Synthesis of 1-aryl-1-phenylpropenes using an alkylation-rearrangement- methylationisomerization one-pot reaction sequence

Article abstract of DOI:10.2478/s11532-011-0074-y

(Z/E)-1-(2-Methoxyaryl)-1-phenylpropenes have been prepared in good yields by heating a mixture of a phenolic substrate, cinnamyl chloride, tetramethylammonium chloride and K₂CO3 in polyethyleneglycol at 180°C. The one-pot synthesis proceeds through four discrete reaction steps: alkylation of the phenol with cinnamyl chloride, Claisen rearrangement, O-methylation and double-bond migration. The configuration of one crystalline product was determined using a single-crystal X-ray diffraction analysis. The thermodynamic and structural features of the products were evaluated using computational chemistry techniques. Versita Sp. z o.o.

Full text of DOI:10.2478/s11532-011-0074-y

Cent. Eur. J. Chem. • 9(5) • 2011 • 904-909
DOI: 10.2478/s11532-011-0074-y
Central European Journal of Chemistry
Synthesis of 1-aryl-1-phenylpropenes using
an alkylation-rearrangement-methylation-
isomerization one-pot reaction sequence
Research Article
Nenad Maraš1, Franc Perdih1,2, Marijan Kočevar*1
1Faculty of Chemistry and Chemical Technology,
University of Ljubljana, SI-1000 Ljubljana, Slovenia
2CO EN-FIST, SI-1000 Ljubljana, Slovenia
Received 6 May 2011; Accepted 10 June 2011
Abstract:
(Z/E)-1-(2-Methoxyaryl)-1-phenylpropenes have been prepared in good yields by heating a mixture of a phenolic substrate, cinnamyl
chloride, tetramethylammonium chloride and K2CO3 in polyethyleneglycol at 180°C. The one-pot synthesis proceeds through four
discrete reaction steps: alkylation of the phenol with cinnamyl chloride, Claisen rearrangement, O-methylation and double-bond
migration. The configuration of one crystalline product was determined using a single-crystal X-ray diffraction analysis.
The thermodynamic and structural features of the products were evaluated using computational chemistry techniques.
Keywords: Tetramethylammonium • Phenols • Claisen rearrangement • Methylation • Atropisomerism
© Versita Sp. z o.o.
required (150–160°C) [8]. Typically, the reactions were
conducted in polyethyleneglycol (PEG) using K2CO3 as
a base.
1. Introduction
Quaternary ammonium salts have seldom been used
as electrophilic alkylating reagents [1]. Their use for the
alkylation of phenols (Scheme 1) was rarely reported,
except for the reactions with phenyltrimethylammonium
salts, in particular due to their ability to chemoselectively
O-methylatephenolicsubstratescontainingaminogroups
[2]. In fact, this methylation method, first described by
Rodionov [3], was mainly used in the O-methylations of
phenolic morphinans [4].
We thus considered the possible applications
that could exploit this lack of reactivity to a synthetic
advantage. For this reason we evaluated the ability of
tetramethylammonium chloride (Me4NCl) to O-methylate
phenols concurrently while they are being formed in a
Claisen rearrangement, a [3,3]-sigmatropic reaction,
which itself requires comparatively harsh conditions. The
thermal variant of the aromatic Claisen rearrangement
is most commonly performed at high temperatures,
typically 180–225°C, either neat or in high-boiling-point
solvents such as N,N-diethylaniline or diphenyl ether
[9]. Most common methylating reagents [10], such as
dimethyl sulfate or methyl iodide, are either too reactive
or volatile to be applicable at such temperatures.
