Solvent-free condensation of arylacetonitrile with aldehydes

Article abstract of DOI:10.1016/j.tet.2005.07.040

The condensation of a series of arylacetonitriles with aldehydes can be carried out by mixing equivalent amounts of reagents with neat powdered KOH at room temperature for 3-60 min depending on the aldehyde steric hindrance. At higher temperature (110°C), yields were generally higher and purity increased within very short reaction times (1-5 min). With pentamethylphenylacetonitrile, a phase transfer agent was necessary to give a satisfactory yield.

Full text of DOI:10.1016/j.tet.2005.07.040

Tetrahedron 61 (2005) 10129–10137
Solvent-free condensation of arylacetonitrile with aldehydes
a
Regis Guillot, Andre Loupy, Abdelkrim Meddour, Michele Pellet and Alain Petit
b,
c
d
b
*
´
´
`
a
´ ´ ´ ˆ
Institut de Chimie Moleculaire et des Materiaux d’Orsay (ICMMO), Universite Paris-Sud, batiment 420, 91405 Orsay cedex, France
´
Laboratoire des Reactions Selectives sur Supports, CNRS UMR 8615, Universite Paris-Sud, batiment 410, 91405 Orsay cedex, France
b
´ ´
ˆ
´ ´ ˆ
Laboratoire ‘ RMN en milieu oriente ’, CNRS 8074, Universite Paris-Sud, batiment 410, 91405 Orsay cedex, France
c
d
´ ˆ
Laboratoire des Carbocycles, CNRS UMR 8615, Universite Paris-Sud, batiment 420, 91405 Orsay cedex, France
Received 25 May 2005; revised 6 July 2005; accepted 14 July 2005
Available online 6 September 2005
Abstract—The condensation of a series of arylacetonitriles with aldehydes can be carried out by mixing equivalent amounts of reagents with
neat powdered KOH at room temperature for 3–60 min depending on the aldehyde steric hindrance. At higher temperature (110 8C), yields
were generally higher and purity increased within very short reaction times (1–5 min). With pentamethylphenylacetonitrile, a phase transfer
agent was necessary to give a satisfactory yield.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
temperatures (Method II, 110 8C), eventually in the
presence of a phase transfer agent (PTA) (Method III).
When a PTA catalyst was added (TBAB, Aliquat 336, TDA-1
or 18-C-6), under microwave irradiation (MW), new
acrylonitriles with phenyl or alkyl group were obtained
(whatever the base) according to a multi-step proposed
mechanism.17 With nonanenitrile, the PTA is necessary to
obtain satisfactory yields, which were enhanced when
using excesses of base (KOCH3 or KOH) and
nonanenitrile. However, a rather high temperature
(130–150 8C) is needed, either under MW irradiation or
conventional heating.
Unsaturated nitriles play a key role in several pathways
proposed for the prebiotic synthesis of biological
molecules.1 Arylacrylonitriles are important synthons of
the synthesis of several biologically active molecules in the
3
preparation of flagrances,2 flavonoıd pigments, sexual
¨
pheromones4 and vitamin A.5 They are directly concerned
for increasing soybean yield as plant growth regulators,6 and
as inhibitors of prostaglandin synthetase.7 Recently, they
were used in the field of organic materials in order to obtain
high-electron affinity polymers, which can be used to
produce light-emitting diodes (LEDs) with air stable
electrodes.8,9
Strengthened by these results and in order to generalize the
method, we now extend this study to the reaction of a series
of aliphatic and aromatic aldehydes, including hindered
ones, with substituted phenylacetonitriles.
The usual preparation of arylacrylonitriles involves the
reaction of aromatic aldehydes with arylacetonitriles
(Meyer and Frost reaction).10 Indeed, they can be obtained
under basic conditions in a polar solvent (NaOH, KOH,
NaOEt, K2CO3 in MeOH or EtOH)11–15 or under liquid–
liquid phase transfer catalysis conditions.3,16
2. Results and discussions
Very recently, we have proposed solvent-free procedures
using neat powdered base.17 When applied to the reaction of
phenylacetonitrile with 4-methoxybenzaldehyde, excellent
results were obtained using KOH at room temperature
(Method I). The reactions were performed at higher
2.1. Reactions with phenylacetonitrile
Reactions were first carried out by mixing equivalent molar
amounts of aldehyde (10 mmol), phenylacetonitrile and
finely ground KOH. The main product was the a,b-
unsaturated nitriles 3(ZCE), contaminated by compound
4 resulting from Michael addition of 2a to 3 (Eq. 1), and
sometimes 5 coming from competitive Cannizzaro
reaction.
Keywords: Solvent-free condensation; Microwave irradiation; Phase
transfer catalysis; X-ray crystallography.
