A Facile, Convenient, and Green Route to (E)-Propenylbenzene Flavors and Fragrances by Alkene Isomerization

Article abstract of DOI:10.1055/s-0035-1560205

(E)-Propenylbenzene flavors and fragrances can be made and isolated in high yield and selectivity by using bifunctional catalyst 1, and the heterogenized analogues. Multigram-scale reactions can be performed neat and the products isolated either by distillation, using homogeneous catalyst 1 (0.1-0.5 mol%, r.t., 10-45 min), or by decantation from heterogeneous catalysts PS-1 or PSL-1 (0.5 mol%, 70 °C, 24 h; catalyst separation and re-use shown for 3-4 cycles; 10 cycles using distilled eugenol feedstock). Both purified starting materials and essential oil feedstocks could be used. Z Isomers were present at very low levels (from 0.4% to less than 0.1%) in the products.

Full text of DOI:10.1055/s-0035-1560205

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2015, 26, 2462–2466
letter
2462
C. R. Larsen et al.
Letter
Synlett
A Facile, Convenient, and Green Route to (E)-Propenylbenzene Fla-
vors and Fragrances by Alkene Isomerization
Casey R. Larsen
Erik R. Paulson1
Gulin Erdogan1
Douglas B. Grotjahn*
San Diego State University, Department of Chemistry and Biochemistry,
5500 Campanile Drive, San Diego, CA, 92182-1030, USA
dbgrotjahn@mail.sdsu.edu
This article is dedicated to Peter Vollhardt with gratitude for his creative,
scientific, and mentoring influences, and his love of one-pot reactions
Received: 30.03.2015
Accepted after revision: 30.07.2015
Published online: 08.09.2015
is the major volatile component in sassafras12 and long pep-
per oil.23 Isosafrole is an important intermediate for the
synthesis of pharmaceutical compounds, such as strigol,24
amphetamines,25 and piperonal fragrance.2,26
DOI: 10.1055/s-0035-1560205; Art ID: st-2015-b0231-l
Abstract (E)-Propenylbenzene flavors and fragrances can be made
and isolated in high yield and selectivity by using bifunctional catalyst
1, and the heterogenized analogues. Multigram-scale reactions can be
performed neat and the products isolated either by distillation, using
homogeneous catalyst 1 (0.1–0.5 mol%, r.t., 10–45 min), or by decan-
tation from heterogeneous catalysts PS-1 or PSL-1 (0.5 mol%, 70 °C, 24 h;
catalyst separation and re-use shown for 3–4 cycles; 10 cycles using dis-
tilled eugenol feedstock). Both purified starting materials and essential
oil feedstocks could be used. Z Isomers were present at very low levels
(from 0.4% to less than 0.1%) in the products.
Early manufacture of valuable phenylpropenoids on
commercial scale was done using stoichiometric or excess
base at temperatures over 200 °C,27 but with modest E/Z se-
lectivity (82:18). According to food regulations, exceeding
any more than 1% cis isomer cannot be tolerated due to its
toxicity and unpleasant taste.28–31 Transition-metal cata-
lysts generally isomerize allyl benzene flavors and fragranc-
es to their phenylpropene analogues at moderate tempera-
tures, but high E/Z selectivity remains a challenge, as re-
ported for complexes of titanium,32 iron,33 nickel,34
ruthenium,35–38 rhodium,39 and platinum,40 where a compi-
lation of such has been documented in a recent review.41
Basic ligands,42 bases grafted onto zeolite43,44 and metals in-
tegrated into hydrotalcites,35,45 have also been reported for
the isomerization of these compounds. A platinum catalyst
converts allyl benzenes at 50 °C into moderate yields (38–
60%) and insufficient E/Z selectivity (63:37 to 97:3).40 Mi-
crowave isomerization of allyl benzenes using KF/Al2O3 al-
lows for high conversions (>96%) with variable E/Z selectivi-
ty (<91:6).46 As far as we are aware, the most promising
combinations of yield and selectivity come from [RuCl2(η6-
C6H5OCH2CH2OH)(L)] [L = P(OMe)3] for the conversion of
estragole into anethole in 99% yield with >99% E selectivity
at 80 °C in 15 minutes.37 [RuCl2(η6-cymene)(P(OMe)3)]
formed in situ achieved similar yield, but the distilled prod-
uct was insufficient in E selectivity (98%) to comply with
regulations cited above.47 Chemical companies Rhone-
Poulenc48 and Givaudan49 explored catalysts for isomeriza-
tion of these compounds, where the best afforded 10% and
6% (Z)-propenylarene, respectively; the latter product also
contained some unreacted starting material.
