Microwave Isomerization Of Safrole And Eugenol

Abstract

Safrole and eugenol isomerization reactions were carried out under microwave irradiation at atmospheric pressure and homogeneous medium with various alcohols used as solvents and different base concentrations. The rate reaction enhancement shown was 9.3 to 13.9 times faster than conventional reflux.

The safrole (1) and eugenol (2) isomerization reactions are of great interest, since the products isosafrole (3) and isoeugenol (4) are used industrially in the process of manufacturing pharmacos and fragrances. Safrole and eugenol are compounds which are easily obtained, once they are the main components in sassafras and clove oils, respectively¹.

Attempts to isomerize these compounds to the more stable alkenes (3) and (4) by methods described in the literature^2-4 were frustrating due to high base and temperature conditions, inconvenient for large scale bench preparations. Among the alternative methods we tried is the use of microwave irradiation.

Table I:

A comparison of times and yields in isomerization reactions
of safrole using microwave and conventional heating.
The results are the mean of three experiments.

Solvent	[KOH]	t_(c)^a	Yield	t_(mw)^b	Yield	t_(c)^a/t_(mw)^b
EtOH	2M	25 h	88%	240 min	90%	6.2
EtOH	4M	5 h	98%	30 min	99%	10.0
EtOH^c	4M	4 h	99%	20 min	99%	12.0
1-PrOH	2M	4 h	95%	60 min	95%	4.0
2-BuOH	2M	3 h	95%	60 min	96%	3.0
1-BuOH	2M	1 h	98%	20 min	99%	3.0
1-BuOH	4M	0.25 h	99%	3 min	99%	5.0

a) Reaction time using conventional heating
b) Reaction time using microwave heating
c) KCl 2M present.

To study the microwave irradiation effect over isomerization reactions of safrole and eugenol at atmospheric pressure and homogeneous medium, experiments with various alcohols used as solvents and different base concentrations (Tables I and II) were carried out in an adapted microwave oven (Scheme I) and in conventional reflux.

The results showed that the isomerization reactions were fastest for safrole in 1-butanol⁵ and for eugenol in glycerol, using either the method of microwave irradiation or conventional reflux.

The reactions carried out under microwave irradiation were 2.7 to 13.2 times faster than in conventional reflux. This ratio between the reaction times in conventional reflux and microwave irradiation - t_(c)/t_(mw) - under the same conditions, quantifies the microwave heating effect.

Table II:

A comparison of times and yields in isomerization reactions
of eugenol using microwave and conventional heating.
The results are the mean of three experiments.

Solvent	[KOH]	t_(c)^a	Yield	t_(mw)^b	Yield	t_(c)^a/t_(mw)^b
EtOH	2M	25 h	85%	480 min	87%	3.1
EtOH	4M	5 h	95%	60 min	96%	5.0
1-BuOH	4M	2 h	98%	40 min	97%	3.0
1-Pentanol	4M	1.2 h	98%	25 min	99%	2.7
Ethanediol	4M	1 h	99%	10 min	98%	6.0
Glycerol	4M	0.75 h	98%	3 min	98%	13.2

a) Reaction time using conventional heating
b) Reaction time using microwave heating

The ratio shows a relationship with the solvent static dielectric permittivity (Table III), also called "dielectric constant" (in which the losses angle tangent is dependent^6,7). The largest ratios were in ethanol to safrole isomerization and in glycerol to eugenol isomerization, the solvents with highest dielectric permitivities.

In the isomerization reactions, a large ratio relationship with ionic species concentration was still observed (the ionic species increase the dielectric-loss tangent^8-10). The reaction ratio of safrole isomerization in ethanol and 2M KOH was 6.2 times. In ethanol and 4M KOH the ratio was 10.0 times, and it was amplified to 12.0 times with the presence of 2M KCl.

Table III:

Static dielectric permittivity - E(s) - of compounds
used in isomerization reactions.

Solvents	E(s)^a	Reactants/Products	E(s)
Ethanol	24.5	Safrole^b	3.0
1,2-Ethanediol	38.7	Isosafrole^b	3.4
1-Propanol	20.3	Eugenol^b	9.7
Glycerol	42.5	Isoeugenol^b	9.8
1-Butanol	17.5
2-Butanol	16.6
1-Pentanol	13.9

a) Tabulated values¹¹ at 25°C.
b) Measured at 25°C on a Dekameter DK03
apparatus.

The results demonstrate that the microwave energy absorption by reactional solutions was due to conductivity effects (conductivity loss), commonly known as "ohmic effects", together with the dipole alignment and realignment losses of polar molecules (dipolar loss), mainly by solvent molecules.