*
Corresponding author. Tel.: C33 1 69 15 76 50; fax: C33 1 69 15 46 79;
e-mail: aloupy@icmo.u-psud.fr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.040

10130
R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
of stirring as the reaction mixture became too solid (entries
2 and 4).
With aldehyde 1c, an important amount of compound 4c
resulting from the Michael addition of 2a to 3cZ is
obtained (8–12%, entries 5 and 6). When using an
excess of nitrile (entry 7), the yield in 4c is increased
up to 20%. Furthermore, 1c was among the tested
aldehydes the only one giving amounts of the
Cannizzaro product 5c.
(1)
Where a highly hindered aromatic aldehyde such as
mesitaldehyde 1d is concerned, reaction time had to
be extended up to 60 min to give a quasi-quantitative
yield (98%, entry 10). Pivalaldehyde 1e, in spite of
steric hindrance due to tert-butyl group, led to a good
yield in 10 min when using a slight excess of aldehyde
(1.5 equiv) (87%, entry 12). No by-products were
observed in these two last cases.
The main results are given in Table 1.
In all the cases, the major isomer was 3Z with only traces of
3E (%2%). The Z configuration of the carbon]carbon
double bond in the major stereoisomer of compounds 3 was
determined by X-ray single crystal analysis and by
13C NMR. The 3J coupling constant between the
ethylenic proton and the carbon of the nitrile group was
A yield of 87% in 3fZ was obtained from L-(K)-citronellal
1f in 10 min (entry 13), together with small amounts of 4f
(4%). Extension of reaction time did not allow any
improvement.
3
measured. In all cases, J(C–H) values larger than 14 Hz
were found.18
The same reactions were next carried out at higher
temperatures (R110 8C) under MW irradiation for very
short times (1–2 min) and compared systematically with
conventional heating (D) under strictly similar conditions
(time, temperature, stirring,.) in order to check the
possible non-thermal MW specific effects.19
With the less hindered aromatic aldehydes 1a–c, good
yields (75–86%, entries 1, 3 and 6) were obtained within
very short reaction time (3 min), needing a slight excess of
aldehyde (1.3 equiv) when bearing a CF3 group in position 4
(entry 6). Extended reaction times up to 10 min induced
only a slight improvement, presumably due to the inefficacy
Table 1. Solvent-free condensation of phenylacetonitrile 2a with aromatic 1a–d and aliphatic 1e–f aldehydes, at room temperature, in the presence of KOH
[Method I]
Entry
Aldehyde
(R) Ar
Ph
Reaction
time
(min)
Conversiona
(%)
Yields (%)a
3Z
3E
4
5
1
2
1a
1b
3
10
96
96
77
81
1
1
4
6
0
0
3
4
3
10
95
98
86
90
1
1
2
2
0
0
5
6
7
1c
3
94
92
—
63
75
67
2
2
2
12
8
20
7
7
5
3b
3c
8
9
10
1d
10
30
60
75
87
100
62
87
98
0
0
0
0
0
0
0
0
0
11
12
1e
1f
10
10d
79
89
77
87
0
0
0
0
0
0
13
10
94
87
1
4
0
a Conversions (based on consumption of 2a) and yields were measured by GC using an internal standard (diethyl phthalate).
b 1c (1.3 equiv).
c 2a (1.2 equiv).
d 1e (1.5 equiv).

R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
10131
Table 2. Solvent-free condensation of 2a with a series of aldehydes 1a–f, in the presence of KOH under MW irradiation or in a thermostated oil bath (D)
[Method II]
Entry
Aldehyde
Activation
method
Reaction time Temperaturea
Conversionb
(%)
Yields (%)b
3E
(min)
(8C)
3Z
4
14
15
1a
1b
1c
MW
D
1
1
113
112
100
99
90
88
3
3
0
2
16
17
MW
D
1
1
120
120
95
95
92
93
2
2
0
0
18
19
20
MW
MW
D
1
2
1
111
125
101
97
99
97
87
94
83
3
1
2
4
2
5
21
22
23
1d
1e
1f
MW
MW
D
1
2
2
111
131
134
42
90
91
42
80
74
0
4
1
0
0
0
24
25
26
MW
MW
D
1
2
1
77
115
80
67
84
60
66
83
58
! 1
! 1
! 1
0
0
0
27
28
MW
D
1
1
123
107
98
96
95
90
3
4
0
2
a Optimal values obtained under MW (assigned temperatureZ100 8C for 1a–d and 1f, 60 8C for 1e) and consequently used for reactions under conventional
heating D (values evaluated inside the reaction mixtures).
b Conversions and yields measured by GC using an internal standard (diethyl phthalate).