Key words alkenes, isomerization, flavors, fragrances, homogeneous
catalysis, heterogeneous catalysis
The flavor and fragrance industry continues to grow,
with a total worldwide market of $16 billion annually in
2002,2 estimated at $25 billion in 2014.3 Allyl benzenes,
such as estragole, eugenol, and safrole are major constitu-
ents of essential oils. Commercial processes convert the
compounds into their propenyl analogues, anethole, isoeu-
genol, and isosafrole. trans-Anethole is an important com-
modity with an annual global production of 750,000 tons
per year4 and is produced on the largest scale from star an-
ise and anise2,5 and fennel oils.2 trans-Anethole is produced
by the isomerization of estragole and finds applications in
the perfumery industry,6 food and beverage industries,7 for-
mulation of oral sanitation products,8 and as an important
intermediate in the synthesis of pharmaceutical com-
pounds.9–11 Eugenol is the major constituent of volatile oils
derived from cloves12–14 and cinnamon,15 whereas isoeuge-
nol is minor.5 Isoeugenol is used in perfumes2,16 and vanil-
lin,17 and used for antioxidant,18,19 anxiolytic, antidepres-
sant,20 insecticidal,21 and antimicrobial22 properties. Safrole
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2462–2466

2463
C. R. Larsen et al.
Letter
Synlett
Industrial demand for phenylpropenoids such as trans-
anethole, isoeugenol, and isosafrole has increased, prompt-
ing more efficient and green processes for their production,
with minimal use of energy, excess reagent base, solvent for
reaction or extraction, or fractional distillation because of
isomeric mixtures.
stituent of rhizome63 and Russian tarragon64 oils. Catalyst 1
interacts selectively with the allyl moiety of allyl tiglate (7),
a flavoring,65 leaving the tiglate moiety untouched. In sum-
mary, at low loadings and ambient temperatures, homoge-
neous catalyst 1 in acetone solvent very easily converts fla-
vors and fragrances into the desired E products.
We have previously shown that homogeneous catalyst 1
(Figure 1) isomerizes many types of substrates, moving ter-
minal alkenes on unhindered chains extensively (up to 30
bonds), with high E selectivity.50,51 In addition, hydrogen–
deuterium exchange occurs in the presence of D2O under
isomerization conditions using 1.52,53 The bifunctional li-
gand basic nitrogen has been shown to lead to >3000-fold
increases in catalytic activity.54 Finally, we reported the
synthesis and application of heterogenized isomerization
catalysts.55 The linker between the active site and the poly-
styrene resin is either a short CH2 bridge (PS-1) or longer
(PSL-1) to allow greater distance and mobility between the
catalytic active site and polymer (Figure 1).
Heterogeneous isomerization catalysts PS-1 and PSL-1
show the same high selectivity as 1 (Table 1). For example,
estragole (2) is completely converted into (E)-anethole (2a)
using 2 mol% PS-1 and PSL-1 in 20 minutes. Looking at the
other entries of Table 1, in a few cases 70 °C was used, but
most reactions could be conducted at room temperature.
Comparing rates of homogeneous and heterogeneous cata-
lysts in entry 1 (Table 1), 40 times more heterogeneous cat-
alyst was used but the reaction time for completion was
half as long, indicating that the heterogeneous systems
were about 20 times slower, but still usefully active; note
that even the best homogeneous allylbenzene-to-propenyl-
benzene catalysts reported by Cadierno and Crochet require
heating at 80 °C to achieve 15 minutes reaction time (5 min
using microwave irradiation).37
Cp
Cp
Ru
N
Isomerization reactions in acetone solvent occur in a
smooth and facile manner using both 1 and its heteroge-
nized analogues, but the ability to conduct completely sol-
vent-free reactions would make for even more convenient
and greener reaction conditions. We examined multigram-
scale reactions of neat liquid substrates using the homoge-
neous catalyst 1, extending our previous single reported at-
tempt to several natural oils.