The less reactive tetramethylammonium hydroxide
(Me4NOH) has been used in the methylation of phenolic
steroids [5]. We reported
a
microwave-assisted
methylation of phenols with tetramethylammonium
chloride (Me4NCl) in 1,2-dimethoxyethane at 145°C in
the presence of K2CO3 or Cs2CO3 [6]. Recently, a related
investigation applying other tetra-alkylammonium salts
(BnEt3NCl, BnEt3NBr and Bu4NBr), under solventless and
microwave-assisted conditions, as well as in acetonitrile,
produced similar results [7]. Our next study, on the
alkylation of phenols with various tetra-alkylammonium
chlorides under conventional heating conditions,
demonstrated that relatively high temperatures are
+ (CH3)3RN+,
-
O
OH
O
N+
R
base
- H+
N
R
+
+
R = phenyl or methyl
General O-methylation reaction of phenols
with phenyltrimethylammonium (PhMe3N+) or
tetramethylammonium (Me4N+) cations (R is phenyl
or methyl).
Scheme 1.
* E-mail: marijan.kocevar@fkkt.uni-lj.si
904

N. Maraš, F. Perdih, M. Kočevar
Table 1. Crystal data for 6d.
2. Experimental Procedure
Parameter
Data
NMR spectra were recorded at 29°C on a Bruker
Avance DPX 300-MHz spectrometer in CDCl3 with
tetramethylsilane (TMS) as the internal standard. The
melting points were uncorrected and measured on a
Kofler micro hot stage. The reactions were monitored
with high-performance liquid chromatography (HPLC)
using a Nucleosil C-18 column with an acetonitrile/water
mobile phase and UV detection at 254 nm. The mass
spectra were recorded with a VG-Analytical AutoSpec
Q instrument. The elemental analyses (C, H, N) were
performed with a Perkin Elmer 2400 CHN Analyzer.
Potassium carbonate was finely ground and dried at
150°C for 12 hours. Polyethyleneglycol (PEG) with an
average molecular mass of 400 was used (PEG400).
All the quantum-mechanical calculations were
conducted with the Gaussian 09 set of programs
[11]. Full geometry optimizations with no symmetry
constraints on the (Z/E)-6a–d were performed using
AM1 semi-empirical quantum chemical calculations.
The same method was used for the calculations of fully
relaxed single-bond torsional potentials on (Z/E)-6a,d;
i.e., for each fixed torsional angle around the central,
all the remaining internal degrees of freedom were
optimized. A rather tight, regular single-bond 10° grid of
points was applied in all cases.
Single-crystal X-ray diffraction data were collected
at room temperature with a Nonius Kappa CCD
diffractometer using graphite monochromated Mo-Kα
radiation (λ = 0.71073 Å). The data were processed
using DENZO [12]. The structures were solved by
direct methods implemented in SHELXS-97 [13] and
refined by a full-matrix least-squares procedure based
on F2 with SHELXL-97 [14]. All the non-hydrogen atoms
were refined anisotropically. All the hydrogen atoms
were readily located in difference Fourier maps and
were placed at calculated positions and treated using
the appropriate riding models. The crystallographic
data are listed in Table 1. CCDC-821481 contains the
supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
Formula
Mr
C20H17BrO
353.25
T (K)
293(2)
Crystal system
Space group
a (Å)
monoclinic
P 21/n
9.1832(3)
9.6147(3)
18.8861(5)
b (Å)
c (Å)
β (°)
V (Å3)
99.599(2)
1644.18(9)
4
Z
Dcalc. (Mg m-3)
μ (mm–1)
1.427
2.499
F(000)
720
Reflections collected
Reflections unique (Rint)
Parameters
R, wR2 [I>2σ (I)]a
R, wR2 (all data)b
GOF, Sc
7203
3752 (0.0363)
201
0.0445, 0.1083
0.0769, 0.1247
1.017
aR = ∑||Fo| – |Fc||/∑Fo|. b wR2 = {∑[w(Fo2 – Fc )2]/∑[w(Fo )2]}1/2
.