In Table 2 the results obtained under these conditions
(MW and D) are given.
2.2. Reactions of several aromatic acetonitriles with
4-methoxybenzaldehyde
Reactions were carried out by mixing equivalent amounts of
4-methoxybenzaldehyde 1b (10 mmol), arylacetonitrile
2a–c and finely ground KOH. The main product was the
a,b-unsaturated nitrile 6, essentially with Z geometry,
eventually accompanied in certain cases of compound 7
derived from Michael addition of 2 to 6 (Eq. 2).
Yields were quite good (R80%) within very short
reaction times (1–2 min). Two opposite behaviours were
shown:
– a significant decrease in yield in the case of
mesitaldehyde 1d (80% within 2 min, entry 22)
remained significantly less than the one resulting
from reaction at room temperature. The yield was
not next improved by extending reaction time up
to 3 and 5 min as the isomer E was appearing (ex
3 min MW 3dZ: 80% 3dE: 10%).
– a clear increase with benzaldehyde 1a (88–90%
instead of 77–81% by Method I). The improve-
ment is even more important with 1c as yield was
94% versus only 63% according to Method I.
Furthermore, it is of interest here to recover much
less by-products (3% instead of 15–25%).
(2)
Aliphatic aldehydes 1e and 1f led to comparable yields
but now without any traces of by-products (compare
entries 25–27, respectively, with entries 11 and 13 in
Table 1).
Finally, as a general rule, Method II seems to be more
suitable than Method I improving the yield and reducing the
secondary reactions. Nevertheless, in all these cases, results
were practically identical whatever the activation mode, that
is, no specific MW effects intervene here. The absence of
such MW effects is justified as expected when considering
the only slight modification of the polarity of the system
during the reaction from the ground state to the transition
state. The increase in polarity (necessary to observe MW
effects) is here evidently limited due to the involvement of
PhCHCNK,MC loose ion pairs concerning a charge
delocalized (soft) anion.20
The main results are given in Table 3.
Satisfactory yields were obtained (R74%) after short
reaction times (%10 min). The Z isomer was preponderant
and accompanied by traces of 6E. However, extension of
the reaction time induced slight modification presumably
due to the heterogeneity of the reaction mixture. This
reaction was next foreseen under MW irradiation and, for
sake of comparison, with classical heating under similar
conditions. Results are given in Table 4.
With nitriles 2a–c, we isolated 6a–cZ in high yields under

10132
R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
Table 3. Solvent-free condensation at room temperature of arylacetonitriles 2a–c with 4-methoxybenzaldehyde 1b in the presence of solid KOH [Method I]
Entry
Nitrile
Ar
Reaction time
(min)
Conversiona
(%)
Yields (%)a
6E
6Z
7
3
4
3
10
95
98
86
90
1
1
2
2
2a
2b
Ph
29
30
3
10
83
94
65
74
2
1
0
0
31
2c
10
92
88
2
0
a Conversions and yields were evaluated by GC using an internal standard (diethyl phthalate).
Table 4. Solvent-free condensation of ArCH2CN 2a–c with 1b in the presence of solid KOH under MW irradiation or in a thermostated oil bath (D) [Method II]
Entry
Nitrile
Ar
Activation Reaction
mode
Temperaturea
(8C)
Conversiona
(%)
Yields (%)b
time
(min)
6Z
6E
7
14
15
32
33
34
35
36
37
38
2a
2b
2c
2d
Ph
MW
D
MW
D
MW
D
MW
D
1
1
1
1
1
1
5
5
3
113
112
124
124
119
119
122
120
140
100
99
99
93
99
100
47
45
90
88
89
83
92
93
19
24
17
3
3
3
2
1
1
14
14
13
0
2
0
0
0
0
0
0
0
MW
43
a Optimal values obtained under MW (assigned temperatureZ100 8C for entries 14, 32 and 34, 120 8C for 36 and 140 8C for 38) and consequently used for
reactions under conventional heating D (values evaluated inside the reaction mixtures).
b Conversions and yields were measured by GC using an internal standard (diethyl phthalate).
MW within 1 min (R89%), even with nitrile 2b (89%),
which proved to be lower at room temperature (74% after
10 min, entry 30).
the reaction after addition of Aliquat 336 (Eq. 3), of which
we report in Table 5 the main results obtained either
under MW irradiation or classical heating with similar
conditions.
With the especially hindered nitrile 2d, the yields remained
very low (33%, entry 36), even when increasing temperature
to 140 8C (entry 38).
