. Regarding to the considerable impact of environmental problems, the production of chemicals using the principles of green chemistry is extensively studied. The environment-friendly reaction becomes the main topic in organic synthesis.
Since discovered in 1912, the Claisen rearrangement reaction has been developed into one of the most powerful C-C bond forming methods in organic synthesis [
A large amount of the Lewis acid is attempted to catalyze the Claisen rearrangement reaction. The Lewis acid has been reported as having the properties that can form transition metal complexes that promote and facilitate the intramolecular rearrangement [
On the other hand, it is known that a directly heating method is conventionally used as the heating source for organic reactions. Because these methods depend on convection currents and the relatively low thermal conductivity of the reaction mixtures, it would be an inefficient way of transferring heat to the sample [
This study used four observation materials. The substrate allyloxybenzene (1a) was obtained from commercial sources (WAKO Chemical Ltd.). The substrates 1-allyloxynaphthalene (2a), 1-crotyloxynaphthalene (3a) and 1-cinnamyloxynaph- thalene (4a) were synthesized based on a previous report [
The reaction mixtures (0.5 mmol substrate, 0.15 molar ratio FeCl3 catalyst and 7 cm3 of 1,2-dichloroethane) were reacted under the microwave irradiation conditions. At a specific time, a 0.1 cm3 sample was taken out by a syringe with a long needle. The reactions were performed at several temperatures of 50˚C, 60˚C, 70˚C and 80˚C.
The ratio of the products was identified by High Performance Liquid Chromatography (HPLC) analysis using a Shimadzu LC-20A system equipped with a UV detector. An ODS column was used with methanol: water (9:1, v/v) as the eluent. The structure of the products was confirmed by Nuclear Magnetic Resonance (NMR) and Gas Chromatography Mass Spectrometer (GC-MS) analysis. The NMR spectra were recorded by an FT-NMR ECS 400 (JEOL) at 400 MHz (1H) and room temperature in CDCl3. The molecular weight and mass fragmentation of the products were determined using a GC-MS QP5050A from Shimadzu. The 1H-NMR relaxation time was measured by the inversion-recovery method to investigate the molecular motion of the proton.
Initially, the Claisen rearrangement of the allyloxybenzene (1a) was investigated in the absence of the FeCl3 catalyst. As the result, the reaction could not take place without the FeCl3 catalyst at 80˚C under microwave irradiation and no product was observed. In the presence of the FeCl3 catalyst, the reaction proceeded. Based on previous reports, the utilization of a metal catalyst induced a sequential reaction [
The reaction mechanism was suggested through rearrangement of 1a affords 1b, followed by cyclization of 1b leading to 1c (Scheme 1). It was postulated that FeCl3 catalyzed the rearrangement and cyclization reaction through coordination to the oxygen atom at the transition state. FeCl3 facilitated the reaction by causing an inductive effect that would effectively polarize the transition state. This interaction would decrease the activation energy so that the reaction could proceed at low temperature.
Scheme 1. The rearrangement and cyclization reaction pathway.
Before investigating the more complex structures, the kinetic behaviors of the reactions were studied. The decreasing amounts of 1a and increasing amounts of 1c were measured as a function of time at four different temperatures between 50˚C and 80˚C in 1,2-dichloroethane. The plots of the natural logarithms of the concentrations of 1a and 1c versus time at each temperature are shown in
From
Temperature (˚C) | k1 × 104 (s−1) | K2 × 104 (s−1) |
---|---|---|
50 | 1.13 | 0.13 |
60 | 1.51 | 0.28 |
70 | 2.05 | 0.75 |
80 | 2.96 | 1.93 |
The Ea values of the rearrangement and cyclization reactions calculated from the slope were 30.22 kJ/mol and 85.92 kJ/mol, respectively. The Ea value of the cyclization reaction was higher than that of the Claisen rearrangement reaction. The proposed energy profile showed that the cyclization reaction of 1b required a higher energy to proceed than the Claisen rearrangement reaction of 1a (
It was then necessary to determine if the reaction was proceeding through an intermolecular mechanism in which the substrate became fragmented into separate nuchleophilic and electrophilic species or through an intramolecular mechanism. Previously, our laboratory reported that naphthalene derivatives have an intermolecular rearrangement character [
As the results, the main product of the reaction of 3a and 4a were the intramolecular rearranged one even in the presence of FeCl3. The intermolecular rearranged product was not observed in the reaction mixtures. This clearly showed that the reaction occurs through the intramolecular mechanism and not the intermolecular mechanism. The authors also reported the use of a crotyloxy group in the aromatic Claisen rearrangement, which is not a well-known starting material for the aromatic Claisen rearrangement unlike the cinnamyloxy group. The product yields of 3a were higher than those of 1a and 2a, however, the dehydrogenation product (3d) was formed. The methyl substituent acts as an electron donating group, thus enhancing the electron density of the carbon atom where the formation of new bond will take place. Therefore, the yield increased for the reaction of 3a. In this case, the additional methyl substituent on the allyl moiety also leads to the dehydrogenation reaction of the coumaran derivatives.