2
2
cS = {∑[(Fo2 – F )2]/(n/p}1/2 where n is the number of reflections
2
and p is the totacl number of parameters refined.
the extract was washed with 2M NaOH(aq) (3×50 mL),
water (60 mL), filtered through a plug of silicagel and
evaporated. This crude product was then purified either
by radial chromatography using elution with petroleum
ether (6a–b) or by crystallizations from methanol or
n-hexane (6c–d). This gave the products (Z/E)-6 as
10:1 mixtures of diastereomers (ratios determined by 1H
NMR spectroscopy).
(Z/E)-1,4-Dimethoxy-2-(1-phenylprop-1-en-1-yl)
benzene (6a). Colorless liquid (1.60 g, 63%). IR (NaCl)
1598, 1584, 1495, 1464, 1442, 1418, 1275, 1220 cm-1;
MS (ESI) m/z 277 (MNa+), 255 (MH+), 236, 145, 106,
104; HRMS (ESI) calcd for C17H19O2 [M+H]+ 255.1385,
1
found 255.1376. NMR data for the major(Z)-isomer: H
NMR δ 1.66 (d, J = 6.9, 3H), 3.64 (s, 3H), 3.76 (s, 3H),
6.28 (q, J = 6.9, 1H), 6.67 (d, J = 2.9, 1H), 6.86 (m, 2H),
7.12–7.30 (m, 5H); 13C NMR δ 15.8, 55.9, 56.6, 112.9,
113.3, 117.4, 125.0, 126.3, 126.7, 128.2, 130.1, 138.9,
142.0, 151.8, 153.8. Selected 1H NMR data for the (E)-
isomer: δ 1.84 (d, J = 7.1, 3H), 3.48 (s, 3H), 3.76 (s, 3H),
5.95 (q, J = 7.1, 1H).
(Z/E)-1,2-Dimethoxy-3-(1-phenylprop-1-en-1-yl)-
5-propylbenzene (6b). Yellowish liquid (2.00 g, 67%).
IR (NaCl) 1581, 1483, 1462, 1424, 1362, 1260, 1232
cm-1; MS (ESI) m/z 319 (MNa+), 297 (MH+), 179, 131,
117; HRMS (ESI) calcd for C20H25O2 [M+H]+ 297.1855,
found 297.1851. NMR data for the major (Z)-isomer: 1H
NMR δ 0.94 (t, J = 7.3, 3H), 1.63 (m, 2H), 2.54 (t, J = 7.6,
2H), 3.50 (s, 3H), 3.86 (s, 3H), 6.25 (q, J = 6.9, 1H), 6.52
General procedure for the synthesis of 1-(2-
methoxyaryl)-1-phenylpropenes 6: A stirring slurry
of the phenolic compound (1a–d; 10 mmol), cinnamyl
chloride (2; 1.68 g, 11 mmol), tetramethylammonium
chloride (2.27 g, 20 mmol) and K2CO3 (2.91 g, 20 mmol)
in PEG (10 mL) was heated from rt to 180°C during the
course of 3 h at a steady rate and then kept stirring at
this temperature for 1 h. The mixture was diluted with
water (100 mL), extracted with diisopropyl ether (60 mL),
905

Synthesis of 1-aryl-1-phenylpropenes using
an alkylation-rearrangement-methylation-isomerization
one-pot reaction sequence
(d, J = 2.1, 3H), 6.71 (d, J = 2.1, 1H), 7.25 (m, 5H); 13
C
derived from a double [3,3]-sigmatropic rearrangement
NMR δ 14.0, 16.0, 24.8, 38.1, 55.9, 60.5, 111.9, 123.3, [9]). Indeed, adding Me4NCl and K2CO3 to the reaction
124.8, 126.6, 126.7, 128.2, 133.7, 138.4, 139.2, 142.5, mixture of para-methoxyphenyl allyl ether in PEG
145.2, 152.9. Selected 1H NMR data for the (E)-isomer: resultedinthesimultaneousO-methylationoftheClaisen
δ 0.95 (t, J = 7.3, 3H), 1.84 (d, J = 7.1, 3H), 3.30 (s, 3H), rearrangement product when heating for 3 h at 180°C,
3.80 (s, 3H), 5.90 (q, J = 7.1, 1H).