The addition of Aliquat 336 allowed to noticeably increase
the yields in 6ZCE from 33% (entry 36, Table 4) up to 56%
(entry 40, Table 5) under similar conditions (5 min at
120 8C). Yields were even more significantly improved up
to 86% (entry 43) using an excess of aldehyde (1.5–3 equiv)
with an optimal yield for 2 equiv. In all cases, Z is the
predominant isomer. However, as discussed above, no
noticeable MW specific effects were evidenced (MWZ86%
versus DZ76%).
Changing the MW heating to conventional heating (entry
37) did not change the yield. In fact, as before, we did not
observe any MW effects (Table 4), since yields and
conversions were quite similar under conventional
heating for the four nitriles (2a–2d). In order to try to
improve the yield with the hindered 2d, we also performed
Table 5. Solvent-free condensation of pentamethylphenylacetonitrile 2d with 1b under solid–liquid phase transfer catalysis (PTC) conditions and MW
irradiation or in a thermostated oil bath (D) [Method III]
Entry
1b
(equiv)
Activation
mode
Reaction time
(min)
Temperaturea
(8C)
Conversionb
(%)
Yields (%)b
6dZ
6dE
39
40
41
42
43
44
45
46
1
MW
MW
MW
MW
MW
D
3
5
5
3
5
5
7
5
117
120
120
120
120
120
120
120
73
96
86
91
90
100
91
75
36
36
48
55
64
57
56
47
16
20
20
20
22
19
20
22
1.5
2
MW
MW
3
a Optimal values obtained under MW (assigned temperatureZ120 8C) and consequently used for under conventional heating D (values evaluated into the
reaction mixtures).
b Conversions and yields were measured by GC using an internal standard (diethyl phthalate).

R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
10133
CCD area detector diffractometer. Intensities were given
with graphite-monochromated Mo Ka radiation (0.71073
˚
A). The data were recorded at room temperature for 6dE
and at 100 K(G1 K) for the three others (3dZ, 6cZ and
6dZ). The structures were solved by direct methods SHELX
8621 and refined using SHELX 9722 suite of programs. Non-
H atoms were refined anisotropically by full-matrix least-
squares techniques. H atoms were calculated geometrically
and included in the refinement.
(3)
Crystal’s data, details of data collections and structures
refinements are given in the Section 4.
3. Conclusions
We have shown that solvent-free conditions, as previously
established for the condensation of phenylacetonitrile with
4-methoxybenzaldehyde,17 can be generalized to a series of
aromatic and aliphatic aldehydes and to more or less
hindered nitriles. At room temperature (Method I), reactions
required from 3–60 min depending of the aldehyde steric
hindrance. At higher temperatures (R110 8C, Method II),
either under MW irradiation or conventional heating,
reaction times are very short (1–5 min) and yields are
generally higher and less by-products are recovered. With
2.3. Crystallographic study
The structures of compounds 3dZ, 6cZ, 6dZ and 6dE have
been established by X-ray crystallography (Fig. 1). The
crystal data were collected using a Bruker X8-APEX II-
Figure 1. Crystal structures for 3dZ, 6cZ, 6dZ and 6dE.

10134
R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
pentamethylphenylacetonitrile, a phase transfer agent
(Method III) is necessary to obtain a satisfactory yield at
120 8C. We have not observed any special MW effects
neither on yields or conversions nor on the selectivity Z/E of
the formed acrylonitriles.
3dZ
6cZ
6dZ
6dE
Number of
data
11,553
35,396
18,750
7461
collected
Number of
unique data
Observed
data
3382
2998
8051
5169
9317
2757
3950
2928
[IO2s(I)]
(nobs)
4. Experimental
Rint (%)
Number of
parameters
(nvar)
2.01
176
4.51
397
8.90
365
2.03
212
Microwave equipment
Reactions were performed in a monomode reactor
Synthewave 402 microwave device from Prolabo.23 The
temperature was measured during the reaction by infrared
detection, which indicates the surface temperature after
previous calibration of emissivity in each case with an
optical fiber thermometer (FTI-10 device from Fiso, optical
fiber up to 250 8C). All reactions were conducted in a
cylindrical Pyrex tube with mechanical stirring to ensure
homogeneity in temperature. The power was monitored
during irradiation to maintain a constant temperature.
R a(%)
6.67
9.82
1.024
K0.564
5.71
21.94
30.10
1.225
K0.785
6.03
8.17
1.035
K0.282
wR b(%)
Sc
Drmin
12.69
0.978
K0.410
K3
(eK
A
)
)
˚
Drmax
A
0.433
0.559
0.939
0.331
K3
(eK
˚
Characterization of products
The dimensions of the crystal 6dZ (20 microns thickness)
did not permit to obtain data of satisfying quality to carry
out a perfect refinement. The factor R for this structure is
21.94%. This structure is not deposited on Cambridge
Crystallographic Data Center but this result is sufficient to
prove that the compound is the expected one.
