Environment-friendly, mild and one-step synthesis of Safrole

Article abstract of DOI:10.14233/ajchem.2015.18083

One-step synthesis of safrole, an important flavor compound, was described. Safrole was prepared by Friedel-Crafts reaction of 1,2-methylenedioxybenzene and allyl alcohol with recyclable Catalysts-Nafion-H. Safrole was obtained with a yield of 80 % and little isosafrole was obtained. The catalyst and excess raw material can be recycled and reused.

Full text of DOI:10.14233/ajchem.2015.18083

Asian Journal of Chemistry; Vol. 27, No. 3 (2015), 1175-1176
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SIAN
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OURNAL OF HEMISTRY
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http://dx.doi.org/10.14233/ajchem.2015.18083
NOTE
Environment-Friendly, Mild and One-Step Synthesis of Safrole
1
2,*
WENHUA OU and HONG HUANG
1School of Perfume and Aroma Technology, Shanghai Institute of Technology, P.R. China
2College of Marine Science, Shanghai Ocean University Shanghai, P.R. China
*Corresponding author: Tel: +86 21 61900332, E-mail: hhung@shou.edu.cn
Received: 26 May 2014;
Accepted: 14 August 2014;
Published online: 19 January 2015;
AJC-16751
One-step synthesis of safrole, an important flavor compound, was described. Safrole was prepared by Friedel-Crafts reaction of 1,2-
methylenedioxybenzene and allyl alcohol with recyclable Catalysts-Nafion-H. Safrole was obtained with a yield of 80 % and little
isosafrole was obtained. The catalyst and excess raw material can be recycled and reused.
Keywords: Safrole, Friedel-Crafts reaction, One-step, Nafion-H.
Great efforts of catalysis research have been devoted in
recent years on the development and application of effective
and safe heterogeneous catalysts. This is an important tendency
in industry but also in the laboratory practice. These studies
have been especially successful in the development of solid
acids to replace aggressive and dangerous homogeneous acid
catalyst.
Solid Brønsted acids with super acidic character, such as
Nafion-H, are of great interest in the synthesis of fine chemicals.
Nafion-H resin is a kind of solid superacid catalyst with the
structure of perfluorinated alkyl sulfuric acid. Due to the easy
separation after the reaction and highly catalytic activity, it
has been widely used in the organic synthesis instead of the
triflic acid and concentrated sulfuric acid. It shows highly
activity towards Friedel-Crafts alkylation and acylation reac-
tions1-3. In order to increase the surface area of the catalyst,
the Nafion resin/silica composite catalyst has also been studied
and it shows highly catalytic activity4-6.
Safrole is an abundant Brazilian natural product from
sassafraz oil (Ocotea preliosa Mer., Lauraceae), which presents
interesting functionality and chemical reactivity that suggests
its use as an efficient and versatile natural synton7-12. The
methylenedioxy unit from safrole, has been identified in some
clinical antitumor agents like etoposide and teniposide13.
Safrole has been used as a flavoring agent in drugs and in the
manufacturing of heliotropin, perfumes, soaps and piperonyl
butoxide (a compound used in a variety of insecticides to
enhance the pesticidal properties of other active ingredients).
Safrole has also been used as a preservative in mucilage and
library paste and as a flotation frother. Oil of sassafras, which
contains safrole, was formerly used to flavor some soft drinks,
such as root beer. With the increasing scarcity of natural
resources and the need for safrole is growing, lots of efforts
have been spent on developing simple and practical synthetic
route for the preparation of safrole recently14-16
.
Tsukada, et al.14 synthesized safrole from allyl alcohol and
1,2-methylenedioxybenzene catalyzed [Rh(nbd)-(CH3CN)2]
PF6. Although it used allyl alcohol as the raw material which
was obtained easily, allyl alcohol should be converted into the
corresponding tosylate and the product was obtained by Friedel-
Crafts reaction using a relatively expensive catalyst, only given
45 % of the isolated yields in the key step (Fig. 1).
Lin and Yang15 synthesized this compound from 1,2-
methylenedioxybenzene by bromination with bromine and
Grignard reaction with allyl bromide. In this process, poly-
brominated product would be produced in the bromination of
1,2-methy-lenedioxybenzene and self-coupling reaction would
also occur inevitably in Grignard reaction of 5-bromobenzo-
[d][1,3]-dioxole reacting with allyl bromide, thus the final yield
of 45.9 % was obtained in this synthetic route. it is feeble that
the reaction given the relatively low yield and needed the
relatively rigid reaction conditions (Fig. 2).
Protti et al.16 synthesized this compound from 1,2-methylene-
dioxybenzene and allyltrimethylsilane irradiated at 310 nm.
Though the use of allyltrimethylsilane (ATMS) ensured a
straightforward formation of the desired allyl benzenes as the
only products and avoided competitive reactions from the 1,2-
methylenedioxybenzenium ion, such as nucleophilic addition