but the presence of the base partially caused a double-
(Z/E)-2,6-Dimethoxy-1-(1-phenylprop-1-en-1-yl) bond migration in the resulting ortho-allylanisole (e.g.
naphthalene (6c). The (E/Z) mixture was obtained as about half of the product isomerized to the E/Z mixture
an amorphous solid that partially crystallized to a white of the ortho-propenylanisoles). Such a rearrangement-
powder over several days (1.70 g, 56%). Mp = 56–66°C; methylation-isomerization sequence could not be
IR (KBr) 1627, 1597, 1507, 1494, 1460, 1422, 1375, optimized to give the ortho-methoxy propenylbenzenes
1341, 1253 cm-1; MS (ESI) m/z 305 (MH+); HRMS (ESI) as the sole products, because the isomerization step
calcd for C21H21O2 [M+H]+ 305.1542, found 305.1548. was inefficient and furthermore led to an inseparable
1
NMR data for the major (Z)-isomer: H NMR δ 1.51 (d, mixture of diastereomers.
J = 6.9, 3H), 3.78 (s, 3H), 3.88 (s, 3H), 6.57 (q, J = 6.9,
Such a portion of double-bond migration is surprising
1H), 7.00–7.35 (m, 8H), 7.60 (d, J = 9.1, 1H), 7.75 (d, considering the relatively low basicity of the K2CO3. In
J = 9.1, 1H); 13C NMR δ 15.7, 55.5, 57.1, 77.2, 106.2, our previous work [8], a stronger base like NaOH had
115.0, 119.6, 123.4, 126.0, 126.1, 126.8, 127.0, 127.8, to be used at 150°C in PEG for the O-methylation of
128.4, 128.6, 129.0, 130.3, 136.5, 141.8, 152.9, 156.3. allylphenols like eugenol and 2-allylphenol, when such
1
Selected H NMR data for the (E)-isomer: δ 2.02 (d, J isomerization was desirable (K2CO3 was still ineffective
= 7.1, 3H), 3.71 (s, 3H), 3.93 (s, 3H), 5.80 (q, J = 7.1, at this temperature). However, we rationalized that if
1H).
using phenyl cinnamyl ethers as substrates, instead
(Z)-6-Bromo-2-methoxy-1-(1-phenylprop-1-en-1- of the plain allyl ethers, the reaction could be more
yl)naphthalene (6d). The (E/Z) mixture was obtained efficient and the isomerization in the last step would be
as an off-white powder (1.90 g, 54%), which upon complete: (a) the intermediate ether 3a rearranges faster
recrystallization from n-hexane gave the pure (Z)-isomer. [9]; (b) the double-bond isomerization of 5a should also
Mp = 124–127°C; 1H NMR δ 1.49 (d, J = 6.9, 3H), 3.80 be considerably easier due to the higher acidity of the
(s, 3H), 6.57 (q, J = 6.9, 1H), 7.17 (m, 5H), 7.35 (d, J benzhydrylic hydrogen in comparison with the benzylic
= 9.0, 1H), 7.39 (dd, J = 2.0, 9.0, 1H), 7.56 (d, J = 9.0, one; (c) the E : Z ratio could be more biased toward one
1H), 7.76 (d, J = 9.0, 1H), 7.96 (d, J = 2.0, 1H); 13C NMR isomer; (d) and therefore, the reaction should proceed
δ 15.5, 56.6, 114.8, 117.3, 119.7, 122.8, 125.7, 126.3, faster toward the end product and thus, overall, be less
126.7, 127.0, 128.1, 128.2, 129.8, 130.2, 131.5, 135.7, prone to side reactions.