Solid products were characterized by their melting points.
All the products were also characterized by GC–MS (Delsi-
NerMag spectrometer with an ionising energy of 70 eV
coupled to a gas chromatography fitted with a capillary
column DB5, 30 m, IDZ0.25 mm).
Their 1H and 13C NMR spectra were registered on a Bruker
instrument (AC 200, AC 250 and DRX 400) as CDCl3
solutions. Chemical shifts are expressed in d units (ppm) and
quoted downfield from TMS as an internal standard. Proton-
coupled 13C NMR experiments were performed on a Bruker
DRX 400 NMR spectrometer using a classical gated
decoupling technique.
Crystallographic data for the structures reported in this
paper, have been deposited with the Cambridge Crystallo-
graphic Data Center, CCDC Nos. 269684–269685 and
269686. Copies of this information may be obtained free of
charge from The Director, CCDC, 12 Union Road,
Cambridge, CB2 1EZ, UK (fax: C44 1223 336033;
e-mail: deposit@ccdc.cam.ac.uk or www: http://www.
ccdc.cam.ac.uk).
X-ray crystallography
GC Analyses
Crystallographic data:
All the yields were determined by GC with diethyl phthalate
as internal standard. The GC devices (GC 9000 series
Fisons, GC 5160 Vega series 2 Carlo Erba) were fitted with
a non-polar capillary column, film thicknessZ0.1 mm,
carrier gasZhelium.
3dZ
18H17
6cZ
6dZ
6dE
Chemical
formula
Crystal
system
Space
C
N
C17H12F3
NO
Monoclinic Monoclinic Triclinic
C21H23
C21H23
NO
Orthorhombic
NO
P21/n
C2/c
P-1
Pbca
GC equipment is fitted with a hardware (NCI 900 series
interface) and software (Turbochrom) system developed by
Perkin Elmer Co.
Group
˚
a (A)
˚
10.27(1)
9.02(1)
14.72(1)
90
90.17(1)
90
1363(1)
4
0.070
15.98(1)
31.32(1)
13.68(1)
90
125.019(1)
90
5607(1)
16
0.117
12.16(1)
18.27(1)
18.64(1)
61.49(1)
70.99(1)
89.87(1)
3382(2)
4
13.31(1)
13.38(1)
19.40(1)
90
90
90
3454(2)
8
0.071
b (A)
˚
c (A)
a (8)
b (8)
g (8)
GC conditions and retention times for reagents and products
are given in Table 6.
3
˚
V (A )
Typical experiment
Z
m (Mo Ka)
(mm-1)
0.073
Aldehydes, arylacetonitriles, Aliquat 336 were purchased
from commercial sources (Acros, Aldrich or Avocado
Chemical Co.). Aldehydes 1a, 1b and 1c were distilled
before use. All others were used without any further
purification. Commercial solid KOH (containing 15%
H2O) was finely grounded.
Crystal size 0.200,
0.200,
0.120,
0.060
2496
1.30–30.98
100(1)
0.100,
0.080,
0.020
1312
1.29–24.05
100(1)
0.250,
0.300,
0.300
1312
2.10–27.48
293(2)
(mm)
0.180,
0.130
528
F (000)
2q range (8) 2.42–30.89
T (K) 100(1)

R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
Table 6. GC conditions and retention times (RT) for reagents and products
10135
Products or reagents
GC column
GC conditions
RT (min)
Internal standard RT (min)
5.87
1a
2a
OV1, 12 m
IDZ0.25 mm
100/250 8C (10 min)
10 8C/min
1.18
1.73
3aZ
3aE
4a
PHeZ50 kPa
9.78
8.40
15.17C15.57
1c
2a
3cZ
3cE
4c
12QC2/BP1, 12 m
IDZ0.22 mm
80/250 8C (5 min)
10 8C/min
PHeZ50 kPa
1.15
1.86
9.88
8.53
14.44C15.03
2.27
6.46
9.38
5c
1b
2a
DB1, 30 mm
IDZ0.25 mm
100/280 8C (10 min)
10 8C/min
5.58
4.50
3bZ^6aZ
3bE^6aE
4b^7a
1d
3dZ
3dE
1f
3fZ
3fE
4f
PHeZ70 kPa
16.40
15.12
22.43C23.24
6.33
15.17
14.05
4.74
14.25
13.93
100/250 8C (10 min)
10 8C/min
9.38
11.14
7.65
23.00C23.42C23.80
In the solvent
5.40
1e
2a
80/250 8C (10 min)
10 8C/min
3eZ
3eE
1b
9.71
9.39
4.75
5.63
120/280 8C (10 min)
10 8C/min
2b
6bZ
6bE
2c
6cZ
6cE
2d
17.22
15.60
4.09
13.91
12.29
9.78
6dZ
6dE
19.44
17.69
4.1. Solvent-free uncatalyzed reaction (Tables 1–4)
4-methoxybenzaldehyde 1b (10 mmol; 0.68 g) were intro-
duced into a Pyrex vessel adapted to the microwave
equipment, fitted with a mechanical stirrer.