PF6
Ru
N
PF6
P
N
MeCN
P
N
MeCN
X
1
PS-1: X = CH2
PSL-1: X = (CH2)3OCH2
To start, using pure estragole (2) as the starting materi-
al, adding 0.1 mol% 1 led quickly (TOF: 22.2/min) to
(E)-anethole (2a) in 93.0% (4.65 g) isolated yield via vacu-
um distillation (Scheme 1). Similarly, pure eugenol (3) was
isomerized to (E)-isoeugenol (3a) using 0.1 mol% catalyst in
20 minutes (TOF: 50/min) to obtain 15.76 g of the isolated
product (Scheme 1). The reactions are somewhat exother-
mic; on the scales mentioned, liquid baths around the
flasks maintained near-ambient temperatures for compara-
tive data. Careful analysis of the distilled product 2a in
CDCl3 led us to determine that no detectable Z-isomer had
been formed, with an estimated lower limit of detection of
0.1%. For 3a, 0.4% Z-isomer was seen. Further optimization
will be done to see if deactivation of catalyst before heating
during distillation will reduce the levels of Z-isomer further.
Essential oils are the volatile aromatic compounds
found in the many parts of plants, such as flowers, stems,
bark, roots, and seeds, where each are unique with regards
to the variation and amount of constituents present in the
oil. For instance, sassafras oil from Sigma Aldrich is >90%
safrole (6), along with reported impurities arsenic, cadmi-
um, mercury, and lead.66 The isomerization of safrole or eu-
genol in nonpurified sassafras or clove oil feedstocks using a
catalyst that is not inhibited by impurities would be attrac-
tive. We found that 0.5 mol% catalyst 1 allows full conver-
sion of 6 in neat sassafras oil in 30 minutes; subsequent
Figure 1 Homogeneous alkene isomerization catalyst 1 and support-
ed catalysts PS-1 and PSL-1 (sphere = polystyrene)
Herein, we focus on applications to flavors and fra-
grances, including multigram (up to 15 g) conversions of al-
lyl benzene starting materials to (E)-propenoid analogues
with complete conversions and exclusive E selectivities de-
manded by these applications. First, we disclose solution-
phase reactions, followed by neat reactions.56
As summarized in Table 1, in acetone solution, allyl ben-
zenes estragole (2), eugenol (3), methyl eugenol (4), and
elemicin (5, Table 1, entries 1–4) were each converted ex-
clusively into E products 2a–5a using 0.1 mol% of 1 in 10–20
min. In two cases tried, half as much catalyst could also be
used, whereas safrole in sassafras oil (6) required the great-
er catalyst loading seen in entry 5 (Table 1). Methyl eugenol
(4) is a minor constituent of bay leaf oil15 and has been
known to be an attractant57 and fumigant58 for fly species,
in addition to containing antifungal properties59 and being
a food additive. Isomerization of methyl eugenol to methyl
isoeugenol, which is a major constituent of pimento
pseudocaryophyllus leaf oil,20 has been reported in moder-
ate to good yield,40,42,60 and the product is used as food fla-
voring.20 Elemicin (5) is a major constituent of elemi, nut-
meg, and mace oil,61,62 and (E)-isoelemicin is a minor con-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2462–2466

2464
C. R. Larsen et al.
Letter
Synlett
Table 1 Alkene Isomerization of Allylbenzene to Propenylbenzene Flavors and Fragrancesa
Entry
1
Substrate
Product
Catalyst
mol (%)
Time (min)
Yield (%)
1
0.05
0.1
2
40
10
20
20
99
100
95
PS-1
PSL-1
MeO
estragole (2)
MeO
anethole (2a)
2
91
MeO
MeO
1
0.05
0.1
1
20
10
45
60
100
100
96
2
3
PS-1
PSL-1
HO
eugenol (3)
HO
1
94 (2.9)b
isoeugenol (3a)
MeO
MeO
1
0.1
1.1
1.1
15
85
220
100
PS-1c
PSL-1c
97 (1.8)b
91 (2.4)b
MeO
methyl eugenol (4)
MeO
methyl isoeugenol (4a)
MeO
MeO
MeO
MeO
1
0.1
1
1.1
20
130
115
98
4
PS-1c
PSL-1c
95 (4.9)b
96 (3.4)b
OMe
OMe
elemicin (5)
isoelemicin (5a)
O
O
1
0.6
1.9
2
10
90
75
98
5d
PS-1c
PSL-1c
98
96 (2.7)b
O
O
safrole (6)
isoafrole (6a)
O
O
6
1
0.9
300
96 (2.9)b
O
O
allyl tiglate (7)
propenyl tiglate (7a)
a Substrate (0.50 mmol), acetone-d6 solvent, r.t., NMR yield. In cases where NMR yield (est. 1% uncertainty) was measured as slightly above 100, the yield is given
as 100. No starting material detectable, unless otherwise specified.
b The amount of starting material remaining (%) is in parentheses; when left longer, reactions did proceed further but for comparative data, ca. 95% yield time
points are given here.
c 70 °C.
d >90% safrole in sassafras oil.