141.2, 154.3; IR (KBr) 1584, 1494, 1459, 1437, 1333,
To further expand the scope of such a one-pot
1270 cm-1; MS (EI) m/z: 354 (M+, 76), 352 (M+, 76), 273 reaction we included the aryl cinnamyl ether formation
(100), 258 (57), 195 (31), 91 (46), 74 (56); Anal. Calcd as the first step of the reaction sequence. Allyl
for C20H17BrO: C 68.00, H 4.85. Found: C 67.99, H 4.90. halides like 2 are quite reactive toward phenolates at
Selected 1H NMR data for the (E)-isomer: δ 2.02 (d, J = temperatures much lower than approximately 150°C,
7.1, 3H), 3.73 (s, 3H), 5.79 (q, J = 7.1, 1H).
as required for the Me4NCl-based methylation. In this
way a complementary use of the two alkylating reagents
together in the same reaction mixture is made possible
duetotheirtemperature-dependentreactivity.Anattempt
was thus made by slowly heating a mixture of para-
methoxyphenol (1a), cinnamyl chloride (2), Me4NCl and
K2CO3 in PEG, from room temperature to 180°C, and
keeping it at this temperature for one hour (Scheme 2).
The reaction was much cleaner and chromatographic
separation gave (Z/E)-6a as a viscous oil. The ratio of
diastereomers was 10 : 1, but their configuration could
not be unambiguously assigned based on the NMR
analysis of the chromatographically inseparable mixture.
This same problem was encountered by another group
of researchers who obtained an inseparable 85 : 15
mixture of (Z/E)-6a by the FeCl3-catalyzed alkenylation
3. Results and discussion
Polar and protic solvents were found to enhance the
reaction rate of the aromatic Claisen rearrangement
[15]. Ethyleneglycol, mono- and diethyl ethers of
diethyleneglycol, which are solvents related to PEG,
were already found to be efficient, but we could find no
examples using PEG for this purpose. Our preliminary
experiments with para-methyl or para-methoxyphenyl
allyl ethers confirmed that PEG is an efficient solvent for
the Claisen rearrangement when heating the reaction
mixture for a minute at 230°C (para substitution was
preferred in order to avoid the common side products
906

N. Maraš, F. Perdih, M. Kočevar
Cl
O
O
O
O
OH
O
O
O
+ Me4NCl, K2CO3 / PEG
+
h, 180 °C
63%
1
O
(
/
)-6a
O
Z E
one-pot
1a
2
phenol
alkylation
R
Br
(Z)-6d
double bond
migration
(Z/E)-6a
(Z/E)-6b
(Z/E)-6c: R = OCH3
(Z/E)-6d: R = Br
OH
O
O
O
O
Claisen
rearrangement
O
-methylation
Figure 1.
Compounds
6
prepared using the alkylation-
rearrangement-methylation-isomerization
reaction sequence.
one-pot
O
3a
4a
5a
Scheme 2. An
example of the direct synthesis of the 1-(2-
methoxyaryl)-1-phenylpropenes directly from
a
phenol derivative (the brackets show a step-wise
representation of the one-pot reaction sequence).
of 1,4-dimethoxybenzene with 1-phenylpropyne [16].
They assigned the major as the (Z)-isomer, based on
the 1H NMR chemical shift correlation with the software
prediction. The same isomer they assigned as (Z) was
also the major product in our case.
The reaction also performed well on dihydroeugenol
(1b),6-methoxy-2-naphthol(1c)and6-bromo-2-naphthol
(1d) giving the corresponding (E/Z)-1-(2-methoxyaryl)-1-
phenylpropenes 6 (Fig. 1). The isolation of the (Z/E)-6c
and (Z/E)-6d required no chromatographic separation
as the solid products were obtained by crystallization. A
recrystallization of 6d allowed the isolation of the major
diastereomer. Yields of the products 6 were relatively
good, ranging from 54 to 67%, representing an average
86–90% yield for each of the four formal reaction steps
that together comprise the one-pot reaction sequence.