A mixture of phenylacetonitrile 2a (10 mmol; 1.17 g), solid
KOH (10 mmol; 0.65 g) and aldehyde 1a–f (10 mmol) were
introduced into a Pyrex vessel adapted to the microwave
equipment fitted with a mechanical stirrer. At room
temperature [Method I] or at temperatures R110 8C
[Method II], the reactions were carried out in Pyrex vessels
according to the conditions indicated in the Tables. At the
end of the reaction, organic products were extracted with
organic solvent (ethyl acetate) and the mixture was then
filtered through sintered-glass.
Treatment remained exactly the same whatever the
catalyzed or non-catalyzed nature of the reactions, under
MW irradiation or conventional heating.
4.2.1. Z-2,3-Diphenylacrylonitrile 3aZ (RN: 2510-95-4).
Commercial product (Lancaster Chemical Co.)
4.2.2. Z-2-Phenyl-3-(4-methoxyphenyl)acrylonitrile 3bZ
or 6aZ (RN: 5432-07-5). This product was already
described in earlier work.17
The products 3a–f(ZCE), 4a–c, 4f and 5c were identified
by GC–MS, NMR, X-ray crystallography, retention time by
comparison with authentic samples, and analyzed by GC
with an internal standard. Under conventional heating
conditions (D) (Tables 2 and 4), the same Pyrex vessel as
for MW experiments was used in the reactions carried out in
the thermostated oil bath, at the same temperature as under
MW irradiation. The same treatments were performed in
both cases.
4.2.3. Z-2-Phenyl-3-(4-trifluoromethylphenyl]acrylo-
nitrile 3cZ (RN: 147728-28-7).
4.2. PTC solvent-free reaction (Tables 5 and 6)[Method
III].
A mixture of arylacetonitrile 2a–d (10 mmol), solid KOH
(10 mmol; 0.65 g), Aliquat 336 (1 mmol; 0.4 g) and
Purified by flash chromatography (ether/n-pentane/ethanol
3:15:0.5). White crystals. MpZ112–114 8C. MS: m/z 273

10136
R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
(MC, 100%), 258 (10.7), 252 (11.4), 204 (78.2), 177 (11),
88 (11), 51 (13.5). H NMR: 7.40–7.55 (m, 3H, HiCHj),
7.58 (s, 1H, He), 7.62–7.70 (m, 2H, Hh), 7.70–7.78 (m, 2H,
Hb), 7.95–8.05 (m, 2H, Hc). 13C NMR: 114.49 (Cf), 117.39
(CN) (JHe–CNZ14.5 Hz), 122.22 (CF3), 125.95 (Cb), 126.17
(Ch), 129.12 (Ci)C129.40 (Cc), 129.85 (Cj), 131.33 (Ca),
133.80 (Cg), 137.02 (Cd), 140.11 (Ce).
Purified by flash column chromatography on silica gel
(n-pentane). Colourless liquid. MS: m/z 253 (MC, 18.1),
238 (20.1), 154 (18.1), 115 (59.2), 109 (77.7), 81 (22.9), 69
(100), 55 (27.4), 41 (87.8). 1H NMR: 0.98 (d, 3H, Ho), 1.15–
1.55 (m, 2H, Hi), 1.61C1.68 (2s, 2!3H, HnCHm), 1.70–
1.85 (m, 1H, Hh), 1.9–2.15 (m, 2H, Hj), 2.37–2.70 (m, 2H,
Hg), 5.09 (m, 1H, Hk), 6.83 (t, 1H, Ha), 7.30–7.48 (m, 3H,
HeCHf), 7.48–7.60 (m, 2H, Hd). 13C NMR: 17.53 (Cn),
19.36 (Co), 25.36 (Cj), 25.58 (Cm), 32.69 (Ch), 36.54 (Ci),
39.21 (Cg), 116.46 (CN) (JHa–CNZ14.4 Hz), 116.55 (Cb),
124.06 (Ck), 125.41 (Cd), 128.65 (Cf), 128.73 (Ce),
131.37C133.13 (CcCCl), 145.83 (Ca).
1
4.2.4. Z-2-Phenyl-3-(2,4,6-trimethylphenyl)acrylonitrile
3dZ (RN: 173975-31-0).