1176 Ou et al.
Asian J. Chem.
O
activity of regenerated catalyst was as good as that of fresh
catalyst.
O
O
O
OH
O
S
Inspired by the literatures17,18, we prepared safrole from
1,2-methylenedioxybenzene and allyl alcohol by catalysis of
Nafion-H resin. The process of this reaction were optimized.
And it was shown that the excess raw material of 1,2-
methylenedioxybenzene and 10 % the amount of catalyst
(wt. %) based on the 1,2-methylenedioxybenzene was more
appropriate than any of the other conditions. The same molar
amounts of 1,2-methylene-dioxybenzene and allyl alcohol
produced only a little safrole. This is probably due to facile
formation of di-allyl ether. Little iso-safrole was detected. This
is probably due to stability of the allyl ion which formed by
the reaction of allyl alcohol and catalysts of Nafion-H resin.
In this process, 1,2-methylenedioxybenzene was successfully
used as raw material and reaction solvent avoid using any other
solvents. Excess 1,2-methylenedioxybenzene could be
recycled and reused. The catalyst Nafion-H could also be
recycled. This would not only save costs of raw materials but
also to avoid adding other substances, making the process
easier.
O
[Rh(nbd)(CH CN) ]PF
6
O
3
2
Fig. 1. First synthetic method of safrole
Br
MgBr
O
O
Br
Br2
O
O
O
O
O
Mg
THF
O
Fig. 2. Second synthetic method of safrole
by the solvent orWagner-Meerwein hydride and alkyl migration,
obtaining the raw material in this process is not easy, the
relatively low yield (54-77 %) and no practical applicability
of this photochemical reactions is evidently (Fig. 3)16 .
O
O
O
O
hv
Si
+
Fig. 3 third synthetic method of safrole
There are still some room for improving synthetic process.
Herein we report an environment-friendly, mild and one-step
synthetic route for the preparation of safrole.
The synthesis was initiated from 1,2-methylenedioxy-
benzene and allyl alcohol (Fig. 4) and catalyzed by Nafion-H
resin, safrole was obtained in 80 % yield and little isosafrole
was obtained.
Conclusion
In conclusion, comparisons of traditional synthesis
methods indicated that its ease of work-up, environment-
friendly, fairly mild reaction conditions provide an improved
access to safrole. The yield of the reaction is 80 % and little
isosafrole is obtained. Other applications of this catalyst
Nafion-H are under investigation in our laboratory.
O
O
O
O
Nafion-H
R.T.
+
HO
ACKNOWLEDGEMENTS
Fig. 4. New synthetic method of safrole
This study was supported by Innovation Program of
Shanghai Municipal Education Commission (12YZ128).
The following reagents and solvents used in this prepara-
tion were sourced from some chemical company in China and
used without further purification. Structure of the product was