However,someothersubstratesgavenodesiredproduct.
Figure 2. X-Ray crystal structure of (Z)-6d.
For example, para-phenylphenol and para-cumylphenol Φ of 105.42(13)° between the 1-naphthyl and propen-
gave no expected product as the reaction stopped at 1-yl moieties. This appears indicative of strong steric
their corresponding cinnamyl ethers, thus indicating the repulsions, of the methyl (C1) and the phenyl group on
reaction conditions were not suitable for the Claisen the 1-phenylpropene moiety, against the peri-hydrogen
rearrangement to occur. Some other substrates, like the (H18) and the methoxy group on the naphthyl moiety. It
dihydric phenol naphthalene-2,7-diol, for example, gave also raised questions about the rotational barrier energy
complex reaction mixtures.
and the possible existence of atropisomerism in (Z)-6d
Having been able to grow crystals of the major at room temperature (both enantiomeric rotamers are
diastereomer of the solid product 6d from n-hexane, present in the crystal packing). Published theoretical
we determined its structure with a single-crystal X-ray evaluations demonstrated that 1-vinylnaphthalene
diffraction analysis (Fig. 2). The configuration around already shows a relatively high steric interference at the
the double bond was found to be (Z), thus with the peri-hydrogen of the naphthyl ring [17]. The additional
methyl and the phenyl groups in trans relation. Semi- substituents in (Z)-6d might thus not only prevent the full
empirical quantum chemical calculations confirmed that rotation, but also effectively block the interconversion of
this double-bond configuration is thermodynamically the two possible atropisomers.
favored; the calculated (Z)- vs. (E)-isomer difference of
We thus performed semi-empirical AM1 calculations
the ground-state energies was found to be 0.94 kJ mol-1 to obtain an estimation of the pertaining potential energy
curve for internal rotation in (Z)-6d. The results show
(Fig. 3) that the compound has a potential energy
curve with a minimum energy valley at Φ values from
70° to 100° (the curve is otherwise symmetrical for
using the AM1 computational model.
No π-π stacking was observed in the crystal packing,
but an interesting feature in the molecular structure
was the relatively high C2-C3-C10-C11 torsion angle
907
907

Synthesis of 1-aryl-1-phenylpropenes using
an alkylation-rearrangement-methylation-isomerization
one-pot reaction sequence
ΔErot of 70 kJ mol-1 is indicative of a relatively fast axial
rotationrateatroomtemperature,withtheinterconversion
of the order of seconds, which is common for barriers
lower than approximately 84 kJ mol-1 (20 kcal mol-1) [18].
The results obtained with our calculations do not support
the existence of atropisomerism in (Z)-6d; however,
a definitive answer cannot be given, relying solely on
semi-empirical calculations.
An analogous calculation for (E)-6d shows a
potential curve with the expected lower maximums
(44 and 57 kJ mol-1, respectively).
The potential curves for the (Z)-6a and (E)-6a
rotations around the corresponding torsion angle are
even lower in energy (Fig. 4), which is understandable,
because the lack of the peri-hydrogen allows for a much
freer rotation. The ortho-hydrogen thus induces only
a much smaller steric repulsion, which is particularly
evident from the larger difference in both maximums for
(E)-6a, showing that the repulsion between the methoxy
and the phenyl groups is left as the major contributor.
A reliable assignment of the (Z)- and (E)-isomers
comprising the diastereomeric 10 : 1 mixtures of (Z/E)-6
using NMR, UV or other spectroscopic techniques is not
straightforward without the actual separation of each
isomer for their comparison. The XRD data obtained
for (Z)-6d can be considered as further evidence that
the other major isomers of the 1-(2-methoxyaryl)-1-
phenylpropenes 6 are also of such a configuration. The
1H NMR spectra of the diastereomeric mixtures of the
products 6 show a recurring pattern in the chemical
shifts and the coupling constant of the methyl group and
the hydrogen substituents on the alkene double bonds
(Table 2). For the major isomers, the doublet of the
methyl group is always upfield (shielded), and the quartet
of the hydrogen is always downfield (deshielded), when
compared to the chemical shifts of the corresponding
signals for the minor isomers. Furthermore, the three-
Figure 3. Calculated
potential curves for rotation around
the C2-C3-C10-C11 torsion angle (Φ) for both
diastereomers of 6d using the AM1 method.