O
O
O
O
vacuum distillation isolated (E)-6a in 87.9% yield (Scheme
2). Similarly, eugenol (3) in neat clove oil is smoothly con-
verted in 10 minutes using catalyst 1 into (E)-isoeugenol
(3a), isolated in 88.3% yield (Scheme 2). Bifunctional cata-
lyst 1 is an attractive tool for the transformation of essential
oils without interference to the catalyst by impurities.
1 (0.5 mol%)
2.86 g
87.9%
neat, 30 min
6a
3a
6
(in sassafras oil)
MeO
HO
MeO
1 (0.5 mol%)
2.90 g
88.3%
neat, 10 min
3
HO
(in clove oil)
Scheme 2 Neat isomerization on essential oils to afford isolated (E)-
propenylbenzene compounds using catalyst 1
1 (0.1 mol%)
4.65 g
93.0%
2a
2
neat, 45 min
MeO
MeO
An even greener approach to desirable trans-propenyl-
benzene flavors and fragrances would be executing the re-
action with a heterogeneous catalyst but without any sol-
vent. Separation of liquid product from solid catalyst should
be facile, and in addition make possible the reuse of the sol-
id catalyst for a subsequent isomerization reaction in batch
format. After experimenting with several possible reaction
setups, batch reactions were performed with neat eugenol
(3, ca. 3 g, Scheme 3) as the substrate and a polyethylene
mesh bag containing solid catalyst submerged in the neat
MeO
HO
MeO
HO
1 (0.1 mol%)
neat, 20 min
3a 15.76 g
3
95.9%
Scheme 1 Neat isomerization to isolated (E)-propenylbenzne flavors
and fragrances on large scale using catalyst 1
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2462–2466

2465
C. R. Larsen et al.
Letter
Synlett
liquid substrate. After conversion of eugenol to (E)-isoeu-
genol was complete, as much product as possible was
drained from the mesh bag and weighed. Only about 3/4 of
product from the first cycle could be obtained in this way,
likely because of retention inside as well as on the surface
of the polymer and the porous mesh bag. Fresh eugenol 3
was added for cycles 2 and, later, cycle 3; after completion
of isomerization, product was isolated in near quantitative
yield, consistent with our explanation that the lower yield
from cycle 1 is due to mechanical losses, an issue that could
be solved by better reactor engineering. Reasonable reac-
tion rates required heating at 70 °C, perhaps related to the
degree of swelling and kinetics of substrate and product ac-
cess to the catalyst active sites. Like PS-1, the linker catalyst
PSL-1 similarly affords multigram quantities of product
(Scheme 3); moreover, for the PSL-1 case, a fourth cycle
with twice the amount of substrate (6.57 g) and hence half
the catalyst loading gave 98% yield. Finally, in a separate se-
ries of experiments on freshly distilled eugenol, 10 cycles
could be achieved with no apparent loss in yield or selectiv-
ity, although the 10th cycle required 48 hours instead of 24
hours. Overall, the amount of catalyst used to convert ca. 33
grams was 0.04 mol%. The tea-bag method for isomeriza-
tion of neat reactants illustrates an extremely convenient
and green route to obtain the title fragrances and flavorings
in high yield and selectivity.
sequent reactions while maintaining reactivity and selec-
tivity. Z Isomers were present from 0.4% to less than 0.1%
levels in the products, highlighting the reliable and superior
selectivity of the bifunctional catalysts used in this work.
Acknowledgment
We thank NSF (CHE 1059107, 1464781) for supporting this and relat-
ed work.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560205.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
References and Notes
(1) These authors contributed equally.
(2) Fahlbusch, K.-G.; Hammerschmidt, F.-J.; Panten, J.; Pickenhagen,
W.; Schatkowski, D.; Bauer, K.; Garbe, D.; Surburg, H. Ullmann's
Encyclopedia of Industrial Chemistry; Wiley-VCH: Weinheim,
2002.