4.2.7. Z-2-(4-Methoxyphenyl)-3-(4-methoxyphenyl)-
acrylonitrile 6bZ (RN: 6443-74-9). This product was
already described in earlier work.17
4.2.8. Z-2-(4-Trifluoromethylphenyl)-3-(4-methoxy-
phenyl)acrylonitrile 6cZ (RN: 146725-29-3).
Purified by washing the crude product with cold n-pentane.
Yellow crystals. MpZ103 8C. MS: m/z 247 (MC, 100%),
231 (59.7), 205 (10.2), 115 (17.1), 91 (14.1), 77 (17.4), 51
1
(12.2). H NMR: 2.31 (s, 9H, HkCHl), 6.91 (s, 2H, Hb),
7.34–7.45 (m, 3H, HiCHj), 7.64 (s, 1H, He), 7.65–7.70 (m,
2H, Hh). 13C NMR: 20.10 (Ck), 20.97 (Cl), 116.72 (Cf),
118.50 (CN) (JHe–CNZ14.5 Hz), 125.72 (Ch), 129.55 (Cb),
128.94 (Ci)C129.23 (Cj), 130.69 (Ca), 133.21 (Cg), 135.81
(Cc), 138.32 (Cd), 142.75 (Ce).
Purified by flash column chromatography on silica gel
(n-pentane then n-pentane/ether 98:2). Yellow crystals.
MpZ127–128 8C. MS: m/z 303 (MC, 100), 284 (13,4), 272
(12.7), 240 (13.7), 234 (29), 233 (55.8), 219 (12.1), 191
(29.1), 190 (57.1). 1H NMR: 3.89 (s, 3H, OCH3), 6.94–7.06
(m, 2H, Hb), 7.54 (s, 1H, He), 7.64–7.85 (m, 2!2H, HhC
Hi), 7.85–8.01 (m, 2H, Hc). 13C NMR: 55.24 (CH3O),
107.07 (Cf), 114.52 (Cb), 118.03 (CN) (JHe–CNZ15.0 Hz),
121.03 (CF3), 124.00 (Cd), 125.99 (Ch), 128.43 (Ci), 129.39
Cj), 131.56 (Cc), 138.34 (Cg), 143.70 (Ce), 161.96 (Ca).
4.2.5. Z-2-Phenyl-3-tert-butylacrylonitrile 3eZ (RN:
110327-47-4).
4.2.9. Z-2-(2,3,4,5,6-Pentamethylphenyl)-3-(4-methoxy-
phenyl)acrylonitrile 6dZ.
Purified by distillation under reduced pressure. Colourless
liquid. BpZ120–122/0.55 mbar. MS: m/z 185 (MC, 73.5),
170 (100), 154 (18.6), 143 (67.4), 128 (46.3), 115 (33.7), 77
1
(34.2), 41 (31.6). H NMR: 1.35 (s, 9H, Hh), 6.75 (s, 2H,
Hb), 7.33–7.43 (m, 3H, HfCHg), 7.52–7.58 (m, 2H, He). 13
C
NMR: 29.53 (Ch), 34.42 (Ca), 112.10 (Cc), 117.20 (CN)
(JHb–CNZ15.0 Hz), 125.73 (Ce), 128.63 (Cg), 128.76 (Cf),
135.08 (Cd), 157.31 (Cb).
4.2.6. Z-2-Phenyl-3-[(2,6-dimethyl)hept-5-en]acrylo-
nitrile 3fZ.
Purified by flash column chromatography on silica gel
(n-pentane then n-pentane/ether 99:1–95:5). White solid.
MpZ157 8C. MS: m/z 305 (MC, 100%), 290 (37.9), 275
1
(29.6), 263 (8.9), 197 (10.1), 182 (17.2), 121 (16.2). H
NMR: 2.24C2.27C2.28 (3s, 15H, HkCHlCHm), 3.87 (s,
3H, OCH3), 6.79 (s, 1H, He), 6.95–7.06 (m, 2H, Hb), 7.81–
7.94 (m, 2H, Hc). 13C NMR: 16.59 (Cl), 16.87 (Cm), 17.87
(Ck), 55.40 (CH3O), 108.07 (Cf), 114.28 (Cb), 118.68 (CN)
(JHe–CNZ15.5 Hz), 126.51 (Cd), 130.62 (Cc), 132.19 (Ch),
132.90 (Cg), 133.05 (Ci), 135.70 (Cj), 146.37 (Ce), 161.23
(Ca).

R. Guillot et al. / Tetrahedron 61 (2005) 10129–10137
10137
6. Peat, J. R.; Jeffcoat, B. Easter School in Agricultural Science
[Proceedings], Nottingham, UK, 1982; Vol. 33, pp 237-249;
Chem. Abstr. 1982, 98, 1617.