Entry | Reactant | Products Yield (%)a,b,c,d | |
---|---|---|---|
1 | |||
2 | |||
3 | |||
4 |
aSolvent: 1,2-dichloroethane, bMethod: microwave 300 W, cReaction time: 60 minutes, dThe yields were determined by HPLC.
Interestingly, the reaction of 4a only produced 4b as the main product in an excellent yield. The cyclization product was not formed in the reaction of 4a. On the other hand, our previous studies showed that the para-rearranged product is accelerated for cinnamyloxyarene derivatives. Because the stable conformation for the cinnamyloxyarene derivatives, in which the C-C double bond is near the naphthalene ring and the phenyl group is situated away from the naphthalene ring, is easily converted in the transition state to the para-rearranged product [
In this study, we suggested that the phenyl ring blocked the binding site between the oxygen atom and the double bond during the reaction. As shown in
The spin-lattice relaxation time (T1) can be used to determine the conformational preference of the molecules [
Based on these results, the T1 of the C3 proton of 4b was determined to be 9.66 s. This T1 value is higher compared to those of the other two substrates. The high T1 suggested that the C3 proton has a high mobility and the phenyl group lies away from the C3 proton. In the case of 3b, the rotation around the C2-Cγ bond axis hinders the motion of the C3 proton, thus the relaxation time would be short.
In this study, the comparison between the microwave irradiation and oil bath heating for the Claisen rearrangement reaction of allyloxyarenes is discussed. The results are summarized below in
As can be seen in
the yield from the microwave 500 W is double that for the oil bath heating. This would be due to the fact that decalin is a nonpolar solvent which does not absorb the microwaves, so the accelerating effect occurs on the polar substrates. However, the microwave accelerating effect was not observed in the Claisen rearrangement of 3a. The additional methyl substituent which attribute to the high reactivity might shade the microwave effect. In the case of 1a reaction, an increase in the microwave power was necessary to increase the product yields. Since decalin has a low dielectric constant, thus a higher energy to promote the reaction during the microwave irradiation was required.
1,2-Dichloroethane has a low polarity compared to decalin. Based on a previous report, the Claisen rearrangement is accelerated by a more polar solvent, because the transition state, in which the oxygen atom has a higher electron density, is stabilized by the coordination of the solvent [
The temperature change in the reaction system under microwave irradiation was found. The substrates 1a and 2a were dissolved in the solvent and irradiated by the microwave. Then temperature versus microwave irradiation time was measured at the same conditions for the reaction system. The results are shown in
complex species was expected to efficiently absorb the microwaves and affected the temperature. The high temperature in the micro region around the species would influence the acceleration effect during the microwave heating reaction.
Based on a 1H-NMR relaxation time study, the expected formation of the ferric-arenes complex was elucidated. Generally, shortening of the proton relaxation time indicates a decreasing of the mobility of the proton [
Entry | Substrate | Chemical shift (ppm) | Relaxation time (s) | |
---|---|---|---|---|
Substrate alone | With FeCl3 | |||
1 | a (δ 7.25 ppm) b (δ 6.94 ppm) | 5.19 5.38 | 4.02 4.13 | |
2 | δ 1.42 ppm | 5.19 | 5.32 | |
3 | a (δ 8.30 ppm) b (δ 7.80 ppm) c (δ 7.48 ppm) d (δ 7.44 ppm) e (δ 7.36 ppm) | 6.93 4.96 4.55 5.45 3.35 | 5.00 4.28 3.88 4.97 3.61 | |
4 | a (δ 1.55 ppm) b (δ 1.23 ppm) c (δ 0.90 ppm) | 2.05 1.78 2.44 | 2.71 2.51 2.55 |
In this study, the combination of the FeCl3 catalyst and microwave irradiation allows the reactions to occur under milder reaction conditions. The FeCl3 catalyst is able to initiate the Claisen rearrangement reaction of allyloxyarenes at the low temperature of 80˚C. FeCl3 coordinates on the etheral oxygen to reduce the transition state energy. The reaction occurs through an intramolecular mechanism, not the intermolecular one, even in the presence of the FeCl3 catalyst. The microwave accelerating effect was observed and it was affected by the type of solvent. Furthermore, the formation of the complex ferric-arenes, which were expected to efficiently absorb microwaves, was confirmed. For the rearrangement of cinnamyloxynaphthalene (4a), FeCl3 coordinates on both the oxygen and the phenyl ring. This structure would efficiently absorb the microwaves as well as reduce the energy of the transition state. Namely, the active species of the Claisen rearrangement efficiently absorbs the microwaves. Finally, the authors expect that these findings can offer such an environment-friendly reaction which leads to the green chemistry reaction.
Pramesti, I.N. and Okada, Y. (2017) Iron (III) Chloride Catalyzed Claisen Rearrangement Reaction of Allyloxyarenes under Microwave Conditions. Green and Sustainable Chemistry, 7, 234-245. https://doi.org/10.4236/gsc.2017.73018