The cis/trans proportion isomers (30/70) were the same for safrole and eugenol isomerization in microwave heating and in conventional reflux¹².

The enhancement reaction rate of safrole and eugenol isomerizations, shown under microwave irradiation (2.45 GHz/500W) at homogeneous medium and atmospheric pressure, was caused by localized superheating (temperature gradients) in the reactional solutions, as reported elsewhere^10,13-15. These hot spots result from the transferred kinetic energy in and unhomogeneous way, characterised by the occurrence of carbonisation.

When these results are amplified to industrial scales, involving significant differences of time and energy savings, the relationship between costs and advantages of this industrial process may well be significantly altered, resulting in successful applications.

Scheme I

General Procedure:

The alcoholic alkaline solution is prepared by prolonged stirring of 8.8g (or 4.4g) of KOH pellets in 30 ml of alcohol (Tables I and II). The KOH and the alcohols were of analytical purity grade.

The alkaline solution is placed in a round-bottom flask provided with a reflux condenser (microwave and conventional systems). Then 4.0g of safrole (or eugenol) is added and the solution heated. The products arising are followed by UV-Visible spectroscopy by aliquot withdrawal, and, after isolation, the products are characterised by ¹H-NMR spectroscopy¹⁶.

Apparatus: The microwave oven used for this study was a 500W Continental 2001. The reflux system was confectioned in Pyrex glass and adapted through a hole in the oven's upper wall, having a diameter smaller than half the wavelength of the radiation to avoid leakage of microwave radiation¹⁰.

References & Notes

Genbala, G.; "Characterization of Ocotea Pretiosa", Rio de Janeiro, 1955, p. 179, PhD. Theses, Faculdade Nacional de Farrnacia do Brasil.
Cram, D. J. ;"Fundamentals of Carbanion Chemistry", Academic, New York, 1965, Chapter V.
Cerveny, L.; Krejcikova, A; Marhoul, A; Ruzicka, V; React. Kinet. Catal. Lett. 33, 471-6 (1987).
Boedekecker, F.; US Patent 1,812,132.
The safrole isomerization reaction showed sub-product formation when it was carried out in solvents whose boiling point was higher than that of 1-butanol.
Partington, J. R.; "An Advanced Treatise on Physical Chemistry", sec. edition, Longmans Co. Ltd., 1960, Vol. IV e V.
Bottcher, C. J. F.; Bardawijk; "Theory of Electric Polarization", sec. edition, Elsevier SPC. 1978, Vols. I and II.
Flugge, S.; "Handbuch der Physik, Dielektrika", Springer-Verlag, 1956, band XVII.
Metaxas, A. C.; Meredith, R. J.; "Industrial Microwave Heating", Peter Peregrinus, 1983.
Baghurst, D.R.; Mingos, D. M.; J. Chem. Soc. Dalton Trans. 1992, 1151-5.
Dean, J. A., "Lange's Handbook of Chemistry", thirteenth edition, Mc. Graw-Hill Book Company, 1985.
The cis/trans ratio was determined by ¹H-NMR analyses of spectral signals at 1.86 ppm (3H, dd, 2 and 8 Hz) for cis isomer and at 1.83 ppm (3H, dd, 1,5 and 8 Hz) for trans isomer.
Lefeuvre, S.; Giboreau, P.; Berlan, J.; Tetrahedron Letters, Vol. 32, 21, 2363-6 (1991).
Abramovitch, R. A.; Iyanar, K.; Tetrahedron Letters, Vol. 32, 39, 5251-4 (1991).
Berlan, J.; Poux, M.; Chemat, F.; J. Chem. Soc. Perkin Trans. 2, 2597-2602 (1994).
Spectral data for Isosafrole: ¹H-NMR (200 MHz, CDCl₃): δ 6.85-6.75 (3H, m, ArH), 6.34 (1H, d, 14 Hz, CH=), 6.25-6.15 (1H, m, =CH), 5.87 (2H, s, OCH₂O), 1.83 (3H, dd, 1,5 and 8 Hz, CH₃).
UV-Vis(EtOH): 260 nm (ε = 12020), 304 nm (ε = 5370).
Spectral data for Iso-eugenol: ¹H-NMR (200 MHz, CDCl₃): δ 6.82-6.76 (3H, m ArH), 6.40 (1H, d, 13 Hz, -CH=), 6.15-6.03 (1H, m, =CH-), 5.65 (1H, s, -OH), 3.82 (3H, s, -OCH₃), 1.83 (3H, dd, 1.5 and 8 Hz, -CH₃).
UV-Vis(EtOH): 260 nm(ε = 16600), 300 nm (ε = 5011).