(3) Tully, T. W. Flavors & Fragrances Industry Update; Tully & Hol-
land: Wellesley (MA, USA), 2014, ; http://www.tullyandhol-
land.com/Thpublic.asp.
(4) Sharma, S. K.; Srivastava, V. K.; Jasra, R. V. J. Mol. Catal. A: Chem.
2006, 245, 200.
(5) Bauer, K.; Garbe, D.; Surburg, H. Common Fragrances and Flavor
Materials: Preparation, Properties and Uses; Wiley-VCH: Wein-
heim, 1990, 2nd ed.
MeO
MeO
cat. (0.5 mol%)
neat
24 h, 70 °C
(6) Chalk, A. J. Flavors and Fragrances: A World Perspective; Elsevier:
Amsterdam, 1988.
3
3a
HO
HO
(7) Leung, A. Y. Encyclopedia of Common Natural Ingredients used in
Food, Drugs and Cosmetics; Wiley: New York, 1980.
(8) Eirew, G. H. US 2009035229, 2009.
(9) Fujita, K.-I.; Fujita, T.; Kubo, I. Phytother. Res. 2007, 21, 47.
(10) Enan, E. WO 2008003007, 2008.
PS-1
3a isolated % yield
PSL-1
3a isolated % yield
cycle I
cycle II
cycle III
2.51 g
3.23 g
3.27 g
76.2%
97.9%
99.6%
cycle I
cycle II
cycle III
2.40 g
3.27 g
3.24 g
73.0%
99.4%
100%
(11) Kouznetsov, V. V.; Merchan Arenas, D. R. Tetrahedron Lett. 2009,
50, 1546.
using 0.39 mol% catalyst on freshly distilled eugenol:
(12) Barnes, J.; Anderson, L. A.; Phillipson, J. D. Herbal Medicines;
Pharmaceutical Press: London, 2007, 3rd ed.
(13) Merchan Arenas, D. R.; Acevedo, A. M.; Vargas Méndez, L. Y.;
Kouznetsov, V. V. Sci. Pharm. 2011, 79, 779.
PSL-1
3a isolated
% yield
cycle I
cycles II–X 3.21-3.30 g
2.39 g
72.3%
97.5–100%
Scheme 3 Neat isomerization of eugenol to (E)-isoeugenol using het-
erogeneous catalysts PS-1 and PSL-1 and recycling studies
(14) Jirovetz, L.; Buchbauer, G.; Stoilova, I.; Stoyanova, A.; Krastanov,
A.; Schmidt, E. J. Agric. Food Chem. 2006, 54, 6303.
(15) Mallavarapu Ramesh, S.; Chandrasekhara, R. S.; Rao, B. R. P.;
Kaul, P. N.; Bhattacharya, A. K. Flav. Fragr. J. 1995, 10, 239.
(16) Takeyoshi, M.; Iida, K.; Suzuki, K.; Yamazaki, S. J. Appl. Toxicol.
2008, 28, 530.
(17) Hua, D.; Ma, C.; Lin, S.; Song, L.; Deng, Z.; Maomy, Z.; Zhang, Z.;
Yu, B.; Xu, P. J. Biotechnol. 2007, 130, 463.
(18) Padmakumari, K. P.; Sasidharan, I.; Sreekumar, M. M. Nat. Prod.
Res. 2011, 25, 152.
(19) Findik, E.; Ceylan, M.; Elmastas, M. Eur. J. Med. Chem. 2011, 46,
4618.
(20) Fajemiroye, J. O.; Galdino, P. M.; De Paula, J. A.; Rocha, F. F.;
Akanmu, M. A.; Vanderlinde, F. A.; Zjawiony, J. K.; Costa, E. A.
Food Funct. 2014, 5, 1819.
In summary, we show that bifunctional catalysts are ca-
pable of extremely rapid and selective transformations of
allyl benzene flavors and fragrances to afford desirable
(E)-propenyl benzene analogues. Homogeneous catalyst 1
performs well either in acetone solution or without solvent,
on multigram scale, with either purified substrates or non-
purified essential oils. Polymer-supported versions PS-1
and PSL-1 are also excellent catalysts for isomerization re-
actions with neat substrate on multigram scale, further-
more the heterogeneous catalysts can be separated from
the products with the ability to recycle the catalyst for sub-
(21) Huang, Y.; Ho, S.-H.; Lee, H.-C.; Yap, Y.-L. J. Stored Prod. Res.