characterized by its physical data as well as the IR and NMR
REFERENCES
1. G.A. Olah, J. Kaspi and J. Bukala, J. Org. Chem., 42, 4187 (1977).
2. K. Arata, H. Nakamura and M. Shouji, Appl. Catal. A, 197, 213 (2000).
3. G.A. Olah, R. Malhotra, S.C. Narang and J.A. Olah, Synthesis, 672
(1978).
4. M.A. Harmer, W.E. Farneth and Q. Sun, J. Am. Chem. Soc., 118, 7708
(1996).
1
spectra. H NMR spectras were recorded using Avance 400
MHz spectrometer. IR spectra were determined as KBr pellets
on a Bruker Vertex 70 spectrophotometer. ESI-MS were
recorded on Dionex MSO Plus Mass Spectrometer.
5. D. Zhou, J.Yang, G. Dong, M. Huang andY. Jiang, J. Mol. Catal. Chem.,
159, 85 (2000).
6. B. Török, I. Kiricsi, Á. Molnár and G.A. Olah, J. Catal., 193, 132
(2000).
7. A.S. Lages, K.C.M. Silva, A.L.P. Miranda, C.A.M. Fraga and E.J.
Barreiro, Bioorg. Med. Chem. Lett., 8, 183 (1998).
8. A.C. Silva, E.S. Mendonça and C. Reis, Quim. Nova, 26, 344 (2003).
9. E.J. Barreiro and C.A.M. Fraga, Quim. Nova, 22, 744 (1999).
10. P.R.R Costa, C.C. Lopes, An. Acad. Brasil Cienc., 54, 758 (1982).
11. E.J. Barreiro, P.R.R. Costa, P.R.V.R. Barros andW.M. Queiroz, J. Chem.
Res. (S), 102 (1982).
12. L.G. French, J. Chem. Educ., 72, 484 (1995).
13. G.L. Chen, L. Yang, T.C. Rowe, B.D. Halligan, K. Tewey and L. Liu,
J. Biol. Chem., 259, 13560 (1984).
General procedure: Nafion-H (14.65 g, 10 % wt. % based
on the 1,2-methylene-dioxybenzene was used) was added to
the mixture of 1,2-methylenedioxybenzene (146.54 g, 1.2 mol)
and allyl alcohol (2.33 g, 0.04 mol) and stirred at room tempe-
rature until the allyl alcohol is disappeared. The Nafion-H
catalyst was filtered off. Excess 1,2-methylenedioxybenzene
was removed under reduced pressure. The crude product was
vacuum distilled, 5.19 g of safrole, boiling at 120-130 °C (10-
15 mm Hg), was obtained. Colourless and typically smelling
1
oil. Total yield (from the allyl alcohol), 80 % of theory. H
NMR (400 MHz, CDCl3) δ 6.78 (d, J = 7.8 Hz, 1 H), 6.71 (s,
1 H), 6.69 (d, J = 7.8 Hz, 1 H), 5.99-5.92 (m, 3 H), 5.13-5.08
(m, 2 H), 3.25 (d, J = 6.4 Hz, 2 H). IR (cm-1): 3032, 2990,
1646, 1590. ESI-MS m/z: 163.3 (M + H)+.
Regeneration of nafion-H catalyst: The used catalyst
was washed several times with acetone and deionized water,
followed by drying at 105-110 °C for 10-12 h. The catalystic
14. N. Tsukada, Y. Yagura, T. Sato and Y. Inoue, Synlett, 1431 (2003).
15. B. Lin and X. Yang, Guangdong Huagong, 30, 6 (2003).
16. S. Protti, M. Fagnoni andA.Albini, Org. Biomol. Chem., 3, 2868 (2005).
17. T.Yamato, C. Hideshima, G.K.S. Prakash and G.A. Olah, J. Org. Chem.,
56, 2089 (1991).
18. B.R. Cho and H.J. Yang, J. Bull. Korean Chem. Soc., 12, 463 (1991).