The article has been mentioned by LR:
Post 108370 (missing)
(dormouse: "Synthesis of asarone from eugenol methyl ether -Labrat", Novel Discourse) - Here follows the actual article (I heard of ppl with too much clove oil to handle
)
Tetrahedron Letters 30(31) (1989) 4037-4040
Electrosynthesis of gamma-asarone
R R Vargas et al.
Abstract: g-asarone is synthesised in high yield, and conveniently, by anodic methoxylation of methyl eugenol, at constant current. The method is extremely simple and inexpensive.
2,4,5-trimethoxyallylbenzene (1) is one of the rarer natural allylbenzenes. It was isolated for the first time from
Caesulia axillaries and named g-asarone.
1 The back and wood of
Aniba hostmanniana, an arboreous species of
Lauraceae contain essential oils composed of ca 95% of (1).
2 The only reported
3 synthesis of (1) is based on the geneneral sequence of reactions: dimethoxyphenol -> allyl dimethoxyphenyl ether -> allyldimethoxyphenol -> trimethoxyallylbenzene, and the overall yield is less than 30%.
Here we report a new synthesis of g-asarone, via the anodic oxidation of methyl eugenol (2) at a platinum electrode in alkaline methanol solution and under controlled current conditions. The average yield, from several experiments, is 80% and the simplicity and low cost clearly show the advantage of this method as compared with the one previously described.
3 This synthesis is another application of anodic methoxylation, a well established method which has been widely used.
4General procedure: The electrolyses were performed in an undivided cell using a Pt foil anode (2.5 x 3.5 cm) and a W wire as cathode. A solution of methyl eugenol (2.8 mmoles) in MeOH (60 mL) containing NaClO4 (6.0 mmoles) and NaOH (30.0 mmoles) was electrolyzed at room temperature (50 mA, 0.0057 Acm
-2 3F/mol). After completion, MeOH was removed under reduced pressure [because of the possible formation of explosive perchlorates the mixture should never be taken completely to dryness]. Water added to the residue, the mixture acidulated with hydrochloric acid until pH 4 and extracted with ether. After concentrating under vacuum, g-asarone was isolated by column chromatography (SiO2, hex-EtOAc 3:2) and fully characterised; spectral data were according to the litterature.
2 When 5.6 moles of (2) were used, under otherwise similar conditions, g-asarone was obtained in lower yields (55%).
The reaction probably proceeds through an intermediate (3) which during acid work-up originates product (1). This type of intermediate was observed during the anodic oxidation of dimethoxybenzenes.
5 CH--CH==CH2 CH--CH==CH2 CH--CH==CH2
| | |
C MeO C C
/ \ \ / \ / \
C C H--C C MeO--C C
| | -2e, 2 MeOH | | H+ | |
C C--OMe -------------> C C--OMe ----------> C C--OMe
\ / -2H+ \ / \ - MeOH \ /
C C OMe C
| | |
OMe OMe OMe
(2) (3) (1)
Intermediate (3) was isolated by work-up under alkaline conditions and characterised by 1H NMR. When analysed by GC/MS (3) gave a peak the at highest mass m/z 194 instead of the expected 240. This is probably due to a fragmentation, in which a molecule of dimethyl ether is lost, and (3) yields (4). [note: fragmentation and molecule (4) not shown].
The g-asarone obtained was isomerized in alkaline solution quantitatively3 into a 5:1 mixture of (E)- and (Z)-2,4,5-trimethoxypropenylbenzenes; the (E) isomer is important as a precursor in a synthesis of magnosalicin.6
As the alkaline isomerization of g-asarone showed to be very time consuming, attempts to prepare (E)-2,4,5-trimethoxybenzene via anodic oxidation directly from methyl isoeugenol (5) were made. However no nuclear methoxylation product could be isolated. In a typical experiment, the electrolysis of a solution of (5) (5.7 mmoles) in MeOH (60 mL) containing NaClO4 (6 mmoles) and NaOH (26.0 mmoles) at room temperature (80 mA, 00.91 Acm-2, 2F/mol), after work-up as described for methyl-eugenol (2), afforded two products derived from the side-chain methoxylation of (5): 1,2-dimethoxy-1-(3,4-dimethoxyphenyl) propane (6) (2.85 mmoles, 50%, erythro/threo, 2.5:1) and 1-(3,4-dimethoxyphenyl)-2-methoxy-propanol (7) (1.14 mmoles, 20%, erythro/threo, 2:1). Both structures were assigned based on GC/MS, IR and 1H/13C NMR measurements.
OMe OMe OH OMe
| | | |
CH==CH--CH3 CH--CH--CH3 CH--CH--CH2
| | |
C C C
/ \ / \ / \
C C C C C C
| | -2e, 2 MeOH | | + | |
C C--OMe -------------> C C--OMe C C--OMe
\ / \ / \ /
C C C
| | |
OMe OMe OMe
(5) (6) (7)
Eugenol (
when oxidized under similar conditions as for (2), but to 1F/mol afforded dehydrodieugenol (9)7 in almost quanitative yield. This electrochemical dimerization has been reported8 but substituting NaClO4 for LiClO4 enabled us to use solutions with eugenol concentrations of up to 0.1 M which is ten times the one originally employed. With LiClO4 and 0.1 M of eugenol the lithium salt of (9) is formed on the electrode impeding the passage of current.
CH--CH==CH3 H2C==CH--CH CH--CH==CH2
| | |
C C C
/ \ / \ / \
C C C C C C
| | -2e, -2 H+ | | | |
C C--OMe -------------> MeO--C C--C C--OMe
\ / \ / \ /
C C C
| | |
OH OH OH
( (9)
Acknowledgements: We are grateful to the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) for a scholarship (RRV) and to Programa de Apoio as Desenvolvimento Cientifico e Tecnologico (PADCT) for financial support.
References:
1. ON Devgan, MM Bokadia, Aust J Chem 21 (1968) 3001
2. OR Gottlieb, AI de Rocha, Phytochem 11 (1972) 1861
3. AT Shulgin, Can J Chem 43 (1965) 3437
4. For leading references see S Torii, "Electroorganic synthesis: methods and applications" Part 1: Oxidations, monographs in modern chemistry, Vol 15, Kodansha, Tokyo and VCH, Weinheim, 1985.
5. NL Weinberg, B Belleau, Tetrahedron 29 (1973) 279
6. K Mori, M Komatsu, M Kido, K Nakagawa, Tetrahedron 42 (1986) 523
7. AF Dias, Phytochem 27 (1988) 3008
8. A Nishiyama, H Eto, Y Terada, M Iguchi, S Yamamura, Chem Pharm Bull 31 (1983) 2820
.: THE END :.
I'm not a specialist in electrochemistry, but I'm sure there are bees who are. This article is intended for them. Enjoy.
Also note that The only reported synthesis of (1) is based on the general... is not completely true, not even for 1989. I've seen several alfa/beta and gamma-asarone synthesis procedures. There even is a procedure involving Elbs persulfate oxidation, but the yields are less then 10%.