2002, 38, 403.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2462–2466

2466
C. R. Larsen et al.
Letter
Synlett
(22) Zemek, J.; Košiková, B.; Augustín, J.; Joniak, D. Folia Microbiol.
1979, 24, 483.
(23) Cremasco, M. A.; Braga, N. d. P. Acta Amazonica 2012, 42, 275.
(24) de Lima, M. E. F.; Gabriel, A. J. A.; Castro, R. N. J. Braz. Chem. Soc.
2000, 11, 371.
(25) Hartung, C. G.; Breindl, C.; Tillack, A.; Beller, M. Tetrahedron
2000, 56, 5157.
(26) Opdyke, D. L. J. Monographs on Fragrance Raw Materials; Perga-
mon Press: Oxford, 1979.
(53) Erdogan, G.; Grotjahn, D. B. Top. Catal. 2010, 53, 1055.
(54) Grotjahn, D. B.; Larsen, C. L.; Erdogan, G. Top. Catal. 2014, 57,
1483.
(55) Erdogan, G.; Grotjahn, D. B. Org. Lett. 2014, 16, 2818.
(56) General Procedures (See Supporting Information for Details)
For Table 1 Solution-Phase Experiments
To substrate and internal standard in acetone-d6 was added cat-
alyst, and NMR integrations for reactants and products were
compared with those of the standard.
(27) Pines, H.; Stalick, W. M. Base Catalyzed Reactions of Hydrocar-
bons and Related Compounds; Academic Press: New York, 1977.
(28) Boissier, J. R.; Simon, P.; Le Bourhis, B. Thérapie 1967, 22, 309.
(29) Taylor, J. M.; Jenner, P. M.; Jones, W. I. Toxicol. Appl. Pharmacol.
1964, 6, 378.
For Schemes 2 and 3
To air-free reactant was added solid catalyst, and aliquots were
then analyzed to determine when to initiate vacuum distillation
to isolate products.
For Scheme 4
(30) Caujolle, F.; Meynier, D. Acad. Sci. 1958, 246, 1465.
(31) Miller, E. C.; Swanson, A. B.; Phillips, D. H.; Fletcher, T. L.; Liem,
A.; Miller, J. A. Cancer Res. 1983, 43, 1124.
(32) Lee, H. S.; Lee, G. Y. Bull. Korean Chem. Soc. 2005, 26, 461.
(33) Rama Reddy, M.; Periasamy, M. J. Organomet. Chem. 1995, 491,
263.
(34) Jinesh, C. M.; Antonyraj, C. A.; Kannan, S. Catal. Today 2009, 141,
176.
(35) Urbala, M.; Krompiec, S.; Penkala, M.; Danikiewicz, W.; Grela,
M. Appl. Catal., A 2013, 451, 101.
(36) Sharma, S. K.; Parikh, P. A.; Jasra, R. V. J. Mol. Catal. A: Chem.
2010, 317, 27.
(37) Lastra-Barreira, B.; Crochet, P. Green Chem. 2010, 12, 1311.
(38) Lastra-Barreira, B.; Díaz-Álvarez, A. E.; Menéndez-Rodríguez, L.;
Crochet, P. RSC Adv. 2013, 3, 19985.
(39) Cerveny, L.; Krejeikova, A.; Marhoul, A.; Ruzicka, V. React. Kinet.
Catal. Lett. 1987, 33, 471.
(40) Scarso, A.; Colladon, M.; Sgarbossa, P.; Santo, C.; Michelin, R. A.;
Strukul, G. Organometallics 2010, 29, 1487.
In a glovebox, heterogeneous catalyst was loaded into a polyeth-
ylene mesh bag that was contacted with neat reactant in a vial,
using a stir bar for mixing. After 24 h, aliquots were analyzed to
verify conversion. The product was squeezed out of the mesh
bag and weighed, and ca. 100 mg samples were analyzed by
NMR spectroscopy to determine isomeric composition.