Figure 4. Calculated
potential curves for rotation around
the C2-C3-C10-C11 torsion angle (Φ) for both
diastereomers of 6a using the AM1 method.
Table 2. Comparison of 1H NMR data for the ethylidene group
(=CH–CH3) of the diastereomers in the mixtures of (Z/E)-6,
and their calculated thermodynamic differences.
Major
Minor
b
diastereomer diastereomer Calculated
Reaction
product
(Z)
δ [ppm] 3JHH δ [ppm] 3JHH
[Hz] [Hz]
(E)
(Z) vs. (E)
ΔE
[kJ mol-1]
CH3
H
CH3
H
6a
6b
6c
1.66 6.28 6.9
1.68 6.25 6.9
1.51 6.57 6.9
1.49 6.57 6.9
1.84 5.95 7.1
1.84 5.90 7.1
2.02 5.80 7.1
2.02 5.79 7.1
-1.20
-2.01
-0.98
-0.94
3
bond coupling constants JHH of the major isomers
c
6d
are consistently 6.9 Hz, while the corresponding
constants in the minor isomer are consistently 7.1 Hz.
The configuration of the major diastereomers was thus
assigned to be (Z) in all the compounds 6. In addition,
a Obtained from the NMR analysis of mixtures in CDCl3.
b The differences of the ground state energies of the (Z)- vs. (E)-isomers as
obtained by the AM1 calculations (Austin Model 1).
c The configuration of the major isomer was confirmed to be (Z) by XRD.
the enantiomeric rotamers in the interval from 0° to semi-empirical calculations for all the compounds
–180°). As expected, there are two maximums in the support the notion that all the (Z)-isomers show an
potential energy, a higher one at 180° (80 kJ mol-1) and increased thermodynamic stability.
a lower one at 0° (70 kJ mol-1). The higher maximum
is therefore where the phenyl group is most strongly
4. Conclusions
repulsed by the methoxy group and the methyl group
by the peri-hydrogen. On the other hand, the repulsion
Tetramethylammonium chloride can be used to
O-methylate ortho-allylphenols, as they are formed
during the Claisen rearrangement. Double-bond
migration occurs due to the basic medium and high
in the opposite rotamer (Φ = 0°) was calculated to be
10 kJ mol-1 lower in energy and this maximum thus
representsthelimitingbarrierΔErot fortheinterconversion
between the two potential atropisomers. The estimated
908
908

N. Maraš, F. Perdih, M. Kočevar
temperature. The substrates for the rearrangement, such
as the aryl cinnamyl ethers, can be prepared as part of
this one-pot process, thus allowing for a new synthetic
method for the preparation of (Z/E)-1-(2-methoxyaryl)-
1-phenylpropenes directly from phenols. The (Z) vs.
(E) selectivity in the formation of 1-(2-methoxyaryl)-1-
phenylpropenes was 10 : 1 and the stereochemistry
Acknowledgements
We thank the Ministry of Higher Education, Science and
TechnologyoftheRepublicofSloveniaandtheSlovenian
Research Agency for financial support (No. P1-0230-
0103 and P1-0230-0175). Dr. B. Kralj and Dr. D. Žigon
(Center for Mass Spectroscopy, ‘‘Jožef Stefan’’ Institute,
Ljubljana, Slovenia) are gratefully acknowledged for the
mass measurements.
1
assignments were made using XRD (for 6d) and H
NMR data. Semi-empirical calculations indicate that
the (Z)-isomers are the thermodynamically more stable
isomers.
References
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