4.2.10. E-2-(2,3,4,5,6-Pentamethylphenyl)-3-(4-methoxy-
phenyl)acrylonitrile 6dE.
7. Michel, F.; Mercklein, L.; Crastes de Paulet, A.; Dore, J. C.;
Gilbert, J.; Miquel, J. F. Prostaglandins 1984, 27, 69–84.
8. Muruyama, S.; Tao, X.-T.; Hokari, H.; Noh, T.; Zhang, Y.;
Wada, T.; Sasabe, H.; Suzuki, H.; Watanabe, T.; Miyata, S.
Chem. Lett. 1998, 749–750.
9. (a) Segura, J. L.; Martin, N.; Hanack, M. Eur. J. Org. Chem.
1999, 643–651. (b) Gomez, R.; Segura, J. L.; Martin, N. Chem.
Commun. 1999, 619–620.
Purified by flash column chromatography on silica gel
(pentane then pentane/ether 99:1–95:5). White solid. MpZ
153 8C. MS: m/z 305 (MC, 100%), 290 (38.5), 275 (26), 263
10. Meyer, G.; Frost, L. N. Ann. 1888, 250, 157.
11. Buu-Hoi, N. P.; Xuong, N. D. Bull. Soc. Chim. France 1957,
650–655.
1
(7.6), 197 (6.8), 182 (11), 121 (10.2). H NMR: 2.19C
2.22C2.28 (3s, 6HC6H 3H, HkCHlCHm), 3.74 (s, 3H,
OCH3), 6.66–6.74 (m, 2H, Hb), 6.89–6.98 (m, 2H, Hc), 7.31
(s, 1H, He). 13C NMR: 16.63 (Cl), 16.94 (Cm), 17.08 (Ck),
55.20 (CH3O), 111.05 (Cf), 114.11 (Cb), 120.46 (CN)
(JHe–CNZ9.3 Hz), 127.11 (Cd), 129.58 (Cg), 131.22 (Ch),
131.35 (Cc), 133.42 (Ci), 135.94 (Cj), 144.19 (Ce), 160.87
(Ca).
12. Ladhar, F.; El, R. Gharbi. Synth. Commun. 1991, 21, 413–417.
13. Van de Velde, C. M. L.; Blockhuys, F.; Van Alsenoy, C.;
Lenstra, A. T. H.; Geise, H. J. J. Chem. Soc., Perkin Trans. 2
2002, 1345–1351.
14. Wawzonek, S.; Smolin, E. M. In Organic Synthesis, Collect.
Vol. III; Wiley: New York, 1955.
15. D’sa, B. A.; Kisanga, P.; Verkade, J. G. J. Org. Chem. 1988,
63, 3961–3967.
16. Zupancic, B.; Kokalj, M. Synthesis 1981, 913–915.
17. Loupy, A.; Pellet, M.; Petit, A.; Vo-Thanh, G. Org. Biomol.
Chem. 2005, 3, 1534–1540.
References and notes
18. Kalinowski, H. O.; Berger, S.; Braun, S. Carbon-13 NMR
Spectroscopy; Wiley: Chichester, 1984; pp 530.
19. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199–9225.
20. Perreux, L.; Loupy, A.; Delmotte, M. Tetrahedron 2003, 59,
2185–2189.
1. Guillemin, J. C.; Breneman, C. M.; Joseph, J. C.; Ferris, J. P.
Chem. Eur. J. 1998, 4, 1074–1082.
2. M. J. Fraysse. Perfumer and Flavorist 1980, 4, 11-12; Chem.
Abstr. 1980, 92, 185698.
3. Fringuelli, F.; Pani, G.; Piermatti, O.; Pizzo, F. Tetrahedron
1994, 50, 11499–11508.
¨
21. Sheldrick, G. M.; Kroeger, C.; Goddard, R. SHELX 86 in
Crystallographic Computing 3; Oxford University Press: New
York, 1985; pp 175–189.
4. Liu, R. S. H.; Matsumoto, H.; Asato, A. E.; Denny, M.;
Shichida, Y.; Yoshizawa, T.; Dahlquist, F. W. J. Am. Chem.
Soc. 1981, 103, 7195–7201.
22. Sheldrick, G. M. SHELX 97: Program for the Refinement of the
¨
Crystal Structures; University of Goettingen: Germany, 1997.
5. Mori, K. Synthetic Chemistry Of Insect Pheromones And
Juvenile Hormones; Recent Developments In The Chemistry
Of Natural Carbon Compounds; Akademiai: Budapest, 1979;
Vol. 9, p 11.
23. Loupy, A.; Petit, A.; Hamelin, J.; Texier-Boullet, F.; Jacquault,
´
P.; Mathe, D. Synthesis 1998, 1213–1234.