Typical Analytical Data
For 5a in the mixture: 1H NMR (500 MHz, acetone-d6): δ = 6.66
(s, 1 H), 6.33 (qd, J = 1.5, 16.0 Hz, 1 H; for the J = 1.5 Hz quartet,
only the inner two peaks were fully resolved), 6.20 (qd, J = 6.5,
16.0 Hz, 1 H), 3.81 (s, 6 H), 3.71 (s, 3 H), 1.83 (dd, J = 1.5, 6.5 Hz,
3 H) ppm. 13C NMR (500 MHz, acetone-d6): δ = 154.56, 138.72,
134.62, 132.16, 125.39, 104.37, 60.64, 56.46, 18.53 ppm.
For 7a in the mixture: 1H NMR (500 MHz, acetone-d6): δ = 7.12
(qd, J = 1.5, 12.5 Hz, 1 H), 6.88–6.95 (m, 1 H), 5.45 (qd, J = 1.5,
12.5 Hz, 1 H), 1.79–1.85 (m, 6 H), 1.63 ppm (dd, J = 1.5, 7.0 Hz,
3 H). 13C NMR (500 MHz, acetone-d6): δ = 165.30, 139.49,
137.24, 128.56, 109.80, 14.56, 12.49, 12.09.
(57) Tan, K. H.; Nishida, R. J. Insect Sci. 2012, 12, 56.
(58) Chang, C. L.; Cho, I. K.; Li, Q. X. J. Econ. Entomol. 2009, 102, 203.
(59) Kurita, N.; Miyaji, M.; Kurane, R.; Takahara, Y. Agric. Biol. Chem.
1981, 45, 945.
(60) Luu, T. X. T.; Lam, T. T.; Le, T. N.; Duus, F. Molecules 2009, 14,
3411.
(41) Hassam, M.; Taher, A.; Arnott, G. E.; Green, I. R.; van Otterlo, W.
A. L. Chem. Rev. 2015, 115, 5462.
(42) Yu, Z.; Yan, S.; Zhang, G.; He, W.; Wang, L.; Li, Y.; Zeng, F. Adv.
Synth. Catal. 2006, 348, 111.
(43) Sobczak, I.; Ziolek, M.; Pérez-Mayoral, E.; Blasco-Jimenéz, D.;
Lópes-Peinado, A. J.; Martín-Aranda, R. M. Catal. Today 2012,
179, 159.
(61) Maya, K. M.; Zachariah, T. J.; Krishnamoorthy, B. J. Spices Aro-
matic Crops 2004, 13, 135.
(44) Jinesh, C. M.; Sen, A.; Ganguly, B.; Kannan, S. RSC Adv. 2012, 2,
6871.
(62) Parthasarathy, V. A.; Chempakam, B.; Zachariah, T. J. Chemistry
of Spices; CAB International: London, 2008.
(45) Kishore, D.; Kannan, S. Green Chem. 2002, 4, 607.
(46) Luu, T. X. T.; Lam, T. T.; Le, T. N.; Duus, F. Molecules 2009, 14,
3411.
(47) Menéndez-Rodríguez, L.; Crochet, P.; Cadierno, V. Curr. Green
Chem. 2014, 1, 128.
(63) Belanger, A.; Collin, G.; Garneau, F.-X.; Gagnon, H.; Pichette, A.
J. Essential Oil Res. 2010, 22, 164.
(64) DeBaggio, T.; Tucker, A. O. The Encyclopedia of Herbs: A Compre-
hensive Reference to Herbs and Flavor and Fragrances; Timber
Press: Portland (OR, USA), 2009.
(48) Gandilhon, P.; Charly, R. DE 1936727, 1970.
(49) Chalk, A. J.; Kinnelon, N. J. DE 2508347, 1975.
(50) Grotjahn, D. B.; Larsen, C. R.; Gustafson, J. L.; Nair, R.; Sharma, A.
J. Am. Chem. Soc. 2007, 129, 9592.
(51) Larsen, C. R. Grotjahn D. B. J. Am. Chem. Soc. 2012, 134, 10357.
(52) Erdogan, G.; Grotjahn, D. B. J. Am. Chem. Soc. 2009, 131, 10354.
(65) Burdock, G. A. Fenaroli's Handbook of Flavor Ingredients; Taylor
Francis Group: Boca Raton, 1995.
(66) Sigma-Aldrich
http://www.sigmaaldrich.com/Graphics/CofAInfo/Sigma-
SAPQM/SPEC/W5/W510483/W510483-BULK-K_ALDRICH_.pdf.
Product
Specification:
Sassafras
Oil,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2462–2466